REVIEW | doi:10.20944/preprints201701.0094.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: theranostics; nuclear medicine; personalized medicine
Online: 22 January 2017 (04:29:27 CET)
The importance of personalized medicine is growing, since there is an urged need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for a specific molecular targeting in means of diagnostics and therapy. The visualisation of potential targets can help to predict if a patient would benefit from a particular treatment or not. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents is constantly rising. In this article important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with the well-known radioiodine therapy in patients with thyroid cancer and then guides through different approaches for the treatment of advanced cancer with targeted therapies. The aim of this review is to provide a summary of background knowledge, current applications and advantages of targeted therapies and imaging in nuclear medicine practice.
ARTICLE | doi:10.20944/preprints202009.0180.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cancer; alternative medicine; complementary medicine; health behaviours
Online: 8 September 2020 (10:11:37 CEST)
An increasing number of persons with cancer decide to choose complementary and alternative medicine. The purpose of the paper was to check the status of the use of complementary and alternative medicine methods in oncological patients and to compare health behaviours of patients using Complementary and Alternative Medicine (CAM) with those using neither of these methods. The studies were conducted from August till January 2020 in the Oncology Center in the south-eastern Poland. A cross-sectional study was conducted in a group of 208 oncological patients. The authors' own questionnaire and the standardized Health Behaviour Inventory were used. Most of the patients (85,09%) declared that they used complementary and alternative medicine methods. The most common methods chosen by the respondents included vitamin C, green tea and prayer. The vast majority of the respondents did not inform their oncologist about the use of CAM. 45,19% of the respondents had a high rate of health behaviours. It was observed that there was no communication related to the use of CAM among the patients and healthcare staff. Patients using CAM demonstrated more positive health behaviours than those who were not using these methods.
REVIEW | doi:10.20944/preprints202104.0326.v1
Subject: Medicine & Pharmacology, Allergology Keywords: microenvironment; radiopharmaceuticals; treatment response; personalised medicine; Nuclear Medicine
Online: 13 April 2021 (08:29:32 CEST)
Background: Molecular nuclear medicine, due to hybrid imaging camera systems and new tailored radiopharmaceuticals, has been gained a clinical relevance for diagnosis, therapy and follow-up of solid tumors. Despite numerous literature studies, many new radiopharmaceuticals for imaging tumor microenvironment, have not yet been used, routinely, in oncological clinical practice to monitor treatments. This is due to poor comparability of published studies, due to poor design and methodology, heterogeneous population and prevalence of preclinical studies. Methods: In this systematic review, we described the use of radiopharmaceuticals for evaluation of tumor treatment response by targeting microenvironment. We reviewed studies published from 2000 to 2020, to provide an updated status of research in this topic. Results: There is a growing role of radiopharmaceuticals and nuclear medicine imaging techniques in the management of cancer treatments, especially immunotherapy. Of the 24 papers included, 16 were preclinical studies. Conclusions: New radiopharmaceuticals could have an excellent impact in molecular imaging, leading to better diagnosis and important clinical information for therapy decision making and follow-up of cancer treatments in different solid tumors. Recently developed radiopharmaceuticals may provide great advantage to improve personalized medicine for patients with a great cost-effectiveness ratio.
REVIEW | doi:10.20944/preprints202110.0011.v1
Subject: Life Sciences, Other Keywords: Machine Learning; Precision Medicine; Genomic Medicine; Therapeutic; Artificial Intelligence
Online: 1 October 2021 (11:41:27 CEST)
The advancement of precision medicine in medical care has led behind the conventional symptom-driven treatment process by allowing early risk prediction of disease through improved diagnostics and customization of more effective treatments. It is necessary to scrutinize overall patient data alongside broad factors to observe and differentiate between ill and relatively healthy people to take the most appropriate path toward precision medicine, resulting in an improved vision of biological indicators that can signal health changes. Precision and genomic medicine combined with artificial intelligence have the potential to improve patient healthcare. Patients with less common therapeutic responses or unique healthcare demands are using genomic medicine technologies. AI provides insights through advanced computation and inference, enabling the system to reason and learn while enhancing physician decision-making. Many cell characteristics, including gene up-regulation, proteins binding to nucleic acids, and splicing, can be measured at high throughput and used as training objectives for predictive models. Researchers can create a new era of effective genomic medicine with the improved availability of a broad range of data sets and modern computer techniques such as machine learning. This review article has elucidated the contributions of ML algorithms in precision and genome medicine.
ARTICLE | doi:10.20944/preprints202105.0550.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Medical Education; Healthcare; Family Medicine; Medicine; Public Administration & Public Policy
Online: 24 May 2021 (10:03:35 CEST)
Little is known about family medicine academic staff in Taiwan, and basic data about this workforce may aid healthcare decision makers. We analysed data on Taiwan’s 13 medical schools collected by the Taiwan Association of Family Medicine from June to September 2019. Items included medical school names and total staff, and the gender, age, degree, working title (part-time/full-time), academic level, and sub-specialty of each current family medicine faculty member. A total of 116 family medicine faculty members were reported; most were male (n= 85, 73.3%). Ages ranged between 30 and 69 years, with a mean (SD) age of 43.3 (8.09). Faculty members with a master’s degree were the largest group (n= 49, 42.2%), and most were academic lecturers (n=49, 42.2%). Additionally, only about one-fourth (n=26, 22.4%) of family medicine faculty in medical schools were full-time, while the other three-fourths (n=90, 77.6%) were part-time faculty; most were located in northern Taiwan (n=79, 68.1%) and specialized in gerontology and geriatrics (n=55, 47.4%) and hospice palliative care (n=53, 45.7%). Our research provides the most complete census of family medicine academic physicians in medical schools in Taiwan. The results inform efforts to improve the establishment and development of family medicine departments in Taiwan.
REVIEW | doi:10.20944/preprints202103.0120.v2
Subject: Medicine & Pharmacology, Allergology Keywords: Artificial Intelligence; Medicine; Applications
Online: 28 October 2022 (09:56:54 CEST)
The medical & the dental field is a never ending field of innovations & developments and each time the reasearchers come up with something new. One such new dimension in the fields of medicine being the incorporation of Artificial intelligence assisted technologies improving diagnosis, treatmemt plan and treatment stategies. This review focusses on the application of different technologies of AI in different fields of medicine.
ARTICLE | doi:10.20944/preprints202207.0430.v1
Online: 28 July 2022 (07:25:22 CEST)
Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1,577 unrelated sequenced Sardinians -- an ancient island population that well accounts for genetic variation in Europe as a whole and, at the same time are enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimate that 99.43% of Sardinian individuals may potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we highlighted 174 pharmacogenetic variants for which the minor allele frequency is at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of the PGx characterization of diverse than European populations as Sardinians.
REVIEW | doi:10.20944/preprints202109.0182.v1
Online: 10 September 2021 (11:07:13 CEST)
The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans and cell culture. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. Organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging and to design personalized approaches for prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging paving the way to personalized interventions targeting the biology of aging.
ARTICLE | doi:10.20944/preprints201905.0091.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Iranian traditional medicine; alternative and complementary medicine; database; natural products; Mizaj; temperament
Online: 8 May 2019 (10:08:54 CEST)
As a holistic medical school, Iranian traditional medicine (ITM) considers the human body as a dynamic and intricate network of interconnecting processes. Currently, systems biology and more precisely systems medicine and pharmacology can be an aid in providing rationalizations for many traditional medications and treatments and elucidating a great deal of knowledge they can offer to guide future research in medicine. Therefore, re-organization and standardization of traditional medicine data are requested more than ever before. To address this issue, we have constructed UNaProd, a Universal Natural Product database for materia medica of ITM. Primarily based on Makhzan al-Advieh, which is the most recent encyclopedia of materia medica in ITM with the largest number of monographs, this database was created using both text mining methods and manual editing. UNaProd is currently hosting to 2696 monographs from herbal to animal to mineral compounds in 16 diverse attributes such as origin and scientific name. In the current version, UNaProd is hyperlinked to IrGO and CMAUP databases for Mizaj and molecular features respectively and it is freely available at http://jafarilab.com/unaprod/.
REVIEW | doi:10.20944/preprints201804.0233.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Alzheimer’s Disease; network medicine; inflammation; network and system pharmacology; traditional Chinese medicine
Online: 18 April 2018 (07:41:00 CEST)
Alzheimer’s Disease (AD) is a neurodegenerative condition that currently has no known cure. The principles of the expanding field of network medicine (NM) have recently been applied to AD research. The main principle of NM proposes that diseases are much more complicated than one mutation in one gene, and incorporate different genes, connections between genes, and pathways that may include multiple diseases to create full scale disease networks. AD research findings as a result of the application of NM principles have suggested that functional network connectivity, myelination, myeloid cells, and genes and pathways may play an integral role in AD progression, and may be integral to the search for a cure. Different aspects of the AD pathology could be potential targets for drug therapy to slow down or stop the disease from advancing, but more research is needed to reach definitive conclusions. Additionally, the holistic approaches of network pharmacology in traditional Chinese medicine (TCM) research may be viable options for the AD treatment, and may lead to an effective cure for AD in the future.
REVIEW | doi:10.20944/preprints202211.0070.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Nutraceuticals; Personalized Medicine; Precision Medicine; Probiotics; Vitamins; Covid; Dietary Supplements; Adverse Drug Effects
Online: 3 November 2022 (06:27:25 CET)
Nutraceuticals have taken the spotlight during the past two decades as evidenced by the exponential publications on them. Long a part of routine in Traditional Medicine Systems, the rise of their mainstream use globally raises both safety concerns and need for better understanding of efficacious dosing. We attempt to answer these questions in this preliminary scoping review by an analysis of current literature on nutraceutical use as a personalized or prescription medicine. Using Covidence, Rayyan, and manual searches of PubMed, 598 unique publications were selected. 32 are systematic reviews, of which we overview the scope. We also overview 30 papers that address adverse drug reactions. To obtain an unbiased landscape of the 598 papers, we analyzed keywords using multiple methods. Expectedly, the most frequent keywords were probiotics and vitamins. Unexpectedly and remarkably, among the highest keyword yield was ‘COVID’. Further exploring this aspect, we review 15 pertinent papers, that not only provide robust evidence for nutraceutical benefits as part of SARS-CoV-2 treatment, but also amplify the notion that nutraceuticals are protective. Overall, the strident note is that further robust targeted research is needed in order to reap the full benefits of nutraceuticals in a safe and efficacious manner.
ARTICLE | doi:10.20944/preprints201911.0024.v1
Subject: Mathematics & Computer Science, Information Technology & Data Management Keywords: Iranian traditional medicine; Persian medicine; ontology; knowledge-base; Mizaj; temperament; new drug discovery
Online: 3 November 2019 (17:07:50 CET)
Background: Iranian traditional medicine is a holistic school of medicine with a long prolific history. It describes numerous concepts and the relationships between them. However, no unified terminology has been proposed for the concepts of this medicine up to the present time. Considering the extensive use of concepts in the numerous textbooks written by the scholars over centuries, comprehending the totality of the terminology is obviously a very challenging task. To resolve this issue and overcome the obstacles, and code the concepts in a reusable manner, constructing an ontology of the concepts of Iranian traditional medicine seems a necessity.Methods: Makhzan al-Advieh, an encyclopedia of materia medica compiled by Mohammad Hossein Aghili Khorasani, was selected as the resource to create an ontology of Mizaj. The steps followed to accomplish this task included (1) compiling the list of classes for Mizaj; (2) arranging the classes in taxonomy; (3) determining object properties and their cardinalities; (4) specifying annotation properties including codes, labels, synonyms, and definitions for each concept; (5) reviewing the fields pertaining to Mizaj of all monographs in Makhzan al-Advieh. The ontology was created using Protégé with adherence to the principles of ontology development provided by the Open Biological and Biomedical Ontology (OBO) foundry. Results: Mizaj ontology was constructed with a final inclusion of 105 classes, three object properties, and 1078 axioms in the Iranian Traditional Medicine General Ontology database, IrGO, freely available at http://jafarilab.com/irgo/. An indented tree view and an interactive graph view using WebVOWL were used to visualize the ontology. All classes were linked to their instances in the UNaProd database to create a knowledge-base of Mizaj. Conclusion: We constructed an ontology-based knowledge base of ITM concepts of Mizaj in the domain of materia medica to help offer a shared and common understanding of this concept, enable reuse of the knowledge, and make the assumptions explicit. Extending IrGO will bridge the gap between traditional and conventional schools of medicine and help guide future research on new treatment options.
REVIEW | doi:10.20944/preprints202209.0205.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Smoothened; cancer; precision medicine; therapy
Online: 14 September 2022 (09:23:16 CEST)
The G protein-coupled receptor (GPCR) Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations of Smo have been identified in various other tumours, although their oncogenic effect remains unknown in these tissues. Drug resistance is a common challenge in cancer therapies targeting Smo, and data analysis shows that healthy individuals also harbour resistance mutations. Based on the importance of Smo in cancer progression and the high incidence of resistance towards Smo inhibitors, this review suggests that detection of Smo variants through tumour profiling could lead to increased precision and improved outcomes of anti-cancer treatments.
HYPOTHESIS | doi:10.20944/preprints202201.0228.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Complex diseases; Nosology; Systems Medicine
Online: 17 January 2022 (13:01:03 CET)
Complex diseases are prevalent medical conditions which are characterized by strong inter-patient differences in symptom profiles, disease trajectory and treatment response. The challenges in understanding and managing these diseases are due to their complex pathophysiology, comprising of a combination of genetic and environmental factors. The traditional model of disease assumes a clear distinction between health and disease, as well as between different diagnoses, but recent findings with regards to diseasomes and network pleiotrophy suggest that this dogma is not useful in understanding complex diseases. This paper presents a novel model, in which the individual disease burden is determined as a function of molecular, physiological and pathological factors simultaneously: disease(symptoms(traits(genes AND environment))). From this a high-dimensional space is defined which includes all individual disease burdens, ranging from healthy (i.e. low disease burden) to multi-morbidity (i.e. high disease burden), termed the disease landscape. This model provides a novel way to conceptualize human physiology and pathophysiology in the context of complex diseases and may present a useful concept to simultaneously address the strong interindividual heterogeneity of diagnose cohorts as well as the lack of clear distinction between diagnoses and health and disease, thus facilitating the progression towards personalized medicine.
ARTICLE | doi:10.20944/preprints201808.0207.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: Telehealth, mHealth, wellness, preventative medicine
Online: 10 August 2018 (14:30:16 CEST)
Objective: Health/wellness applications on mobile devices (Apps) may positively affect the health of seniors (persons age 65+). But for an App to promote health in its target audience, it must achieve meaningful use. Method: For one and a half years, residents at a Life Plan Community (mean age 86) used a wellness App running on iPad. In a digital survey, residents rated their overall satisfaction with the App on a scale from 1 (strongly dislike) to 10 (strongly enjoy). Results: User satisfaction (96 respondents of 252; 38% response rate) was distributed with maximum 8, median 7, mean 6.6, and standard deviation 2.3. Discussion: The results suggest that it is feasible to inspire seniors to pursue whole-person wellness using an App: technology may promote “active aging.”
REVIEW | doi:10.20944/preprints202108.0321.v1
Subject: Keywords: cancer; mutations; cancer drivers; precision medicine; protein structure; personalized medicine; cancer therapies; genetic signatures
Online: 16 August 2021 (11:15:11 CEST)
Cancer is fundamentally a disease of perturbed genes. Although many mutations can be marked in the genome of a cancer or transformed cell, the initiation and progression were shown to be driven by only a few mutational events viz. driver mutations that progressively govern and execute the functional impacts. The driver mutations are thus believed to dictate and dysregulate the subsequent cellular proliferative function/decisions thereby producing a cancerous state. Therefore, identifying the driver events from the genomic alterations in a patient’s cancer cell gained large attention recently for designing better targeting therapies towards paving way for the precision cancer medicine. With rolling advancements in high-throughput omics technologies, analysis of genetic variations and gene expression profiles for cancer patients has become a routine clinical practice. However, it is anticipated that protein structural alterations resulting from such driver mutations can provide more direct and clinically relevant evidence of disease states than genetic signatures alone. This review comprehensively discusses various aspects and approaches that have been developed for the prediction of cancer drivers using genetic signatures and protein structures, and their potential application in developing precision cancer therapies.Keywords:
ARTICLE | doi:10.20944/preprints202011.0325.v1
Subject: Medicine & Pharmacology, Allergology Keywords: single-subject studies, personalized medicine, precision medicine, reference standards; gold standards; biomarkers; open-source
Online: 10 November 2020 (16:36:56 CET)
Background: Developing patient-centric baseline standards that enable the detection of clinically significant outlier gene products on a genome-scale remains an unaddressed challenge required for advancing personalized medicine beyond the small pools of subjects implied by “precision medicine”. This manuscript proposes a novel approach for reference standard development to evaluate the accuracy of single-subject analyses of metabolomes, proteomes, or transcriptomes. Since distributional assumptions of statistical testing may inadequately model genome dynamics of gene products, the so-called significant results of previous studies may artefactually conflate with real signals. Model confirmation biases escalate when studies use the same analytical methods in the discovery sets and reference standards, as corroboration of results leads to an evaluation of reproducibility confounded with replicated biases rather than a measure of accuracy. We hypothesized that developing method-agnostic reference standards using effect-size and expression-level filtering of results, obtained from multiple discovery methods that are distinct from the one evaluated, would maximize the evaluation of clinical-transcriptomic signals and minimize statistical artefactual biases. We developed and released an R package “referenceNof1” to facilitate the construction of robust reference standards. Results: Since RNA-Seq data analysis methods often rely on binomial and negative binomial assumptions to non-parametric analyses, the differences create statistical noise and make the reference standards method dependent. In our experimental design, the accuracy of 30 distinct combinations of fold changes (FC) and expression levels (EL) were determined for five types of RNA analyses in two different datasets. This design was applied to two distinct datasets: breast cancer cell lines and a yeast study with isogenic biological replicates in two experimental conditions. In addition, the reference standard (RS) comprised all RNA analytical methods with the exception of the method testing accuracy. To mitigate for biased optimization of the RS parameters towards a specific analytical method, similarity between observed results of distinct analytical methods were calculated across all methods (Jaccard Concordance Index). The greatest differences were observed across diametric extremes. For example, filtering out differentially expressed genes (DEGs) using a fold change < 1.2 leads to a 50% increase in concordance between techniques when compared to results with FC > 1.2. Combining this FC cutoff with genes with mean expressions > 30 counts leads to a 65% increase in concordance in comparison to genes with expression levels < 30 counts and with FC < 1.2. Conclusions: We have demonstrated that comparing accuracies of different single-subject analysis methods for clinical optimization requires a new evaluation framework. Reliable and robust reference standards, independent of the evaluated method, can be obtained under a limited number of parameter combinations: fold change (FC) ranges thresholds, expression level cutoffs, and exclusion of the tested method from the RS development process. When applying anticonservative reference standard frameworks (e.g., using the same method for RS development and for prediction), a majority of the concordant signal between prediction and Gold Standard (GS) cannot be confirmed by other methods, which we conclude as biased results. Statistical tests to determine DEGs from a single-subject study generate many biased results that require subsequent filtering for increasing their reliability. Conventional single-subject studies pertain to one or a few measures in one patient over time and need a substantial conceptual framework extension in order to address the tens of thousands of measures in genome-wide analyses of gene products. The proposed referenceNof1 framework addresses some of the inherent challenges in improving transcriptome scale single-subject analyses by providing a robust approach to constructing reference standards. Github: https://github.com/SamirRachidZaim/referenceNof1
ARTICLE | doi:10.20944/preprints201906.0260.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: complementary and alternative medicine; integrative medicine; knowledge; training and education; psychology; mental health; qualitative
Online: 26 June 2019 (05:31:14 CEST)
Background and objectives: The inadequate knowledge of complementary and alternative medicine (CAM) among health professionals may put their clients in risky situation because they then would find information about CAM from unreliable sources. Clinical psychologists (CPs), as health professionals, have also the opportunity to provide psychoeducation on the latest CAM scientific research to their clients. The current study aimed to explore knowledge and educational needs of CAM among CPs in Indonesia because previous studies on exploring CAM knowledge and educational needs of CAM were primarily conducted in Western countries. Materials and Methods: Data were collected through semi-structured face-to-face interviews with 43 CPs in public health centers (PHCs) in Indonesia. Most interviews were held at the PHCs where participants worked and interviews lasted for 55 minutes, on average. The interview recordings were transcribed and were analyzed using deductive thematic analysis. Results: Five main themes emerged within participants’ responses regarding CAM knowledge and educational needs. First (CAM understanding), participants’ responses ranged from those with little or no prior knowledge of CAM treatments and uses, to those with much greater familiarity. Second (source of knowledge), participants’ access ranged widely in terms of references, from popular to scientific literature. Third (why is it important?), participants identified CAM essentially as part of Indonesian culture and it was therefore crucial to have this cultural knowledge. Fourth (the challenges and what is needed?), the challenges for improving participants’ knowledge came from personal and institutional levels. Fifth (what and how to learn?), participants advised that only CAM treatments that fit in brief psychotherapy sessions should be introduced in professional training. Conclusions: This qualitative study discovered that CAM was neither well-known nor understood widely. Participants advised that professional associations and health institutions should work together in enhancing knowledge of CAM and incorporating CAM education into psychology education.
COMMENTARY | doi:10.3390/sci2030070
Subject: Keywords: small molecule inhibitor; personalized medicine; precision medicine; oncology; targeted therapy; drug delivery; drug screening; chemotherapy
Online: 8 September 2020 (00:00:00 CEST)
The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.
ARTICLE | doi:10.20944/preprints201908.0131.v1
Subject: Biology, Physiology Keywords: pharmacogenomics; immune checkpoint blockade; immunotherapy; drug response prediction; algorithm; mathematical model; precision medicine; personalized medicine
Online: 11 August 2019 (14:51:14 CEST)
Background: Accurate prediction of patients’ response to therapy is clinically indispensable, howbeit challenging. With increased understanding of the human genome and malignancies, there is the renaissance of in silico pharmacogenomics with renewed interest in drug response predictability based on gene-drug interaction. Objective: Evidence-based transcript-proteome profiling is essential for synthesizing clinically applicable algorithms for predicting response to anticancer therapy, including immune checkpoint blockade (ICBT); thus, saving physicians’ time, reducing polypharmacy, and curtailing unnecessary treatment expense. In this study, we tested and validated the hypothesis that a selected proteomic signature in ICBT-naïve patients is sufficient for the prediction of response to ICBT. Methods: Using a multimodal approach consisting of computational pharmacogenomics, transcript-proteome analytics, mathematical modeling, and machine learning systems; we delineated therapy-sensitivity and stratified patients into graduated response groups based on their proteomic profile. Protein expression levels in our cohort tissue specimens were evaluated based on T cell- and non-T cell- inflamed phenotypes by immunohistochemistry. Results: We established β-catenin, PDL1, CD3 and CD8 expression-based ICBT response model. Statistical regression models validated the predictive association between our predefined algorithms and therapeutic outcome. Interestingly, our 4-gene prediction classifier was constitutively independent of tumor tissue origin, correctly stratified patients into high-, low-, and non- responders pre-treatment, with high prediction accuracy, and exhibited good association with patients’ performance status and prognosis (p < 0.01). Conclusion: Our findings demonstrate the possibility of accurate proteomics based ICBT response prediction and provide a putative basis for drug response prediction based on selective proteome profile in untreated cancer patients.
ARTICLE | doi:10.20944/preprints201809.0498.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: nasopharyngeal carcinoma; traditional Chinese medicine; Chinese herbal products; complementary and alternative medicine; Gan-Lu-Yin
Online: 26 September 2018 (05:09:08 CEST)
In most countries, the incidence of nasopharyngeal carcinoma (NPC) is no more than 1 per 100,000 for both men and women; however, it is much higher for men and women in Taiwan. The use of traditional Chinese medicine (TCM) as complementary and alternative medicine for the treatment of NPC and its treatment-related side effects has been increasing. The National Health Insurance (NHI) covers 99.6% of Taiwan’s residents. In the present population-based cohort study, we aimed to investigate the pattern of utilization of Chinese herbal products (CHPs) for NPC from 2001 through 2011 in Taiwan. We identified a total of 30294 patients with newly diagnosed NPC from the Registry for Catastrophic Illnesses Patient Database (RCIPD). Descriptive statistics and multiple logistic regression analysis were employed to estimate the adjusted odds ratios (aORs) for CHP utilization. From 2001 through 2011, 17816 patients aged ≥20 years were newly diagnosed with NPC. Of these, 4749 patients used TCM outpatient services for NPC treatment. TCM users were more likely to be women, young, residents of Central Taiwan, and white-collar workers. The most commonly prescribed formula CHP was Gan-Lu-Yin, followed by Xin-Yi-Qing Fei-Tang and Shan-Shen-Mai-Men-Dong-Tang. The most commonly prescribed single CHP was Hedyotis diffusa, followed by Radix Scrophulariae and Radix Ophiopogonis. These findings provide information regarding personalized therapies for NPC and can promote further clinical experiments and pharmacological research on CHPs for NPC treatment in Taiwan. Further well-designed randomized controlled studies and basic mechanistic studies should assess the safety and effectiveness of CHPs for NPC treatment.
REVIEW | doi:10.20944/preprints201809.0185.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: predictive preventive personalized medicine; Lactobacillus; Bifidobacterium; probiotics, gut microbiota; patient phenotype, individualized medicine; metabolic syndrome
Online: 11 September 2018 (06:00:03 CEST)
The modification the gut microbiota in metabolic syndrome and associated chronic diseases is among leading tasks of microbiome research and needs for clinical use of probiotics. Evidence lack for the implications for microbiome modification to improve metabolic health in particular when applied impersonalized. Probiotics have tremendous potential in personalized nutrition and medicine to develop healthy diets. The aim was to to conduct comprehensive overview of recent updates of role of microbiota on human health and development of metabolic syndrome and efficacy of microbiota modulation considering specific properties of probiotic strain and particular aspects of metabolic syndrome and patient`s phenotype to fill the gap between probiotic product and individual to facilitate development of individualized / personalized probiotic and prebiotic treatments. We discuss the relevance of using host phenotype-associated biomarkers, those based on imaging and molecular and patrient`s history, reliable and accessible to facilitate person-specific appication of probiotics and prebiotic substances. Microbiome phenotypes can be parameters of predictive medicine to recognize patient`s predispositions and evaluate treatment responses; the number of phenotype markers can be effectively involved to monitor microbiome modulation. The studied strain-dependent properties of probiotic strains are potentially relevant for individualized treatment for gut and distant sites microbiome modulation. The evidence regarding probiotic strains properties can be taken to account via pathophysiology-based approach for most effective individualized treatment via gut, oral and vaginal and other sites microbiome modulation according to phenotype of the patient providing individualized and personalized medical approaches. Preventive potential of probiotics is strong and well-documented. Recommendations for individualized clinical use of probiotics, and for probiotic studies design have been suggested.
ARTICLE | doi:10.20944/preprints201710.0151.v1
Subject: Life Sciences, Other Keywords: shelter medicine; animal sheltering; shelter surgery; veterinary medical education; veterinary student training; population medicine; biosecurity
Online: 24 October 2017 (03:47:43 CEST)
While referral-level medicine is important in the veterinary curriculum, students also need a solid base knowledge of clinically relevant routine surgery and diagnostic skills. Veterinary hospitals must maintain a steady caseload that provides wellness cases and commonly encountered conditions. Shelter Medicine programs can create the opportunities to meet these challenges. Students can gain quantifiable surgical experience in spay/neuter with measured growth in surgical efficiency and competency while providing needed community service for animal shelters. Students can directly interact with shelter animals by performing examinations, diagnostic testing, and development of treatment protocols and recommendations for commonly encountered problems. Furthermore, students can obtain a working knowledge of biosecurity on a population level to minimize risk of infectious diseases spreading to healthy populations.
REVIEW | doi:10.20944/preprints202202.0259.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Epilepsy; Neuroimmunology; Neuroinflammation; Epileptogenesis; Personalized medicine
Online: 21 February 2022 (14:59:18 CET)
Background: Immunologic and neuro-inflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. Methods: We performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Results: Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways in-volved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Conclusions: Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.
ARTICLE | doi:10.20944/preprints202201.0275.v1
Online: 19 January 2022 (14:24:50 CET)
According to several evidence, forest environmental seems able to provide beneficial effects on functional and psychological parameters, related to cardiovascular, metabolic, respiratory functions as well depression and anxiety. The aim of this study is to investigate the effect of a one-day forest walking in Selva di Castelfidardo (AN, Italy) on 37 participants aged 21-68, most of them living in either urban or suburban areas of large cities. We observed a statistically significant effect on sympathovagal balance by the means of heart rate, systolic and diastolic blood pressure, body temperature, skin temperature, skin conductance, HRV parameters (AVNN, SDNN, rMSSD, pNN50, LF, HF, LF/HF ratio), oxygen oximetry, PEF, FEV1. A significant difference was also detected on the Perceived Stress Scale responses (19.27 pre vs 13.81 post-immersion, p=<0,05; -28,3% variation). Our data contribute to increase the body of literature about the effect of forest walking, adding data on an Italian area qualified for forest bathing.
REVIEW | doi:10.20944/preprints202110.0242.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Translational Medicine; Machine Learning; Artificial Intelligence
Online: 18 October 2021 (11:06:18 CEST)
The huge advancement of Internet web facilities as well as the progress in computing and algorithm development, along with current innovations regarding high-throughput techniques enables the scientific community to gain access to biological datasets, clinical data, and several databases containing billions of information concerning scientific knowledge. Consequently, during the last decade the system for managing, analyzing, processing and extrapolating information from scientific data has been considerably modified in several fields including the medical one. As a consequence of the mentioned scenario, scientific vocabulary was enriched by novel lexicons such as Machine Learning (ML)/Deep Learning (DL) and overall Artificial Intelligence (AI). Beyond the terminology, these computational techniques are revolutionizing the scientific research in drug discovery pitch, from the preclinical studies to clinical investigation. Interestingly, between preclinical and clinical research, the translational research is benefitting from computer-based approaches, transforming the design and execution of the translational research, resulting in breakthroughs for advancing human health. Accordingly, in this review article, we analyze the most advanced applications of AI in translational medicine, providing an up-to-date outlook regarding this emerging field.
Online: 30 July 2021 (10:04:43 CEST)
This survey was conducted on 4 tribes (Ababda, Bisharia, Nubian and Rashayda) live in the south of the Nile and the Eastern Desert of Egypt with the aim to document and compare the traditional herbal medicines and assess the relationships among these tribes. A total of 180 interviews were conducted with the Bedouins and herb healers. Thirty-nine species belonged to 36 genera and 27 families were employed. Fabaceae and Poaceae and Rutaceae were the species-rich families. The used wild species comprised 43.6%, cultivated species (38.5%) and the imported from herbalist shops (17.9%). The leaves were the most used parts (31%), followed by stems and fruits with about 22% each. Distinct species included Acacia nilotica is used in the treatment of dental pain with use value 33.3%, Cymbopogon schoenanthus subsp. proximus in treatment of both cough or headache with use values 35 and 30.6% and a combination of Acacia nilotica with Lawsonia inermis in the treatment of sore throat with use value 22.2%. The highest similarity was recorded between Nubian and Rashayda tribes (55.3%), Ababda and Bisharia (46.8%). Diarrhea and headache were the most popular diseases with 7 different treatments, cough and dental pains with 6 treatments.
REVIEW | doi:10.20944/preprints202107.0532.v1
Subject: Life Sciences, Biochemistry Keywords: extracellular vesicles; exosomes; platelets; regenerative medicine
Online: 23 July 2021 (09:58:26 CEST)
Extracellular vesicles (EVs) present a great potential for the development of new treatments in the biomedical field. To be used as therapeutics, many different sources have been used for EVs obtention, while only few studies have addressed the use of platelet derived EVs (pEVs). In fact, pEVs have been shown to intervene in different healing responses, thus some studies have evaluated their regenerative capability in wound healing or hemorrhagic shock. Even more, pEVs have proven to induce cellular differentiation, enhancing musculoskeletal or neural regeneration. However, the obtention and characterization of pEVs is widely heterogeneous and differs from the recommendations of the International Society for Extracellular Vesicles. Therefore, in this review, we aim to present the main advances in the therapeutical use of pEVs in the regenerative medicine field while highlighting the isolation and characterization steps followed. The main goal of this review is to portray the studies performed in order to enhance the translation of the pEVs research into feasible therapeutical applications.
ARTICLE | doi:10.20944/preprints202104.0401.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Colorectal cancer; personalized medicine; biomarker; variant
Online: 15 April 2021 (08:10:42 CEST)
Discovery of novel variants from data derived from local population provides confident targets for developing biomarkers for personalized medicine. Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. We identified the need to generate high quality sequencing data from local population and understand the pattern of occurrence of variants in colorectal cancer patients. In this report, we used archived samples from Saudi Arabia and used Ampliseq Comprehensive Cancer panel to identify novel somatic variants. We report a comprehensive analysis of next generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in large intestine. APC, RET and EGFR genes were most frequently mutated. Higher number of variants were identified in left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.
REVIEW | doi:10.20944/preprints202102.0393.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Microbiome; Personalized Medicine; Integrative Oncology; Oncobiotic
Online: 17 February 2021 (13:29:27 CET)
Sound evidence recognizes the microbiota as one of the major players in human health and disease, including cancer. Every human being is an holobiont, a shared human and microbial ecosystem, in which microbial composition is individually set by behaviours and environmental factors during the first years of life. Thereafter it is modulated by diet, physical activity, emotions and drugs (in particularly antibiotics and chemotherapeutics). As a consequence, a shift in medicine is needed toward a more comprehensive practice that takes into account every individual's genoma and, in addition, his or her metagenome, known as microbiome: a "microbiota revolution". As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Specific microbes display unique features regulating their host niche in a number of body sites, which can result in an increased risk of cancer; in addition, gut microbiota composition plays a role in immune modulation within the intestinal barrier, affecting local and systemic inflammation, recognized drivers of cancer. Moreover, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and subsequentely may impact on the onset, progression and treatment of hormonal dependent cancers. Microbiota is also clearly involved in modulating the response to anticancer treatments, and above all to the emerging immunotherapy. Based on these premises, the microbiome is becoming a potential target, in order to enhance efficacy of antitumoral treatments as well as to lower their toxicity. The complex scenario that links microbiome composition to oncogenesis and response to anticancer treatments defines the frames of a new “oncobiotic” perspective.
REVIEW | doi:10.20944/preprints202010.0326.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Ionised Magnesium; Preoperative Medicine; ICU; Dysmagnesemia
Online: 15 October 2020 (15:08:40 CEST)
Monitoring and measuring magnesium (Mg) values are essential to prevent the development of numerous complications in perioperative medicine and critically ill patients. Although previous studies suggest that measuring free ionized magnesium (iMg) is more useful for estimating Mg status, clinicians currently rely on measurement of total serum magnesium to determine if supplemental magnesium is needed. In this review, we analyzed the recent literature to decide whether it is better to measure ionized serum Mg or total serum Mg when assessing magnesium status, whether iMg predicts clinical outcome, and what are the difficulties in measuring serum iMg levels in intensive care patients and perioperative medicine.
ARTICLE | doi:10.20944/preprints202009.0028.v1
Online: 2 September 2020 (05:27:55 CEST)
The soccer injury rate is distinctly higher during matches than the training sessions. Rules determine how to play, generating specific kinds of fatigue which is associated with the injury incidence. No research has evaluated the impact of potential rule-induced physical demands in soccer or comparing sports. Understanding the differences might be useful for enhancing rules (e.g., safer sport). Therefore, the aims of this study were: a) to described the differences in the rule-induced physical demands of soccer, futsal, basketball, and handball; and b) to evaluate whether soccer rule-induced physical demands are different than the other invasion intermittent team sports, focusing the impact of the substitutions rules. Data were collected from different sports rules (i.e., soccer, futsal, basketball, and handball), and performed hypothetical corrections to equate the other team sports to the soccer (i.e., court dimensions/number of players). The data showed that soccer has higher rule-induced physical demands: lower substitutions, higher dimensions in absolute (eight to 15 times), and relative (four to eight times) values. Hypothetical corrections showed that soccer has remarkably large differences. Therefore, we conclude that soccer has remarkably higher rule-induced physical demands than other team sports, and allowing unlimited substitutions in soccer is a must.
REVIEW | doi:10.20944/preprints201908.0242.v1
Subject: Life Sciences, Immunology Keywords: rheumatology, immunology, precision medicine, biologic drugs
Online: 23 August 2019 (09:54:02 CEST)
Tumour necrosis factor-α is a key mediator of inflammation in rheumatoid arthritis its discovery led to the development of highly successful anti-TNF therapy. Subsequently, other biologic drugs targeting immune pathways, namely interleukin-6 blockade, B cell depletion, and T cell co-stimulation blockade, have been developed. Not all patients respond to a biologic drug leading to a knowledge gap between biologic therapies available and the confident prediction of response. So far, genetic studies have failed to uncover clinically informative biomarkers to predict response. Given that the targets of biologics are immune pathways, immunological study has become all the more pertinent. Furthermore, advances in single cell technology have enabled the characterisation of many leucocyte subsets. Studying the blood immunophenotype may therefore define biomarker profiles relevant to each individual patient’s disease and treatment outcome. This review summarises our current understanding of how immune biomarkers might be able to predict treatment response to biologic drugs.
ARTICLE | doi:10.20944/preprints201805.0174.v1
Subject: Medicine & Pharmacology, Other Keywords: e-portfolio; clinical skills; competences; medicine
Online: 11 May 2018 (04:45:11 CEST)
Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.
CASE REPORT | doi:10.20944/preprints201708.0075.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: emergency; hospital; emergency health; medicine; management
Online: 21 August 2017 (12:47:01 CEST)
Introduction: The management performance of hospitals in emergency departments in coping with clinical hazards is necessary for their success in providing quality services. The purpose of this study is to provide an optimization procedure and applying management performance in health and medical emergency on the rate of emergency preparedness of the suburb city hospitals. Research method: A semi-experimental and interventional descriptive study in the emergency department of Shahid Motahari Hospital in 2015-2016. Data was collected through the standard checklist of hospital emergency responsiveness test to WHO disasters with 90 questions in 9 domains which is codified by the World Health Organization, in the form of interviews and observing evidences , and if necessary a numerical analysis. Initially, the situation was measured according to this checklist. In the next stage, a set of solutions was developed and then the solutions were implemented according to the obtained information. Data analysis before and after proposing the procedure and its application in order to improve the quality of health management performance and emergency preparedness was performed using central indices, and for describing and presenting the survey results, tables and graphs were used. Results: The highest and lowest emergency preparedness rates for disasters and emergencies before the proposed procedure were the Communication Factor (%77/8) and Human resource factor (%2/8) respectively. The degree of preparedness of the medical center was measured in the management performance according to the model (WHO) before proposing the procedure (%77.98). The researcher's procedure provided and applied based on the information obtained from survey environment, location and type of hospital structure. After providing the procedure, the maximum and minimum rates were the continuity of service factor (%58.3) and post-accident rebuilding factor (%100), respectively. Generally, the rate of emergency preparedness of studied medical center in management performance for coping with disasters and medical emergencies was measured (%97.2) according to hospital emergency responsiveness test for accidents and (WHO). The significance level is less than 0.05, so we can say that the effectiveness with confidence (95%) was effective. Conclusion: According to the statistics of accidents and disasters in the suburb cities, the results of the research and the importance of the role of emergency departments in interurban hospitals in controlling accidents, the need for planning and implementation of practical measures such as conducting training courses on health management in disasters and emergencies, having an estimate of critical and essential resources, changing the structure, providing manpower (emergency management) in order to more precise control and ease of service, maintenance and repair of equipment, timely triage and retrofitting of hospitals were effective in improving their preparedness.
BRIEF REPORT | doi:10.20944/preprints202204.0287.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; Influenza; Morbidity; Mortality; Flu; Pneumonia; Virus Infections; Preventive Medicine; Hospitalization; Internal Medicine; Respiratory illness.
Online: 29 April 2022 (04:22:05 CEST)
Abstract: Background: Our goal was to evaluate whether wearing personal protective equipment (PPE) such as an N95, or a surgical mask during the (COVID-19) pandemic had really reduced the cases of influenza in the state of Wisconsin. Methods: Respiratory Virus Surveillance Reports from the Wisconsin Department of Health Services (DHS) and the Centers for Disease Control and Prevention (CDC) were used to compare the rates of Influenza during the seasons of 2018-2019 and 2020-2021. Results: The number of cases, hospitalizations, and mortality rates with Influenza had significantly decreased in the 2020-2021 season compared to the Influenza season of 2018-2019. Discussion: Reducing the burden of influenza illnesses, hospitalizations, and deaths on the health care system is imperative. Wearing masks should be addressed for the most vulnerable.
ARTICLE | doi:10.20944/preprints202207.0337.v1
Subject: Life Sciences, Biochemistry Keywords: Wharton's jelly; Regenerative Medicine; Osteoarthritis; Cartilage Defects
Online: 22 July 2022 (13:08:45 CEST)
The primary objective of this study is to report the initial efficacy data observed with the use of cryopreserved human umbilical tissue allograft for the supplementation of cartilage defects in patients with symptomatic knee osteoarthritis. Our primary endpoints were pain, stiffness, and functional recovery scores. In this ongoing study, 55 participants (age 56-93 years) received a single Wharton's jelly tissue allograft application. The study dose consisted of 150mg of Wharton's jelly allograft suspended in approximately 2mL of sterile Sodium Chloride 0.9% solution (normal saline). Each study knee application was performed under ultrasound guidance in a physician's office. The research methodology consisted of NPRS scores and WOMAC subsection scores including pain, stiffness, and physical function. Study enrollment consisted of 55 patients followed for a post-application duration of 90 days. No adverse events or adverse reactions were reported. The results demonstrated statistically significant improvements of NPRS and WOMAC in initial versus 90-day examination. The data represents Wharton's jelly tissue allograft applications are a safe, non-surgical, and efficacious for patients with symptomatic articular cartilage defects associated with osteoarthritis of the knee.
REVIEW | doi:10.20944/preprints202205.0218.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Microbiome; Endocrine disruptors; Estrobolome; Personalized medicine; Oncobiotic
Online: 17 May 2022 (03:25:56 CEST)
The microbiota is now recognized as one of the major players in human health and disease, in-cluding cancer. As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, it may impact on the onset, progression, and treatment of hormonal dependent cancers, which account for more than 70% of all BCs. The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on one side disruptors can alter the composition and functions of the estrobolome, on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new “oncobiotic” perspective.
REVIEW | doi:10.20944/preprints202204.0054.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Medical Cannabis; history of cannabis; medicine; cannabinoids
Online: 7 April 2022 (04:14:19 CEST)
The cannabis plant has been known for millennia for its properties such as textile fiber, food, recreational and medicinal use. Since the origin of its domestication in Asia, cannabis has been transported to the rest of the continents by merchants, nomads, settlers, and slaves, who have also carried with them valuable knowledge about its uses. Its medical use was one of the major contributions of this plant in the various civilizations through which it passed. This article aims to understand its origins, dissemination, and medical use over the years to the present day.
CASE REPORT | doi:10.20944/preprints202111.0513.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: lung ultrasound; LUS, children; asthma; personalized medicine
Online: 29 November 2021 (07:48:13 CET)
In recent years, lung ultrasound (LUS) has been increasingly used for the diagnosis of respiratory diseases in both adult and pediatric patients. However, asthma is a field in which the use of LUS is not yet well defined or is in development. In the following case series, we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of 6 children with asthma: some of them with acute asthma attack and with inadequately controlled allergic asthma or childhood asthma; others with acute asthma and allergic or infantile asthma adequately controlled by preventive therapy. Finally we describe the clinical, laboratory and imaging parameters of a child with severe allergic asthma in the absence of exacerbation. In these cases, albeit at different times, LUS played an important role in both the initial diagnostic process and follow-up. It also showed different ultrasound features depending on the severity of the individual asthma based on the type of asthmatic phenotype and control of it.
REVIEW | doi:10.20944/preprints202105.0643.v1
Subject: Life Sciences, Biochemistry Keywords: Nanocarriers; Nanotheranostics; Nuclear Medicine; Nanoparticles; Drug delivery
Online: 26 May 2021 (14:00:58 CEST)
Background: Convectional methods for drug delivery often faces setbacks due to systemic distribution, short half-life and degradation of therapeutics and therefore reduce concentrations of drug available to target tissue. Nanotheranostic provide a novel method for treating and diagnosing diseases Methodology: collection and review of relevant literatureResult: while nanotheranostic offer advantage of personalized medicine and often combines diagnosis and therapy using single molecular approach, nuclear medicine relies on radioactive isotopes to diagnosed and destroys cancer cells. In both cases, nanocarriers such as lipid-based, polymer-based, drug-conjugate, inorganic nanoparticles are used to deliver drugs/probes/isotopes to target site, generating images and thereafter chemotherapy/radiotherapy begins.Conclusion: Nanotheranostic plays important role in diseases diagnostic, therapy, imaging, monitoring of disease progression / response through the use of nanocarriers. This is made possible through nanoparticles/nanocarriers that delivers drug to the target tissues/cells.
ARTICLE | doi:10.20944/preprints202004.0166.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: osteopathic manipulation; cranial osteopathy; reproducibility; osteopathic medicine
Online: 10 April 2020 (03:26:52 CEST)
Background and Objectives: The techniques directed to the cranial field in osteopathy are the most questioned due to the lack of scientific evidence. In osteopathic practice, manual palpation is essential and, therefore, measuring reliability is fundamental. The objective of study is to assess the reliability and validity of osteopathic treatment depending on experience. Materials and Methods: A cross-sectional study of reliability and validity was conducted. For measurements, a strain gauge was placed on the sphenobasilar synchondrosis of the skull base, and three maneuvers (lateral compression, anteroposterior compression and compression maneuver of the mastoids) were repeated 25 times each by osteopaths with different time of experience (5-10 years, 1-5 years, <1 year). Measurement averages were computed for each of the three maneuvers to verify the average effect of each group in comparison to that of the Gold Standard (GS) (>10 years of experience). Data were analyzed to check for inter- and intra-observer reliability using intra-class correlation coefficients (ICC). Results: Reliability and validity in 5-10 experience of observer 1 and observer 2 in the tree maneuvers was excellent (p<0.001) against GS. Poor or enough reproducibility and concordance were observed in osteopaths with less experience. Conclusion: Experience of osteopaths determines the efficacy of cranial maneuvers in osteopathic treatment for patients’ rehabilitation.
REVIEW | doi:10.20944/preprints202003.0151.v1
Subject: Social Sciences, Other Keywords: efficacy; ethno-veterinary; livestock; medicine; smallholder farmer
Online: 9 March 2020 (10:03:51 CET)
Often touted as an ancient and sustainable practice among indigenous livestock farmers in developing countries, the use of ethno-veterinary medicine is examined within the context of its efficacy. While there are undoubtedly positive implications for adopting knowledge and practice that align with nature, there is both prevalence and ambivalence to the adoption of indigenous plant knowledge and resources for the treatment of livestock infections and diseases. This situation is due to the lack of validation and standardization of the practice in low-income countries, requiring scholarly efforts in developing this indigenous knowledge system.
ARTICLE | doi:10.20944/preprints201907.0284.v1
Online: 25 July 2019 (08:12:19 CEST)
Reducing carbohydrates digestion by having low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107, an eight-herb formula that is modified from the RCM-104, has indicated significant weight-loss action in clinical trials. However, no research has been conducted to study its effect on the activity of porcine pancreatic alpha-amylase (PPA), which is involved in carbohydrate absorption. In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were also detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact.
ARTICLE | doi:10.20944/preprints202210.0281.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Covid-19; Medicine; Practice; Bedelle city; Self-Medication
Online: 19 October 2022 (10:09:14 CEST)
Abstract Introduction There is a clear link between self-medication practice and ongoing pandemic diseases like COVID-19, According to studies conducted globally and the general Ethiopian population turned to self-medication and symptomatic treatment as a result of inadequate COVID-19 treatment and also about 80% of the population amassed drugs for pandemic use. Objective: The objective of this study was to assess self-medication practice for treatment of Covid-19 and reason to use self- medication among residents in Bedelle city and its surrounding, Southwest Oromia, Ethiopia. Methodology: A cross sectional study design was employed and the standardized questionnaire was developed by reviewing relevant literatures then the data was collected using face to face interview. Final data was analyzed by using SPSS version 23. Result: The final study contained 415 respondents in total, with a response rate of 98.5%. The majority of responses were females and between the ages of 18 - 25 Category. In this study population, the use of self-medication since the onset of the Covid-19 epidemic was reported by participants were around 50.6%. Analgesics (42.4%) and cold medicines (29.5%) were the most frequently used medications for treatment of COVID-19. Also the reported uses of these drugs included treatment of Covid-19 symptoms like the Headache (22.2%), Fever (13.2%), respiratory infective (14.3%), and cold (21.4%) were the most frequently reported symptoms for self-medication. Self-medication methods were used more frequently by women than Men. Conclusion: According to this study, analgesics and cold medications are commonly self- medicated drugs used for Covid-19 therapy. It is a serious health concern, particularly when COVID-19 symptoms are present, and high consumption of self-medication has been linked to COVID-19 prevention or treatment. Key words: Covid-19, Medicine, Practice, Bedelle city, Self-Medication
ARTICLE | doi:10.20944/preprints202209.0093.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Polypharmacy management, COVID -19, Gender medicine, economic perspective
Online: 7 September 2022 (02:29:58 CEST)
Background: Covid-19 patients with any pre-existing cardio-vascular disease (CVD) are at highest risk for viral infection and for developing of severe disease. Pathophysiological mechanism is characterized by the viral link to Angioten-sin-Converting Enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and direct damage on myocardium, micro throm-bosis, and alterations of oxygen diffusion. Aim of the study is to analyze clinical course, treatment and outcome in patients (gender stratified) with pre-existing CVD. Methods: Out of the 1299 (700 M/599 F) patients admitted to Internal Medicine COVID Unit of “Castelli Hospital”, Lazio, Italy, from 01/01/2021 to 31/12/2021, 278 patients (167 M/111 F), mean age 76 (76 M/ 75 F) had previous CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated. Results: Most common CVD pathologies were Hearth Failure (HF): 131 (72 M/59 F), Atrial Fibrillation (AF): 45 (25 M/20 F), Myocardial Infarction (MI): 26 (19 M/7 F) and associations among them. 100% of CVD COVID patients under-went Non-Invasive Ventilation (NIV) and were treated with more than 5 drugs. HF was linked with increased LOS (23 days) compared to AF (21 days), MI (18 days) and no CVD (16 days). Overall mean LOS was 16,5 days. 21,4% of total pa-tients had CVD. Conclusions: Timely identification and evaluation of patients with pre-existing CVD are fundamental for adequate treatment based on gender, severity and state of illness and for risk reduction. Keywords: polypharmacy, gender medicine; COVID 19; Sars CoV 2; cardiovas-cular disease.
ARTICLE | doi:10.20944/preprints202107.0281.v1
Subject: Life Sciences, Biochemistry Keywords: Glioblastoma; Precision Medicine; Targeted Therapy; Genomics; Neuro-Oncology
Online: 13 July 2021 (09:28:35 CEST)
BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.
REVIEW | doi:10.20944/preprints202107.0116.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Parkinson’s disease; Alzheimer’s Disease; Clinical trial; Precision medicine.
Online: 5 July 2021 (16:08:41 CEST)
Concomitant neuropathological hallmarks of Alzheimer’s Disease (AD) are common in the brains of people with Parkinson’s disease (PD). Furthermore, AD biomarkers are associated with cognitive decline and dementia in PD patients during life. Here, we highlight the considerable overlap between AD and PD, emphasizing neuropathological, biomarker, and mechanistic studies. We suggest that precision medicine approaches may successfully identify PD patients most likely to develop concomitant AD. The ability to identify PD patients at high risk for future concomitant AD in turn provides an ideal cohort for trials of AD-directed therapies in PD patients, aimed at delaying or preventing cognitive symptoms.
ARTICLE | doi:10.20944/preprints202106.0102.v1
Subject: Life Sciences, Biochemistry Keywords: colorectal cancer; alternative splicing; mucins; biomarkers; precision medicine
Online: 3 June 2021 (11:30:37 CEST)
Colorectal cancer prognosis get worse with advancement of disease into metastatic stage. There is a pertinent need to develop prognostic biomarkers that can be used for personalized and precision medicine. Alternative splicing provides an insight into understanding of changes at isoform expression level which may not be evident at gene level. In this direction, we utilized our prior knowledge about significant alternatively spliced genes and chose ADAM12 and MUC4 for further characterization in a metastatic cell line model. These genes were found to be good prognostic indicators in The Cancer Genome Atlas database. We studied the gene organization and designed primers to specifically amplify a group of isoforms. Differential expression of these group of isoforms was observed in normal, primary and metastatic colorectal cancer cell lines. We further validated the results using sanger sequencing. Isoform expression was found to respond to the 5-fluorouracil treatment. RNAseq analysis of the cell lines further validated the differential expression of gene isoforms. Successful detection of ADAM12 and MUC4 in cell lysates varied according to the antibody used which may reflect differential expression of isoforms. This comprehensive study underscores the importance of studying alternatively spliced isoforms and their probable used as prognostic or predictive biomarkers.
REVIEW | doi:10.20944/preprints202101.0425.v1
Subject: Life Sciences, Biochemistry Keywords: Goat; Sheep; Small Ruminants; Animal Models; Regenerative Medicine.
Online: 21 January 2021 (15:01:17 CET)
Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.
ARTICLE | doi:10.20944/preprints202002.0118.v1
Online: 10 February 2020 (04:05:21 CET)
Introduction: Travel-based continuing medical education (CME) has become a popular format for physicians looking to combine education with travel. Emergency Medicine Update Europe is a biennial accredited CME program combining high quality Emergency Medicine education with structured group activities including cycling, hiking and social activities. This unique design incorporates innovative educational practices but as a whole has not yet been evaluated. Methods: This was a participant observation-based, ethnographic-style case study of the Emergency Medicine Update Europe conference in Provence, France in 2015. Participant interviews and embedded observation methods were used to collect data. Data was then analyzed using thematic content analysis techniques. Results: We describe three phenomena from the data that we feel are highly influential in the success of the program and impact on learning. These include “social engagement and a sense of community”; “the value of a stimulating escape” and “the ‘flat’ faculty-learner relationships”. Discussion: These unique features, prioritized by participants, seem to be key to the apparent success of this model over more traditional CME approaches. To our knowledge this is the first empirical research in this area and improves our understanding of how to leverage these more sociologic components for more effective continuing medical education.
REVIEW | doi:10.20944/preprints201807.0057.v1
Subject: Medicine & Pharmacology, Other Keywords: Fibromyalgia; CFS/ME; manual therapy; integrative medicine; physiotherapy
Online: 18 July 2018 (12:26:20 CEST)
Application of protocols without parameter standardization and rigorous controls has led manual therapy (MT) and other physiotherapy approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way this can be achieved is by studying gene expression and additional physiological changes that associate to particular, parameter-controlled, treatments in animal models and translating this knowledge to properly design objective, quantitatively-monitored clinical trials. Here, we propose a Molecular Physiotherapy Approach (MPTA), requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports of MT that historically attribute benefits to these treatments. The review focuses in the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and CFS/ME. The systemic effect associated to mechanical-load responses is considered of particular relevance as it suggests that defined, low-pain areas could be selected for treatments with overall benefits, an aspect that might result essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to treat FM and CFS/ME.
REVIEW | doi:10.20944/preprints201807.0303.v1
Subject: Social Sciences, Other Keywords: community engagement; health disparities; precision medicine; participant recruitment
Online: 17 July 2018 (10:21:34 CEST)
In response to the National Institutes of Health (NIH) All of Us Medicine Research Initiative, the Precision Medicine Research (PreMeR) Diversity Consortium was formed by four institutions from the Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN). This synergistic approach proposed evidence-based, best practices used by experienced researchers to engage, recruit and retain diverse populations in the All of Us initiative. Conceptualization of the proposed approach was aided by social influence theories to better understand how people’s beliefs and opinions should be modified to affect change leading to action . The Social-Ecological Model (SEM), for Health Promotion , from Stokols  and Community-Based Participatory (CBPR) Models, guided proposed engagement, recruitment, and retention strategies contextualized with the individual, interpersonal, organizational, community, and policy spheres of influence. The PreMeR produced a partnership to evaluate and improve the effectiveness of current engagement, recruitment, and retention strategies for minority participation in scientific studies. This approach illustrates the need to incorporate multiple methods of engagement to reach a diverse audience to participate in scientific research. Engagement, recruitment, and retention strategies in community and biomedical research must be viewed as community engaged public health interventions, utilizing the same theoretical principles and approaches.
REVIEW | doi:10.20944/preprints201803.0115.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: regenerative medicine; reprogramming; cardiac differentiation; secretoma; tissue engineering
Online: 15 March 2018 (05:02:41 CET)
Human induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them human attractive disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as source cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs. We also cover the phenotypic characteristics of the hiPSCs derived CMs, their ability to rescue injured CMs through paracrine effects, the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their potential use in biomedical applications.
REVIEW | doi:10.20944/preprints201905.0338.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: castor bean; cancer therapy; immunotoxins; plant toxins; ribosome-inactivating proteins; ricin; rRNA N-glycosylase activity; traditional medicine; folk medicine; bioterrorism.
Online: 28 May 2019 (11:54:43 CEST)
The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for biocrimes in several cases. Here, the main steps of ricin research are reported with particular regards to its enzymatic activity, structure and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation amongst bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been of great utility to develop a number of immunotoxins specific for the elimination of unwanted cells, mainly cancer cells; some of these immunotoxins gave promising results also in clinical trials.
REVIEW | doi:10.20944/preprints202211.0433.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: hydrogel; active motifs modification; regenerative medicine; Self-assembling peptide
Online: 23 November 2022 (05:11:24 CET)
Ion-complementary self-assembling peptides have been studied in many fields for their distinct advantages mainly due to their self-assembly properties. However, their shortcomings, such as insufficient specific activity and poor mechanical properties, also limited their application. For better and wider application of this kind of promising biomaterials, ion-complementary self-assembling peptides can be modified with their self-assembly properties not being destroyed to the greatest extent. The modification strategies were reviewed by taking RADA16-Ⅰ as an example. For the insufficient specific activity, RADA16-Ⅰ can be structurally modified with active motifs derived from the active domain of the extracellular matrix or other related active factors. For weak mechanical properties, materials with strong mechanical properties or materials that can undergo chemical crosslinking were used to mix with RADA16-Ⅰto enhance the mechanical properties of RADA16-Ⅰ. To improve the performance of RADA16-Ⅰ as drug carriers, appropriate adjustment of the RADA16-Ⅰ sequence and/ or modification of the RADA16-Ⅰ-related delivery system with polymer materials or specific molecules can be considered to achieve sustained and controlled release of specific drugs or active factors. The modification strategies reviewed in this paper may provide some references for the further basic research and clinical application of ion-complementary self-assembling peptides and their derivatives.
ARTICLE | doi:10.20944/preprints202207.0073.v1
Subject: Materials Science, Biomaterials Keywords: calcium pyrophosphate; calcium polyphosphate; biocompatibility; bone implants; regenerative medicine
Online: 5 July 2022 (13:13:30 CEST)
Biocompatibility of ceramic materials in CaO-P2O5 system was investigated using different methods, including in vitro and in vivo tests. Ceramics based on calcium pyrophosphate Ca2P2O7 were obtained by annealing cement-salt stone from highly concentrated hardening suspensions (HCHS). Cement-salt stone was prepared using powder mixtures of calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate (MCPM) Ca(H2PO4)2·H2O. These salts were mixed with each other in such a way that calcium pyrophosphate and calcium polyphosphate were present in the final ceramic product in the following weight ratios: Ca(PO3)2/Ca2P2O7 = 0/100; 5/95; 10/90 and 20/80. Distilled water was added to a homogenized powder mixtures of Ca3(C6H5O7)2·4H2O and Ca(H2PO4)2·H2O by a water/solid ratio of 0,5 by weight. The obtained suspensions were shaped using silicon molds and left to dry in air for a week. The phase composition of the obtained samples of cement-salt stone was represented by brushite CaHPO4·2H2O, monetite CaHPO4, calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate Ca(H2PO4)2·H2O. According to the XRD data, the phase composition of ceramic materials after annealing in the temperature range of 800-1000 0C was mainly represented by the β-Ca2P2O7 phase. In vivo tests shown that obtained ceramic materials can be recommended for regenerative treatments for bone defects.
ARTICLE | doi:10.20944/preprints202205.0213.v1
Subject: Medicine & Pharmacology, Other Keywords: Toxicity; Diagnosis; Personal care; Patient encounter; Patient-based medicine
Online: 16 May 2022 (14:06:25 CEST)
Clinicians are key in reclaiming the medical arts ceded to clinically irrelevant technology and thereby aligning patient with fast-changing biological realities. Narrowing the chasm between virtual and real perceptions of health hazards requires: 1) becoming acutely aware of the habitat loss aggravating the pervasive dissemination of chemicals via conventional food, air, and consumer products and the proliferation of non-ionizing radiation; and 2) making strategic use of slow, system 2 thinking so as to respond wisely to the rampant epidemics of chronic low-dose toxicity disregarded or misdiagnosed for half a century. To respond adaptively, take a moment during each patient encounter to add chronic ambient poisoning to the differential diagnosis and investigate subtle symptoms and signs of irritation in vulnerable organ systems. Enacting adaptive response across our profession could ease the suffering of millions, help avert the sixth extinction, and contribute to continuation of evolved life as we know it.
ARTICLE | doi:10.20944/preprints202204.0147.v1
Subject: Medicine & Pharmacology, Other Keywords: behaviour change technique; medicine use optimisation; nudge; prescribing behaviour
Online: 15 April 2022 (14:27:22 CEST)
Providing healthcare workers with cost information about the medications they prescribe can influence their decisions, particularly when that information is provided at the very moment they are faced with a prescribing decision. The current study aimed to analyse the impact of nudges that presented cost information to prescribers through their organisation's electronic prescribing system. The nudges were co-created by the research team (composed of behavioural scientists) and the lead hospital pharmacist. One nudge provided simple cost information (percentage difference between two brands of Mesalazine – Asacol and Octasa). The second nudge provided the potential annual cost-saving that could result if the cheaper medication was selected across the organisation. While the statistical analyses revealed that these nudges were not effective, several administrative barriers were overcome, which may inform future research. For example, presenting aggregated cost information to the prescribers is possible even when the actual cost of medicine is confidential and can not be displaced. In addition, future research could reveal more behavioural factors that facilitate medication optimisation.
REVIEW | doi:10.20944/preprints202109.0104.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: hyrogel; cardiotoxicity; regenerative medicine; antineoplastic drugs; polydioxanone; pulmonary autograft
Online: 6 September 2021 (14:01:12 CEST)
Hydrogels, hydrophilic polymeric compounds, have been recently put under investigation as regenerative medicine applications and delivery systems for antineoplastic drugs, particularly chemotherapeutics (anthracyclines, alkylating agents), target drugs (trastuzumab) and immunotherapies. Porosity, conductivity, biodegradability and physical states are some of the peculiarities that render hydrogels suitable for therapies implementation. Chemically-modifying agents and enzymes can be also coupled to hydrogels for pharmacokinetical parameters improvement and side effects avoidance. Cardiotoxicity is in fact one of the major issues for oncological patients after treatment efficacy. Heart failure, myocarditis and hypertension are causes of morbidity and mortality that can possibly be avoided. Specific reaching of the target tumor site has been achieved by several authors in preclinical in vivo studies but clinical studies are currently under design processes. Polydioxanone, a hydrogel-mimicking agent, is capable to interact with the elastic properties of pulmonary artery. An advantageous characteristic is that can be also reabsorbed within biological systems and can cause a remodeling process of the vessel wall. Hydrogels currently represent a strong topic of interest for researchers and probably will guide future clinical investigations and practice.
REVIEW | doi:10.20944/preprints202108.0238.v1
Subject: Medicine & Pharmacology, Other Keywords: self-supervised learning; medicine; healthcare; representation learning; unlabeled data
Online: 11 August 2021 (08:27:57 CEST)
Machine learning has become an increasingly ubiquitous technology, as big data continues to inform and influence everyday life and decision-making. Currently in healthcare, as well as in most other industries, the two most prevalent machine learning paradigms are supervised learning and transfer learning. Both practices rely on large-scale, manually annotated datasets to train increasingly complex models. However, the requirement of data to be manually labeled leaves an excess of unused, unlabeled data available in both public and private data repositories. Self-supervised learning (SSL) is a growing area of machine learning that has the ability to take advantage of unlabeled data. Contrary to other machine learning paradigms, SSL algorithms create artificial supervisory signals from unlabeled data and pretrain algorithms on these signals. The aim of this review is two-fold: firstly, we provide a formal definition of SSL, divide SSL algorithms into their four unique subsets, and review the state-of-the-art published in each of those subsets between the years of 2014-2020. Second, this work surveys recent SSL algorithms published in healthcare, in order to provide medical experts with a clearer picture of how they can integrate SSL into their research, with the objective of leveraging unlabeled data.
REVIEW | doi:10.20944/preprints202105.0376.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Gene Editing; Gene Therapy; Oncology; Comparative Medicine; One Health
Online: 17 May 2021 (09:45:43 CEST)
With rapid advances in gene editing and gene therapy technologies, the development of genetic, cell, or protein-based cures to disease are no longer the realm of science fiction but that of today’s practice. The impact of these technologies are rapidly bringing them to the veterinary market as both enhanced therapeutics and towards modeling their outcomes for translational application. Simply put, gene editing enables scientists to modify an organism’s DNA a priori through the use of site-specific DNA targeting tools like clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Gene therapy is a broader definition that encompasses the addition of exogenous genetic materials into specific cells to correct a genetic defect. More precisely, the U.S Food and Drug Administration (FDA) defines gene therapy as “a technique that modifies a person’s genes to treat or cure disease” by either (i) replacing a disease-causing gene with a healthy copy of the gene; (ii) inactivating a disease-causing gene that was not functioning properly; or (iii) introducing a new or modified gene into the body to help treat a disease. In some instances, this can be accomplished through direct transfer of DNA or RNA into target cells of interest or more broadly through gene editing. While gene therapy is possible through the simple addition of genetic information into cells of interest, gene editing allows the genome to be reprogrammed intentionally through the deletion of diseased alleles, reconstitution of wild type sequence, or targeted integration of exogenous DNA to impart new function. Cells can be removed from the body, altered, and reinfused, or edited in vivo. Indeed, manufacturing and production efficiencies in gene editing and gene therapy in the 21st century has brought the therapeutic potential of in vitro and in vivo reprogrammed cells, to the front lines of therapeutic intervention (Brooks et al., 2016). For example, CAR-T cell therapy is revolutionizing hematologic cancer care in humans and is being translated to canines by us and others, and gene therapy trials are ongoing for mitral valve disease in dogs.
REVIEW | doi:10.20944/preprints202103.0114.v1
Subject: Medicine & Pharmacology, Allergology Keywords: organoid; stem cell; cancer; glioblastoma; glioma; oncology; precision medicine
Online: 2 March 2021 (21:59:47 CET)
The emergence of three-dimensional human organoids has opened the door for development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. Mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource- and time-intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell-cell and cell-stromal interactions, tumor microenvironment, and therapeutic responsiveness. PDO models and drug screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant timeframes and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.
ARTICLE | doi:10.20944/preprints202011.0023.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: Computers in Medicine; Segmentation; Machine Learning; Deep Learning; MRI
Online: 2 November 2020 (11:02:44 CET)
Segmentation of Magnetic Resonance Images (MRI) of abdominal organs is useful for analysis prior to surgical procedures and for further processing. Deep Learning (DL) has become the standard, researchers have proposed improvements that include multiple views, ensembles and voting. Loss function alternatives, while being crucial to guide automated learning, have not been compared in detail. In this work we analyze limitations of popular metrics and their use as loss, study alternative loss variations based on those and other modifications and search for the best approach. An experimental setup was necessary to assess the alternatives. Results for the top scoring network and top scoring loss show improvements between 2 and 11 percentage points (pp) in Jaccard Index (JI), depending on organ and patient (sequence), for a total of 22 pp over 4 organs, all this being obtained just by choosing the best performing loss function instead of cross-entropy or dice. Our results apply directly to MRI of abdominal organs, with important practical implications for other architectures, as they can be applied easily to any of them. They also show the worth of variants of loss function and loss tuning, with future work needed to generalize and test in other contexts.
REVIEW | doi:10.20944/preprints202004.0394.v1
Subject: Life Sciences, Genetics Keywords: bioinformatics; population structure; population stratification bias; genomic medicine; biobanks
Online: 22 April 2020 (07:39:22 CEST)
The past years saw the rise of genomic biobanks and mega-scale meta-analysis of genomic data that promise to reveal the genetic underpinnings of health and disease. However, the over-representation of Europeans in genomic studies not only limit the global understanding of disease risk and intervention efficacy, but also inhibit viable research into the genomic differences between carriers and patients. Whilst the community has agreed that more diverse samples are required, it is not enough to blindly increase diversity; the diversity must be quantified, compared, and annotated to lead to insight. Genetic annotations from separate biobanks need to be comparable, computable, operate without access to raw data due to privacy concerns. But they must be comparable, both for regular research and to allow international comparison in response to pandemics. Here, we evaluate the appropriateness of commonly used genomic tools used to depict population structure in a standardized and comparable manner. The end goal is to reduce the effects of confounding and learn from genuine variation in genetic effects on phenotypes across populations, which will improve the value of biobanks, locally and internationally, increase the accuracy of association analyses, and inform developmental efforts.
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: glioblastoma; miRNA; MGMT; survival; radiotherapy; chemotherapy; temozolomide; translational medicine
Online: 9 April 2020 (08:27:12 CEST)
Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O6-methylguanine–DNA methyltransferase (MGMT) is nowadays routinely analyzed, since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.
REVIEW | doi:10.20944/preprints201911.0278.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Machine learning; clinical decision-making; personalized medicine; digital health
Online: 24 November 2019 (13:26:16 CET)
The use of machine learning (ML) approaches to target clinical problems is called to revolutionize clinical decision-making. The success of these tools is subjected to the understanding of the intrinsic processes being used during the classical pathway by which clinicians make decisions. In a parallelism with this pathway, ML can have an impact at four levels: for data acquisition, predominantly by extracting standardized, high-quality information with the smallest possible learning curve; for feature extraction, by discharging healthcare practitioners from performing tedious measurements on raw data; for interpretation, by digesting complex, heterogeneous data in order to augment the understanding of the patient status; and for decision support, by leveraging the previous step to predict clinical outcomes, response to treatment or to recommend a specific intervention. This paper discusses the state-of-the-art, as well as the current clinical status and challenges associated with each of these tasks, together with the challenges related to the learning process, the auditability/traceability, the system infrastructure and the integration within clinical processes.
ARTICLE | doi:10.20944/preprints201801.0111.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: hypertension; GWAS; precision medicine; rural population; SNP-age interaction
Online: 12 January 2018 (07:34:37 CET)
Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Parkinson’s disease; precision medicine; personalized medicine; GBA; Glucocerebrosidase; GCase; LRRK2; Leucine-rich repeat kinase-2; Dopamine; PD drug trials; PD risk variants
Online: 14 September 2020 (00:22:59 CEST)
Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.
ARTICLE | doi:10.20944/preprints202201.0176.v2
Subject: Social Sciences, Other Keywords: Disaster; Disability; Disaster Management; NCCD; UNCRPD; Disability & Disaster; Disaster Medicine
Online: 25 May 2022 (11:19:53 CEST)
Disabled children on the one hand have a wide range of impairments that translate into functional limitations but at the same time they possess various talents and capacities. These are manifested into the dynamics of society and the environment that they interact with. This article discusses disaster management with disabled children as a focus group. Disaster, disability and its management is discussed in the context of international practices in general and suited to India in particular. The research follows a review of the recommendations of the United States National Commission on Children and Disaster. In addition to this Disaster Medicine as one approach to Disaster Management concerning disabled children has been explored. The research concludes that the understanding of particular issues of Children with disabilities as one stakeholder, their capacity to engage and a shift in mindset and power relations in which they can contribute to disability inclusive disaster management are fundamental to disability-inclusive DRR.
REVIEW | doi:10.20944/preprints202203.0071.v2
Subject: Medicine & Pharmacology, General Medical Research Keywords: rheumatoid arthritis; precision medicine; new treatment; drug development; method development
Online: 25 May 2022 (04:59:01 CEST)
Rheumatoid arthritis (RA) is a chronic, systemic, abnormal inflammatory immune response. It is characterized by the involvement of the synovium and multiple organs and the destruction of joints and articular cartilage. Over the past 30 years, several promising novel compounds and antibodies have been developed for the treatment of RA. The introduction of new drugs and precision medicine for all forms of RA raises several issues related to access to novel treatments by patients, optimal regimen selection, cost-effectiveness, prognosis monitoring and outcome surveillance, particularly with regarding to the development of low drug response rates, drug resistance and adverse side effects. Tremendous attention has been given to the identification of optimized drug combinations for the treatment of RA, particularly in early high-risk vulnerable and early individuals. Addressing these issues requires novel therapeutic approaches with new mechanisms and the establishment of accurate guidelines for drug selection, drug recombination, and non-chemical therapeutic efforts. In this study, we reviewed the most exciting recently established or ongoing novel drugs and methods according to the clinical trial database maintained by the United States National Library of Medicine and discussed the trends in RA drug development and challenges in the treatment, providing a reference significant for the accurate treatment of RA and the research direction in the future.
REVIEW | doi:10.20944/preprints202106.0295.v1
Subject: Medicine & Pharmacology, Allergology Keywords: machine learning; deep learning; neural network; tricorder; laboratory medicine; extraanalytics
Online: 10 June 2021 (13:30:26 CEST)
Laboratory medicine has evolved from a mainly manual profession, providing few selected test results to a highly automated and standardized medical discipline, generating millions of test results per year. As next inevitable evolutional step, artificial intelligence (AI) algorithms will need to assist us in structuring and making sense of the masses of diagnostic data collected today. Such systems will be able to connect clinical and diagnostic data and to provide valuable suggestions in diagnosis, prognosis or therapeutic options. They will merge the often so separated worlds of the laboratory and the clinics. When used correctly, it will be a tool, capable of freeing the physicians time so that he/she can refocus on the patient. In this narrative review I therefore aim to provide an overview of what AI is, what applications currently are available in healthcare and in laboratory medicine in particular. I will discuss the challenges and pitfalls of applying AI algorithms and I will elaborate on the question if healthcare workers will be replaced by such systems in the near future.
ARTICLE | doi:10.20944/preprints202105.0728.v1
Subject: Life Sciences, Biochemistry Keywords: theratyping; cystic fibrosis; functional characterization; personalized medicine; CFTR; rare mutation
Online: 31 May 2021 (10:11:41 CEST)
The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 12 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. Today these patients are excluded from treatment with Trikafta. In Italy CF patients carrying F508del/unknown represent about 3% (156 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment.This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine.
ARTICLE | doi:10.20944/preprints202102.0270.v1
Subject: Biology, Anatomy & Morphology Keywords: MPDB2.0,; medicinal plant; medicinal plant database of Bangladesh; folk medicine
Online: 10 February 2021 (16:29:00 CET)
Medicinal plants are generally defined as rare herbals with potent medicinal activities that can be used as an alternative treatment for diseases. Recent studies exploring novel medicine developments, originating from folk-medicinal practices challenges this notion and suggests that both the circumference of the term medicinal plant and their potential application covers a substantially extensive verse than previously suggested. While medicinal plants are not limited to the borders of any country, Bangladesh and its south-east Asian neighbors do boast a huge collection of potent medicinal plants with considerable folk-medicine history compared to most other countries of the world. MPDB 2.0 is the continuation of MPDB 1.0, it serves as both a data repertoire for medicinal of Bangladesh and a user-friendly interface for researchers, health practitioners, drug developers, and students who wish to study the various medicinal & nutritive plants scattered around Bangladesh and the underlying phytochemicals contributing to their efficacy in folk medicine. While in developing MPDB 2.0 human diseases have been highly focused upon, the information in this database is not limited in its application for human diseases or diseases only, as many of the plants indexed here can serve in developing biofuel or bioremediation technologies or nutritive diets or cosmetics, etc. MPDB 2.0 comprises a collection of more than five hundred medicinal plants from Bangladesh along with a record of their corresponding scientific, family, and local names together with their utilized parts, information regarding ailments, active compounds, and PubMed ID of related publications.
ARTICLE | doi:10.20944/preprints202012.0132.v1
Subject: Life Sciences, Biochemistry Keywords: Herbal Informatics; Ayurveda; Lung Cancer; Ethnopharmacology; Natural Compounds; Alternative Medicine
Online: 7 December 2020 (09:35:10 CET)
The incidence of lung cancer has increased in recent years and causes major mortalities across the globe. Besides, the availability of the several chemotherapeutics modalities in the management, there is still a challenge to find out an efficient remedy with lesser or no toxic effects. Hence, there is a necessity to employ complementary research to establish effective management for lung cancer. In this study, we have implemented a novel herbal informatics model to find out the alternative remedy in the treatment of lung cancer. This model utilizes five major steps of the bioprospection process based on the classical surge followed by the binary index and rationale-based selection of herbal products targeting the cancer-causing factors which are explained in detail in the methodology section of this model. This study revealed 07 herbals such as Withania somnifera (Ws), Berberis vulgaris(Bv), Glycyrrhiza glabra(Gg), Andrographis paniculate(Ap), Azadirachta indica(Ai), Cinnamomum Verum(Cv), Piper longum(Pl) based on the fuzzy set optimization scoring(0.6-1) that could be further studied in vitro and in vivo level for utilization in the management of lung cancer.
REVIEW | doi:10.20944/preprints202011.0745.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Pancreatic Cancer; Adjuvant therapy; neoadjuvant therapy; biomarkers; Precision medicine; timing
Online: 30 November 2020 (16:45:30 CET)
Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or Gemcitabine-Nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/- chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.
ARTICLE | doi:10.20944/preprints202002.0230.v1
Subject: Keywords: side effect; tranditional Chinese medicine; COVID-19; artificial intelligence; coronavirus
Online: 17 February 2020 (01:18:13 CET)
Ethnopharmacological relevance: Novel coronavirus disease (COVID-19) outbroke in Wuhan has imposed a huge influence onto the society in term of the public heath and economy. However, so far, no effective drugs or vaccines have been developed. Whereas, the Traditional Chinese Medicine (TCM) has been considered as a promising supplementary treatment for the disease owing to its clinically proven performance on many diseases even like severe acute respiratory syndrome (SARS). Meanwhile, many side-effect (SE) reports suggest the SE of the TCM prescriptions cannot be ignored in curing the COVID-19, especially because COVID-19 always simultaneously leads to dramatic degradation of the patients’ physical condition. How to evaluate the TCM regarding to their latent SE is a urgent challenge. Aim of the study: In this study, we use an ontology-based side-effect prediction framework (OSPF) developed in our previous work and Artificial Neural Network (ANN)-based deep learning to evaluate the TCM prescriptions that are officially recommended in China for novel coronavirus (COVID-19). Materials and methods: Firstly, we adopted the OSPF developed in our previous work, where an ontology-based model separate all the ingredients in a TCM prescription into two categories: hot and cold. Then, we established a database by converting each TCM prescription into a vector containing the ingredient dosage and the according hot/cold attribution as well as the safe/unsafe label. And, we trained the ANN model using this database, after which a safety indicator (SI), as the complementary percentage of side-effect (SE) possibility, is then given for each TCM prescription. According to the proposed SI from high to low, we re-organize the recommended prescription list. Secondly, by using this method, we also evaluate the safety indicators of some other famous TCM prescriptions that are not in the recommended list but are used traditionally to cure flu-like diseases for extending the potential treatments. Results: Based on the SI generated in the ANN model, FTS, PMSP, and SF are the safest ones in recommended list, which all own a more-than-0.8 SI. Whereas, JHQG, LHQW, SFJD, XBJ, and SHL are the prescriptions that are most likely unsafe, where the indicators are all below 0.2. In the extra list, the indicators of XC, XQRS, CC, and CHBX are all above 0.8, and at the meantime, XZXS, SJ, QW, and KBD’s indicators are all below 0.2. Conclusions: In total, there are seven TCM prescriptions which own the indicators more than 0.8, suggesting these prescriptions should be considered firstly in curing COVID-19, if suitable. We believe this work will provide a reasonable suggestion for the society to choose proper TCM as the supplementary treatment for COVID-19. Besides, this work also introduces a pilot and enlightening method for creating a more reasonable recommendation list of TCM to other diseases.
REVIEW | doi:10.20944/preprints201804.0322.v2
Subject: Biology, Other Keywords: antisense oligonucleotides; antisense therapy; DNA insecticides; RNAi; medicine; agriculture; forestry
Online: 31 May 2018 (12:11:59 CEST)
Antisense oligonucleotides (ASO), short single-stranded polymers based on DNA or RNA chemistries and synthesized in vitro, regulate gene expression by binding in a sequence-specific manner to an RNA target. The functional activity and selectivity in the action of ASOs largely depends on the combination of nitrogenous bases in a target sequence. This simple and natural property of nucleic acids provides an attractive route by which scientists can create different ASO-based techniques. Over the last 50 years, planned and realized applications in the field of antisense and nucleic acid nanotechnologies have produced astonishing results and posed new challenges for further developments, exemplifying the essence of the post-genomic era. Today the majority of ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake. This review critically analyzes some successful cases using the antisense approach in medicine to address severe diseases, such as Duchenne muscular dystrophy and spinal muscular atrophy, and suggests some prospective directions for future research. We also examine in detail the elaboration of unmodified insect-specific DNA insecticides and RNA preparations in the areas of agriculture and forestry, a relatively new branch of ASO that allows circumvention of the use of non-selective chemical insecticides. When considering the variety of successful ASO modifications with an efficient signal-to-noise ratio of action, coupled with the affordability of in vitro oligonucleotide synthesis and post-synthesis procedures, we predict that the next half-century will produce a fruitful yield of tools created from effective ASO-based end products.
REVIEW | doi:10.20944/preprints201706.0067.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Transition Medicine; Pediatric migraine; Pediatric; Migraine; Migraine in young adults
Online: 14 June 2017 (09:26:13 CEST)
Migraine is a common condition that affects children as they develop into adults. Transition of care from pediatric to adult care has becoming an increasingly popular topic in the medical literature. It has been suggested that discussions between patients, their families and providers should be initiated as early as age 13. Patients who are un or underprepared have poorer outcomes due to increased morbidity and worsening of their medical condition. Many children continue to have migraine into adulthood and if efforts are taken to ensure patients receive appropriate transfer of care, the results can significantly decrease the economic burden of this disease.
ARTICLE | doi:10.20944/preprints201704.0169.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: thermopile sensor; actimetry; thermal camera, data classification; tele-medicine; polysomnography;
Online: 26 April 2017 (12:27:38 CEST)
This paper address the development of a new technic in the sleep analysis domain. Sleep is defined as a periodic physiological state during which vigilance is suspended and reactivity to external stimulations diminished. We sleep on average between six and nine hours per night and our sleep is composed of four to six cycles of about 90-minutes each. Each of these cycles is composed of a succession of several stages of sleep, more or less deep. The analysis of sleep is usually done using a polysomnography. This examination consists of recording, among other things, electrical cerebral activity by electroencephalography (EEG), ocular movements by electrooculography (EOG) and chin muscle tone by electromyography (EMG). The recording is done mostly in a hospital, more specifically in a service for monitoring the pathologies related to sleep. The readings are then interpreted manually by an expert to generate a hypnogram, a curve showing the succession of sleep stages during the night in 30-second epochs. The proposed method is based on the follow-up of the thermal signature that makes it possible to classify the activity into three classes: "awakening", "calm sleep" and "agitated sleep". The contribution of this non-invasive method is part of the screening of sleep disorders, to be validated by a more complete analysis of the sleep. The measure provided by this new system, based on temperature monitoring (patient and ambient), aims to be integrated into the tele-medicine platform developed within the framework of the Smart-EEG project by the SYEL - SYstèmes ELectroniques team. Analysis of the data collected during the first surveys carried out with this method showed a correlation between thermal signature and activity during sleep. The advantage of this method lies in its simplicity and the possibility of carrying out measurements of activity during sleep and without direct contact with the patient at home or hospitals.
REVIEW | doi:10.20944/preprints202109.0453.v3
Subject: Medicine & Pharmacology, General Medical Research Keywords: BNCT; targeted therapy; biological dosimetry; boron imaging; personalized oncology; personalized medicine
Online: 16 May 2022 (15:22:13 CEST)
Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (10B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of 10B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of 10B in a specific tissue in real-time using noninvasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. Moreover, functional imaging technologies such as PET can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Anyway, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.
REVIEW | doi:10.20944/preprints202204.0055.v1
Subject: Life Sciences, Molecular Biology Keywords: cell; biology; aging; medicine; transcription; activity; neurons; brain; immune system; muscle
Online: 7 April 2022 (04:24:23 CEST)
In several mammalian species including humans, complex stimulation patterns such as cognitive challenge and physical exercise lead to improvements in organ function, organism health and performance, as well as possibly longer lifespans. The hypothesis is presented here that activity-dependent transcriptional programs, induced by these environmental stimuli, temporarily and lightly de-differentiate somatic cells such as neurons and muscle cells into a state that resembles functionally younger cells to allow cellular remodeling and adaptation of the organism to environmental change. This cellular adaptation program targets several process classes that are heavily implicated in aging, such as mitochondrial metabolism, cell-cell communication, intracellular signaling and epigenetic information processing and leads to functional improvements in these areas. I reverse engineer these activity-dependent gene programs, identify critical molecular nexus points such as CREB, MEF2 and cFos and speculate as to how one might leverage them to prevent and attenuate human aging-related decline of body function, enhance human performance and restore more youthful levels of function and morphology. The findings presented here can serve as a basis for the study and development of effective longevity efforts as the underlying gene programs could be used as markers for treatment success and as targets for therapy development.
ARTICLE | doi:10.20944/preprints202203.0278.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: point-of-care ultrasound; internal medicine; lung ultrasound; echocardiography; abdominal ultrasound
Online: 21 March 2022 (08:39:57 CET)
Accumulated data show the utility of diagnostic multi-organ point-of-care ultrasound (PoCUS) in the assessment of patients admitted to an internal medicine ward. Assess whether multi-organ PoCUS (lung, cardiac, and abdomen) provides relevant diagnostic and/or therapeutic information in patients admitted for any reason to an internal medicine ward. Prospective, observational, and single-center study, at a secondary hospital. Multi-organ PoCUS was performed during the first 24 hours of admission. The sonographer had access to the patients’ medical history, physical examination, and basic complementary tests performed in the ED (laboratory, X-ray, electrocardiogram). We considered a relevant ultrasound finding if it implied a significant diagnostic and/or therapeutic change. In the second semester of 2019, 310 patients were enrolled (48.7% men, mean age 70.5 years). Relevant ultrasound findings were detected in 86 patients (27.7%) and in 60 (19.3%) triggered a therapeutic change. These findings were associated with older age (Mantel-Haenszel 2 = 25.6; p< .001) and higher degree of dependency (Mantel Haenszel 2 = 5.7; p = .017). Multi-organ PoCUS provides relevant diagnostic information, complementing traditional physical exam, and facilitates therapy adjustment, regardless of the cause of admission. Multi-organ PoCUS to be useful need to be systematically integrated into the decision-making process in internal medicine.
ARTICLE | doi:10.20944/preprints202203.0186.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: rehabilitation medicine; magnetic resonance imaging; brain injury; executive function; personalized treatment
Online: 14 March 2022 (11:27:15 CET)
Cognitive rehabilitation is useful for many after traumatic brain injury (TBI), but we lack critical knowledge about which patients benefit the most from different approaches. Advanced neuroimaging techniques have provided important insight into brain pathology and systems plasticity after TBI and have potential to inform new practices in cognitive rehabilitation. In this study, we aimed to identify candidate structural brain measures with relevance for rehabilitation of cognitive control (executive) function after TBI. Twenty-eight patients (9 female, mean age 40.5 (SD = 13.04) years) with moderate/severe TBI (>21 months since injury) that participated in a randomized controlled cognitive rehabilitation trial (NCT02692352) were included in the analyses. Regional brain volume was extracted from T1-weighted MRI scans before treatment using tensor-based morphometry. Both positive and negative associations between treatment outcome (everyday cognitive control function) and regional brain volume were observed. The most robust structural brain measures with relevance for improvement in function were observed in midline fronto-parietal regions, including the anterior and posterior cingulate cortices. The study pro-vides proof of concept and valuable insight for planning future studies focusing on neuroimaging in cognitive rehabilitation after TBI.
ARTICLE | doi:10.20944/preprints202201.0234.v1
Subject: Life Sciences, Microbiology Keywords: AMR, Surveillance; One Health Approach; Alternative Antibiotics; Comparative Medicine; Phage Therapy
Online: 17 January 2022 (14:46:22 CET)
Antibiotics are in excessive use that has extensively increased antimicrobial resistance worldwide which has become the major public concern among the countries. To control this threat proper monitoring of the antimicrobial usage along with the increasing rate of antimicrobial resistance (AMR) is required. Further, surveillance of both the parameters is highly recommended for comparing the differences in distinct countries. Moreover, alternatives for antibiotics are also surveyed and are being researched for quick use in the near future. AMR is an issue that needs immense attention from various sectors. Thus, intervention of multisector is highly encouraged for better outcomes. One Health is one of the approaches that play a vital role in resolving this issue. In this research paper, six different European countries are discussed in terms of antimicrobial usage and AMR in the human and livestock sectors with the help of literature study and various reports published by different organizations. Data study has been conducted to collect the data for comparison study. Data sources of AMR and antimicrobial usage are analyzed and a thorough comparison of both antimicrobial use and AMR are conducted. Also, the application of One Health is studied for a balanced system. This article provides about various surveillance systems that are formed only to keep a track on the upcoming situation of AMR and the consumption of antimicrobials by the humans as well as animals. The article does not provide about all the details required to monitor the AMR issue but firmly allow the readers to get acknowledged with the broad information about the antimicrobial resistance across the six countries of Europe. The regular data collected by the different organizations play a vital role in monitoring the status of AMR and antimicrobial usage by humans and in live stocks. These annual reports have highly helped the government to decide for alternatives and have focused in many training activities to combat the AMR situation globally. AMR prevention is linked to the One Health concept. As antibiotic resistance genes persist on an interface between environment and animal and animal health, an approach is required in all three areas that stress the concept of 'One Approach to Health.'
ARTICLE | doi:10.20944/preprints202110.0021.v1
Subject: Medicine & Pharmacology, Other Keywords: chitosan; dexketoprofen trometamol; drug delivery; gelatin; NSAIDs; personalized medicine; smart polymers
Online: 1 October 2021 (13:53:53 CEST)
Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improve patient adherence. This work aims to develop a suitable chitosan-based scaffold to provide 24 hours controlled release of DKT, by taking advantage of chitosan’s thermo-responsive behavior as well as local hyperthermia in wounds. Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and IR spectroscopy. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C to evaluate the release profiles, which were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 hours (77.75 ± 2.72 %), and reduced the burst release in the initial 6 hours (40.18 ± 1.00 %), while at 38 °C the release reached 88.52 ± 2.07 % at 12 hours. The release profile for this formulation fits with Hixson-Crowell and Korsmeyer-Peppas kinetic models at both temperatures. Therefore, the developed chitosan/gelatin thermo-responsive scaffold provides a suitable system for wound healing with a controlled release of DKT for 24 hour-use, which can overcome adherence issues and wound complications.
TECHNICAL NOTE | doi:10.20944/preprints202109.0505.v1
Subject: Medicine & Pharmacology, Other Keywords: Semantics; standards; clinical research infrastructure; terminology; graph data; data-driven medicine
Online: 29 September 2021 (17:32:40 CEST)
Health-related data originating from diverse sources are commonly stored in manifold databases and formats, making it difficult to find, access and gather data for research purposes. In addition, so-called secondary use scenarios for health data are usually hindered by local data codes, missing dictionaries and the lack of metadata and context descriptions. Following the FAIR principles (Findable, Accessible, Interoperable and Reusable), we developed a decentralized infrastructure to overcome these hurdles and enable collaborative research by making the meaning of health-related data understandable to both, humans and machines. This infrastructure is currently being implemented in the realm of the Swiss Personalized Health Network (SPHN), a research infrastructure initiative for enabling the use and exchange of health-related data for research in Switzerland. The SPHN ecosystem for FAIR data consists of the SPHN Dataset (semantic definitions), the SPHN RDF Schema (linkage and transport of the semantics in a machine-readable format), a project RDF template, extensive guidelines and conventions on how to generate SPHN RDF schema, a Terminology Service (converter of clinical terminologies in RDF), and a Quality Assurance Framework (automated data validation with SHACLs and SPARQLs). The SPHN ecosystem has been built in a way that it can easily be adapted and extended by any SPHN project to fit individual needs. By providing such a national ecosystem, SPHN supports researchers in generating, processing and sharing FAIR data.
ARTICLE | doi:10.20944/preprints202109.0193.v1
Subject: Life Sciences, Microbiology Keywords: bioassay; chromatography; folkloric medicine; methicillin-resistant Staphylococcus aureus; Senna alata; spectroscopy
Online: 13 September 2021 (07:21:28 CEST)
Senna alata (Linn) Roxb. plant is widely used to manage various infections in folkloric medicine. Methicillin-resistant Staphylococcus aureus (MRSA) infection continues to be a major global public health problem. This study aims to investigate the bioactive components of S. alata leaves active against MRSA. The leaves of S. alata were sequentially extracted and fractionated using standard methods and screened for activities against MRSA. The diethyl ether active thin layer chromatography (TLC) spot was subjected to infrared (IR) and gas chromatography-mass spectroscopic (GC-MS) studies. The aqueous extract and diethyl ether fraction of S. alata leaves elicited the highest activity against the MRSA. The GC-MS analysis of the fraction produced 15 eluates; only the sub-fraction 13 was effective. The TLC analysis of the sub-fraction 13 revealed three spots; only the second spot produced activity. The GC-MS result of the spot showed six peaks. The spectral results for peak 3 match the data from the IR study suggestive of 9-octadecenoic acid methyl ester. Senna alata leaves possess bioactive compounds closely related to 9-octadecenoic acid methyl ester with potent antibacterial activity against MRSA.
Subject: Materials Science, Biomaterials Keywords: Silver nano dots; DNA; Biobar code assays; nano sensors; nano medicine
Online: 27 January 2021 (11:44:48 CET)
Nano medicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future. The current medical field is in dire need of new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging. Here in this experimental study, the nano materials used in DNA biosensors like silver nano dots were incorporated as nano biosensors are used for both therapeutic and diagnostic applications. The most important step while preparing a DNA biosensor is the immobilization of DNA probe on the surface of a sensing device such as an electrode. The amount of immobilized DNA probe will influence the accuracy sensitivity, selectivity and life of a DNA biosensor directly. Because of the high surface to volume ratio and excellent biological compatibility, nano materials can enlarge the sensing surface area to increase the amount of immobilized DNA and the DNA mixed with nano materials can keep its biologically activity well.In this study,silver nano dots created in our lab were functionalized with thio nucleides and were used as nano sensor probes in bio bar code assays.
REVIEW | doi:10.20944/preprints202012.0738.v1
Subject: Life Sciences, Biochemistry Keywords: Next generation sequencing; Genetic disorders; Genomic medicine; Genetic counseling; Rare diseases
Online: 29 December 2020 (16:47:01 CET)
Genetic disorders are preeminent determinants of infant mortality. The inherited pediatric-onset genetic disorders have consequential stress on child growth and development: several congenital, complex and rare disorders with indistinguishable clinical symptoms where diagnosis always remains a challenging task. Traditional diagnosis methods include biochemical tests followed by chromosomal microarray and sequencing of a single gene or panel of genes. These methods had several limitations, but with the advent of whole-exome sequencing (WES), genetic testing has become cost-effective and transformative. Exome sequencing has been known for its effectiveness, which appropriately elucidates and distinguishes the heterogeneous disorders to avoid misdiagnosis and decode the underlying genetic alterations. WES has led to discovering genes and genomic variants in a broad spectrum of diseases, including autism, epilepsy, congenital heart diseases, neurodevelopmental diseases, cancer, nephrotic disorders, neural tube defects and fetal structural anomalies. WES is significant in producing immense genomic biomarkers that can be made as appropriate pharmacogenomic targets for drug therapy. In this article, we analyze the recent exploration of WES technology to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and targeted drug discovery.
REVIEW | doi:10.20944/preprints202007.0737.v3
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: oxidative stress; redox; antioxidant; multiple sclerosis; biomarker; neurodegenerative disease; personalized medicine
Online: 22 September 2020 (08:42:20 CEST)
Worldwide, over 2.2 million people are suffered from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients evidenced the disturbance of reduction-oxidation (redox) homeostasis such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discussed the components of redox homeostasis including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species covered frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive as well as pro-oxidative stressors. The antioxidative enzyme systems covered the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring a battery of reactive chemical species, oxidative enzymes, antioxidative enzymes and degradation products helps evaluate the redox status of MS patients to expedite building personalized treatment plans for the sake of better quality of life.
REVIEW | doi:10.20944/preprints202004.0242.v1
Subject: Life Sciences, Other Keywords: extracellular vesicles; stem cells; induced pluripotent stem cells (iPSCs); regenerative medicine
Online: 15 April 2020 (10:08:44 CEST)
Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: traditional korean medicine; hippocampus; neuronal cell death; oxidative stress; medicinal herbs
Online: 10 November 2019 (14:53:14 CET)
Incident rates of neurodegenerative diseases have steadily increased globally, but there is no therapeutic access available. We newly prescribed medicinal herbal remedy including five different herbal plants called, Chen-Ma-Dan-Sam-Ga-Mi-Bang (CMST), purposed to prove for pharmacological properties and corresponded actions on hippocampus neuronal cell injury by hypoxia-induced mice model. Mice were adapted to normoxia or hypoxia with or without CMST for 5 days. We gathered pharmacological effects of CMST on cell injury by enhancement of dihydroethidium and 4-hydroxynonenal signals which were correlated with abnormal redox status in the protein or gene expression levels (abnormal elevations of nitric oxide, reactive oxygen species, lipid peroxidation and deteriorations of total glutathione, total antioxidant capacity, and activities of superoxide dismutase and catalase) due to hypoxia. CMST also notably exerted to attenuates molecules for neuronal cell injury markers such as p-tau, cleaved caspase-3 due to DNA oxidations (53bp1and phosphor-histone H2AX), inflammatory cytokines, and hemeoxigenase-1. We further figured out the underlying actions of CMST by in vitro experiment through inactivation of microglial cell which can mediate neuronal cell injury. Collectively, CMST prevented from hippocampal neuronal cells via inactivation of microglial cell with normalization of redox status on hypoxia-induced hippocampus neuronal cell injury.
ARTICLE | doi:10.20944/preprints201907.0037.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: clinical psychology; cultural psychology; ethic and professionalism; holistic medicine; qualitative methods
Online: 2 July 2019 (09:39:40 CEST)
This study aimed to explore how Indonesian clinical psychologists (CPs) address aspects of spirituality and religion (SR), particularly their attitudes towards and experience of it, on the mental health context. Semi-structured interviews were conducted with 43 CPs in public health centres in Yogyakarta Province, Indonesia. Data were anyalsed using deductive thematic analysis and they generated ten sub-themes which were merged into three central themes. The first theme was experiences related to SR, particularly in Indonesian sociocultural context. The second theme concentrated on participants’ clinical experience related to SR integration into clinical practice. The last theme highlighted the effort made by participants to create holistic mental health services. The originality of this study was represented by the interview quote in the title, “Doing my profession is also part of worship”. It was found that SR is part of culture and belief among Indonesian people, including CPs and mental health treatment clients. In summary, participants genuinely acknowledged that they were not able to completely detach SR from their professional practice. However, participants also pointed out that they were different with spiritual-religious healers (SRHs) and favourably welcomed future collaboration with credible SRHs. This positive attitude embodied a holistic care approach that recognises the diverse biopsycho-social-spiritual needs of clients. Therefore, professional organisations and psychology faculties should establish regulations and education of SR in psychology curricula and conventional psychotherapy to achieve this holistic mental health services in Indonesia.
REVIEW | doi:10.20944/preprints201807.0071.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: precision medicine; next generation sequencing; oncology, patient outcomes; health insurance coverage
Online: 4 July 2018 (11:06:43 CEST)
Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.
ARTICLE | doi:10.20944/preprints201802.0013.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: pancreatic cancer; proteomics; PI3K pathway; precision medicine; predictor of therapeutic response
Online: 2 February 2018 (06:57:47 CET)
In metastatic pancreatic cancer patients non eligible to surgery, signal-targeted therapies so far failed to show a significant amelioration of survival. These therapeutic options were tested in Phase II/III clinical trials mostly in combination with the reference treatment Gemcitabine. These innovative therapies aim at annihilating the oncogene dependency; they also aim at renormalizing the tumoral stroma to allow immune cell function or re-vascularisation. Transcriptomics and genomics large scale analysis show the great heterogeneity of pancreatic cancers and failed to clearly delineate specific oncogene dependency besides oncogenic Kras. In this review, we will describe the most recent proteomic data in pancreatic tumors and its metastasis, which could help at identifying their major signalling dependencies, as well as explain why they are intrinsically resistant to signal-targeted therapies. We will also discuss why PI3K signalling, as a paradigm of pro-tumorigenic cell signalling and of tumoral adaptative resistance to drugs, is a relevant target in this context.
REVIEW | doi:10.20944/preprints201802.0011.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Pancreatic cancer, proteomics, PI3K pathway, precision medicine, predictor of therapeutic response
Online: 1 February 2018 (17:16:04 CET)
In metastatic pancreatic cancer patients non eligible to surgery, signal-targeted therapies so far failed to show a significant amelioration of survival. These therapeutic options were tested in Phase II/III clinical trials mostly in combination with the reference treatment Gemcitabine. These innovative therapies aim at annihilating the oncogene dependency; they also aim at renormalizing the tumoral stroma to allow immune cell function or re-vascularisation. Transcriptomics and genomics large scale analysis show the great heterogeneity of pancreatic cancers and failed to clearly delineate specific oncogene dependency besides oncogenic Kras. In this review, we will describe the most recent proteomic data in pancreatic tumors and its metastasis, which could help at identifying their major signalling dependencies, as well as explain why they are intrinsically resistant to signal-targeted therapies. We will also discuss why PI3K signalling, as a paradigm of pro-tumorigenic cell signalling and of tumoral adaptative resistance to drugs, is a relevant target in this context.
REVIEW | doi:10.20944/preprints201612.0113.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: breast cancer; brain metastases; clonal evolution; precision medicine; genomics; tumour microenvironment
Online: 22 December 2016 (09:57:33 CET)
Brain metastases are highly evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a far more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management.
ARTICLE | doi:10.20944/preprints202208.0098.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: machine learning; dysglycemia; blood glucose, ECG, personalized medicine, noninvasive blood glucose monitor
Online: 4 August 2022 (04:00:20 CEST)
Blood glucose (BG) monitoring is an important issue for critically ill patients. Previous studies reported that poor sugar control was associated with increased mortality in admitted patients. However, repeated blood glucose monitoring can be resource-consuming and cause a healthcare burden in clinical practice. In this study, we aimed to develop a personalized machine-learning model to predict dysglycemia based on electrocardiogram (ECG) findings. The study included patients with more than 20 ECG records during single hospital admission in the Medical Information Mart for Intensive Care III database, focusing on the lead II recordings, along with the corresponding blood sugar data. We processed the data and used ECG features from each heartbeat as inputs to develop a one-class support vector machine (SVM) algorithm to predict dysglycemia. The model prediction for dysglycemia using a single heartbeat had an AUC level of 0.92 ± 0.09, with a sensitivity of 0.92 ± 0.10 and specificity of 0.84 ± 0.04. Based on 10 s majority voting, the model prediction for dysglycemia improved to an AUC of 0.97 ± 0.06. In this study, we found that a personalized machine-learning algorithm could accurately detect dysglycemia using a single-lead ECG.
REVIEW | doi:10.20944/preprints202206.0403.v1
Subject: Life Sciences, Molecular Biology Keywords: Endothelium; Endothelium dysfunction; Newer omics technologies; network medicine; biomarkers and therapeutic targets
Online: 29 June 2022 (09:48:20 CEST)
The endothelium has multiple functions from maintaining vascular homeostasis, providing nutrition and oxygen to tissues, to evocating inflammation, under adverse conditions, and determining endo-thelial barrier disruption resulting in dysfunction. Endothelial dysfunction represents the typical condition associated with the pathogenesis of all the diseases of cardiovascular system, as well as of diseases of all the other human body’s systems, also including sepsis, acute respiratory distress syn-drome and COVID-19 respiratory distress. Such evidence is leading to identifying potential bi-omarkers and therapeutic targets for preserving, reverting, or restoring endothelium integrity and functionality by early treating its dysfunction. Here, it stresses some strategies for achieving these goals, even if diverse challenges exist and require a significant bench work associated with an in-creased number of clinical studies.