Hashimoto’s thyroiditis (HT) is a gender autoimmune disease that is manifested by chronic inflammation of thyroid. Clinical trial studies (CTSs) use molecular biotechnologies (MB) to approach HT appearance. Aims of this study was to analyze the applications of MB in CTSs carried out in HT populations (HT-CTSs). Further, to evaluate the role of MB in the context of hygiene hypothesis (HH). From 75 HT-CTSs found at https://beta.clinicaltrials.gov/ web place, forty-five were considered for this investigation. Finally, six HT-CTSs were reported as molecular HT-CTSs (mHT-CTSs) because of these were planning to utilize MB. Two of mHT-CTSs were settled on French population to isolate DNA viral sequences. Blood, urine, and thyroid tissues biospecimens were analyzed to pick out parvo and polyoma viruses. Two mHT-CTSs carried out in China, were aimed to identify oral and fecal microbiotas by measuring PCR sequencing of 16S rRNA gene. Two mHT-CTSs were programmed in USA and Greece, respectively, for interception of DNA polymorphisms to associate with genetic susceptibility to HT. In conclusion, MB are mainly employed in HT-CTSs for infective pathogenesis and genetic fingerprinting of HT. Besides, MB don't prove the evidence of HH; however, they are useful for direct evidence of the presence of viruses.

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study’s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (“industry”), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.

With the growing hope that disease-modifying treatments could target the molecular basis of neurodegenerative diseases even before the onset of symptoms, there is mounting pressure to define disease entities based on pathophysiology rather than on clinical syndromes. The Alzheimer’s disease research community has recently transitioned from diagnostic criteria based on an amnestic syndrome to a purely biomarker-based disease definition, relying on the demonstration of amyloid-beta pathology, tau pathology, and neurodegeneration. In contrast, current diagnostic criteria for Parkinson’s disease still rely on the presence of the well-described clinical syndrome of parkinsonism, with the addition of characteristic motor- and non-motor signs and symptoms. However, there is now unequivocal evidence that Parkinson’s disease starts years before the onset of parkinsonism. Furthermore, neuropathologically defined Lewy body disease is clinically heterogeneous, combining a range of motor, non-motor, dopaminergic and non-dopaminergic features. Finally, clinically defined Parkinson’s disease has diverse underlying etiologies most, but not all, associated with α-synuclein positive Lewy pathology. In light of recent scientific advances, we propose a biologically based definition for the diagnosis of Parkinson's disease, initially to be used for research purposes. The criteria use a three-component ‘G-S-N’ system. The first is documentation of defined gene variants (‘G’), which cause or strongly predispose to PD as the most upstream component. The second is α-synuclein pathology (‘S’), currently defined as pathological α-synuclein deposition in tissue or positive α-synuclein seeding assays. The third is evidence of underlying neurodegeneration (‘N’), currently defined by specific neuroimaging procedures. The associated clinical syndrome (‘C’) is defined by a single high-specificity feature or multiple lower-specificity features. Initiating this transition will enable the field to fuel both basic and clinical research and move closer to the precision medicine required to develop clinically meaningful disease-modifying therapies. We acknowledge current limitations, ethical implications, and the need for prospective validation of this approach.

The study of the human psyche has elucidated a bipartite structure of logic reflecting the quantum--classical nature of the world. Accordingly, we posited an approach toward studying the brain by means of the quantum--classical dynamics of a mixed Weyl symbol. The mixed Weyl symbol can be used to describe brain processes at the microscopic level and, when averaged over an appropriate ensemble, can provide a link to the results of measurements made at the meso and macro scale. Within this approach, quantum variables (such as, for example, nuclear and electron spins, dipole momenta of particles or molecules, tunneling degrees of freedom, and so on) can be represented by spinors, whereas the electromagnetic fields and phonon modes can be treated either classically or semi-classically in phase space by also considering quantum zero-point fluctuations. Quantum zero-point effects can be incorporated into numerical simulations by controlling the temperature of each field mode via coupling to a dedicated Nos\'e-Hoover chain thermostat. The temperature of each thermostat was chosen in order to reproduce quantum statistics in the canonical ensemble. In this first paper, we introduce a general quantum--classical Hamiltonian model that can be tailored to study physical processes at the interface between the quantum and the classical world in the brain. While the approach is discussed in detail, numerical calculations are not reported in the present paper, but they are planned for future work. Our theory of brain dynamics subsumes some compatible aspects of three well-known quantum approaches to brain dynamics, namely the electromagnetic field theory approach, the orchestrated objective reduction theory, and the dissipative quantum model of the brain. All three models are reviewed.

Obstructive Sleep Apnea (OSA) is nowadays one of the respiratory pathologies with a higher in-cidence globally in developed countries. This situation led to an increase in the demand for medical appointments and diagnostic studies related to that condition, especially those based on poly-somnographies and cardiorespiratory polygraphies. These studies are limited in resources, causing long waiting lists with the subsequent impact on the patients’ health. Furthermore, it is necessary to mention that OSA’s symptomatology is not very specific, and it is typically present in the general population (excessive sleepiness, snore, etc.). In this regard, this paper proposes a novel intelligent clinical decision support system for the diagnosis of OSA which could be used to help medical teams, both in primary care settings and in units specialized in respiratory pathologies. The aim of the proposed system is to help discriminate the patients suspected of suffering from the pathology from those who are not. To this end, two types of information sets of heterogeneous nature are consid-ered. The first one encompasses objective data, related to the patient's health profile with infor-mation usually available in electronic health records. The second type comprises subjective data, referred to the symptomatology reported by the patient in a previous interview. To process the first group of information, a Machine Learning classification algorithm is used, Bagged Trees in this case. For processing the second information set, related with the symptomatology of the patient, a col-lection of expert systems based on fuzzy inferential systems arranged in cascade are employed. As a result, the system is able to determine two risk indicators related to the patient's risk of suffering from OSA: the Statistical Risk and the Symbolic Risk respectively. Subsequently, by interpreting both risk indicators mentioned it will be possible to determine the severity of the patients’ health, proposing a preliminary evaluation on their condition. For the initial tests of the system, a software artifact has been built using a dataset with 4,978 selected patients, suspected of suffering from OSA, from the Álvaro Cunqueiro Hospital in Vigo. The results obtained are promising, demonstrating the potential usefulness of this type of tools in medical diagnosis. Once the system has been validated with new data from clinical environments, it is considered as possible to obtain a relevant improvement in the quality of the healthcare services, and a reduction in the associated costs.

In New Orleans, Louisiana the population’s poor baseline health led to its establishment as an early epicenter for severe acute COVID-19. Antici-pating future outbreaks of COVID-19 and other respiratory viruses, we need to identify correlates of outcome, from real clinical experience. 89 patients were recruited into the ClinSeqSer acute COVID-19 longitudinal observational study, from the beginning of the outbreak in March to July 2020. Patients admitted for acute COVID-19 were enrolled in person. The cohort is unique as it is 68% Black, 53% female, of average age of early 60s, and prevalence of obesity and hypertension respectively of 55% and 83%. The outcomes are: 53% severe (20% fatal, 33% non-fatal) and 47% non-severe, with severe defined as death or requiring mechanical ventila-tion or high flow oxygen. Obesity and admit systolic blood pressure (SBP) >140mmHg are each associated with severe outcome and, despite respective sensitivity of 71% and 76%, specificity ~66% for both, and ac-curacy of 60% and 70% by ROC analysis, would likely provide useful predictors of outcome in critically stressed health care systems. We discuss pathophysiologic hypotheses to explain why high admit SBP is observed only in half of patients with pre-COVID hypertension and is associated with severe outcome.

Background: Aluminum phosphide (AlP), also known as “rice tablet,” is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture and acid. Phosphine is a robust mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models.Methods: Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning rather than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n =18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5% DHA solution w/v, i.v.) in addition to routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and time of hospitalization were evaluated in both DHA-treated (n = 58) and AlP-poisoned patients without DHA administration (n = 18). Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K+ and Na+), WBC, RBC, hemoglobin, INR, carbonate (HCO3), blood pH, PaCO2, and PaO2 and SGPT, SGOT, BUN, Cr. Results: Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO₂, and HCO₃ levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients’ survival rate compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study.Interpretation: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning.Trial registration: IR.SUMS.REC.1394.102

ChatGPT is gaining widespread acceptance for its ability to generate natural language sentences in response to various inputs and is expected to become a supplementary tool for diagnosing and determining treatment policies in clinical settings. ChatGPT was used to evaluate its ability to perform clinical inference and accuracy in answering questions on the 117th Japanese National Medical Licensing Examination held in February 2023. The exam questions were manually inputted into ChatGPT's window, and the accuracy of ChatGPT's responses was determined based on answers provided by a preparatory school. ChatGPT provided answers for 389 out of 400 questions, and its overall correct answer rate was 55.0%. The correct answer rate for 5-choice-1, 5-choice-2, and 5-choice-3 were 57.8%, 42.9%, and 41.2%, respectively. The highest correct answer rate was for the compulsory exam (67.0%), followed by the specific knowledge exam (54.1%) and the cross category exam (47.9%). The correct answer rate for non-image questions was 56.2% and for image questions, it was 51.5%. The study suggests that ChatGPT has potential to support healthcare professionals in clinical decision-making in Japanese clinical settings, but caution should be exercised in interpreting and using the answers generated by ChatGPT due to room for improvement in performance.

Tendons and ligaments injuries are frequent in sport horses and humans, representing a great therapeutic challenge. Tissue regeneration and function recovery are the paramount of tendon and ligament lesions management. Nowadays, several regenerative treatments are being developed, based on the use of stem cell and stem cell-based therapies. In the present study, the preparation of equine synovial membrane mesenchymal stem cells (eSM-MSCs) for clinical use - collection, transport, isolation, differentiation, characterization, and application is described. These cells are fibroblast-like and grow in clusters. They retain an osteogenic, chondrogenic and adipogenic differentiation potential. 16 clinical cases of tendonitis and desmitis, treated with allogenic eSM-MSCs and autologous serum are also presented, including their evaluation, treatment and follow-up. The use of autologous serum as a vehicle concern to a decreased immunogenic response after the administration of this combination and to its healing properties, due to the presence of growth factors and immunoglobulins. Most of the cases (14/16), healed in 30 days and presented a good outcome. Treatment of tendon and ligament lesions with the mixture of eSM-MSCs and autologous serum appears to be a promising clinical option for this category of lesions in equine patients.

Background: Chikungunya virus (CHIKV) diagnosis have become a challenge for primary care physicians in areas where zika virus and/or dengue virus are present. Case definitions for the three arboviral infections are overlapping. Methods: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. Results: 295 patients with confirmed CHIKV infection were included. A screening tool was made using symmetric arthritis (4 points), fatigue (3 points), rash (2 points) and ankle joint pain (1 point). The ROC curve identified a cut-off value and a score ≥ 5.5 was considered positive to identify CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. Conclusion: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

The overall objective of this mixed-method digital-based observational study was to determine the mental health impact among CTU staff working during the COVID-19 pandemic. The Qualtrics Core XM platform was used to deploy the questionnaire where a quantitative analysis was conducted. The qualitative part of the study used the Microsoft Teams digital application to complete the interviews. Various validated mental health assessments were administered: Vancouver Index of Acculturation (VIA), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Pandemic Stress Index (PSI), Burnout Assessment Tool-12 (BAT-12), General Self Efficacy Scale (GSE) and The Everyday Discrimination Scale (EDS). A total of 485 participants took part, of which 73.4% were female and 70.1% of the sample were white British. A high prevalence of anxiety, exhaustion and depression were identified across all participants. A significant mental health impact was identified among the CTU workforce where wellbeing was compromised during the course of the COVID-19 pandemic.

Background: Transient Hypogammaglobulinemia of Infancy (THI) is a primary immunodeficiency caused by a temporary decline of serum levels of immunoglobulin G (IgG) greater than 2 standard deviations below the mean age-specific reference values in an infant between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as, in the third trimester of pregnancy, IgG is transferred across the placenta from mother to infant.Objective: To systematically review the diagnostic criteria of Transient Hypogammaglobulinemia of infants.Design & Methods: Systematic Review. Manual searching of 3 electronic databases (PubMed, Medline, & Google Scholar) from September 2021 – April 2022. Abstracts were screened to assess fit to the inclusion criteria. Data was extracted from the selected studies by using an adapted extraction tool from Cochrane.org. Studies were then assessed for bias by using an assessment tool also adapted from Cochrane.org.Results: Of the 215 articles identified, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in 6 domains. 5 studies (31%) had a low risk of bias, while 4 studies (25%) had a high risk of bias, & 7 studies (44%) were unclear for bias.Conclusion: We can conclude that THI is only definitively diagnosed after the abnormal IgG levels have normalized, hence THI is mostly a benign condition, but must be monitored for subsequent recurrent infections. The diagnostic criterion also includes vaccine & isohaemagglutinin responses to differentiate against other immunological disorders in infants.

This paper aims to list the current challenges in the study of Sports Medicine in Brazil based on a review of the literature and the author's experience as a member of a transdisciplinary team in this field, as well as to discuss methods for establishing an appropriate and organized course of health activities in this context. The authors identified four significant contemporary difficulties in the field of sports medicine in Brazil that, while minor, are complicated. There is a need to publish a greater number of national studies, generate integrated knowledge through transdisciplinary research, propose sports and movement as a tool for the prevention of degenerative conditions, and research and develop better therapeutic options through transdisciplinary research. It is expected that a transdisciplinary approach will reduce divergences between the real world and science, putting an end to dogmatism, prejudice, and theoretical thinking, increasing the scientificity of sports, bringing competitive advantages, improving training, performance, and athlete health management, and contributing to the advancement of sports medicine.

Simulation-Based Medical Education that uses Virtual Patients has become increasingly important during the COVID-19 pandemic. With the need for social distancing and minimizing contact, medical simulation technology has provided a valuable tool for healthcare professionals to practice and improve their skills without the need for face-to-face interactions. MedSIM is a medically accurate simulation platform with Virtual Patients designed for undergraduate medical education. Our study involved two groups of students. The PreCOVID group, before the pandemic, underwent conventional teaching methods. The COVID group, during the pandemic, had students exposed to conventions skills taught earlier and were taught again with MedSIM. Students indicated high satisfaction with the clinical skills demonstrated by the Virtual Patients. More than half agreed that MedSIM had enabled them to perform all kinds of procedures on patients (PreCOVID group 68.8%, COVID group 71.3%), showed cues and consequences much like those in natural clinical environments (PreCOVID 68.4%, COVID 71.3%). Also, MedSIM allowed them to have a repetitive practice that helps in critical skills transfer to actual patients (PreCOVID 72.7%, COVID 74.7%). MedSIM met the expectations of most of the students. Students from both groups rated the online performance of the MedSIM simulator as "Very good." Analysis from a customized word cloud indicated that most students found MedSIM to be good and of educational value. MedSIM platform enhances healthcare professionals' skills and knowledge, leading to better patient outcomes and increased access to healthcare, supporting SDG 3 (Good Health and Well-being). It also provides a safe and controlled environment for healthcare professionals to learn and practice essential skills, supporting SDG 4 (Quality Education).

A consistent factor in the epidemic of chronic disease is a pro-inflammatory metabolic state. The ability of clinicians to use nutrients to balance inflammation by supporting oxidant homeostasis rests on the quality of research within the field of antioxidants. Understanding the intersection of two prominent theories regarding the role of antioxidants in quelling inflammation, nutritional hormesis and oxidant scavenging, will enable the therapeutic use of antioxidants in clinical practice. This review investigates the less well-established theory, nutritional hormesis, which has not been comprehensively reviewed recently to our knowledge. To understand the state of research on the hormetic response, we conducted a comprehensive literature review describing the relationship between dietary antioxidants, hormesis, and chronic disease. We used an adaptive search strategy in PubMed and Scopus, retrieving a total of 343 articles, of which 218 were unique. Title and abstract screenings were conducted by two reviewers independently with a third as a tiebreaker, resulting in 152 articles included in this review. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were conducted in humans. Limitations exist in translating plant/cell/animal models into the complexities of human biochemistry and physiology that warrant consideration before extrapolating such results into clinical practice. A critical hurdle in our literature review process is the lack of standardized nomenclature describing the hormetic effect in the research community that challenges the ability to comprehensively review the subject matter. Further, aA knowledge gap exists between the cell culture and animal model research that shows a biphasic, hormetic quality to the role of antioxidants and the observational human studies, which have yet to corroborate these findings. Therefore, we cannot accurately translate this research into clinical care at this time.

As exemplified by the global response to the SARS-CoV-2 pandemic, whole genome sequencing played an important role in monitoring the evolution of novel viral variants and provided guidance on potential antiviral treatments. The recent rapid and extensive introduction and spread of highly pathogenic avian influenza virus in Europe, North America and elsewhere raises the need for similarly rapid sequencing to aid in appropriate response and mitigation activities. To facilitate this objective, we investigated a next generation sequencing platform that uses a portable nanopore sequencing device to generate and present data in real time. This platform offers the potential to extend in-house sequencing capacities to laboratories that may otherwise lack resources to adopt sequencing technologies requiring large benchtop instruments. We evaluated this platform for routine use in a diagnostic laboratory. In this study we evaluated different primer sets for the whole genome amplification of influenza A virus and evaluated five different library preparation approaches for sequencing on the nanopore platform using the MinION flow-cell. A limited amplification procedure and a rapid procedure were found to be best among the approaches taken.

This study was aimed to examine the recent trends of antibiotic resistance (AR) prevalence in Staphylococcus aureus isolated from milk of animals with clinical mastitis in areas of the Abruzzo and Molise regions in central Italy. Fifty-four S. aureus isolates could be obtained from routine testing for clinical mastitis agents carried out in the author institution in years 2021 and 2022. These were analyzed for phenotypic resistance to eight antibiotics recommended for testing by European norms and belonging to the antibiotic classes used for mastitis treatment in milk producing animals. Moreover, the presence of 14 transferable genetic determinants encoding resistance to the same antibiotics was analyzed by qPCR tests developed in this study. Phenotypic resistance to non-β-lactams was infrequent, with only one 2022 isolate resistant to clindamycin. However, low level resistance to the β-lactam cefoxitin was observed in 59.2% isolates in both years making these isolates classifiable as methicillin resistant. The AR genotypes detected were blaZ gene (50% 2021 isolates and 44.4% 2022 isolates), ermC/T- aphA3-blaZ (one 2021 isolate), ant6-ermC/T-aphA3-blaZ (one 2021 isolate), ermB-blaZ (one 2022 isolate) and mecA-mph (one 2022 isolate). An interview to the veterinarians who conferred the samples, regarding antimicrobials prescribed for mastitis treatment and criteria of usage, indicated a possible causal relation with the AR test results. The low prevalence of AR genotypes, not increasing in time, most probably reflecting the reported management of antibiotic therapies in farms. However, the frequently observed cefoxitin resistance needs to be explained genotypically, further monitored and limited by modifying antibiotic usage practices. The identification of a mecA positive isolate in 2022 suggests to investigate further if this genotype is emerging locally.

Objective: Determine the feasibility of utilizing longitudinal electronic dental record (EDR) data to track change over time in patient periodontal disease (PD) and to generate three patient cohorts: 1) patients whose disease did not change over time, 2) patients whose PD progressed, and 3) patients whose disease improved over time using informatics approaches. Methods: We conducted a retrospective study of 28,908 patients who received a comprehensive oral evaluation between January 1, 2009, and December 31, 2014, at the Indiana University School of Dentistry (IUSD) clinics. We developed and tested three automated computer applications to: 1) diagnose periodontitis cases from periodontal charting, 2) retrieve clinician-documented diagnoses from clinical notes, and 3) track disease change over time. We also evaluated the density of longi-tudinal EDR data for the following follow-up times: 1) none, 2) up to 5 years, 3) >5 and <=10 years, and 4) >10 and <=15 years Results: Thirty-four percent (n=9,954) of the study cohort had up to five years of follow-up visits with an average of 2.78 visits with periodontal charting information. An average of three patient visits per year that contained periodontal charts (63,552) were utilized to obtain a diagnosis, which is considered excellent. For clinician-documented diagnoses from clinical notes, 42% of patients (n=5,562) had at least two PD diagnoses to determine their disease change. In this cohort with cli-nician-documented diagnoses, 72% percent of patients (n=3,919) did not have a disease status change between their first and last visits, 669 (13%) patients' disease status progressed, and 589 (11%) patients’ disease improved. Conclusions: This study demonstrated the feasibility of utilizing longitudinal EDR data to track disease changes over 15 years during the observation study period. We found excellent longitudinal data when diagnoses generated from periodontal charting were considered (three visits per pa-tient). This information can be now utilized for studying the clinical course of periodontitis.

Predicting Length of Stay (LoS) and understanding its underlying factors is essential to minimize the risk of hospital-acquired conditions, improve financial, operational, and clinical outcomes, and to better manage future pandemics. The purpose of this study is to forecast patients’ LoS using a deep learning model and analyze cohorts of risk factors minimizing or maximizing LoS. We employed various pre-processing techniques, SMOTE-N to balance data, and Tab-Transformer model to forecast LoS. Finally, Apriori algorithm was applied to analyze cohorts of risk factors influencing LoS at hospital. The Tab-Transformer outperformed the base Machine Learning models with an F1-score (.92), precision (.83), recall (.93), and accuracy (.73) for discharge dataset, and F1-score (.84), precision (.75), recall (.98), and accuracy (.77) for deceased dataset. The association mining algorithm was able to identify significant risk factors/indicators belonging to lab, X-Ray, and clinical data such as elevated LDH, and D-Dimer, lymphocytes count, and comorbidities such as hypertension and diabetes responsible for extending patients LoS. It also reveals what treatments has reduced the symptoms of COVID-19 patients leading to reduction in LoS particularly when no vaccines or medication such as Paxlovid were available.

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

The transition from undergraduate dental student to the actual practicing dentist is a crucial phase and ensuring the preparedness of graduates for the complexity and demands of contempo-rary dental practice is a challenging task. This study aimed to evaluate the self-perceived prepar-edness of undergraduate dental students and house officers in the dental colleges of Pakistan. Cross-sectional national study was planned to collect the information from dental students and new graduates in Pakistan. The pre-validated Dental Undergraduates Preparedness Assessment Scale (DU-PAS) was used. Purposive sampling technique was utilized to recruit house officers and undergraduate dental students from 27 dental schools in Pakistan. The data analysis was car-ried out using the R statistical environment for Windows (R Core Team, 2015). The total of 862 responses with 642 females and 219 males were analyzed in the study. Overall, clinical skills score was 30.56+9.08 and score for soft skills was 30.54+10.6. The mean age of the participants was 23.42+1.28. Deficiencies were reported in various soft skills and clinical skills attributes.The results highlighted the strengths and weaknesses of dental students and new graduates in Pakistani den-tal institutions. The findings may be used to further develop and strengthen teaching and training of dental students in Pakistan.

Colonoscopy is used for colorectal cancer (CRC) screening. Extracting details of the colonoscopy findings from free text in electronic health records (EHRs) can be used to determine patient risk for CRC and colorectal screening strategies. In this study, we developed and evaluated the accuracy of a deep learning model framework to extract information for the clinical decision support system to analyze relevant free-text colonoscopy reports, including indications, pathology, and findings notes. The Bio-Bi-LSTM-CRF framework was developed using Bidirectional Long Short-term Memory (Bi-LSTM) and Conditional Random Fields (CRF) to extract several clinical features from these free-text reports, including indications for the colonoscopy, findings during the colonoscopy, and pathology of the resected material. We then trained the Bio-Bi-LSTM-CRF and existing Bi-LSTM-CRF models on 80% of 4,000 manually annotated notes obtained from the colonoscopy reports of 3,867 patients. The clinical notes were from a group of patients aged over 40 years old enrolled in four Veterans Affairs Medical Centers. A total of 10% of the remaining annotated notes were used to train hyperparameter, while the remaining 10% were used to evaluate the accuracy of our model (Bio-Bi-LSTM-CRF) and to compare the results with the outcomes obtained using Bi-LSTM-CRF. The results of our experiments showed that the bidirectional encoder representations by integrating dictionary function vector from Bio-Bi-LSTM-CRF and strategies character sequence embedding approach is an effective way to identify colonoscopy features from EHR-extracted clinical notes. Therefore, the Bio-Bi-LSTM-CRF model is concluded to be capable of creating new opportunities to identify patients at risk for colon cancer and to study their health outcomes.

Implementing the methodology of clinical simulation in the nursing degree course is a necessity in the European framework of higher education to acquire competences. The objectives of this research were to evaluate the strategies and techniques used during the simulations, identify the contents learned, and determine which of them are transferred to the nursing practice. We performed an observational, descriptive, and cross-sectional study from the nursing students’ perspective during the 2020-21-year course. On the one hand, our results show that the DASH scale helped us to obtain an internal validity of the simulations obtaining a mean score of 6.61 out of 7. On the other hand, the Ad Hoc scale, based on the competences were acquired in the simulations were transferred to the care practices. In conclusion, it is possible to improve care practices by integrating knowledge through clinical simulations.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

The study comprehensively evaluated the prognostic roles of PLR, NLR, MLR, BLR, and ELR in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD). 619 patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics containing laboratory findings of the AECOPD patients and the blood cell counts (CBCs) of the healthy volunteers were collected. Compared with the healthy volunteers, PLR, NLR, and MLR were elevated in COPD patients in stable condition, and were further ele-vated during exacerbation. ELR showed the opposite trend. PLR, NLR, and MLR were all posi-tively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more serious airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while Elevated ELR was associated with decreased in-hospital mortality in AECOPD. A nomogram was construct to predict in-hospital mortality in AECOPD. The nomo-gram had a C-index of 0.850 (95% CI: 0.799 – 0.901) with good predictive value and clinical ap-plicability. In summary, PLR, NLR, MLR, and ELR served as predictors for clinical outcomes in patients with AECOPD.

Biological drugs are inaccessible to more than 80% of the world population due mainly to their high costs; this is a significant concern of the World Health Organization. Biosimilars are supposed to reduce the cost burden, but their approval process is complex, including expensive and irrelevant studies. While the Stringent Regulatory Authorities (SRAs) have adopted the guidance of the FDA or EMA, such adoptions are neither necessary nor practical for the rest of the world (ROW). We present a science-driven, rational approach to formulate regulatory guidelines that will enable faster biosimilars' entry into the ROW without compromising their safety and efficacy. The key recommendations include removing animal and safety efficacy testing, making analytical assessment more robust, and cGMP compliance assured through third-party audits. The ROW countries are also recommended to initiate a rapporteur system available in the EU, to overcome the biases and assure state-of-the-science evaluation as the common understanding of the critical quality attributes evolves. It is anticipated that stronger regional agencies like those in the MENA region, with the leadership of the Kingdom of Saudi Arabia, will help propel the idea faster across the globe.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined as exocrine gland hypofunction resulting in dry eyes and dry mouth. Recent interest in biological therapies for pSS has been garnered, however achieving FDA-approval has been challenging due to the numerous complications in the trials. Current literature lacks insight and a molecular target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term “Primary Sjögren's syndrome”. Articles published between 2000 and 2021 in English language were included. Our findings revealed the potential targets for pSS treatment in clinical trials and the most recent advances in understand-ing of molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is overlooking the treatment of extraglandular symptoms such as fatigue, depression and anxiety which pervade most patients with pSS. Based on dryness and these symptom-directed therapies, emerging biological agents targeting inflammatory cytokines, signal pathways and immune reaction have been studied and proved the efficacy and safety. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grad-ing systems adding extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene therapy, stem cell and tissue engineering ther-apy.

Introduction: Leprosy, caused by Mycobacterium leprae is one of the oldest infectious diseases in human history and its eradication is linked to poverty control, lack of basic sanitation, the fragility of health, and education services. Objective: To evaluate the frequency of blood groups (ABO/Rh) and the sociodemographic and clinical profile of Angolan patients with Leprosy treated at the Anti-Tuberculosis and Leprosy Dispensary in Luanda, the capital city of Angola. Methodology: A descriptive, introspective, cross-sectional study with a quantitative approach was carried out with 102 patients of Luanda, in the second half of 2021. Results: Of the 102 patients included in the study, the majority belonged to the ORh+ group (51.9%), followed by the BRh+ group (27.4%) and ARh+ (18.6%), most were under 51 years of age ( 87.3%), with low education (54.9%), coming from urban areas (44.1%). As for clinical conditions, most had a multibacillary infection (93.1%), diagnosed mainly by smear microscopy (75.5%) without other infection (79.4%), some of them with complications (28.4%) and individuals with non-O blood group showed changes in the blood count. Conclusion: Leprosy seems to be common in ORh+ individuals, it continues to affect especially those residing in areas of population agglomerations and with low education, presenting itself as a multibacillary infection, where changes in the blood count are greater in non-O individuals.

Objectives: Human herpes viruses can cause life-threatening diseases in immunocompromised children, especially leukemic patients. Therefore, the aim of this study is to detect the human herpes viruses (HHV1-7) and to investigate its clinical significance in Middle Eastern Pediatric Leukemia Patients by using 2 Independent PCR assays. Methods: Detection of human herpes virus DNA has been done in blood samples of 200 pediatric leukemia patients in addition to 90 blood donors as a control group using multiplex PCR assays. When a ‘‘positive’’ result was observed, real-time PCR was performed to measure the viral load. Results: The most frequent herpes virus infection in Middle Eastern Pediatric Leukemia cases was CMV, followed by EBV, then HHV6, VZV, HHV7, HSV1, and HSV2, where they were 92/200 (46%), 76/200 (38%), 72/200 (36%), 48/200 (24%), 12/200 (6%), 8/200 (4%), and 2/200 (1%) respectively. Also, there was a statistically significance difference between leukemic patients and their controls regarding CMV, EBV, HHV6, and VZV (P <0.05). Correlation between percentage of co-infection, and clinical parameters for the 7 herpes viruses has been studied, and there is an increase in absolute neutrophilic count (ANC), total leukocyte count (TLC) and duration of fever and neutropenia in age group 6-11 years for HHV6/CMV, then in age group 12-18 years especially for EBV/CMV and CMV/HHV6. Also, our results show that multiplex PCR assay is close to single PCR assay in relation to specificity and sensitivity which in turn prove its validity for early diagnosis of herpes viral infection. Conclusions: Adopting multiplex PCR technique is helpful in screening of virus infections. It will save time, effort, cost effective and will assist in rapid diagnosis. However, the clinical relevance of the virus infection needs to be evaluated by quantitative real-time PCR which in turn will help patient's management by using appropriate antiviral treatment.

The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.

Scientific, technical and bioinformatics advances have made it possible to establish analytics-based molecular biosimilarity for the approval of biosimilars. If the molecular structure and other product- and process-related attributes are comparable within the limits of testing then a biosimilar candidate would have safe safety and efficacy as its reference products. The current model of animal and human testing becomes redundant since all of these studies have much lower sensitivity and reproducibility in confirming biosimilarity. The recent AI-based protein structure prediction model has confirmed that the 3D structure can be predicted from the amino acid sequence, reducing the need for structural analysis; however, the new test methods based on MS are millions of times more sensitive and accurate. While the regulatory agencies have begun waiving animal testing and, in some cases, clinical efficacy testing, removing clinical pharmacology profiling brings a dramatic paradigm shift, reducing development costs without compromising safety and efficacy. Also shared is a list of 160+ products ready to enter as biosimilars. Major actions from regulatory agencies and developers are required to make this paradigm shift.

Pulmonary thromboembolism is a very common cardiovascular disease, with a still high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. Heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decision on the therapeutic regimen also represents a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only the effectiveness of the drugs must be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

Background: Given the potential for additional development to clarify a better knowledge of the overall impact of COVID-19 on the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study's goal was to compare clinical aspects of 230 pediatric patients who tested positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: In a retrospective analysis, we compared two groups hospitalized in the infectious diseases clinical ward IX at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest, Romania. The first group of 88 patients was admitted between (April–December 2020) and their clinical manifestations were compared with the second group of 142 children followed between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 (interquartile range 0.6-17) years, 53.9% were male. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged < 5 years old, and experienced digestive manifestations like fever (p=0.001), and diarrhoea (p=0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to those of acute respiratory viral infections. The proportion in the second group increased, and 64.5% had symptoms for a median interval of 5 days; age (0-4 -years old) and length of stay were both proportionally inversely (p<0.01) and with correlation with hospital admission (p = 0.04). We report two Paediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favourable evolution under treatment. Comorbidities were risk factors for complications appear (p < 0.001) in both groups. All paediatric cases admitted to our clinic evolved favourably and no death was recorded. Conclusions: In the first group children experienced digestive symptoms, whereas the second group experienced mild and moderate respiratory symptoms. We confirmed risk factors for severe cases as manifestations across the age spectrum, 0-4 (digestive symptoms) and 5-12 years old (for respiratory symptoms), associated comorbidities, fever, and male gender. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

Laboratory medicine is a digital science. Every large hospital produces a wealth of data each day - from simple numerical results from e.g. sodium measurements to highly complex output of “-omics” analyses, as well as quality control results and meta-data. Processing, connecting, storing, and ordering extensive parts of these individual data requires Big Data techniques. Whereas novel technologies such as artificial intelligence and machine learning have exciting application for the augmentation of laboratory medicine, the Big Data concept remains fundamental for any sophisticated data analysis in large databases. To make laboratory medicine data optimally usable for clinical and research purposes, they need to be FAIR: findable, accessible, interoperable, and reusable. This can be achieved for example by automated recording, connection of devices, efficient ETL (Extract, Transform, Load) processes, careful data governance, and modern data security solutions. Enriched with clinical data, laboratory medicine data allow a gain in pathophysiological insights, can improve patient care, or they can be used to develop reference intervals for diagnostic purposes. Nevertheless, Big Data in laboratory medicine do not come without challenges: The growing number of analyses and data derived from them is a demanding task to be taken care of. Laboratory medicine experts are and will be needed to drive this development, take an active role in the ongoing digitalization, and provide guidance for their clinical colleagues engaging with the laboratory data in research.

The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.

We have previously reported that a single test measuring oVEMP n10 to 4000Hz stimuli (either bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients with a sensitivity of 1.0 and specificity of 1.0. Such a single short screening test has great advantages of speed, minimizing testing time and the exposure of patients to stimulation. However some studies of the 4000Hz test for SCD have reported sensitivity and sensitivity values somewhat less that what we reported.

Thrombosis has threatened human health in past decades. Bacillus nattokinase is a potential thrombolytic drug without side-effect and low cost and has been introduced into the consumer market as a functional food or dietary supplement. This review firstly summarizes the biodiversity sources and fermentation process of nattokinase, and systematically expounds the structure, cata-lytic mechanism and enzymatic properties of nattokinase; In view of the problems of low fermen-tation yield, insufficient activity and stability of nattokinase, this review discusses the heterologous expression of nattokinase in different microbial hosts, and summarizes the protein and genetic en-gineering progress of nattokinase-producing strains; Finally, this review summarizes the clinical application of nattokinase.

ABSTRACT Background It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under- or over-treatment. Deep Neural Network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tunning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15-years after the initial treatment. We developed DNN models as well as models using 9 other machine learning methods including Naive Bayes (NB), Logistic Regression (LR), Support Vector Machine (SVM), LASSO, Decision Tree (DT), k-Nearest Neighbors (KNN), Random Forrest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared the deep learning models to the models trained using the 9 other machine learning methods. Results Based on the mean test AUC results, DNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM respectively, out of 10 machine learning methods. The top performing methods in predicting 5-year BCM are XGB(1^st), RF(2^nd), and KNN(3^rd). For predicting 10-year BCM the top performers are XGB (1^st), RF(2^nd), and NB(3^rd) . Finally, for 15-year BCM the top performers are SVM (1^st), LR and LASSO (tied for 2^nd), and DNN (3^rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05 DNN overall performs no worse than other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods such as XGB, RF, and SVM are very strong competitors of DNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DNN is way more than that required to do grid search with the other 9 machine learning methods.

The use of inertial measurement units (IMUs) to compute gait outputs such as the 3D lower limb kinematics is of huge potential, but no consensus on the procedures and algorithms exists. This study aimed at evaluating the validity of a 7-IMUs system against the optoelectronic system. Ten asymptomatic subjects were included. They wore IMUs on their feet, shanks, thighs and pelvis. The IMUs were embedded in clusters with reflective markers. Reference kinematics was computed from anatomical markers. Gait kinematics was obtained from accelerometer and gyroscope data after sensor orientation estimation and sensor-to-segment (S2S) calibration steps. The S2S calibration steps were also applied to the cluster data. IMU-based and cluster-based kinematics were compared to the reference through root mean square errors (RMSEs), centered RMSEs (after mean removal), correlation coefficients (CCs) and differences of amplitude. The mean RMSE and centered RMSE were respectively 7.5° and 4.0° for IMU-kinematics, and 7.9° and 3.8° for cluster-kinematics. Very good CCs were found in the sagittal plane for both IMUs and cluster-based kinematics at the hip, knee and ankle levels (CCs&gt;0.85). The overall mean amplitude difference was about 7°. These results reflected good accordance of our system with the reference, especially in the sagittal plane, but the presence of offsets requires caution for clinical use.

Deep learning has shown remarkable results in every field, especially in the biomedical field, due to its ability to exploit large-scale datasets. A convolutional neural network (CNN) is a widely used deep learning approach to solve medical imaging problems. Over the past few years, many studies have focused on CNN-based techniques for brain tumor diagnosis. There are, however, still some critical challenges that CNNs face towards clinic application. This study presents a comprehensive review of current literature that involves CNN architectures for brain tumor classification. We compare the key achievements in the performance evaluation metrics of the applied classification algorithms. In addition, this review assesses the clinical effectiveness of the included studies to elaborate on the limitations and directions of this area for future work. No review focusing on the clinical effectiveness of previous works in this field has been published. We believe that this study has the potential to elevate the application of CNN-based deep learning methods in clinical practice and also can be a quick reference for biomedical researchers who are interested in this field.

Background: Media coverage of Lyme disease (LD) has led to an increase in consultations for presumed LD in Europe. However, LD is confirmed in only 10-20% of patients, with a significant number remaining in a diagnostic dead-end. Objectives: To reach a deeper understanding of how patients themselves contribute to the diagnostic process. To describe the genesis of the LD hypothesis in care pathways. Methods: In 2019, 30 patients from a prospective cohort consulting in the infectious diseases department at University Hospital in Marseille for presumed LD were recruited for semi-structured interviews. The inclusion criteria were : suffering from subjective symptoms for 6 months, no clinical or paraclinical argument suggesting current LD. The patients’ medical trajectories were collected using a biographical approach. Results: The diagnosis of Lyme disease was primarily triggered by identification with personal testimonies found on the internet. Most of patients were leading their own diagnostic investigation. The majority of participants were convinced they had LD despite the lack of medical evidence and the scepticism of their referring GP. Conclusion: GPs should first systematically explore patients’ etiologic representations in order to improve adherence to the diagnosis especially in the management of medically unexplained symptoms. Long COVID-19 syndrome challenge offers an opportunity to promote active patient involvement in diagnosis.

Financial capacity instruments are psychometric tools designed to evaluate individual decisional capacity based on financial decisions. As tests are complex and need special conditions for administration and evaluation, it is difficult to use them in daily geriatric clinics. Our scoping review objective was to evaluate existing financial capacity instruments from the perspective of simplicity and portability. We evaluated one English speaking knowledge database (Medline) using a dedicated MeSH terminology. The review yielded one independent instrument, The Semi-Structured Clinical Interview for Financial Capacity, that can be easy adapted for every-day clinical use. It is simple to understand and perform and do not need trained personnel for administration. It can be finalized in 15 minutes. Initially validated on 261 subjects (with different forms of cognitive impairment), it showed good accuracy and precision mainly in subjects with cognitive impairment. The test is less apt to detect early or fluctuating cognitive impairment. Simplicity, the main advantage of the test, allows gamification fact that increases portability. Familiar images (coins, money) that are used for performing simple tasks does not need complex translation and adaptation. In form of a game, the test is suitable for serial administration, increasing the chance for early capacity reduction detection. Results reflect a physician judgement related to the subjects’ capacity to understand and execute simple financial instructions and not financial proficiency scores. The main limitation of our review is that we investigated only one, English speaking, knowledge database. The scoping strategy generated a financial capacity instrument that can be used in geriatric clinics for early diagnostic of decisional capacity reduction. Further studies are needed to evaluate the reliability and validity of the test in conditions of serial administration and in populations having various financial experience.

Background: Handover is a critical process for ensuring quality and safety in healthcare. Considerable research suggests that poor handover results in significant morbidity, mortality, dissatisfaction, and excess financial costs. Despite this, little formal attention, education, and evaluation has been given to handover. There is also paucity of data on the opinions of practitioners on the safety of handover.Objectives: The aim of this study was to measure the perceived risk, degree of patient harm and the systems used to support handover, and to understand how this varied by care setting, type of clinical practice, location, or level of experience. Methods: An open, anonymous and confidential online questionnaire covering: (a) respondent characteristics; (b) peer-to-peer handover; (c) internal referrals; (d) discharges and transfers between organisations; and (e) leading and improving handover was conducted with healthcare practitioners and managers from various settings. Results: We gathered a total of 432 completed responses from 26 countries. The average reported performance of handover was rated as 3.9 out of 5.For each type of handover, 12 - 14% reported errors occurring more than weekly. Of those that knew the outcome of such errors, between 29% and 34% reported that they had witnessed moderate or severe harm. 12% and 17% of respondents believed that handover was high or very high risk (See table 4). These respondents were more likely to have witnessed moderate or severe harm, or to be more senior.A wide combination of handover systems was utilised by respondents. 28% - 32% relied exclusively on EPRs (with or without face-to-face contact). 21% used Office documents such as Word and Excel for peer-to-peer handover, and over 30% used hand-written or manual systems. Conclusions: This study suggests the need to do more — and go further — to improve communication and reduce risk during all types of handovers. Clinical leaders should find ways to train and support handover with effective systems, with less experienced staff being the primary focus. More research is needed to demonstrate the interventions that improve the safety of handover.

The emergence of acute, severe non hepA–E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs, and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendations very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA–E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

Background: One way to demonstrate the existence of nursing is to develop a nursing theory model through nursing research which can ultimately be implemented in nursing practice. RAM is one of the most frequently used models in guiding nursing research. Roy's Adaptation Model (RAM) is one of the most useful conceptual frameworks that guide nursing practice, direct research, and influence education. Theory-guided nursing practice is fundamental in providing the framework for developing superior and quality nursing care.Objectives: This systematic review aims to critically analyze recent studies using RAM as a conceptual framework to identify the effectiveness of this model in guiding nursing research.Methods: A literature search was conducted on five databases, namely SCOPUS, PubMed, ProQuest, ScienceDirect, and SAGEPub. There were no population boundaries and diagnoses involved in the study. The study is a quantitative design focused on publication between 2015-2021. The methodological quality of applying the Cochrane and JBI bias tools. The analysis uses narrative synthesis.Results: 20 studies were found out of 1,315 studies. The research population found is very diverse. The given intervention follows the conceptual framework of RAM. RAM-based interventions effectively overcome the problems experienced by patients and reduce the perceived symptoms and improve the patient's quality of life.Conclusion: The conceptual use of RAM theory in nursing research has been widely reported. RAM-based interventions have a significant impact and have strong evidence-based practice in improving patient health status.

The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumanii. Furthermore, an ATCC control strain was selected for all species tested. MICs were performed according to the standard method, with some modifications. PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0,12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4-64 mg/L), butstill promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.

Predicting change from multivariate time series has relevant applications ranging from medical to engineering fields. Multisensory stimulation therapy in patients with dementia aims to change the patient’s behavioral state. For example, patients who exhibit a baseline of agitation may be paced to change their behavioral state to relaxed. This study aims to predict changes in behavioral state from the analysis of the physiological and neurovegetative parameters to support the therapist during the stimulation session. In order to extract valuable indicators for predicting changes, both handcrafted and learned features were evaluated and compared. The handcrafted features were defined starting from the CATCH22 feature collection, while the learned ones were extracted using a Temporal Convolutional Network, and the behavioral state was predicted through Bidirectional Long Short-Term Memory Auto-Encoder, operating jointly. From the comparison with the state-of-the-art, the learned features-based approach exhibits superior performance with accuracy rates of up to 99.42% with a time window of 70 seconds and up to 98.44% with a time window of 10 seconds.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

Background. It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. Methods. We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cut-off points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. Results. Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95%CI 0.10-0.54, p=0.001). Conclusion. PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

Combination treatment, i.e., the use of two or more drugs for the same condition, is frequent in medicine if monotherapy yields an insufficient therapeutic response. We here review and challenge clinical study designs and formats of reporting outcomes for the evaluation of the benefit/risk ratio of combination treatment over monotherapy. We demonstrate that benefits of combination treatment at the group level over-estimate the probability of benefit at the single patient level based on outcome simulations under almost any imaginable setting. Based on these findings we propose that studies testing combination treatment should always report on percentages of responders to monotherapy and combination treatment. We provide equations that allow calculation of the percentage of patients truly benefitting from combination (responders to both monotherapies) and that of patients exposed to risk of harm from adverse effects without a reasonable expectation of individual benefit. These considerations are explained based on real clinical data, mostly from the field of functional urology (male lower urinary tract symptoms).

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Background: There is a high bureaucratic and administrative burden associated with health care tasks (test requesting, visits scheduling, supporting documents provision) that has historically largely fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. Objective: To evaluate the impact of the clinical assistant’s introduction in the Sant Joan de Déu Barcelona Children’s Hospital’s pediatric oncology department, in terms of displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians. Methodology: Observational and retrospective study using administrative data based on the analysis of the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians, based on in situ timekeeping, to approximate the potential skill mix productivity increase. Results: Since its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69.93% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74.25% of outpatient surgical requests in the oncology department, 87.5% of day hospital requests and 54.13% of total requests in the outpatient consultations area. Conclusion: The introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a good part of the bureaucratic and administrative tasks previously performed by health care professionals. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks. In terms of efficiency, this role change enables to optimize the clinical process, reducing the cost by 56% compared to the conventional model.

In a wide range of lymphoid neoplasms, the process of malignant transformation is associated to somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in non-Hodgkin B-cell lymphoma. Furthermore, we aim to present in close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have greatest potential to improve the prognosis of lymphoma patients.

Scrub typhus is a neglected tropical disease predominantly occurring in Asia. The causative agent is a bacterium transmitted by the larval stage of mites found in rural vegetation in endemic regions. Cases of scrub typhus frequently present as acute undifferentiated febrile illness, and without early diagnosis and treatment, the disease can develop fatal complications. We retrospectively reviewed de-identified data from a 23-year-old woman who presented to an emergency department with complaints of worsening abdominal pain. On presentation, she appeared jaundiced and toxic-looking. Other positive findings on abdominal examination were a positive Murphey’s sign, abdominal guarding and hepatosplenomegaly. Magnetic resonance cholangiopancreatography demonstrated acalculous cholecystitis. Additional findings included eschar on the medial aspect of the left thigh with inguinal regional lymphadenopathy. Further, positive results were obtained for immunoglobulins M and G, confirming scrub typhus. Workups for other infectious causes of acute acalculous cholecystitis detected human herpesvirus 4 (Epstein-Barr virus). Whether that represented acute infection or re-activation of the Epstein-Barr virus could not be determined. As other reports have described acute acalculous cholecystitis in adult scrub typhus patients, we recommend doxycycline to treat acute acalculous cholecystitis in endemic regions while awaiting serological confirmation.

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.

Background: Mucormycosis is a worldwide angio-invasive fungal infection that is associated with high morbidity and mortality. A few European studies have focused on the epidemiology. Methodology: A retrospective longitudinal descriptive study was performed with inpatients diagnosed with mucormycosis (ICD-9-CM, code 117.7, cases 1997-2015; and ICD-10, code B46, cases 2016-2018; along with length of hospital stay) in Spanish public hospitals between 1 January 1997 and 31 December 2018. Data were obtained from the Minimum Basic Data Set (CMBD in Spanish). Principal findings: A total of 962 patients were recorded; 665 were men. The mean age (±SD) was 55±18.8 years. The annual incidence rate increased from 0.74 to 1.24 cases per million person-years. The lethality rate was 31.3%. Renal failure (41.6%) and hematological malignancy (36.3%) were the main factors involved. Conclusions: Mucormycosis is a rare infectious disease in Spain, but it has had a significantly increased incidence in the last two decades. Being an adult male and having diabetes, neoplasm or renal failure are the main factors associated. High mortality is usually associated mainly with hematological malignancy and renal failure. CMBD studies could be an efficient tool for assessing changes in the epidemiology of mucormycosis.

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.

Clinical trials for Alzheimer’s disease (AD) face multiple challenges, such as the high screen failure rate and even allocation of heterogeneous participants. Artificial intelligence (AI), which has become a potent tool of modern science with the expansion in the volume, variety, and velocity of biological data, offers promising potential to address these issues in AD clinical trials. In this review, we introduce the current status of AD clinical trials and topic of machine learning. Then, a comprehensive review is focused on the potential applications of AI in the steps of AD clinical trials, including the prediction of AD biomarkers and differential diagnosis of AD in the prescreen during eligibility assessment and the likelihood stratification of patients who will progress to AD dementia and fast cognitive decline group from the slow decline group in randomization. Finally, this review provides challenges, developments and the future outlook on the integration of AI into AD clinical trials.

All the available botulinum type A neurotoxins for clinical uses are of A1 subtype. We developed a subtype A2 low molecular weight (150kD) neurotoxin (A2NTX), with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed its efficacy superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (onabotulinumtoxinA) and low molecular weight (150kD) A1 neurotoxin (A1NTX). Those who had been using A1LL (n=90; 50-360 mouse LD50 units) or A1NTX (n=30; 50-580 units) were switched to A2NTX (n=120; 25-600 units) from 2010 till 2018 (number of sessions ~ 27, cumulative doses ~11,640 units per patient). Adverse events for A2NTX included weakness (n=1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness (n=2, A1NTX), dysphagia (8), ptosis (6), local weakness (7) and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had the clinical safety up to the dose of 500 units, and was well tolerated compared to A1 toxins.

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.

Clinical agreement between two quantitative measurements on a group of subjects is generally assessed with the help of the Bland-Altman (B-A) limits. The interpretation regarding agreement is based on whether B-A limits are within the pre-specified clinical tolerance. Thus, clinical tolerance limits are necessary for this method. We argue in this communication that such limits of clinical tolerance can be directly used for assessing agreement and plead that this nonparametric approach is simple and robust to the distribution pattern and outliers. Such direct use of clinical tolerance limits has more flexibility, and it is more effective in assessing the extent of agreement.

Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

The purpose of the study was to investigate the bacterial viability of the initial biofilm on the surface of experimental modified dental resin composites. Twenty-five healthy individuals with good oral hygiene were included in this study. In a split-mouth design, they received acrylic splints with five experimental composite resin specimens. Four of them were modified with either a novel polymeric hollow beads delivery system or methacrylated polymerizable Irgasan (Antibacterial B), while one specimen served as unmodified control (ST). The delivery system based on Poly-Pore® was loaded with one of the active agents Tego® Protect 5000 (Antiadhesive A), Dimethicone (Antiadhesive B) or Irgasan (Antibacterial A). All study subjects refrained from toothbrushing during the study period. Specimens were detached from the splints after 8h and given a live/dead staining before fluorescence microscopy. Friedman test and post-hoc Nemenyi test were applied with significance level at p &lt; 0.05. In summary all materials but Antibacterial B showed a significant antibacterial effect compared to ST. In conclusion dental resin composites with Poly-Pore loaded active agents show antibacterial effectiveness in situ.

African swine fever (ASF) is one of the most important and devastating viral diseases in wild boar and domestic pigs worldwide. In the absence of vaccines or treatment options, early clinical detection is key and requires sound knowledge of disease characteristics. To provide practitioners and state veterinarians with detailed information, the objective of the present study was to characterize the ASF virus (ASFV) isolate “Belgium 2018/1” in subadult and weaning domestic pigs. To this end, two animal trials were performed. Trial A included eight subadult domestic pigs and trial B five weaner pigs. In general, clinical signs and pathological lesions were in line with previous studies utilizing highly virulent ASF genotype II viruses. However, in trial A, four subadult domestic pigs survived and recovered pointing to an age dependent outcome. The long-term fate of those survivors remains under discussion and would need further investigations.

Background In this study, we describe our clinical experience with the fifth-generation of a breast implant with a smooth, fine surface from a Korean manufacturer (BellaGel^Ò SmoothFine; HansBiomed Co. Ltd., Seoul, Korea) in Asian women. Methods We analyzed 223 women (mean age=35.28±9.45 years and mean follow-up period=12.03±2.48 months), comprising 118 bilateral cases and 109 unilateral ones, who received breast augmentation using the BellaGel^Ò SmoothFine at our hospital between June 4, 2018 and February 28, 2019. For safety assessment, we analyzed frequencies of postoperative complications and overall survival of the BellaGel^Ò SmoothFine. Results Postoperatively, complications (12 cases, 5.38%) include asymmetry (3 cases, 1.35%), hematoma (2 cases, 0.90%), hypertrophic scars (2 cases, 0.90%), wound disruption (2 cases, 0.90%), rippling (1 case, 0.45%), capsular contracture (1 case, 0.45%), stretch deformities with skin excess (1 case, 0.45%). In addition, time-to-events were calculated as 10.94±0.64 months (95% CI 9.69-12.19) and the survival rate reached 0.290±0.168 (95% CI 0.094-0.901) at 12 months postoperatively. Conclusions Here, we describe our clinical experience with the BellaGel^Ò SmoothFine. Our results are of significance in that this is the first report about the fifth-generation of a breast implant with a smooth, fine surface from a Korean manufacturer in Asian women.

Enhance®Fitness (EF) is an evidence-based exercise program recommended for management of osteoarthritis (OA). However, access to EF is limited in rural areas. Accordingly, we evaluated the feasibility and acceptability of remotely delivered EF in rural, community-dwelling older adults with symptomatic knee OA. A single arm pilot trial of remotely delivered EF classes was conducted. Videoconferencing was used to livestream the instructor-led, 1-hour EF classes 3 days/week for 12 weeks. Outcomes were assessed at baseline and immediately post-intervention. A total of 15 participants were enrolled with a median age of 70 years (interquartile range [IQR]: 67-75) and 14 (93%) were women. Median EF class attendance rate was 91% (IQR: 85-94%). Knee pain, as measured by the Knee injury and Osteoarthritis Outcome Score (KOOS), improved significantly from baseline to 12-week endpoint (mean difference=-11.4 [95% CI:-20.9, -2.0); P=0.02). In addition, participants’ self-reported knee function improved significantly (mean difference in KOOS Function score=-11.8 [95% CI:-18.4, -5.2]; P&lt;0.01) as well as their physical capacity (mean difference in Timed Up and Go test time=1.8 seconds [95% CI: 0.2, 3.4]; P=0.03). All participants (100%) were very satisfied with remotely delivered EF classes and there were no serious adverse events. Findings from this pilot trial indicate that remotely delivered EF is feasible and acceptable in rural older adults with knee OA.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

The purpose of this Individually Randomized Group Treatment Trial was to compare an Acceptance and Commitment Therapy-based (ACT) group intervention and a Cog-nitive Behavioral Therapy-based (CBT) group intervention for weight loss maintenance in a sample of adult patients with obesity seeking treatment for weight loss. 155 over-weight adults (BMI: Kg/m2= 43.8[6.8]) attending a multidisciplinary rehabilitation program for weight loss were randomized into two conditions: ACT and CBT. Demo-graphical, physical, and clinical data were assessed at the beginning of the program (t0), at discharge (t1), and at 6-month follow-up (t2). The following measures were ad-ministered: The Acceptance and Action Questionnaire-II (AAQ-II) and the Clinical Outcome in Routine Evaluation-Outcome Measure (CORE-OM). Generalized linear mixed models were performed to assess differences between groups. Moderation ef-fects for gender and eating disorders (ED) have been considered. From baseline to dis-charge no significant differences between interventions were found, with the only ex-ception of an improvement in the CORE-OM total score and in the CORE-OM subjective well-being subscale for those in the CBT condition. From discharge to follow-up ACT group participants showed significant results in terms of weight loss maintenance, CORE-OM total score, and CORE-OM and AAQ-II’s wellbeing, symptoms, and psy-chological problems subscales. Gender moderated the effects of time and intervention on the CORE-OM’ subscale reporting the risk for self-harm or harm others. The pres-ence of an eating disorder moderated the effect of time and intervention on the CORE-OM total score, on the CORE-Om’ symptoms and psychological problems sub-scales, and on the AAQ-II. Patients who received the ACT intervention were more likely to achieve a ≥5% weight loss from baseline to follow-up and to maintain the weight loss after discharge. The ACT intervention was thus effective in maintaining weight loss over time.

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.

Abstract: The objective of this meta-analysis was to evaluate the factors associated with mortality of elderly Italians diagnosed with the new coronavirus who resided in institutions or who were hospitalized as a result of the disease. Methods: A systematic review following the recommenda-tions of The Joanna Briggs Institute (JBI), where the PEO strategy was utilized - Population, Exposure and Outcome. P, being the elderly over 65 years old. E, the SARS-CoV_2 pandemic. O, mortality. The NCBI / PubMed, LILACS, EMBASE and CINAHL databases were used until July 31, 2020.; Results: Five Italian studies were included in the meta-analysis, with the number of elderly people varying between 18 and 1591 patients. The main morbidities presented by the elderly in the studies were: dementia, diabetes, chronic kidney disease and hypertension. Conclusions: The factors as-sociated with the mortality of elderly Italian people diagnosed with SARS-CoV-2 who lived in in-stitutions or who were hospitalized because of the disease were evaluated. It was found that de-mentia, diabetes, chronic kidney disease and hypertension are the main the main diagnosed dis-eases for mortality in elderly people with Covid-19.

A face serum composed of a combination of biologically active compounds was evaluated for safety and efficacy in vitro, in a repeat insult patch test and in a human clinical efficacy trial. The serum inhibited tyrosinase activity modestly, decreased collagenase activity and exhibited notable free radical scavenging activity in vitro. It is gentle to the skin, as the serum did not irritate the skin or produce symptoms of allergic contact dermatitis in the 55 healthy adults that participated in the repeat insult patch test. In the efficacy trial, daily application of the face serum for 30 days significantly increased skin hydration, with all 35 volunteers experiencing improvement. Substantial improvements in skin elasticity, roughness (fine lines and wrinkles), and brightness also occurred during the trial. Dermatological examination also revealed a trend for reduced comedone count with use of the serum. Self-assessment responses revealed that all volunteers experienced improvements in multiple skin quality parameters and that participant perceptions are consistent with the results of the instrumental analyses. These findings indicated that the measured improvements in skin quality are not only statistically significant but are also clinically relevant as they were great enough for users of the face serum to feel and recognize.

This post-hoc analysis of an Italian active pharmacovigilance study describes pharmacological differences of ADEs leading to emergency department (ED) visit and hospitalization in women and men. During the study period (January 2007 – December 2018), 61,855 reports of ADE leading to ED visit were collected. Overall, 30.6% of ADEs resulted in hospitalization (30% in women and 31% in men). Multivariate logistic regression showed that, among women, drug classes significantly associated with an increased risk of hospitalization were heparins (ROR 1.41, CI 1.13-176), antidepressants (ROR 1.12, CI 1.03-1.23) and antidiabetics (ROR 1.13, CI 1.02-1.24). Among men only vitamin K antagonists (ROR 1.28, CI 1.09-1.50), opioids (ROR 1.30, CI 1.06-1.60) and digitalis glycosides (ROR 1.32, CI 1.09-1.59) were associated with a higher risk of hospitalization. Overall, older age, multiple suspected drugs and the presence of comorbidi-ties were significantly associated with a higher risk of hospitalization. A significantly reduced risk of hospitalization was observed in both women and men experiencing and adverse event following immunization (ROR 0.36, CI 0.27-0.48 and 0.83, 0.42-0.74, respectively) compared to drugs. Results obtained from this real-world analysis highlight important aspects of drug safety between sexes.

Background. Until now, cost of allergy treatment in insured public health care system and non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. Objective. To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in non-insured self-financing private health care system. Methods. A retrospective cohort study conducted from 2015 until 2020, compared clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1,098 subjects Results. Decrease of sp-HDM-IgE level (kU/ml) from 20.5 + 8.75 kU/ml to 12.1 + 3.07 kU/ml had been observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT it costs IDR 21,753,062.7 per child, for non SCIT it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT it costs Rp. 17,024,138.8 while with non SCIT it costs Rp. 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT it costs IDR 9,550,126.6, while with non SCIT it costs IDR 52,073,938.9. Conclusion. In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog population. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralisation antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.

Background: The purpose of this article is to update the diagnostic assessment, therapeutic approach, and 12-18 month follow up of patients added in the Italian Lombardy ADHD Register. Methods: Data on patients evaluated by the 18 Regional ADHD Reference Centres in the ten year period from 2011 to April 2021 were analysed. Results: 4091 of 5934 added patients received a diagnosis of ADHD. In 20.3% of cases, there was a family history of ADHD. 2879 children (70.4%) had at least one comorbidity disorder, the most common of which was learning disorder (39%). Nearly all (95.9%) received at least one psychological prescription, 17.9% of them almost one pharmacological treatment, and 15.6% a combination of both. Values of ≥5 of the Clinical Global Impressions- Severity (CGI-S) are more commonly presented by patients with a pharmacological prescription than with a psychological treatment (p < .0001). A significant improvement was reported in half of the patients followed after 1 year, with Clinical Global Impressions- Improvement (CGI-I ≤ 3). In all, 233 of 4091 are 18 year old patients. Conclusion: A ten year systematic monitoring of models of care was a fruitful shared and collaborative initiative in order to promote significant improvement in clinical practice, providing effective and continuous quality of care. The unique experience here reported should spread.

Open domain question answering (OpenQA) tasks have been recently attracting more and more attention from the natural language processing (NLP) community. In this work, we present the first free-form multiple-choice OpenQA dataset for solving medical problems, MedQA, collected from the professional medical board exams. It covers three languages: English, simplified Chinese, and traditional Chinese, and contains 12,723, 34,251, and 14,123 questions for the three languages, respectively. We implement both rule-based and popular neural methods by sequentially combining a document retriever and a machine comprehension model. Through experiments, we find that even the current best method can only achieve 36.7%, 42.0%, and 70.1% of test accuracy on the English, traditional Chinese, and simplified Chinese questions, respectively. We expect MedQA to present great challenges to existing OpenQA systems and hope that it can serve as a platform to promote much stronger OpenQA models from the NLP community in the future.

Chikungunya is a mosquito-borne viral disease caused by Chikungunya virus (CHIKV. We conducted this study determine the seroprevalence and clinical presentation of Chikungunya infection among outpatients seeking healthcare in Mzuzu City, Malawi. Blood samples were collected from malaria negative and non-septic febrile outpatients with fevers ≥38 °C, for not more than 5 days. The enzyme- linked immunosorbent assay (ELISA) test was used to detect anti-CHIKV IgM antibodies and its results were used to determine seroprevalence of Chikungunya. A total of 119 serum samples were tested, of these, 73 (61.3%) tested positive for anti-CHIKV IgM antibodies by ELISA. Laboratory requisition forms were used to capture demographic information such as age, sex, clinical signs and symptoms presented by the enrolled patients. Age groups of 1-9, 10- 19, 20- 29, 30- 39, 40- 49, and ≥50 years had 17.8% (n= 13), 12.3 %,( n=9), 15.1%) (n=11), 19.2%; (n=14), 17.8% (n=13) and 17.8% (n=13) proportion of seroprevalence respectively. Most of the CHIKV infected individuals presented with fever (52.05%), joint pain (45.21%) and abdominal pain (42.67%). The presence of anti- CHIKV IgM antibodies suggest the presence of recent CHIKV infection and therefore accurate laboratory assays are highly recommended for CHIKV diagnosis and appropriate management of febrile patients.

Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase implicated in a wide variety of regulatory cellular functions. PP2A is abundant in the mammalian nervous system and dysregulation of its cellular functions are associated with myriad neurodegenerative disorders. Additionally, PP2A has oncologic implications, recently garnering attention and emerging as a therapeutic target because of the antitumor effects of a potent PP2A inhibitor, LB100. LB100 abrogation of PP2A is believed to exert its inhibitory effects on tumor progression through cellular chemo- and radio-sensitization to adjuvant agents. An updated and unifying review of PP2A biology and inhibition with LB100 as a therapeutic strategy for targeting cancers of the nervous system is needed, as other reviews have mainly covered broader applications of LB100. In this review, we discuss the role of PP2A in normal cells and tumor cells of the nervous system. Further, we summarize current evidence regarding the therapeutic potential of LB100 for treating solid tumors of the nervous system.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

There is a growing number of evidence-based indications for pharmacogenetic (PGx) testing. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. In an observational cohort study we included subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. PGx-guided pharmacotherapy management was supported by the PGx expert system SONOGEN XP. The primary study outcome was PGx-based changes and recommendations regarding current and potential future medication. PGx-testing was triggered by specific drug-gene pairs in 102 subjects, and by screening in 33. Based on PharmGKB expert guidelines we identified at least one “actionable” variant in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized expert consultations with interdisciplinary collaborations.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

Clinical education is a method that is applied to formal nurse education as a step to provide real and direct learning experiences in the nursing environment correctly and effectively. The success of education in a clinical setting certainly requires the support of teaching nurses (clinical instructors) who have credibility and competence in terms of knowledge, attitudes and skills and are actively involved in professional activities. The diversity of backgrounds of nurses and students, including patients, certainly contributes to a shift in paradigms and perspectives for the nursing environment both in education and in clinical settings in health services. Responding to this cultural diversity, it is important to prepare knowledge and understanding related to transcultural nursing issues, intercultural communication and clinical education which explores the socio-cultural elements in the implementation of staff, students and patients. Purpose: The purpose of this literature review is to identify the extent to which nurse educators play a role by including socio-cultural and transcultural aspects in efforts to develop the quality of education in clinical practice environments in the millennium era. Method: The method of writing this article uses 11 literature review, the publication year period 2019,2020 and 2021 with sources from 4 databases such as science Direct, Scopus, ProQues and Elsevier. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology as well as the type of scholarly journal and full text. Results: The results of the reviews found are presented in a narrative form. The results of the review study found that there were 11 articles explaining the competence of clinical education based on the socio-cultural approach, which is an educational strategy in the clinical area that integrates transcultural elements of nursing, intercultural communication, collaboration, self-directed with the principles of openness, honesty, and mutual respect in the implementation of team interaction and collaboration. The development of interpersonal relationships is also an important role that educators must have in helping to introduce the nurse orientation process to the organizational environment and other professional teams so that the achievement of satisfaction with clinical education is able to improve the performance of nurses and students perfectly. Conclusion: Clinical education which is supported by the competence of nurse educators (clinical instructors) who have individual and professional competences has a role to play in improving clinical learning outcomes by both students and nurses with a socio-cultural and transcultural strategic approach that will create satisfaction with the achievement of clinical competence and performance effectively.

Background: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as etiological or favoring factor of laryngeal, oral, sinonasal or otological diseases. In this case-series, we reported atypical clinical presentation of LPR in patients presenting in our clinic with reflux. Methods: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with 24-hour hypopharyngeal-esophageal impedance pH-study and patients were treated with a combination of diet, proton pump inhibitors and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment Results: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N=9), recurrent burps and abdominal disorders (N=2), posterior nasal obstruction (N=2), recurrent acute suppurative otitis media (N=2), severe vocal fold dysplasia (N=2), and recurrent acute rhinopharyngitis (N=1), tearing (N=1), aspirations (N=1) or tracheobronchitis (N=1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate anti-reflux treatment. Conclusion: LPR may present with various clinical presentations including mouth, eye, tracheobronchial, nasal or laryngeal findings, which may all regress with an adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzyme in the enflamed tissue.

Porous tantalum (Ta) is a promising biomaterial and has been applied in orthopedics and dentistry for nearly two decades. The high porosity and interconnected pore structure of porous Ta promise fine bone ingrowth and new bone formation within the inner space, which further guarantee rapid osteointegration and bone-implant stability in long term. Porous Ta has high wettability and surface energy that can facilitate adherence, proliferation and mineralization of osteoblasts. Meanwhile, low elastic modulus and high friction coefficient of porous Ta can effectively avoid stress shield effect, minimize marginal bone loss and ensure primary stability. Accordingly, the satisfactory clinical application of porous Ta based implants or prostheses are mainly derived from its excellent biological and mechanical properties. With the advent of additive manufacturing, personalized porous Ta based implants or prostheses have shown their clinical value in the treatment of individual patient who need specially designed implant or prosthesis. In addition, many modification methods have been introduced to enhance the bioactivity and antibacterial property of porous Ta with promising in vitro and in vivo research results. In any case, choosing suitable patients is of great importance to guarantee surgical success after porous Ta insertion.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Students' knowledge of the concept of patient safety in infection prevention and control and treatment safety is still low. Real-life problem-based learning approaches in the area of ​​clinical education assist in patient safety education. This study was designed to identify, evaluate and summarize available evidence on the effectiveness of clinical education on student achievement of patient safety competencies. The Methode that use in this study is systematic review. Search for articles in research journals obtained from Sciencedirect, Ebscohost, Garuda, Proquest and Scopus. As many as 228 articles were obtained consisting of nursing journals and health journals with the keywords clinical education, competence, and patient safety. After that, the screening process was carried out based on the inclusion criteria and obtained 25 articles that met the criteria. The result of this study are the contribution of educational institutions in the achievement of patient safety competencies for nursing students is still low and the achievement of patient safety competencies for students at the professional level is better than for students who are still learning theory in educational institutions. The conclusion of this study is clinical education carried out by educational institutions is considered ineffective in achieving the competence of patient safety for nursing students. Therefore, it is necessary to develop a patient safety model or curriculum that is attached to clinical education in nursing education institutions

Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study included all adults with UTI caused by K. pneumoniae admitted to a tertiary care hospital in Barcelona, Spain, between 2011 and 2015. Demographic, clinical and economic data were analyzed. Results: One hundred and seventy-three episodes of UTI caused by K. pneumoniae were studied; 112 were non-ESBL-producing and 61 ESBL-producing. Multivariate analysis identified ESBL production, acute confusional state associated with UTI, shock, and time to adequate treatment as risk factors for clinical failure during the first 7 days. Economic analysis showed differences between ESBL-producing and non-ESBL-producing K. pneumoniae for the total cost of hospitalization per episode (mean 6,718 € vs 3,688 € respectively). Multivariate analysis of the higher costs of UTI episodes found statistically significant differences for ESBL production and time to adequate treatment. Conclusion: UTI caused by ESBL-producing K. pneumoniae requiring hospitalization, and time to adequate antimicrobial therapy are associated with worse clinical and economic outcomes.

Delirium occurs in 50-80% of end-of-life patients but it is often misdiagnosed. Identification of clinical factors potentially associated with delirium onset can lead to a correct early diagnosis. To this aim, we conducted an observational prospective study on patients from an Italian Palliative Care Unit (PCU) in 2018-2019 and evaluated the presence of clinical factors at patients’ admission. We then compared their presence in patients who developed delirium and in those who did not during follow-up. On 503 enrolled patients, 95 (18.9%) developed delirium. In univariate analyses, factors significantly more frequent in patients with delirium were advanced age, care in hospice, very compromised performance status, hypoxia, high number of simultaneous clinical factors, presence of breathlessness, poor well-being, severe drowsiness, and background therapy with haloperidol and drugs acting on CNS. In multivariate analyses, setting of care (odds ratio, OR, 1.68 for hospice versus home care, 95% confidence interval, CI 1.02-2.75; p=0.040), and administration of psychiatric drugs (OR 1.74 for administration versus no administration, 95% CI 1.08-2.81; p=0.023) were significantly associated with the risk of developing delirium, while the associations with age (OR 1.82 for > 80 years versus ≤ 70 years, 95% CI=0.98-3.36; p=0.046) and presence of breathlessness (OR 1.70, 95%, CI 0.99-2.89, p=0.053) were of borderline significance. The study indicates that some clinical factors are associated with the probability of delirium onset. Their evaluation in PC patients could help the healthcare professionals to timely identify the development of delirium in those patients.

Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS’ CE-IVD Hereditary Cancer Solution™ (HCS) libraries preparation workflow on the Hamilton’s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory’s walk-away scenario.

During 2019, the number of patients suffering from cough, fever and reduction of WBC’s count increased. At the beginning, this mysterious illness was called “fever with unknown origin”. At the present time, the cause of this pneumonia is known as the 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The SARS-CoV-2 is one member of great family of coronaviruses. Coronaviruses can cause different kind of illnesses including respiratory, enteric, hepatic, and neurological diseases in animals like cat and bat. Coronaviruses are enveloped positive-stranded RNA viruses. The SARS-CoV-2 has some particular structures for binding to host cells, reproducing itself in cells and damaging human cells. The SARS-CoV-2 can bind angiotensin-converting enzyme 2 (ACE‐2) receptors and cause various difficulties for human. The SARS-CoV-2 can cause either not-serious issues like fever and cough or serious concerns such as multi-organ failure. Source(s) of SARS-CoV-2 is under debate. Malayan pangolin and bat are the most suspicious candidate for being sources of the SARS-CoV-2. The SARS-CoV-2 can be transmitted by various ways such as transmitting from infected human to healthy human and can make severe pneumonia, which can lead to death. The SARS-CoV-2 can infect different kind of people with different ages, races, and social and economic levels. The SARS‐CoV‐2 infection can cause various sorts of clinical manifestations like cough and fever and intensity of signs and symptoms depends on sufferer conditions. Clinicians use all of available documents and tests like laboratory, histopathological and radiological findings for diagnosing new cases and curing patients with high accuracy. At the present time, there is no particular way for treating SARS-CoV-2 infection; neither antiviral drugs nor palliative agents. It seems that the best way for standing against the SARS-CoV-2 infection is preventing from it by social distancing and vaccination. This review tries to prepare an essential brief update about SARS-CoV-2 infection for clinicians.

Caesarean scar ectopic pregnancy (CSEP) is an uncommon form of ectopic pregnancy. This review defines types of CSEP, discusses pathophysiology, clinical presentation and diagnosis and compares common treatment options and outcomes. The pathophysiology is not yet fully understood. One third of patient are asymptomatic. In symptomatic patients vaginal bleeding and pelvic pain which is usually misdiagnosed as threatened or missed abortion. The main principles of treatment for CSEP are early diagnose, quick management, and maintain reproductive function as much as possible. Up to date; no consensus or guidelines for the treatment and management of CSEP. Management of CSEP depends on the clinical presentation and gestational age. Significant controversy exists regarding management, for this reason, several factors should be considered including age of the patient, myometrial thickness, clinical symptoms, hemodynamic status, fertility preservation.

The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

Direct and indirect anthropogenic factors play a massive role in driving wildlife species towards extinction. Longitudinal retrospective studies identify key ‘factors’ responsible for the decline in numbers of wildlife, however, lack the reasoning behind the events leading to mortality. The overarching aim of this study was to categorize these ‘factors’ into different stressor categories faced by reptiles to understand its impact on an individual, and to compare how each stressor category influences the survival of an individual. The results from this study indicated that almost half of the number of reptiles being hospitalized were due to exposure to preliminary stressors such as lawn mowing incidents and pet attack. Primary and secondary admissions were fairly equal in number, however the mortality rate for secondary admissions was drastically high (~80%). The discussion integrates species’ ecology and stress physiology which can prove to have multi-faceted benefits across the fields of ecology and animal welfare. Ecologists can use the results from this study to comprehend species’ activity patterns to better plan reptilian conservation programs, whereas, for wildlife clinicians and rehabilitators, assignment of stressor categories could be a beneficial tool for bolstering the welfare monitoring program for small native reptiles in clinical settings.

Significant efforts in the past decades to teach evidence-based practice (EBP) implementation has emphasized increasing knowledge of EBP and developing interventions to support adoption to practice. These efforts have resulted in only limited sustained improvements in the daily use of evidence-based interventions in clinical practice in most health professions. Many new interven-tions with limited evidence of effectiveness are readily adopted each year - indicating openness to change is not the problem. The selection of an intervention is the outcome of an elaborate and complex cognitive process which is shaped by how they represent the problem in their mind and is mostly invisible processes to others. Therefore, the complex thinking process which support appropriate adoption of interventions should be taught more explicitly. Making the process visible to clinicians increases the acquisition of the skills required to judiciously select one in-tervention over others. The purpose of this paper is to provide a review of the selection process and the critical analysis that is required to appropriately decide to trial or not trial new intervention strategies with patients.

Electronic health records (EHRs) are becoming a vital source of data for healthcare quality improvement, research, and operations. However, much of the most valuable information contained in EHRs remains buried in unstructured text. The field of clinical text mining has advanced rapidly in recent years, transitioning from rule-based approaches to machine learning and, more recently, deep learning. With new methods come new challenges, however, especially for those new to the field. This review provides an overview of clinical text mining for those who are encountering it for the first time (e.g. physician researchers, operational analytics teams, machine learning scientists from other domains). While not a comprehensive survey, it describes the state of the art, with a particular focus on new tasks and methods developed over the past few years. It also identifies key barriers between these remarkable technical advances and the practical realities of implementation at health systems and in industry.

Background: Risk tratification based on pre-test probability may improve the diagnostic accuracy of temporal artery high-resolution compression sonography (hrTCS) in the diagnostic workup of cranial giant cell arteriitis (cGCA). Methods: A logistic regression model with candidate items was derived from a cohort of patients with suspected cGCA (n = 87). The diagnostic accuracy of the model was tested in the derivation cohort and in an independent validation cohort (n = 114) by receiver operator characteristics (ROC)-analysis. The clinical items were composed to a clinical prediction rule, integrated into a stepwise diagnostic algorithm together with CRP-values and hrTCS-values. Results: The model consisted of 4 clinical variables (age &gt; 70, headache, jaw claudication, anterior ischemic optic neuropathy). The diagnostic accuracy of the model for discrimination of patients with and without a final clinical diagnosis of cGCA was excellent in both cohorts (AUC 0.96 and AUC 0.92, respectively). The diagnostic algorithm improved the positive predictive value of hrCTS substantially. Within the algorithm, 32.8% of patients (derivation cohort) and 49.1% (validation cohort) would not have been tested by hrtCS. None of these patients had a final diagnosis of cGCA. Conclusion: A diagnostic algorithm based on a clinical prediction rule improves the diagnostic accuracy of hrTCS.