Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1^st, 2020 and March 21^st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8^th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

Clinical trials often involve new substances characterized or developed for a specific pathology or class of pathologies. At other times, a clinical trial is observational; in other words, a known sub-stance has a range of effects on a given cohort of subjects. The types of trials are different and complex, and often, young clinical novice and the inexperienced researchers may struggle to evaluate how to proceed correctly. In this paper, we aim to create a mini-guide for beginners in clinical trials and provide elements for designing a clinical trial. Our intention is to highlight where to find the materials and how to adapt, even in the absence of sponsors, so that even the most inexperienced and under-resourced researcher can gain an understqanding of the complexi-ty of the process andaddress it appropriately. We do not claim to be exhaustive or cover all ele-ments, but rather, we aim to create a checklist. With this approach, starting discussioms about the experimental phases of the drug and concluding with the clinical trial, we aim to assist those facing this challenging "world."

Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

High oxidative stress in cells due to inflammation process or excessive cell proliferation would produce oxidants or free radicals with biomarkers, one of which is malondialdehyde (MDA). Passion fruit seed’s contain high antioxidant and are expected to decrease the level of cholesterol and MDA. The objective is to identify the effect of passion fruit seed’s ethanol extract in Wistar rats that have been fed with atherogenic feed. The method was preclinical trial (post-test control group design) in rats, by administering passion fruit seed’s ethanol extract for 14 days. This study used 26 male rats aged two months, divided into 5 groups. The result showed significant difference in MDA level which was found in group that was given passion fruit seed extract 10mg/kg BW with positive control group that was given standard feed. Passion fruit seed’s extract showed significant difference in level of triglyceride, which was found in negative control group that was given atherogenic feed with group that was given passion fruit seed’s extract 5mg/kg BW (mean±standard deviation: 1.09±0.30 mg/dL vs 0.77±0.25mg/dL; p=0.048). This study showed that passion fruit seed’s ethanol extract had significant lowering effect in level of MDA, total cholesterol, and triglyceride for 14 days.

Abstract: In network science and big data, the concept of finding meaningful infrastructures in networks has emerged as a method of finding groups of entities with similar properties within very complex systems. The whole concept is generally based on finding subnetworks which have more properties (links) amongst nodes belonging to the same cluster than nodes in other groups (A concept presented by Girvan and Newman, 2002). Today meaningful infrastructure identification is applied in all types of networks from computer networks, to social networks to biological networks. In this article we will look at how meaningful infrastructure identification is applied in biological networks. This concept is important in biological networks as it helps scientist discover patterns in proteins or drugs which helps in solving many medical mysteries. This article will encompass the different algorithms that are used for meaningful infrastructure identification in biological networks. These include Genetic Algorithm, Differential Evolution, Water Cycle Algorithm (WCA), Walktrap Algorithm, Connect Intensity Iteration Algorithm (CIIA), Firefly algorithms and Overlapping Multiple Label Propagation Algorithm. These al-gorithms are compared with using performance measurement parameters such as the Mod-ularity, Normalized Mutual Information, Functional Enrichment, Recall and Precision, Re-dundancy, Purity and Surprise, which we will also discuss here.

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.

Noni juice is a globally popular health beverage that originates from the tropics. Traditional Tahitian healers believe the noni plant to be useful for a wide range of maladies, and noni juice consumers throughout the world have similar perceptions. Nevertheless, human clinical trials are necessary for an understanding of what the health benefits of noni juice truly are. A review of published human intervention studies suggest that noni juice may provide protection against tobacco smoke-induced DNA damage, blood lipid and homocysteine elevation, and systemic inflammation. Human interventions studies also suggest that noni juice may improve joint health, increase physical endurance, increase immune activity, inhibit glycation of proteins, aid weight management, help maintain bone health in women, help maintain normal blood pressure, and improve gum health. Further, these studies point to noni juice possessing notable antioxidant activity, more so than the other fruit juices that served as placebos. It is this antioxidant effect, and its interaction with the immune system and inflammation pathways, that may account for many of the observed health benefits of noni juice. However, the existing evidence does have some limitations in its application to noni juice products in general as all the peer-reviewed human interventions studies to-date have involved only one source of French Polynesian noni juice. Geographical factors and variations in processing methods are known to produce commercial noni juice products with divergent phytochemical and nutrient compositions. Therefore, other sources of noni products may have different toxicological and pharmacological profiles.

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.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects the motor system of the human body. Currently, the available treatments are limited and often have undesirable side effects. In this context, the aim of this study was to develop a novel combinational formulation of Apomorphine and Quetiapine and evaluate its efficacy in a rat model of PD. The formulation was prepared using the solvent evaporation technique and characterized for its physicochemical properties. The in-vitro drug release was evaluated using the Franz diffusion cell method, and the pharmacokinetics of the combination was studied in rats. The behavioural and biochemical parameters were evaluated in the rats using the Rotarod, pole test, and biochemical assays. The results showed that the developed formulation had satisfactory physicochemical properties and exhibited sustained drug release. The pharmacokinetic studies showed that the combination exhibited a longer residence time than the individual drugs. The behavioural and biochemical parameters showed that the combination was effective in improving motor function and reducing oxidative stress. In conclusion, the developed Apomorphine and Quetiapine combination formulation showed promising results in improving motor function and reducing oxidative stress in rat model of PD. Further studies are required to evaluate the safety and efficacy of the developed formulation in humans.

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.

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.

The clinical neurophysiological tests allow determine the type, extent, and nature of brachial plexus damage. They are crucial in decision-making regarding surgical procedures or conservative treatment. This report aimed to present an algorithm for rehabilitation procedures in patients with brachial plexus injury of various origins based on the results of neurophysiology findings for the selection of procedures supporting the process of nerve and muscle regeneration. The research group consisted of patients whose medical documentation was analyzed concerning the reason, level, and localization of damage to the brachial plexus structures, surgical and or rehabilitative treatment as well as the MRI results. Among the group of ten patients, the clinical studies showed the greatest incidence of brachial plexus injuries of the mixed (both pre- and postganglionic), all trunks, and cervical root injuries, respectively. Results of the motor evoked potentials (MEP) and electroneurography (ENG) recordings induced at levels of spinal roots and Erb's point showed a decrease of more than 40% in amplitudes on the symptomatic side in comparison to the asymptomatic side. This difference was recorded for the axillary and radial innervation and the C5, C6, and C7 root domains, ranging from 56% to 71%; the lowest decrease was recorded following electrical stimulation at Erb's point for the ulnar nerve (41.5%). The latency prolongation on the symptomatic side in CMAP and MEP tests ranged from 0.2 to 1.9 ms, the most following magnetic stimulation of the C5 cervical root for the axillary innervation. All results indicated the axonotmesis and neuropraxia type of injury in motor fibers (40%) confirmed by EMG results. The sensory conduction studies (SNCS) in distal nerve branches did not confirm the severe advancement of the brachial plexus injury (22%). The proposed algorithm of the physiotherapeutic procedures should be mainly targeted for recovery of motor dysfunction as the consequence of brachial plexus injury. Rehabilitation should incorporate the treatment supporting nerve regeneration, muscle strengthening, and maintaining functional ranges of motion of the injured extremities. The rehabilitation treatment for patients with brachial plexus injuries is an individualized process, and the selection of procedures and the effectiveness of the treatment undertaken should be confronted with results of neurophysiological tests verifying the motor neural transmission from the level of the cervical motor center to the effector, peripheral nerve function, and muscle’s motor unit activity.

Optoacoustic imaging is an emerging technology that holds great promise for improving general clinical practice since it offers a unique combination of optical absorption contrast, high resolution, and high penetration depth. This combination of factors provides a distinct advantage over alternative imaging modalities in oncology, cardiology, dermatology, or endocrinology among other medical fields. Optoacoustic technology affords the medical practitioner the possibility of visualizing light-absorbing biomolecules like water, lipids, oxy/deoxy hemoglobin, or melanin in deep tissue with relatively cheap and small form factor instruments, without the need of contrast agents or ionizing radiation. Moreover, exogenous fluorescent contrast agents like indocyanine green or methylene blue can also be observed. Driven by its potential for new applications in the clinic, the field has experienced intense changes in the last 20 years. Continuous technological advancements in instrumentation, image formation methods, or acquisition geometries, have led to the development of numerous clinical devices also motivating the creation of several startup companies that aim to translate the technology from the lab to the clinic. Thus, the question arises: how far are we from clinical adoption? In this article, we aim to shed light on such question by reviewing the clinical studies that have been performed in the last 10 years. Our intention is to go beyond the classical review format by providing a brief general overview of the steps that new imaging methods undergo on their journey from the lab to clinical adoption. Then we examine the progress that optoacoustic technology has made on such a journey.

Background: Good clinical practice (GCP) training is the industry standard for ensuring the quality conduct of registrational clinical trials. However, concerns have been raised about whether the current structure and delivery of GCP training sufficiently prepares clinical investigators and their delegates to conduct clinical trials. Methods: We conducted qualitative semi-structured interviews with 13 clinical investigators and 10 research sponsors to 1) examine characteristics of the quality conduct of sponsored clinical trials, including critical tasks and concerns perceived as essential for trial quality, 2) identify key knowledge and skills required to perform critical tasks, and 3) identify gaps and redundancies in GCP training and areas of improvement to ensure the quality conduct of clinical trials. We used applied thematic analysis to analyze the data. Results: The top three tasks identified as critical for the quality conduct of clinical trials were obtaining informed consent, ensuring protocol compliance, and protecting participants’ health and safety. Respondents acknowledged that GCP principles address each of these critical tasks; however, they described many challenges and burdens of GCP training, including high training frequency and repetitive content. Respondents suggested moving beyond GCP training as a mere check-box activity by making it more effective, engaging, and interactive. They also emphasized that applying GCP principles in a real-world, skills-based environment would increase the relevance of GCP training to investigators and their delegates. Conclusion: Our findings indicate that although investigators and sponsors recognize that GCP training addresses critical tasks necessary to the quality conduct of clinical trials, they articulated the need for significant improvement in the design, content, and presentation of GCP training.

COVID-19 Pandemic management has become the top priority of Government Institutions globally, which is justifiable seeing the high mortality of the disease. In India, Lockdowns by National, State and Local level administrations have greatly reduced the spread of the SARS COV-2 Virus. Some areas with a greater proportion of COVID-19 patients have been declared hotspots with increased restrictions on public activities through law enforcement. But quite often delay in identification of these hotspots leads to community transmission of the Virus thus aggravating the problem. A method to identify the areas which are at risk of becoming the next hotspot for the disease is the need of the hour[1]. In this Research document we will find the probable risk factors and make an appropriate scale to measure the vulnerability of an area, identified by its Postal code. To help with this a Pan India survey by the title of “Survey on General Indian population on the level of preparedness for COVID-19 pandemic” was launched and received around 1250 submissions, with the acquired data we will evaluate the risk factors and make appropriate scale to identify ‘pre-hotspots’.

In order to achieve the target, several activities are being undertaken, including the development of multipurpose reservoir planning for the water supply and sanitation infrastructure, irrigation, and hydropower development for the H project. To undertake this work, the main data given was rainfall data, flow data, catchment area, base population for water supply, and so on. This report presents a specifically preliminary study and design of water supply, irrigation, and hydropower development for the project, which is carried out in accordance with the scope of work given by our professor. The preliminary study and design are therefore to investigate scenarios and alternatives and prepare a document of water supply, irrigation, and hydropower infrastructures for the provision of the assignment. This report, as required in the assignment, contains project background, water sources assessment, selection of suitable hydropower potential, and irrigation sizing, design criteria, descriptions of the proposed scheme, preliminary design of water supply components. The objective of the project is to recommend and design a cost-effective water supply system, irrigation, and hydropower development to supply reliable, sufficient, and safe water from a defined water source to the H project. The specific objectives of the investigation works are: • To assess potential water source alternatives for water supply • Selecting appropriate size for the reservoir which could satisfy all water demand • Assess and select suitable irrigation development and hydropower potential. • Preliminary study and design of all components of the reservoir and appurtenant structures The scope of the project generally focuses on preliminary study and design of water supply, irrigation and hydropower development components from water sources potential and the water balance output.

Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy that involves the continuous administration of antiretroviral drugs to HIV-negative individuals wit a substantial risk of contracting an HIV infection. The use of PrEP has shown a reduction in the risk of HIV acquisition through sexual intercourse by up to 99%. Despite its effectiveness, PrEP uptake remains low among populations at high risk of HIV infection. This highlights the need for further research in stratetegies to enhance awareness and uptake of PrEP amongst these specific populations

The intricate nature of congenital heart disease requires understanding of complex, patient-specific three-dimensional dynamic anatomy of the heart, from imaging data such as three-dimensional echocardiography for successful outcomes from surgical and interventional procedures. Conventional clinical systems use flat screens and therefore display remains two-dimensional, which undermines the full understanding of the three-dimensional dynamic data. Additionally, control of three-dimensional visualisation with two-dimensional tools is often difficult, so used only by imaging specialists. In this paper we describe a virtual reality system for immersive surgery planning using dynamic three-dimensional echocardiography, which enables fast prototyping for visualisation such as volume rendering, multi-planar reformatting, flow visualisation, and advanced interaction such as three-dimensional cropping, windowing, measurement, haptic feedback, automatic image orientation, and multi-user interactions. The available features were evaluated by imaging and non-imaging clinicians, showing that the virtual reality system can help improve understanding and communication of the three-dimensional echocardiography imaging and potentially benefit congenital heart disease treatment.

We aimed to assess the caffeine intake before and during pregnancy, compliance with caffeine recommendations during pregnancy (200 mg/day) and factors associated with higher intakes before and in first trimester of pregnancy. Caffeine consumption was collected in a Spanish cohort of pregnant women through a validated food questionnaire, before and in each trimester of gestation (T1, T2 and T3). 463 pregnant women were recruited and follow-up through pregnancy. Compliance with caffeine intake recommendations during pregnancy and quintiles of mg/day of caffeine before and in T1 of pregnancy were calculated. A multivariate logistic regression, comparing extreme quintiles of consumption (Q1 vs Q5) was used. Mean caffeine intake before pregnancy was 120.05 mg/day (SD 117.85), 42.76 mg/day (SD 63.90) at 12th GW, 42.00 mg/day (SD 59.76) at 24th GW and 39.34 mg/day (SD 50.9) at 32nd GW (p<0.001). 86% of women complied with caffeine recommendations during pregnancy. At pregnancy (T1), being an active smoker was associated with Q5 > 100.1 mg/day, aOR = 22.69; 95% CI 4.67- 110.26. igh diet quality, aOR = 0.30; 95% CI, 0.13- 0.68, and moderate physical activity level, aOR= 0.44; 95% CI, 0.19-1.00, were inversely associated with Q5 > 100.1 mg/day. Pregnant women are mostly adhering to current caffeine intake guidelines. Higher caffeine intake at pregnancy is associated with other unhealthy habits during pregnancy.

The Clinical Trials Transformation Initiative (CTTI) Investigator Qualification Project addresses the need for a more efficient and effective means of identifying qualified clinical investigators and delegates. Selection of investigators and delegates who are qualified by training and experience to conduct clinical trials is essential to safeguarding protections for study participants and ensuring data quality and integrity. Sponsors generally document investigator qualification through training on the principles of good clinical practice (GCP), as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), adopted by regulatory authorities in the US, Japan and the European Union. Although these GCP principles provide an important foundation for promoting the conduct of quality clinical trials, the industry standard “one-size-fits-all” GCP training may not fully prepare investigators and delegates for conducting quality clinical trials. Routine GCP training alone may not be sufficient to prepare an inexperienced member of a site team, while repeating such training is unlikely to enhance the qualifications of an experienced researcher. The CTTI project team used findings from qualitative research activities, as well as input from an expert meeting with multiple stakeholders, to identify gaps and redundancies in the current training of investigators and their delegates and recommend practical, action-based solutions. CTTI provides recommendations on how to implement a more efficient and effective means of qualification for investigators and delegates, determine whether a site team is a good fit for a particular protocol, and improve the quality of clinical trial conduct.

This study aimed to evaluate the level of skill in observing teaching competency in pre-service physical education (PE) teachers and provide basic data to cultivate teaching competency. A total of 21 third-year pre-service PE teachers were selected as participants. The study derived descriptive statistics to analyze the participants’ observation skills regarding teaching competency in different class stages using evaluation results of class demonstrations by pre-service teachers. Mann–Whitney U test was conducted to verify the statistical significance of the evaluation between in-service and pre-service teachers. Compared with in-service teachers, pre-service teachers reported high agreement with intuitive teaching behaviors. However, pre-service teachers indicated low agreement with skills that required complex teaching behaviors depending on various situations. Based on theories by Schon (1983), pre-service teachers showed high “knowledge for practice” and low “knowledge in practice.” Thus, pre-service education must balance practical knowledge and theory rather than focus on theory-based education. This study provided directions for pre-service teacher education to enhance the competency of pre-service teachers for leading and analyzing classes.

Multicompartment compliance aids (MCAs) are devices with each discrete section denoting a single dosing occasion. The purpose of an MCA is to maximize patient adherence and thereby optimize the treatment benefits. These devices are widely employed throughout western Europe and UK and use appears to be rapidly increasing (2) although the RPS as moved away from these devices as a means to improve adherence. We analysed MCAs from various pharmacies over a wide geographic area in England and North Wales. We concluded that most MCA users are elderly patients. Also, most of the patients suffer of combined cardiovascular disease. However, a significant proportion of patients falls in the mental/ neurological disease category. Additionally, most of the externals added to MCAs are inhalers and painkillers. Moreover, SDIs are more frequent in female patients and these SDI are mainly related with mental health medication, cardiovascular disease medication and neurological medication. In conclusion, a directive for dispensing of MCAs in pharmacies by pharmacists through an enhanced service should be elaborated having in consideration PIMs, SDIs, drug stability and use of externals and MCA design and brand.

The purpose of this study was to develop a reflective evaluation tool that can enhance the teaching competency of pre-service physical education teachers. A Delphi survey was conducted to modify the questions based on the evaluation tool for the teaching competency of physical education teachers, and each evaluation standard based on teaching competency was developed. The evaluation tool consisted of 46 questions for class preparation (the creation of the learning environment), the introduction (routine activities, learning goals, and task presentation), development (class strategy, observation and interaction, and the maintenance of the learning environment), and conclusion (routine activities, summary, and closure). It was designed to increase the accuracy of evaluation by developing evaluation criteria for each question. An evaluation tool including quantitative and qualitative methods for use in pre-service physical education teacher education was developed. The significance of this study was the development of an effective evaluation tool that can evaluate the core teaching behaviors in the field of physical education. This evaluation tool should be used as a learning tool that includes planning, operation, evaluation, and seeking improvement measures through reflective activities. If pre-service teacher education institutions apply this evaluation tool in their teacher training programs, it would be a great chance to learn how to develop and sustain teaching abilities and effectiveness.

This study aimed to determine clinical instructors’ perceptions of the assessments used to evaluate the clinical knowledge of undergraduate nursing students. This study uses a descriptive phenomenological approach. Purposive sampling was used to recruit sixteen clinical instructors for semi-structured interviews between August to December 2019. All interviews were audio-recorded and transcribed verbatim. Data were analyzed using Colaizzi’s seven-step method. Four criteria were used to ensure the study’s validity: credibility, transferability, dependability, and confirmability. Three themes were identified in the clinical instructors’ views on evaluating the clinical performance of student nurses: familiarity with students, patchwork clinical learning, and differing perceptions of the same scoring system. Study results suggest the need for a reliable, valid, and consistent approach to evaluating students’ clinical knowledge. If the use of patchwork clinical internships for student nurses is unavoidable, a method for assessing student nurses’ clinical performance that requires instructor consensus is necessary.

Cocoa beans of the CCN-51 clone harvested in the Tumaco region (Nariño, Colombia) were fermented following four different treatments: (1) spontaneously (at room temperature for 120 h) in traditional conditions (Control); (2) traditional processing with a pre-drying (sun-dried for 24 h) treatment (PD); (3) with fermentation (for 120 h) after inoculation of a yeast starter culture (YS); and (4) including both treatments, pre-drying and yeast inoculation (PD+YS). Chemical composition, fatty acids, total polyphenol, methylxanthines (theobromine and caffeine) and lactic acid content of cocoa beans were determined. Chemical and fatty acid composition and theobromine content were not affected by the different fermentation treatment applied. When analysing total polyphenol content, YS and PD+YS treatments significantly increased the content of these compounds at the end of the fermentation process, while PD treatment decreased the caffeine content of cocoa beans. Finally, lactic acid content decreased as a consequence of both inoculation of yeast starter and mainly the pre-drying treatment. In conclusion, solar pre-drying in the open air and the inoculation of a yeast starter treatments could improve the final quality of coca beans.

BACKGROUND: Pre-marital sex is a sexual interest practiced by people who are yet to get married and has ended up being accepted specifically in western countries. Sex before marriage is sexual behavior engaged in by single people. In the past, having sex before getting married is seen as a moral dilemma that many cultures forbade and that many people regarded to be sin in many religions, although it has gained wider acceptance across the board. OBJECTIVES: This study was carried out to determine the perception, practices, and factors associated with pre-marital sex, courtship, and its influences among Osun State University Undergraduates, Osogbo, Osun State. METHODOLOGY: The study was a descriptive study, and respondents were selected using multi-stage sampling technique. Students of Osun State University, Osogbo main campus form the population of the study and its sample size was calculated using Leslie Kish’s formula. A total of 387 responses were validated from the survey. The instrument for data collection was a self-administered semi-structured questionnaire consisting of four sections. The data obtained were collated, examined for completion, coded, imputed, and analyzed using SPSS v21. RESULTS: The mean age of the respondents was between 19.19±2.17, and the majority were between 18 – 24 years. About 52% of the respondents show a positive perception of premarital sex and courtship. Also, in the practice of courtship majority (88.3%) of the respondents think those that go around together are courting and from the responses obtained and analyzed from the factors leading to pre-marital sex, the findings revealed that peer pressure (90.4%), Internet (86.7%), pornography (83.9%) and drugs (82.9%) are the leading factors which contribute to pre-marital sex among undergraduates. CONCLUSION: The study hereby recommends that Parents should as a matter of responsibility monitor and pays regular visits to their children in the universities and provide them with materials that will make them stay comfortable for them not to fall victim to peer pressure.Pre-marital sex is a practice that should be avoided by undergraduate students, though most students consider courtship as a normal practice, it is still used as a normal factor that leads them to practice pre-marital sex.

Among the plant resources in pre-Columbian Mexico and Central America, the Chia (Salvia hispanica L.) is unique in being the only member of the Lamiaceae cultivated for the mericarps. Recently the crop has gained considerable attention due to its high of content omega-3 polyunsaturated fatty acid, antioxidants, fibre and protein classifying it as a nutraceutical.

Introduction: Exams are a relatively stressful period for all students, especially undergraduate medical students. Exams bring anxiety and stress for the students. Some students experience such high stress that it hinders their academic productivity and reduces their exam performance. The aim of this study is to assess the effects of pre-exam anxiety on the academic performance of medical students. Methods: Two hundred and twenty-five final year medical students completed Westside Test Anxiety (WTA) Scale one month before their exams. Grade Point Average (GPA) of these students was noted when the results were announced. Data was processed and analyzed using SPSS v 22.0Results: The mean anxiety score on WTA scale was 3.46 ± 0.87. All students (100%) who scored ≤ 2.50 GPA were highly-extremely highly anxious. In the 2.51-3.00 GPA group, 46% were highly-extremely highly anxious, 32% were moderately anxious, and 21% had low to normal anxiety. In the 3.01-3.50 GPA group, 30% were highly-extremely highly anxious, 30% were moderately anxious, and 39% had low to normal anxiety. In the 3.51-4.00 GPA group, 29% were highly-extremely highly anxious, 23% were moderately anxious, and 47% had low to normal anxiety. The correlation coefficient between GPA and test anxiety of students was -.314 which shows inverse relationship.Conclusion: Pre-exam anxiety and stress imparts negative effects on the exam performance of final year medical students. Poor academic performance was associated with high to extremely high pre-exam anxiety while high achievers had relatively lower anxiety levels.

A divergent selection experiment on environmental sensitivity was performed in rabbits. The aim of this study was to estimate the correlated response in kits’ weight and its survival, and weight distance from birth to weaning. Weight distance was calculated as the absolute values of the differences between the individual value and the mean value of its litter. Also, relationship between probability of survival at 4 d of age and weight at birth was studied. Environmental sensitivity was measured as litter size variability. A total of 2484 kits from 127 does of the low line (selected for reducing litter size variability) and 1916 kits of 114 does of the high line (selected for increasing litter size variability) of the 12th generation were weighed. Bayesian methodology was used to estimate the correlated response to selection, and LOGISTIC procedure of SAS was used to estimate the relationship between weight and probability of survival. Both lines showed similar individual weight at birth and at weaning, and similar survival at birth and at 4 d of age. Survival at weaning was higher in the low line than in the high line (0.67 and 0.62; P= 0.93). Weight distance was higher at birth but lower at weaning in the low line (47.8 g and 54.1 g; P=0.98). Kit’s weight at birth affected its survival. In conclusion, selection for environmental sensitivity showed correlated response in kits survival and in homogeneity of litter weight at weaning.

Lymphoma diagnoses in the U.S. are substantial, with an estimated 89,380 new cases in 2023, necessitating innovative treatment approaches. Phase 1 clinical trials play a pivotal role in this context. We developed a binary predictive model to assess trial adherence to expected average durations, analyzing 1,089 completed Phase 1 lymphoma trials from clinicaltrials.gov. Using machine learning, the Random Forest model demonstrated high efficacy with an accuracy of 0.7248 and ROC-AUC of 0.7701 for lymphoma trials. Importantly, this model maintained an accuracy of 0.7405 when applied to lung cancer trials, showcasing its versatility. A key insight is the correlation between higher predicted probabilities and extended trial durations, offering nuanced insights beyond binary predictions. Our research contributes to enhanced clinical research planning and potential improvements in patient outcomes in oncology.

Genome-based testing in oncology is a rapidly expanding area of health care which is the basis of the emerging area of precision medicine. Efficient and considered adoption of novel genomic medicine testing is hampered in Canada by the fragmented nature of health care oversight as well as by lack of clear and transparent processes to support rapid evaluation, assessment and implementation of genomic tests. This article provides an overview of some key barriers and proposes approaches to addressing these challenges as a potential pathway to developing a national approach to genomic medicine in oncology.

Worldwide, the cesarean section rate has steadily increased from 6.7% in 1990 to 21.1% in 2018 and is expected to rise even more. World Health Organization propose the adoption of the Robson classification system as a global standard for monitoring, evaluating, and comparing delivery rates. The purpose of the current study is to use the Robson classification system to investigate how, independently of medical factors, the day of the week and time of delivery may affect the mode of birth. In the sample analysis, we included the records of 8572 women giving birth in one private health facility in Greece. Over 60% of deliveries during the study period were performed by a cesarean section and 8.5% of deliveries were performed by operative vaginal delivery. The results of this study indicate that the lowest birth rates are observed on Monday, Saturday, and Sunday. In Robson category 1 women are 73% more likely to deliver by cesarean section between 08:00 a.m. - 03:59 p.m. compared to those who give birth between 12:00 a.m. - 07:59 a.m. Also, women in group 5.1 are 16.7 times more likely to deliver by cesarean section in the morning compared to overnight deliveries. These result point out two non-clinical variables that influences the CS rate. The Robson classification system was a useful tool for the above comparisons.

Background: Clinical trials, by contributing to the development of diagnostics and to the search for modern, more effective, and safer therapies, have become one of the most important elements of the healthcare system. The aim of this study was to assess Poles' knowledge and beliefs about clinical trials. Methods: The survey was conducted among Poles aged 18 and over with the help of external company. The questionnaire contained 22 questions, of which 13 questions concerned beliefs and attitudes towards clinical trials. Results: Data were obtained from 1079 Poles (52.6% women). Among the respondents, 86.5% were aware of clinical trials. The main source of information about clinical trials was the media (53.8%) including the Internet (32.9%) and TV (16.2%). 43.2% of respondents reported little knowledge of clinical trials, while more than three quarters (75.2%) said they would like to learn more about clinical trials. Most respondents (81.4%) agreed with the statement that participation in a clinical trial is completely voluntary, and more than half (53.7%) agreed with the statement that hospitals participating in clinical trials provide better healthcare. The statement that the results of clinical trials are made available to the public was disagreed with by 37.2% of participants. Only 30.3% of participants agreed that clinical trials should be conducted with children. Conclusions: Poles rate their knowledge of clinical trials as low and would like to learn more. To reach the largest possible group of Polish patients, parallel educational activities on multiple levels may have the best effect. Poles' knowledge of clinical trials is mainly based on commercial sources. Further studies in different groups, i.e., clinical trial patients and investigators, are needed.

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.

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.

The objectives of this study were to evaluate fixed risk factors associated with PWM and to estimate genetic parameters for PWM. A total of 927 birth records from a mixed population of purebred and crossbred Boer and Spanish goats born between 2016 and 2023 at the International Goat Research Center (IGRC) were used for this study. Four binary traits were studied: D0-3 (death within 3 days after birth), D4-60 (death between 4 and 60 days), D61-90 (death between 61 and 90 days), and D0-90 (death within 90 days). Logistic regression models were used to evaluate the risk factors associated with PWM traits. Bayesian threshold models and Gibbs sampling were used to estimate the genetic parameters. Birth weight, season, litter size, sex, dam age, breed, and heterosis were found to be significantly associated with at least one of the PWM traits. Heritability estimates were 0.263, 0.124, 0.080, and 0.207, for D0-3, D4-60, D61-90, and D0-90, respectively. The genetic correlations between the studied traits ranged from 0.892 (D0-3 and D0-90) to 0.999 (D0-3 and D61-90). These results suggest that PWM in goats is influenced by both non-genetic and genetic factors and can be reduced by management, genetic selection, and crossbreeding approaches.

Introduction Infections caused by multidrug-resistant bacteria (MDR) occur more frequently after pancreaticoduodenectomy (PD) compared to other abdominal surgeries, and infective complications are a leading cause of postoperative morbidity following PD. Pre-operative biliary stent (PBS) placement often leads to biliary contamination, which in turn plays a significant role in postoperative infections. The aim of this study is to evaluate the impact of MDR contamination on short-term postoperative outcomes in patients undergoing PD and to examine the relationship between MDR bacteria, PBS, and bile contamination. Methods This is a retrospective study based on a prospectively maintained database comprising 825 consecutive patients who underwent pancreaticoduodenectomy (PD) between January 2010 and December 2020 at our center. All procedures were conducted with a standardized resection by a dedicated group of surgeons in a specialized pancreatic surgery unit, and the patients were managed according to the same perioperative enhanced recovery protocol. Results MDR bacteria were present in 17.5% of bile cultures, exclusively within the stented group. In our multivariate analysis, the development of a major postoperative complication (MPC) was correlated with the presence of MDR bacteria in the bile (OR 1.66, 95% CI: 1.1-2.52; p = 0.02). MDR bacteria were detected early in the surgical drainage in 144 out of 825 patients (12.1%), with 72.2% having a previous biliary stent placement and 27.8% without stents (p < 0.001). In our multivariate analysis, the development of an MPC was associated with the presence of MDR bacteria in the drainage (OR=1.81, 95% CI: 1.21-2.73, p= 0.0042). Conclusions We demonstrated that MDR contamination worsens the short-term outcomes of patients undergoing PD. Specifically, when MDR bacteria are present in both the bile and drainage, there is a statistically significant increase in the incidence of major postoperative complications (MPC). Our data suggest that the majority of MDR surgical site infections stem from biliary contamination resulting from the placement of a pre-operative biliary stent (PBS).

The Chat Generative Pre-training Transformer (GPT), also known as ChatGPT, is a powerful generative AI model that can simulate human-like dialogues across a variety of domains. However, this popularity has attracted the attention of malicious actors who exploit ChatGPT to launch cyberattacks. This paper examines the tactics that adversaries use to leverage ChatGPT in a variety of cyberattacks. Attackers pose as regular users and manipulate ChatGPT’s vulnerability to malicious interactions, particularly in the context of cyber assault. The paper presents illustrative examples of cyberattacks that are possible with ChatGPT and discusses the realm of ChatGPT-fueled cybersecurity threats. The paper also investigates the extent of user awareness of the relationship between ChatGPT and cyberattacks. A survey of 253 participants was conducted, and their responses were measured on a three-point Likert scale. The results provide a comprehensive understanding of how ChatGPT can be used to improve business processes and identify areas for improvement. Over 80% of the participants agreed that cyber criminals use ChatGPT for malicious purposes. This finding underscores the importance of improving the security of this novel model. Organizations must take steps to protect their computational infrastructure. This analysis also highlights opportunities for streamlining processes, improving service quality, and increasing efficiency. Finally, the paper provides recommendations for using ChatGPT in a secure manner, outlining ways to mitigate potential cyberattacks and strengthen defenses against adversaries.

The violence against women is a theme that extrapolates health issues, since after a victim seek for a health care, there is the notification of the act [1]. In Brazil, many times, these women are first assisted by mobile urgency services (SAMU/SIATE) and, as far as we have concern, there are no other studies with specific data about these assistance. The present paper aimed to analyze SAMU/SIATE assistance to abused women. Qualitative and retrospective epidemiological study of assistance to assaulted women carried out by SIATE and SAMU Maringá/Norte Novo between 2011 and 2020. Women between 20 and 39 years old, non-pregnant, were the main victims, and 19,52% of them have used some kind of drug. The (ex)partner figured as the perpetrator in 17,35%, but there were no information about this variable in 73,75% of the records. The Qui-square test shows a mortality rate superior to 70% among the severe traumatized victims. This is one of the first studies to analyze this kind of care provided by SAMU/SIATE, and reveals some gaps in its “modus-operandi” that can limitate an extrapolation of the results to bigger spheres. More researches in mobile urgency care services, in other provinces also, are needed to propose strategies to fight against this epidemic.

The log data generated during the operation of a software system contains information about the system, and using logs for anomaly detection can detect system failures in a timely manner. Most of the existing log anomaly detection methods are specific to a particular system, have cold start problems, and are sensitive to updates in log format. In this paper, we propose a log anomaly detection method LogBD based on pre-training model and domain adaptation, which uses the pre-training model BERT to learn the semantic information of logs, and can solve the problems caused by multiple meaning words and log statement updates. An anomaly detection method LogBD based on distance to determine anomalies is constructed based on domain adaptation, using TCN networks to extract common features of different system logs and map them to the same hypersphere space. Finally, experiments are conducted on two publicly available datasets to evaluate the method, and the experimental results show that the method can better solve the log instability problem and has some improvement in the cross-system log anomaly detection effect.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted by a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2010 determined LF that LF was endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. Post-MDA pre-transmission assessment survey (pre-TAS) was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence rate. We conducted a cross-sectional seroprevalence study involving 600 participants in each Evaluation Unit (EU) or each district. The study sites (sentinel and spot-check sites) were the districts that were the Implementation Unites (IUs) where MDA, preventive chemotherapy against LF was conducted. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052 of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic district a prevalence of Wb anti-gens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2 percent, except for Chibombo district. The majority of participants that tested positive for Wb Ag were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts except for Chibombo, passed Pre-TAS. This further implies that there is a need to conduct a TAS in these districts in order to decide whether to stop MDA or not. Keywords: Lymphatic Filariasis; pre-TAS; Prevalence; Antigenaemia; Microfilariae; Zambia

Wild germplasm can be classified as the raw material essential for crop improvement. Introgression of wild germplasm is normally used in breeding to increase crop quality or resilience to evolving biotic and abiotic threats. Here, we explore the potential of introgressing Vaccinium elliottii into commercial blueberry germplasm. Vaccinium elliottii is a wild diploid blueberry species endemic to the southeastern United States that possesses highly desirable and economically important traits for blueberry breeding such as: short bloom to ripe period, adaptation to upland sandy soils, disease resistance, firmness, and pleasant flavor. To examine the potential of hybridization, we evaluated populations of interspecific hybrids across multiples stages of breeding (i.e., F1, F2, and backcrosses) in two crop seasons. We used our extensive pedigree data to generate breeding values for pre-breeding blueberry hybrid populations. Hybrid performance was evaluated considering fitness (i.e., plant vigor and plant height) in addition to evaluating six fruit-quality and marketable-related traits (i.e., size, firmness, acidity, soluble solids, weight, and yield). Overall, F2 and backcrosses rapidly achieved market thresholds, presenting values not significantly different from commercial blueberry germplasm. Our results confirmed the potential of exploiting the high genetic variability contained in V. elliotii for interspecific hybridization. Additionally, we developed germplasm resources that can be further evaluated and utilized in the breeding process, advancing selections for fruit quality and environmental adaptation.

Background: The world-wide rate of obesity is increasing continuously, representing a serious medical threat since it is associated with a variety of diseases including type 2 diabetes, cardiovascular disease, and numerous cancers. Sophora japonica is used as a traditional herb for medicinal purposes in eastern Asia. However, the anti-obesity effects of S. japonica fruit have not been explored. Objective: The aim of this study is to investigate the inhibition of adipocyte differentiation and adipogenesis by an ethanol extract of S. japonica fruit (EESF) in 3T3-L1 pre-adipocytes. Methods: MTT assay, Oil Red O staining, and Triglyceride contents were used to investigate lipid accumulation in 3T3-L1 cells to clarify adipocyte differentiation. The expression levels of various molecular signals associated with adipogenesis and lipogenesis were examined by western blot analysis. Results: Our results demonstrate that EESF suppressed the terminal differentiation of 3T3-L1 pre-adipocytes in a dose-dependent manner, as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. EESF significantly reduced the accumulation of cellular triglyceride, which was associated with a significant inhibition of the levels of pro-adipogenic transcription factors, downregulated the expression levels of adipocyte-specific proteins. Furthermore, EESF treatment effectively increased the phosphorylation of AMPK and ACC. Conclusions: These results together indicate that EESF has significant effects on the inhibition of adipogenesis and acts by stimulating the AMPK signaling pathway. Further studies will be needed to identify the active compounds in S. japonica.

Inspired by the work of S. D. Odintsov and V. K. Oikonomou, Phys. Rev. D 92, 024016 (2015) [1], the present study reports a reconstruction scheme for f (R) gravity with the scale factor a(t) µ (t _* - t) _c²²describing the pre-bounce ekpyrotic contraction, where t is the big crunch time. The reconstructed f (R) is used to derive expressions for density and pressure contributions and the equation of state parameter resulting from this reconstruction is found to behave like "quintom". It has also been observed that the reconstructed f (R) has satisfied a sufficient condition for a realistic model. In the subsequent phase the reconstructed f (R) is applied to the model of chameleon scalar field and the scalar field f and the potential V(f) are tested for quasi-exponential ex pansion. It has been observed that although the reconstructed f (R) satisfies one of the sufficient conditions for realistic model, the quasi-exponential expansion is not available due to this reconstruction. Finally, the consequences pre-bounce ekpyrotic inflation i n f (R) gravity are compared to the background solution for f (R) matter bounce.

Objective. To describe patient satisfaction with pre-hospital emergency knowledge and determine if patients and professionals share a common vision on the satisfaction predictors. Methods. A qualitative study conducted in two phases. First, a systematic review following the PRISMA protocol was carried out searching publications between January 2000 and July 2016 in Medline, Scopus, and Cochrane. Second, three focus groups involving professionals (advisers and healthcare providers) and a total of 79 semi-structured interviews involving patients were conducted to obtain information about what dimensions of care were a priority for patients. Results. Thirty-three relevant studies were identified. A majority conducted in Europe using questionnaires. They pointed out a very high level of satisfaction of callers and patients. Delay with the assistance and the ability for resolution of the case are the elements that overlap in fostering satisfaction. The published studies neither reviewed the overall care process nor related the measurement of the real time in responding to an emergency with the satisfaction. The patients and professionals concurred in their assessments about the most relevant elements for patient satisfaction, although safety was not a predictive factor for patients. Response capacity and perceived capacity for resolving the situation were crucial factors for satisfaction. This qualitative approach yielded assistance targets to be improved. Conclusions. Published studies have assessed similar dimensions of satisfaction. Furthermore, despite the fact that few explanations may be given due to the no face to face attention, taking into account the patient’s emotional needs or maintaining contact with the patient until the emergency services arrive are high predictors of the satisfaction.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.

Background The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs in patients with COVID-19 was the basis for conducting this study. Aim The objective of this study was to assess DOACs consumption and expenditures in Russian Federation during COVID-19 pandemic and to analyse domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. Methods We searched Russian databases for CPGs, published between 2020 and 2023. We identified 7 relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using a AGREE II questionnaire. We calculated DOACs DDD consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020-2022. Results 7 clinical CPGs were analyzed with the AGREE II tool, it was revealed that experts gave the highest scores for the sections scope and purpose (from 62.98% to 100%), clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections stakenholder involment (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), editory independence ( from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores - ROPNIZ (Livzan), ROPNIZ (Drapkina). The minimum score is registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020 – 26.59 DDD per patient with COVID-19; in 2021 – 15.75 DDD per patient with COVID-19), and in 2022 – 10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 – 5.48 DDD, which is 2.74 times less than recommended.

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.

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.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

Clinical pharmacists are employed at many hospital departments in Denmark, but not yet on the Faroe Islands. The purpose of this study was to test feasibility of a clinical pharmacist-led medication review service at the surgical ward of the National Hospital on the Faroe Islands. Hospitalised surgical patients were offered a medication review service by a clinical pharmacist. Identified drug related problems (DRPs) were classified according to the Pharmaceutical Care Network Europe (PCNE) model. The qualitative inputs from the ward’s staff were collected. In total, 42 patients with 171 identified DRPs were included. The majority of the DRPs concerned suboptimal effect and the safety of the drug treatment. The 49.6 % of the proposed medication changes were accepted by the ward physicians. According to the qualitative inputs, the interest for the service was greater among the younger physicians compared to the older ones, and among nurses compared to physicians. Identified barriers for the optimal service implementation were an absence of medication ordinations and poor visibility of pharmacist’s notes in electronic health records. For a successful implementation of the service, work on the physicians’ interest in an interdisciplinary cooperation and optimization of the electronic health records are warranted.

Pharmacogenomics may improve patient care by guiding drug selection and dosing, however this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe co-morbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV, and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using literature, a list of pharmacogenes vital in disposition of the top 20 drugs was constructed leading to drug-gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants and statins were frequently prescribed cholesterol lowering drugs. HIV was reported in 20.3% of the study participants with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.

In recent years, the consumption of over-the-counter probiotics used to promote health has grown rapidly worldwide and become an industry. In medicine, various studies have proven that probiotics can help improve the immune system and intestinal health. They are usually safe, but in some rare cases, they may cause concerning adverse reactions. Although the use of probiotics has been widely popularized in the public, the results of many probiotics clinical trials are contradictory. Especially for the cancer patients, the feasibility of probiotics management to provide benefits by targeting cancer and lessening anti-cancer side effects requires further investigations. And this review summarizes the interactions between probiotics and the host and current pros and cons of applying probiotics in the cancer patients.

The mechanical pre-treatment constitutes an unavoidable pre-step prior to biofuels conversion. As the cost of this step is often underestimated, recently researchers have striven to identify and characterize the mechanical pre-treatment effects in terms of post-treatment physical characterization, derived improvement of enzymatic digestibility, and output yields. The status of existing mechanical pre-treatment techniques is reviewed by substrate’s typology for lignocellulose biomass, focusing on comminution techniques. Emphasis has been dedicated to the particle size achieved after treatment, crystallinity breakage and eventual inhibitory phenomena deriving from the application of particle size reduction, which are analysed and discussed.

Screening of pollen traits in diploid wild potatoes (Solanum sect. Petota, Solanaceae) is desirable to develop heat-tolerant potato (S. tuberosum) cultivars. To accomplish this goal requires exploring potato genetic resources that are conserved in genebanks. The goal of this study was to assess pollen viability and 2n pollen production of the diploid potato wild relatives under heat stress condition. We assessed pollen viability and size of nine potato accessions conserved at the Embrapa Potato Gene Bank, including S. chacoense (BRA 00167447-2, BRA 00167017-3, BRA 00167023-1, BRA 00167028-0), S. commersonii (BRA00167007-4, BRA00167420-9, BRA00183760-8), and S. malmeanum (BRA 00183755-8), along with a control accession from the cultivated species S. tuberosum (BRA 00167251-8). The plant accessions were cultivated in different growth chambers, simulating both control temperature (ranging from 14 to 27°C) and supraoptimal temperature conditions (ranging from 24 to 34°C). At heat stress, the accessions BRA 00167251-8 did not bloom, and BRA 00167023-1 did not produce pollen. The remaining accessions did not exhibit a significant reduction in pollen viability as the temperature increased. Pollen viability at the control temperature had the lowest value in BRA-00167420-9 (S. commersonii) with 68.5% and the highest in BRA 00183755-8 (S. malmeanum) with 100%. At the supraoptimal temperature the lowest value was in BRA 00167420-9 (S. commersonii) with 54.5% and the highest in BRA 00183755-8 (S. malmeanum). The average of pollen size was 20 μm in all wild potato genotypes, and the increase of temperature did not lead to 2n pollen production. Estimated Genotypic Coefficient of Variation (GCV) was lower than Phenotypic Coefficient of Variation (PCV) for pollen viability. The observed heritability values ranged from 58.82% in BRA00167007-4 to 91.32% in BRA 00183755-8. Our results highlight the genetic variability available in wild potato germplasm concerning pollen viability under heat stress. Furthermore, these first insights offer valuable guidance for ongoing and future endeavors in diploid potato breeding.

MicroRNAs (miRNAs) within the exosomes are short non-coding RNAs that are associated with many diseases including cancers and are crucial players in regulating gene expression and regula-tion. Owing to their potential role as emerging biomarkers, efficient isolation, and quantification methods of miRNA from the exosomes in the cell’s supernatant are complicated and challenging. The quantitative PCR method is the gold standard for miRNA identification and estimation. Nucleic acid-based assays are expensive, labour-intensive, and require expertise. In this work, we demon-strated an aptamer-based magnetic separation of the exosomes, and quantification of the miRNA using a fluorescence switching assay. The fluorescence assay relies on the fluorescence of the fluorophore labelled cDNA quenched by carbon nanomaterials coated on magnetic beads (OFF state). When the target miRNA210 is introduced to the system, the cDNA detaches from the quenching surface. As a result, the fluorescence intensity increases (ON state) with increasing miRNA concentration within the dynamic range of 0-100 nM. This method can detect miR210 as low as 5 pM. This method does not exhibit any cross-reactivity with other closely related miRNAs. The method was validated by spiking miRNA with the standard RT-PCR method using SYBR green as a fluorescent probe. This method can be used for the minimally invasive detection of cancer biomarkers in breast cancer patients.

Tixagevimab/cilgavimab (TIXA/CILGA) was introduced in early 2022 as a promising new drug for pre-exposure prophylaxis against COVID-19 in immunocompromised patients. The aim of our study was to evaluate the efficacy and safety of TIXA/CILGA in a Slovenian national cohort of kidney transplant recipients as pre-exposure prophylaxis in the Omicron era. Demographic, clinical, laboratory, and therapeutic data were collected from electronic and paper medical rec-ords. Of the 106 patients who received TIXA/CILGA, 6 patients (5.7%) subsequently acquired SARS-CoV-2 breakthrough infection. The incidence of SARS-CoV-2 infection was only slightly lower compared with patients who did not receive TIXA/CILGA (7.0%). All patients who re-ceived TIXA/CILGA had a mild disease course, whereas 20% of patients who did not receive TIXA/CILGA required hospitalization and two patients died. Adverse effects most likely related to TIXA/CILGA occurred in 12% of patients, one of whom experienced deep vein thrombosis. None of the patients suffered acute myocardial infarction or cerebrovascular insult. Overall, the benefit of added protection for kidney transplant patients appears to outweigh the potential risk of adverse events and provide additional protection against severe COVID-19 protection.

Proposed in 1889 by Svante Arrhenius, the Arrhenius equation is an important result in physical chemistry which aims to find the relationship between temperature and reaction rates. It is also an essential equation for analytic chemistry which helps to determine the energy barrier for a given reaction. In this article, we will go through a detailed derivation of the exponential factor in the Arrhenius Equation based on the Boltzmann distribution of particle energy probability. Then, we will attempt to model the pre-exponential factor in accordance with the principles of collision theory for bi-molecular reaction with gaseous reactants. Understanding the basic principles of chemical reaction provides valuable tools to analyze complex reaction mechanisms in the perspective of optimizing existing industrial processes.

Dynamic Realistic Failure Process Analysis (DRFPA) is a numerical software based on FEM it is firstly validated by comparing with the experimental test. Such validation is carried out under two consistent concrete specimens under uniaxial compression. After validation, DRFPA is used to study the influence of two parallel pre-existing crack inclination angles on the fracture of concrete under dynamic loads. The evolution of wing cracks and secondary cracks is investigated by observing the initiation, coalescence, and propagation of them. Meanwhile, the relationship between failure mode and inclination angles is discussed via analyzing the acoustic emission events. Finally, it is concluded the relationship between inclination angles of pre-cracks and performance/stability of concrete structure.

BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.

Ionic liquids have been recognised as interesting solvents applicable in the efficient lignocellulosic biomass valorisation, especially in the biomass fractionation into individual polymeric components or direct hydrolysis some of biomass fractions. Considering the chemical character of ionic liquids, two different approaches, paved the way for a fractionation of biomass. The first strategy integrated a pre-treatment, hydrolysis and conversion of biomass through the employment of hydrogen-bond acidic 1-ethyl-3-methyimidazolim hydrogen sulfate ionic liquid. The second one relied on the use of a three-step fractionation process with hydrogen-bond basic 1-ethyl-3-methylimidazolium acetate to produce high purity cellulose, hemicellulose and lignin fractions. The proposed approaches were scrutinised for wheat straw and eucalyptus residues. Those different biomasses allowed understanding that enzymatic hydrolysis yields are dependent on the crystallinity of pre-treated biomass. The use of acetate based ionic liquid allowed to change crystalline cellulose I to cellulose II and consequently enhanced glucan to glucose yield to 93.14.1 mol% and 82.91.2 mol% for wheat straw and eucalyptus, respectively. Whereas for hydrogen sulfate ionic liquid, the same enzymatic hydrolysis yields were 61.6  0.2 mol% for wheat straw and only 7.90.3 mol% for eucalyptus residues. These results demonstrate the importance of either ionic liquid character or biomass type on the efficient biomass processing.

Memphis aquifer is the primary drinking water source in Shelby County (Tennessee, USA) and supplies industrial, commercial, and residential water. Memphis aquifer is separated from the Shallow aquifer by a clayey layer known as Upper Claiborne Confining Unit (UCCU). All of the production wells in the Memphis area are screened in the Memphis aquifer or even deeper in the Fort Pillow aquifer. Traditionally, it was assumed that the UCCU could fully protect the Memphis aquifer from the contaminated Shallow aquifer groundwater. However, recent studies show that at some locations the UCCU is thin or absent which possibly leads to the contribution of Shallow aquifer to the Memphis aquifer. Accurately locating the breaches demands expensive and difficult geological or geochemical investigations, especially within an urban area. Hence, a pre-field investigation to identify the locations where the presence of breaches is likely can significantly reduce the cost of field investigations and improve the their results. In this study, to identify the locations where the presence of breaches in the UCCU is likely we use three different analyses: (1) pilot point calibration (PPC), (2) velocity and flow budget (VFB), and (3) particle tracking (PT) to post-process the developed groundwater results. These pre-field numerical investigations provide relevant and defensible explanations for groundwater flow anomalies in an aquifer system for informed decision-making and future field investigations. In this study, we identify five specific zones within the broad study area which are reasonable candidates for the future field investigations. Finally, we test the results of each analysis against other evidence for breaches to demonstrate that the results of the numerical analyses are reliable and supported by previous studies.

The Visible Infrared Imaging Radiometer Suite (VIIRS) on-board the second Joint Polar Satellite System (JPSS) completed its sensor level testing in February 2018. The JPSS-2 (J2) mission is scheduled to launch in 2022, and will be very similar to its two predecessor missions, the Suomi National Polar-orbiting Partnership (SNPP) mission, launched on 28 October 2011, and JPSS-1 (renamed NOAA-20) launched on 18 November 2017. VIIRS instrument has 22 spectral bands covering the spectrum between 0.4 and 12.6 mircron: 14 reflective solar bands (RSB), 7 thermal emissive bands (TEB), and one day-night band (DNB). It is a cross-track scanning radiometer capable of providing global measurements through observations at two spatial resolutions, 375 m and 750 m at nadir for the imaging bands and moderate bands, respectively. This paper will provide an overview of J2 VIIRS characterization methodologies and calibration performance during the pre-launch testing phases performed by the National Aeronautics and Space Administration (NASA) VIIRS Characterization Support Team (VCST) to evaluate the at-launch baseline radiometric performance and generate the parameters needed to populate the sensor data record (SDR) Look-Up-Tables (LUTs). Key sensor performance metrics include the signal to noise ratio (SNR), radiance dynamic range, reflective and emissive bands calibration performance, polarization sensitivity, spectral performance, response versus scan-angle (RVS), and scattered light response. A set of performance metrics generated during the pre-launch testing program will be compared to both the SNPP and JPSS-1 VIIRS sensors.

Global food security for the increasing world population not only requires increased sustainable production of food but a significant reduction in pre- and post-harvest waste. The timing of when a fruit is harvested is critical for reducing waste along the supply chain and increasing fruit quality for consumers. The early in field assessment of fruit ripeness and prediction of the harvest date and yield by non-destructive technologies have the potential to revolutionize farming practices and enable the consumer to eat the tastiest and freshest fruit possible. A variety of non-destructive techniques have been applied to estimate the ripeness or maturity but not all of them are applicable for in situ (field or glasshouse) assessment. This review focuses on the non-destructive methods which are promising, or have already been, applied to the pre-harvest in field measurement including colorimetry, visible imaging, spectroscopy and spectroscopic imaging. Machine learning and regression models used in assessing ripeness are also discussed.

Background: Measuring vital signs has always been a central task for Critical Care Nurse´s (CCNs) and Registered Nurse Anesthetist`s (RNAs) providing care in the post-anesthesia care unit (PACU) and a prerequisite for their decision-making. Properly measuring and understanding pediatric vital signs is a challenge in younger pediatric patients up to 36 months old. Purpose: gain a greater understanding of CCNs' and RNAs' perceptions of decision-making regarding the level of vital sign monitoring children require in the PACU. Method: A qualitative study design involving the critical-incident technique was used. Interviews were carried out with a purposeful sample of CCNs and RNAs (n=17) from two different hospitals. Findings: According to the nurses' experience, grounds for decisions concerning children’s need of vital-sign monitoring were both adequate and inadequate. They used actions to adjust the monitoring of vital signs to optimise conditions for assessment and the prospects of a safe recovery for the child. Conclusions: Evidence-based care and safety are compromised when the technology has limitations and is not adapted for children. Its use means that experience and clinical assessment are relied on to a greater extent. This not only makes experience important for reliable assessment, but also means that greater risks are accepted.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

The UN Sustainable Development Goal 7 Report 2022 is about ensuring access to clean and affordable energy, which is key to the development of agriculture, business, communications, education, healthcare, and transportation. The lack of access to energy hinders economic and human development. Nevertheless, the current pace of progress is insufficient to achieve Goal 7 by 2030. Huge disparities in access to modern sustainable energy persist. Rising commodity, energy and shipping prices have increased the cost of producing and transporting solar photovoltaics modules, wind turbines and biofuels worldwide, adding uncertainty to a development trajectory that is already far below Goal 7 ambitions. Achieving energy and climate goals will require continued policy support and a massive mobilization of public and private capital for clean and renewable energy such as methane from biomass. An important factor in improving methane yield from biomass waste is pre-treatment of the biomass prior to anaerobic digestion. Size reduction of lignocellulose biomass is important for changing and increasing digestibility thus increasing methane yield. A Hollander beater was used as the mechanical pre-treatment machine throughout this study. Results indicate that methane yield is directly proportional to feedstock/Inoculum (F/I) ratio as higher F/I ratio led to higher methane yield. It was observed at an F/I ratio of 0.5 that 5 minutes pre-treatment time produced highest methane yield, while the lowest methane yield was observed at an F/I ratio of 0.2 with 1 minute of pre-treatment time. Methane yield decreased by 30% from 140 mL gTS-1 at F/I ratio 0.5 with 5 minutes pre-treatment time to 98 mL gTS-1 at F/I 0.2 with 5 minutes pre-treatment time. The optimum methane yield was attained at high F/I ratio allowing sufficient nutrient essential for complete degradation of biomass. Overall, this research shows the Hollander beater is not efficient in optimizing methane yield for cardboard.

In this paper, the extraction of essential oil (EO) from thyme by consecutive use of ultrasound and microwave treatments is presented. The aim of the study was to apply an ultrasound pre-treatment of thyme leaves to enhance the thymol content and the extraction yield of the EO obtained by microwave-assisted hydro-distillation (MWHD). Compared with the conventional hydro-distillation (CHD), the consecutive use of ultrasound and microwave treatments resulted in a 72% lower extraction time. When the ultrasound pre-treatment (using the ultrasonic processor with an amplitude of 70%) was applied, the EO content was 23% higher compared to the extraction without pre-treatment. The EO samples were analyzed by GC/MS. The results showed that the major component, thymol, varied from 43.54% (by CHD) to 65.94% (by consecutive use of ultrasound and microwave treatments).

Context. During the COVID-19 pandemic, patient care was mainly organised around the hospital. Pre-hospital care has, to our knowledge, never been evaluated. Objective: To evaluate the impact of pre-hospital pathways on hospitalisation during the last part of the pandemic. Design. This was a monocentric retrospective analysis of prospectively collected medical records. Data from patients admitted to our institute between 1 February and 7 March 2022 were analysed. Main Outcome Measure(s): The primary outcomes were defined as the number of hospitalisations, resuscitations, and deaths at the time of interview and in the subsequent 30 days. The main explanatory variables were times from onset of symptoms to care, age, gender, News2 score, comorbidities, and pre-hospital pathways and their duration. Results: Three pre-hospital pathways have been identified: a pathway in which the patient consults a general practitioner for a test (PHP1); a pathway in which the patient consulted for care (PHP2); and no pre-hospital pathway and direct admission to hospital (PHP3). Factors independently associated with outcome (hospitalisation) were being male (OR 95% CI; 2.21 [1.01–4.84], p=0,04), News2 score (OR 95% CI; 2.04 [1.65–2.51], p<0.001), obesity (OR 95% CI; 3.45 [1.48–8.09], p=0.005), D-dimers > 0.5 µg/ml (OR 95% CI; 3.45 [1.47–8.12], p=0.005), prolonged time from symptoms to hospital care (PHP duration) (OR 95% CI; 1.07 [1.01–1.14], p=0.03). All things being equal, patients with a “PHP2” pre-hospital pathway had a higher probability of hospitalisation compared to those with a “PHP3” pre-hospital pathway (OR 95% CI; 4.31 [1.48–12.55], p=0.007). Conclusions. Along with recognised risk factors such as gender, News 2 score, and obesity, the patient’s pre-hospital pathway is an important risk factor associated with hospitalisation.

Today, concepts such as Emotional Education and Emotional Intelligence are recognized by many authors and researchers, emphasizing the importance of their development in all people, but especially in schools, specifically in teachers or educators and children. However, we still find many shortcomings within the schools that are needed to continue working. The aim of this study is to investigate the presence of emotional intelligence and empathy in teachers, through a sample of 42 participants. The research was conducted based on two validated and highly reliable assessment tools, called TMMS-24 and TECA. The results of the TMMS-24 indicate that a large percentage of participants have an adequate score of emotional intelligence. The results of the TECA indicate that most of the participants are in the middle, high or extremely high scores in relation to the level of empathy.

The introduction of tenofovir-derived prodrugs has revolutionised the prevention and management of HIV, which has coincided with 23% reduction in new HIV incidences globally. To date, there are two formulations of tenofovir-derived nucleoside reverse transcriptase inhibitor (NRTI): tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and tenofovir alafenamide fumarate/emtricitabine (TAF/FTC). Although these prodrugs have shown favourable safety profile, their effects on cardiovascular health are differ from one another: TDF/FTC exhibits potential lipid-lowering effect, TAF/FTC demonstrates potential lipid-inducing effect, which is a major risk factor for cardiovascular diseases. However, this issue has not been previously elucidated, especially among the marginalised populations [lesbian, gay, bisexual and transgender (LGBT) and men who have sex with men (MSM)] who are likely be the main users of these prodrugs. This is of clinically significance as the cardiovascular health in these populations is often overlooked, in addition to a lack of appropriate cardiovascular risk prediction algorithm. Therefore, this review aims to (1) highlight the cardiovascular risks of tenofovir-derived prodrugs in the marginalized populations, and also to (2) establish the importance of having a cardiovascular risk prediction model that is specific to this particular populations so that their health management could be more comprehensive.

A vivid debate is ongoing in the scientific community about statistical malpractice and the related publication bias. No general consensus exists on the consequences and this is reflected in heterogeneous rules defined by scientific journals on the use and reporting of statistical inference. This paper aims at discussing how the debate is perceived by the agricultural economics community and implications for our roles as researchers, contributors to the scientific publication process, and teachers. We start by summarizing the current state of the p-value debate and the replication crisis, and commonly applied statistical practices in our community. This is followed by motivation, design, results and discussion of a survey on statistical knowledge and practice among the researchers in the agricultural economics community in Austria, Germany and Switzerland. We conclude that beyond short-term measures like changing rules of reporting in publications, a cultural change regarding empirical scientific practices is needed that stretches across all our roles in the scientific process. Acceptance of scientific work should largely be based on the theoretical and methodological rigor and where the perceived relevance arises from the questions asked, the methodology employed, and the data used but not from the results generated. Revised and clear journal guidelines, the creation of resources for teaching and research, and public recognition of good practice are suggested measures to move forward.

This study explores the impact of the ‘pre-intervention effects’ of a community-based interventions. This refers to participatory research processes and parallel publicity in the media on changes in alcohol use and relevant mechanisms (rules and norms about alcohol, accessibility of alcohol in a formal setting) among adolescents before any intervention is implemented. In a quasi-experimental study, adolescent data were collected twice by means of self-report among adolescents living in two municipalities (control and experimental condition). Regression analysis showed pre-intervention main effects on adolescents’ perceived accessibility of alcohol in a formal setting. Moreover, among adolescents aged 15 years and older, the normative decline in strictness of rules and norms was less steep in the experimental condition compared to the control condition. Also, adolescents aged 14 years and younger in the experimental condition reported more weekly drinking compared to their peers in the control condition. No differential effects across gender were found. To conclude, applying a co-creational approach in the development of an intervention, not only contributes to more effective interventions in the end, but involvement of and discussions in the community at the start of intervention planning are contributing to changes in targeted factors. This implies that public discussions about the development of intervention strategies should be considered as an essential feature of co-creation in community-based interventions.

This work presents updated reconstructions of watershed runoff to San Francisco Estuary from tree-ring data to AD 903, coupled with models relating runoff to freshwater flow to the estuary and salinity intrusion. We characterize pre-development freshwater flow and salinity conditions in the estuary over the past millennium and compare this characterization with contemporary conditions to better understand the magnitude and seasonality of changes over this time. This work shows that the instrumented flow record spans the range of runoff patterns over the past millennium (averaged over five, ten, twenty and one hundred years), and thus serves as a reasonable basis for planning-level evaluations of historical hydrologic conditions in the estuary. Over annual timescales we show that, although median freshwater flow to the estuary has not changed significantly, it has been more variable over the past century compared to pre-development flow conditions. We further show that the contemporary period is generally associated with greater spring salinity intrusion and lesser summer-fall salinity intrusion relative to the pre-development period. Thus, salinity intrusion in summer and fall months was a common occurrence under pre-development conditions and has been moderated in the contemporary period due to the operations of upstream reservoirs, which were designed to hold winter and spring runoff for release in summer and fall. This work also confirms a dramatic decadal-scale hydrologic shift in the watershed from very wet to very dry conditions during the late 19th and early 20th centuries; while not unprecedented, these shifts have been seen only a few times in the past millennium. This shift resulted in an increase in salinity intrusion in the first three decades of the 20th century, as documented through early records. Population growth and extensive watershed modification during this period exacerbated this underlying hydrologic shift. Putting this shift in the context of other anthropogenic drivers is important in understanding the historical response of the estuary and in setting salinity targets for estuarine restoration. By characterizing the long-term behavior of San Francisco Estuary, this work supports decision-making in the State of California related to flow and salinity management for restoration of the estuarine ecosystem.

Modern day civilization is dependent on energy generation by fossil fuels. But the major drawback of using fossil fuels is environmental pollution. Microalgae are potential candidate for production of various products of interest, such as proteins, mini food, pigments and triglycerides that can be converted into biofuels. Lignocellulosic feedstocks are the most abundantly available raw material of plants that can serve as a promising feedstock for cultivating bacteria, fungi, yeasts and microalgae to produce biofuels and other value-added products. Owing to the abundant availability of these low/no cost substrates, can be utilized as feedstocks for cultivating microalgae to generate biogas/biodiesel. Likewise, there is much room to exploit defatted algal biomass to be used as animal/fish feed and oil producing/accumulating genes knowledge in future to produce high and good quality biodiesel and biogas.

Cardiotonic glycoside toxins, originally isolated from plants or amphibians, have been proposed as mammalian cardiotonic hormones. This paper is a review and update of the discovery of [i] a new class of steroid hormones, [ii] the path for their biosynthesis and [iii] some preliminary data on their function. The compounds are phosphoester conjugates and share a characteristic structural feature, a lactone ring, with [a] one class of synthetic potassium sparing diuretics and with [b] plant and amphibian cardiotonic steroids. Purification was initially monitored by cross reaction with steroid sulfate assays and later with digoxin-specific assays. Six compounds were purified by HPLC to near homogeneity and characterized by Tandem mass spectroscopy (MS-MS) and 31P-NMR. Three were digoxin-like materials (DLM) with 23 carbon atoms. The two extra carbon atoms form a spiral lactone E-ring. Several additional spiral lactones have been identified by MS-MS. In a pilot study, based on MS analysis, we evaluated phosphocholine steroid levels in individual serum samples in patients with pre-eclampsia (n=20). The control group of normotensive pregnant women (n=20) was used to estimate the mean and standard deviation. Twelve of the women with pre-eclampsia had a z-score over 2 for at least one of the four phosphocholine steroids. In contrast, only 1 sample from the normotensive women had a z-score over 2. The observation that there are two patterns, one with elevated phosphocholine steroid levels and one without the elevation, suggests that there may be two different underlying causes of pre-eclampsia. We now need to extend the study to determine which pattern predicts progression to life-threatening hypertension in pregnant women. This pilot study illustrates that it is possible to evaluate individual endogenous cardiotonic hormones without relying on antibodies developed to plant or amphibian toxins.

Several articles have reported that the low number of COVID-19 cases in Japan is attributed to the small number of diagnostic RT-PCR tests performed. The criticism is based on the low number of the tests performed, and they suspected there would be more potential cases in Japan. The use of pre-test probability among tested subjects is proposed in order to evaluate of the sufficiency of test availability instead of the number of the tests. The pre-test probability means the average probability, i.e., ‘suspicion level’, of having coronavirus among the tested subject in a country. The higher pre-test probability is regarded as less sufficient opportunity of the tests, and the test availability could be evaluated by the pre-test probability. Thus, potential problems of underestimation of COVID-19 cases by insufficient amount of the test would be clear by using pre-test probability. The comparison of the pre-test probability could be replaced with that of the positive rate of the test because of the linear relationship between them under the assumption of common sensitivity and specificity. Japan shows the third lowest rate (8.6%), and is considered that the considerably sufficient number of the tests have been performed. In conclusion, the positive rate of the test as a surrogate index of the pre-test probability is useful to evaluate the sufficiency of test amount instead of the number of the tests performed. In present, the potential problem of underestimation by insufficient test availability would be less serious in Japan.

The ability to replicate scientific experiments is a cornerstone of the scientific method. Sharing ideas, workflows, data, and protocols facilitates testing the generalizability of results, increases the speed that science progresses, and enhances quality control of published work. Fields of science such as medicine, the social sciences, and the physical sciences have embraced practices designed to increase replicability. Granting agencies, for example, may require data management plans and journals may require data and code availability statements along with the deposition of data and code in publicly available repositories. While many tools commonly used in replicable workflows such as distributed version control systems (e.g. “git”) or scripted programming languages for data cleaning and analysis may have a steep learning curve, their adoption can increase individual efficiency and facilitate collaborations both within entomology and across disciplines. The open science movement is developing within the discipline of entomology, but practitioners of these concepts or those desiring to work more collaboratively across disciplines may be unsure where or how to embrace these initiatives. This article is meant to introduce some of the tools entomologists can incorporate into their workflows to increase the replicability and openness of their work. We describe these tools and others, recommend additional resources for learning more about these tools, and discuss the benefits to both individuals and the scientific community and potential drawbacks associated with implementing a replicable workflow.

This study presents a pre-processing approach adopted for the radar reflectivity data assimilation and results of simulations with the Harmonie numerical weather prediction model. The method shows an improvement of precipitation prediction within the radar location area in both the rain rates and spatial pattern presentation. With the assimilation of radar data, the model simulates larger water content in the middle troposphere within the layer from 1 to 6 km, with major variations at 2.5–3 km; it also reproduces better the mesoscale belt and cell patterns of precipitation fields.

The effect of low cycle fatigue (LCF) pre-damage on the subsequent very high cycle fatigue (VHCF) behavior is investigated in TC21 titanium alloy. LCF pre-damage is applied under 1.8% strain amplitude up to various fractions of the expected life and subsequent VHCF properties are determined using ultrasonic fatigue tests. Results show that 5% of LCF pre-damage insignificantly affects the VHCF limit due to the absent of pre-crack, but decreases the subsequent fatigue crack initiation life estimated by Pairs’ law. Pre-cracks introduced by 10% and 20% of LCF pre-damage significantly reduce the subsequent VHCF limits. The crack initiation site shifts from subsurface-induced fracture for undamaged and 5% of LCF pre-damage specimens to surface pre-crack for 10% and 20% of LCF pre-damage specimens in very high cycle region. The fracture mechanism analysis indicate that LCF pre-crack will re-start to propagate under subsequently low stress amplitude when stress intensity factor of pre-crack is larger than its threshold. Furthermore, the predicted fatigue limits based on EI Haddad model for the LCF pre-damage specimens well agree with the experimental results.

This study investigates the effect of perceived discrimination on the mental health of Afghan refugees, and secondly, tests the distress moderating effects of pre-migration traumatic experiences and post-resettlement adjustment factors. In a cross-sectional design, 259 Afghans completed surveys assessing perceived discrimination and a number of other factors using scales developed through inductive techniques. Multivariate analyses consisted of a series of hierarchical regressions testing the effect of perceived discrimination on distress, followed by a sequential analysis of moderator variables. Perceived discrimination was significantly associated with higher distress, and this relationship was stronger among those with a strong intra-ethnic identity, high civic engagement, and high pre-resettlement traumatic experiences. Discrimination is a significant source of stress for Afghan refugees, which may exacerbate stresses associated with other post-migration stressors. Future research is needed to tailor interventions that can help mitigate the stress associated with discrimination among this highly vulnerable group.

Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

Ketamine as an old - new drug has variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine at standard doses is principally utilized for the induction and maintenance in surgical procedures. Beside its use in anesthesia and analgesia, recently studies had shown that ketamine find the place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Its mechanism of action is complex, but it mostly acts as a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Ketamine is generally considered relatively secure and does not result in serious adverse effects when used at low doses and for short periods- Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drug.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancers, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development [1]. Therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options [1-4]. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection [5-7]. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy and targeted agents are occurring.

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.

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: 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.

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.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed diagnosis when initial clinical symptoms do not fulfill the traditional criteria. We aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method: We retrospectively enrolled a total of 83 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data. Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A patient with a neutrophil to lymphocyte ratio greater than 1.33 combined with a C-reactive protein more than 33 mg/L was more likely to have KD. Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

The aim of this work was to classify the business incubators in Spain according to the four phases of startups incubation. Taking into account that the graduation rate implies greater survival and business success of the incubated companies, they have been identified at each stage of the incubation (spread of entrepreneurship, pre-incubation, advanced incubation, and graduation). The activities that present higher impacts on the success of the incubated companies and the activities carried out by the incubator that have a greater relevance on the graduation of the companies have concretely been considered. Principal component (PC) cluster analysis have been applied. All the incubation variables were used simultaneously, reducing their number, and grouping them into factors, finally the cases were grouped according to these latent variables. Principal components analysis reduced dimensionality to 8 factors with a 74 % of explained variance. Factor 1 was positively related to pre-incubation variables, factor 2 was linked to training and collaboration variables within the entrepreneurship diffusion phase. Factor 3 called activity monitoring and control and was related to phase 3 or basic incubation variables. Clusters analysis facilitates the grouping of incubators into three clusters: Group 1 (16 % of the total), incubators with strong deficits in incubation phases 1, 2 and 3. They are small Business Incubators, often located in rural areas or cities and low graduation rate. Group 2 (30 %), business incubators with very high graduation rate, and strongly positive values in factor 1 and 2. Factor 3 although positive is susceptible to improvement. They are the largest incubators and usually located in industrial and technological parks. Group 3 (54 %) is the majority, with values close to cluster 2 and 3.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labour, and preeclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This review summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidenced-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

As for their large surface area and pore volume, three-dimensional covalent organic frameworks (3D COFs) have emerged as competitive porous materials. However, due to the structural dynamic behavior particularly for imine-linked 3D COFs, potentially unlock their potential for gas storage application. Herein, we showed a pre-locked linker strategy introduces breaking dynamic behavior in 3D COFs. A predesigned planar linker based 3,8-diamino-6-phenylphenanthridine (DPP) was prepared to produce non-dynamic 3D JUC-595, as benzylideneamine moiety in DPP locked the linker flexibility and restrict the molecular-bond rotation of the imine linkages. Upon solvent inclusion and release, the PXRD profile of JUC-595 remained intake, while JUC-594 with flexible benzidine linker experienced crystal transformation due to framework contraction-expansion. As a result, the activated JUC-595 achieved higher surface areas (754 m² g-1) than that of JUC-594 (548 m² g-1). Furthermore, improved CO2 and CH4 storages were also seen in JUC-595 compared with JUC-594. Impressively, JUC-595 recorded high normalized H2 storage capacity that surpass other reported high surface area 3D COFs. This works shows important insight on manipulating structural properties of 3D COF to tune the gas storage performance.

Artificial intelligence (AI)-based models hold the potential to transform higher education if adopted properly and ethically. A prime example is ChatGPT with earlier studies indicating its widespread adoption in academia and by university students. The current study aimed to identify the factors influencing the attitude towards ChatGPT and its usage among university students in Arab countries. A previous survey instrument termed Technology Acceptance Model Edited to Assess ChatGPT Adoption (TAME-ChatGPT) was administered online using a convenience-based approach among the contacts of the authors. Confirmatory factor analysis (CFA) for the survey constructs was done using root mean square error of approximation (RMSEA), standardized root mean square residual (SRMR), comparative fit index (CFI), and Tucker-Lewis index (TLI). The final study sample comprised a total of 2240 participant divided as follows: Iraq (n=736, 32.9%), Kuwait (n=582, 26.0%), Egypt (n=417, 18.6%), Lebanon (n=263, 11.7%), and Jordan (n=242, 10.8%). A total of 1048 respondents heard of ChatGPT before the study (46.8%), of which 551 used ChatGPT (52.6%). The mean scores of TAME-ChatGPT constructs showed that the ease of ChatGPT use, positive attitude towards technology and social influence, higher perceived usefulness, the influence of behavioral/cognitive factors, low perceived risks and low anxiety were the determinants of positive attitude to ChatGPT and its use. For both the attitude and usage scales of TAME-ChatGPT, CFA collectively yielded satisfactory fit indices as indicated by low RMSEA and SRMR together with high CFI and TLI. Multivariate analysis showed that attitude to ChatGPT use was significantly influenced by country of residence, age, university type, and the latest grade point average of the students. The current study confirmed the validity of TAME-ChatGPT as a survey instrument to assess the possible determinants of ChatGPT use among university students in Arab countries. The study findings highlighted that successful adoption of ChatGPT in higher education could be dependent on perceived ease of use, usefulness, positive attitudes to technology, social influence, behavioral/cognitive factors, lower anxiety, and minimal perceived risks. The utility of ChatGPT in higher education requires policies that should be tailored for various settings, considering the differences observed in attitude towards ChatGPT among participating students in this study.

The pre-chamber technologies can improve the ignition performance of IC engines by more than two orders in magnitude and thereby substantial economic benefits. Compared with the common pre-chamber, a plug-and-play passive scheme is suitable for quick retrofit, which is getting more attention from the automobile industry. Good scavenging is the precondition for improving turbulent jet ignition performance for a passive pre-chamber. Therefore, detailed evaluations of the scavenging process and turbulent jet ignition deserve investigations for new pre-chamber schemes. In this paper, the effects of design parameters on ignition processes of plug-and-play passive pre-chamber were numerically studied, allowing for the lateral angle, orifice diameter, and vertical angle design. Seven pre-chamber schemes were evaluated, and four optimal ones were selected for bench tests. The characteristics of the scavenging process, turbulent jet ignition, and main-chamber combustion were investigated and analyzed. The results show that allowing for the trade-off between ignition energy and scavenging efficiency, the volume ratio of the pre-chamber to clearance is recommended to be 0.2~0.7%, and the corresponding area-volume ratio is 0.003~0.006 mm-1. Compared with the original natural gas engine, the pre-chamber retrofit can save up to 13.2% fuel consumption, which presents a significant improvement in fuel economy.

Artificial intelligence, a key technological tool in the era of the 4th Industrial Revolution, is being actively applied to education beyond industry, economy, and culture. In the future society, understanding and using artificial intelligence technology will be considered an essential skill for everyone, and the professionalism of AI education for pre-service teachers nurturing future talents is also important. This study verifies the effectiveness of pre-service teachers after undergoing a 15-week extension program consisting of AI Literacy Education (10 weeks), AI-Linked Subjet Education (3 weeks), and Micro-teaching (2 weeks) which was designed to enhance the AI ​​education professionalism of pre-service teachers. The AI Literacy Education section consisted of understanding AI, AI ethics, and basic programming, and the education was conducted through both experience and practice. After that, the pre-service teachers analyzed the curriculum of the 5th and 6th grades of an elementary school, and developed a subject-related education program using AI tools in three stages. Using the developed program, micro-teaching classes were conducted twice. The study results are as follows. First, there was a change in the positive perception of AI (p<.05). Second, the understanding of AI educational technology tools was improved and the recognition of the usefulness of developing a curriculum-related program was expanded. Third, the importance of teacher competency development was learned through the micro-teaching, and the students' understanding of the learning process was expanded.

The aim of this study was to investigate the potential of converting potato peel waste into bio ethanol using an in-house produced multi-enzyme preparation. To achieve this, a variety of pre-treatment strategies, including thermal, chemical, and thermo-chemical methods, were applied to the potato peels. These included boiling for 30 and 60 min, steam at varying pressures and times, and different concentrations of chemicals such as H2SO4, HNO3, CH3COOH, HCl, NaOH, Ca(OH)2, KOH, NH3, and H2O2, either alone or in combination with steam. The pre-treated potato peels were then enzymatically hydrolyzed using a crude multi-enzyme cocktail derived from solid-state fermentation of wheat bran by a natural variety of Aspergillus niger P-19, containing cellulases, hemicellulases, pectinase, and amylases. The most effective pre-treatment combination was found to be 3% H2SO4 followed by steam under pressure and enzymatic hydrolysis using the crude multi-enzyme preparation. This combination resulted in the highest yield of reducing sugars (141.04 ±12.31 g/l) with a 98.49% carbohydrate conversion at a 20% substrate loading, giving an ethanol yield of 43.2 g/l. Furthermore, supplementing the medium with peptone, (NH4)(H2PO4), and ZnSO4 at 0.1%w/v each with 22% and 24% solid, respectively, resulted in appreciable yields of 51.67 and 54.75 g/l, further enhancing the ethanol yield.