Enhancing medical training in conflict zones and remote areas through innovation: introducing the Canadian Virtual Medical University Initiative.

Background: The WHO projects a global shortage of 4.3 million physicians by 2030, with the largest deficits in developing and conflict-affected regions. Our aim is to train competent physicians rapidly and affordably through remote education programs. Methods: We developed an online medical training curriculum with four levels, focusing on different aspects of human body systems using a competency-based, student-centered approach. This study evaluates the first three levels; level four (internship) is outside this scope. The 105 medical students from eight Afghan universities were randomly assigned to nine groups. The curriculum includes Entrustable Professional Activities (EPA) for the cardiovascular system: level 1 covers basic medical sciences, level 2 pathology and basic clinical skills, and level 3 full clinical competencies. EPAs were delivered asynchronously online via Lecturio, CyberPatient, and Zoom. The 30-day intervention included 4 h of weekly online classes for formative assessment, collaborative learning, and evaluation, supervised by medical faculty members. Virtual pre- and post-intervention evaluations used multiple-choice questions and objective structured clinical examination (OSCE). We also conducted a satisfaction survey and open interview forum. Data triangulation from observations, surveys, and interviews validated curriculum effectiveness. The benchmarking method assessed cost-effectiveness. Findings: Pre- and post-intervention analysis showed a significant increase in clinical competencies and knowledge acquisition (P < 0.0001). The CyberPatient intervention improved clinical competency quality (P < 0.0001) and shortened decision-making time (P < 0.001). Cost analysis revealed that a virtual medical university would be 95% more cost-effective than traditional medical education. Interpretation: Integrating virtual technology with modern curriculum concepts in pre-internship years can effectively address healthcare training gaps and enhance education quality for healthcare workers at a low cost. Funding: Provided by CanHealth International. A UBC spin-off not-for-profit organization.

Evaporation from thin porous Coatings: Pore size effects and predictive equation for homogeneous coatings.

Evaporation of small water droplets on solids is hindered because surface tension pulls the droplet into a spherical cap that has a small perimeter. Our solution is to coat a solid with a very thin, porous layer into which the droplet flows to create a large-area disk with concomitant high rate of evaporation. We investigate evaporation by varying factors that have not been previously considered: pore size and distribution, contact angle, temperature, and relative humidity (RH).A larger pore size resulted in faster evaporation, which we explain through faster transport within the coating. Even faster evaporation occurred for a bilayer structure with small particles on the air side and larger particles on the solid side. The water advancing contact angle had an insignificant effect in the range from < 10° through to 60°.Our results for different pore sizes, temperature, humidity, and contact angle all collapse onto a single curve when appropriately normalized. This validates an equation that can be used for the evaporation from a homogeneous coating that depends only one empirical factor and the droplet volume. Since the volume is often user-controlled, we envisage that this equation can be used to predict evaporation and guide design of fast-drying coatings.

Infectious Diarrhea Risks as a Public Health Emergency in Floods; a Systematic Review and Meta-Analysis.

Introduction: Infectious diarrhea, a significant global health challenge, is exacerbated by flooding, a consequence of climate change and environmental disruption. This comprehensive study aims to quantify the association between flooding events and the incidence of infectious diarrhea, considering diverse demographic, environmental, and pathogen-specific factors. Methods: In this systematic review and meta-analysis, adhering to PROSPERO protocol (CRD42024498899), we evaluated observational studies from January 2000 to December 2023. The analysis incorporated global data from PubMed, Scopus, Embase, Web of Science, and ProQuest, focusing on the relative risk (RR) of diarrhea post-flooding. The study encompassed diverse variables like age, sex, pathogen type, environmental context, and statistical modeling approaches. Results: The meta-analysis, involving 42 high-quality studies, revealed a substantial increase (RR = 1.40, 95% CI [1.29-1.52]) in the incidence of diarrhea following floods. Notably, bacterial and parasitic diarrheas demonstrated higher RRs (1.82 and 1.35, respectively) compared to viral etiologies (RR = 1.15). A significant sex disparity was observed, with women exhibiting a higher susceptibility (RR = 1.55) than men (RR = 1.35). Adults (over 15 years) faced a greater risk than younger individuals, highlighting age-dependent vulnerability. Conclusion: This extensive analysis confirms a significant correlation between flood events and increased infectious diarrhea risk, varying across pathogens and demographic groups. The findings highlight an urgent need for tailored public health interventions in flood-prone areas, focusing on enhanced sanitation, disease surveillance, and targeted education to mitigate this elevated risk. Our study underscores the critical importance of integrating flood-related health risks into global public health planning and climate change adaptation strategies.

Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans.

Post-traumatic stress disorder (PTSD) is one of the most widespread and disabling psychiatric disorders among combat veterans. Substantial interindividual variability in susceptibility to PTSD suggests the presence of different risk factors for this disorder. Twin and family studies confirm genetic factors as important risk factors for PTSD. In addition to genetic factors, epigenetic factors, especially DNA methylation, can be considered as a potential mechanism in changing the risk of PTSD. So far, many genetic and epigenetic association studies have been conducted in relation to PTSD. In genetic studies, many single nucleotide polymorphisms have been identified as PTSD risk factors. Meanwhile, the variations in catecholamines-related genes, serotonin transporter and receptors, brain-derived neurotrophic factor, inflammatory factors, and apolipoprotein E are the most prominent candidates. CpG methylation in the upstream regions of many genes is also considered a PTSD risk factor. Accurate identification of genetic and epigenetic changes associated with PTSD can lead to the presentation of suitable biomarkers for susceptible individuals to this disorder. This study aimed to delineate prominent genetic variations and epigenetic changes associated with post-traumatic stress disorder in military veterans who have experienced combat, focusing on genetic and epigenetic association studies.

Metformin reduces the clonal fitness of Dnmt3aR878H hematopoietic stem and progenitor cells by reversing their aberrant metabolic and epigenetic state.

Clonal hematopoiesis (CH) arises when a hematopoietic stem cell (HSC) acquires a mutation that confers a competitive advantage over wild-type (WT) HSCs, resulting in its clonal expansion. Individuals with CH are at an increased risk of developing hematologic neoplasms and a range of age-related inflammatory illnesses1-3. Therapeutic interventions that suppress the expansion of mutant HSCs have the potential to prevent these CH-related illnesses; however, such interventions have not yet been identified. The most common CH driver mutations are in the DNA methyltransferase 3 alpha (DNMT3A) gene with arginine 882 (R882) being a mutation hotspot. Here we show that murine hematopoietic stem and progenitor cells (HSPCs) carrying the Dnmt3aR878H/+ mutation, which is equivalent to human DNMT3AR882H/+, have increased mitochondrial respiration compared with WT cells and are dependent on this metabolic reprogramming for their competitive advantage. Importantly, treatment with metformin, an oral anti-diabetic drug with inhibitory activity against complex I in the electron transport chain (ETC), reduced the fitness of Dnmt3aR878H/+ HSCs. Through a multi-omics approach, we discovered that metformin acts by enhancing the methylation potential in Dnmt3aR878H/+ HSPCs and reversing their aberrant DNA CpG methylation and histone H3K27 trimethylation (H3K27me3) profiles. Metformin also reduced the fitness of human DNMT3AR882H HSPCs generated by prime editing. Our findings provide preclinical rationale for investigating metformin as a preventive intervention against illnesses associated with DNMT3AR882 mutation-driven CH in humans.

Can gamified surgical sets improve surgical instrument recognition and student performance retention in the operating room? A multi-institutional experimental crossover study.

INTRODUCTION: Surgery requires a high degree of precision, speed, and concentration. Owing to the complexity of the modern world, traditional methods cannot meet these requirements. Therefore, in this study, we investigated students' diagnostic skills in the Operating Room in the context of surgical instruments by using gamification of surgical instruments and a crossover design. METHOD: The study design was a multi-institutional quasi-experimental crossover and involved a three-arm intervention (with gender-specific block randomisation: Group A, B, and C) with a pre-test and three post-tests. A total of 90 students fell into three groups of 30 participants each. The surgical sets were learned for one semester through game-based instruction and traditional teaching, and then three OSCE tests were administered with time and location differences. Using one-way ANOVA, OSCE results were compared in the game, traditional, and control groups. The effectiveness of the intervention was tested in each group by repeated measures. RESULT: The pretest scores of all three groups did not differ significantly. In the OSCE tests, both groups, A and B, performed similarly. However, these tests showed a significant difference in grouping between training through games and training in the traditional way. There was no significant difference between OSCE tests 2 and 3 in the game-based training group, indicating that what was learned was retained, while in the traditional method training group, OSCE 3 test scores declined significantly. Furthermore, repeated measures showed the effectiveness of game-based training. CONCLUSION: In this study, gamification has turned out to be very effective in helping learners learn practical skills and leading to more sustainable learning.

Smartwatches in healthcare medicine: assistance and monitoring; a scoping review.

Smartwatches have become increasingly popular in recent times because of their capacity to track different health indicators, including heart rate, patterns of sleep, and physical movements. This scoping review aims to explore the utilisation of smartwatches within the healthcare sector. According to Arksey and O'Malley's methodology, an organised search was performed in PubMed/Medline, Scopus, Embase, Web of Science, ERIC and Google Scholar. In our search strategy, 761 articles were returned. The exclusion/inclusion criteria were applied. Finally, 35 articles were selected for extracting data. These included six studies on stress monitoring, six on movement disorders, three on sleep tracking, three on blood pressure, two on heart disease, six on covid pandemic, three on safety and six on validation. The use of smartwatches has been found to be effective in diagnosing the symptoms of various diseases. In particular, smartwatches have shown promise in detecting heart diseases, movement disorders, and even early signs of COVID-19. Nevertheless, it should be emphasised that there is an ongoing discussion concerning the reliability of smartwatch diagnoses within healthcare systems. Despite the potential advantages offered by utilising smartwatches for disease detection, it is imperative to approach their data interpretation with prudence. The discrepancies in detection between smartwatches and their algorithms have important implications for healthcare use. The accuracy and reliability of the algorithms used are crucial, as well as high accuracy in detecting changes in health status by the smartwatches themselves. This calls for the development of medical watches and the creation of AI-hospital assistants. These assistants will be designed to help with patient monitoring, appointment scheduling, and medication management tasks. They can educate patients and answer common questions, freeing healthcare providers to focus on more complex tasks.

Low-temperature acclimation related with developmental regulations of polyamines and ethylene metabolism in wheat recombinant inbred lines.

Winter survival is determined by complicated developmental regulations enabling wheat to adjust their transcriptome and metabolome to develop low temperature (LT) tolerance. The aim of the study was to clarify the metabolic responses developmentally regulated in six F6 recombinant inbred lines from a cross between Pishtaz (spring parent) and Mironovskaya 808 (winter parent). Spring genotypes, including pishtaz, RILs 4006 and 4014 showed lower LT tolerance, PAs (except the spermin), GABA and proline contents and DPPH• scavenging capacity. In these genotypes, genes and enzymes involved in the pathways of PAs and GABA degradation and ethylene biosynthesis were more active than other genotypes. RILs 4012 and 4016 with short vernalization displayed higher tolerance and lower H2O2 content compared to Pishtaz. Strong vernalization requirements in winter and facultative genotypes (Mironovskaya 808 parent and RILs 4003 and 4005) results in up-regulation of the metabolites and genes involved in PAs and GABA biosynthesis pathways (particularly when vernalization fulfillment occurred) to establish high tolerance as compared to genotypes without vernalization requirement. LT tolerance in all genotypes significantly decreased after vernalization fulfillment in February. Results indicated that LT tolerance was partly validated from developmental regulation of PAs, GABA, and ethylene metabolism during venalization and LT acclimation.

Crossover design in triage education: the effectiveness of simulated interactive vs. routine training on student nurses' performance in a disaster situation.

INTRODUCTION: This study investigates the effectiveness of incorporating simulated interactive guidelines in nursing students' performance during disaster situations, compared to routine training. METHOD: This study was a crossover design with pre-and post-tests for two groups. Each group consisted of 60 students selected using the census method. SIG and routine (Face-to-Face) training sessions were conducted as a crossover design. Triage knowledge questionnaires were used in the pretest to assess triage knowledge. An OSCE test was administered in the posttest to assess student performance, followed by a triage skills questionnaire. Both questionnaires were highly reliable, as indicated by Cronbach's alpha coefficients (0.9 and 0.95, respectively). Statistical analysis was performed using SPSS version 26 software at a significance level 0.05. RESULT: The chi-square test showed that the two groups were homogeneous regarding age. Regarding knowledge level, both groups were homogeneous before the intervention (P = 0.99). Nevertheless, the results of the OSCE test showed that the students in Group A had a higher level of skill than the students in Group B (93% versus 70%). Also, 18% of the students in group B had low skills. DISCUSSION: The study found that student outcomes improved in both groups receiving SIG, suggesting that interaction and simulation improve learning. However, gamification is an ideal precursor to learning and not a substitute for education. Therefore, gamification should not be used as a stand-alone teaching method. CONCLUSIONS: The crossover study found that simulators and games should not be considered stand-alone teaching methods but can contribute to learning sustainability when used alongside instruction.

Inverse correlation between vitamin D and CRP levels in alopecia areata: A pilot study.

INTRODUCTION: Alopecia areata (AA) is an autoimmune non-scarring hair loss. The role of micronutrients such as iron, zinc, and vitamins, especially vitamin D, on the natural hair cycle is well defined in literature. This study aims to evaluate the correlation between vitamin D and CRP levels in patients with alopecia areata. METHODS: This cross-sectional study was performed from beginning of October 2020 until end of December 2021. Alopecia areata patients over 18 years of age gave their written consent to participate in the study. The severity of the patients' disease was assessed using the Severity of Alopecia Tool. Serum vitamin D and CRP levels were measured and CBC and LFT were also performed. RESULTS: There were significant differences between the patients with the localized form of AA and its universal form in the following variables: Vitamin D levels, SALT score, WBC, ALKP, and CRP. There was also a significant inverse correlation between CRP and vitamin D levels (p < 0.0001). CONCLUSION: Vitamin D deficiency is associated with higher CRP levels, and patients with low serum vitamin D and high CRP levels are at a higher risk of developing the universalis form of AA; therefore, these patients should undergo more aggressive treatments.

Dietary and Sleep Quality Association in Hemodialysis Patients.

Background: Poor sleep quality is a common issue among patients with end-stage renal disease (ESRD) who undergo dialysis. Nutritional habits are associated with sleep hygiene in patients undergoing dialysis. The objective of this study was to examine the potential correlation between nutritional status and sleep quality in individuals receiving hemodialysis treatment. Materials and Methods: This cross-sectional study included 160 hemodialysis patients. A food frequency questionnaire (FFQ) was used to measure food intake in participants. The Persian-validated version of the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Patients were classified as poor or good sleepers with a PSQI score of <5 and >5, respectively. Results: Eighty-four percent of hemodialysis patients had bad sleep hygiene. There was a significant association between sleep quality and educational status and age (P < 0.001). Poor sleepers were older (61.65 years versus 51.12) and less educated (31.1% versus 4%). However, there was no significant difference in the intake of micro- and macronutrients between poor and good sleepers (P > 0.05). Conclusion: The results of this study suggest that sleep quality has no significant relationship with nutrient intake in hemodialysis patients. Demographic factors, such as age and educational status, have played a more effective role than nutritional factors in patients' sleep quality.

Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study.

BACKGROUND: COVID-19 is a respiratory illness caused by SARS-CoV-2. Pharmaceutical companies aim to control virus spread through effective drugs. This study investigates chromone compound derivatives' ability to inhibit viral entry and prevent replication. METHOD: This study investigated the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 from Severe Acute Respiratory Syndrome CoV-2, Homo sapiens, and 6LU7 from Bat SARS-like CoV using molecular docking. The crystal structure of these proteins was obtained from the Protein Data Bank, and the inhibition site was determined using ligand binding interaction options. The 3D structure was protonated and energetically minimised using MOE software. Chromone derivatives were designed in three dimensions, and their energy was minimised using MOE 2019. The molecular drug-likeness was calculated using SwissADME, Lipinski and Benigni-Bossa's rule, and toxicity was calculated using Toxtree v3.1.0 software. Compounds with pharmacological properties were selected for molecular docking, and interactions were assessed using MOE 2019. MD simulations of Mpro-ch-p complexes were performed to evaluate root mean square fluctuations (RMSF) and measure protein stability. RESULT: The pharmacokinetic tests revealed that chromone derivatives of the peptidomimetic family have acceptable pharmacokinetic activity in the human body. Some compounds, such as Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13, have pronounced medicinal properties. Molecular docking revealed high affinity for binding to SARS-CoV-2 protease. Ch-p7 had the highest binding energy, likely due to its inhibitory property. A 10 ns molecular dynamics study confirmed the stability of the protein-ligand complex, resulting in minimal fluctuations in the system's backbone. The MM-GBSA analysis revealed free energies of binding of - 19.54 kcal/mol. CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.

The Aspects of Running Artificial Intelligence in Emergency Care; a Scoping Review.

Introduction: Artificial Inteligence (AI) application in emergency medicine is subject to ethical and legal inconsistencies. The purposes of this study were to map the extent of AI applications in emergency medicine, to identify ethical issues related to the use of AI, and to propose an ethical framework for its use. Methods: A comprehensive literature collection was compiled through electronic databases/internet search engines (PubMed, Web of Science Platform, MEDLINE, Scopus, Google Scholar/Academia, and ERIC) and reference lists. We considered studies published between 1 January 2014 and 6 October 2022. Articles that did not self-classify as studies of an AI intervention, those that were not relevant to Emergency Departments (EDs), and articles that did not report outcomes or evaluations were excluded. Descriptive and thematic analyses of data extracted from the included articles were conducted. Results: A total of 137 out of the 2175 citations in the original database were eligible for full-text evaluation. Of these articles, 47 were included in the scoping review and considered for theme extraction. This review covers seven main areas of AI techniques in emergency medicine: Machine Learning (ML) Algorithms (10.64%), prehospital emergency management (12.76%), triage, patient acuity and disposition of patients (19.15%), disease and condition prediction (23.40%), emergency department management (17.03%), the future impact of AI on Emergency Medical Services (EMS) (8.51%), and ethical issues (8.51%). Conclusion: There has been a rapid increase in AI research in emergency medicine in recent years. Several studies have demonstrated the potential of AI in diverse contexts, particularly when improving patient outcomes through predictive modelling. According to the synthesis of studies in our review, AI-based decision-making lacks transparency. This feature makes AI decision-making opaque.

Super-enhanced evaporation of droplets from porous coatings.

HYPOTHESIS: The addition of a thin, hydrophilic, porous, coating to an impermeable solid will lead to more rapid evaporation of liquid droplets that impinge on the solid. The droplet will imbibe quickly, but the progress normal to the interface will be limited to the thickness of the coating, and therefore the liquid will spread laterally into a broad disk to expose a large liquid-vapor interface for evaporation. EXPERIMENTS: Liquid droplets of volume 2.5-25 µL were placed on solids and then both the mass and area of each droplet were monitored over time. We compared data for smooth, impermeable hydrophilic glass to the same glass that was coated in thin (35-109 µm) porous, hydrophilic-glass layer fabricated from glass beads. FINDINGS: The droplet was imbibed (wicked) into the coating within seconds, and the liquid spread laterally to form a thin, broad, disk. Critically, evaporation of a droplet was enhanced by a factor of 7-8 on the thin coating. The evaporation rate was not proportional to the reciprocal thickness of the coating. The ability to enhance evaporation of small droplets on a solid may have practical applications, for example, in speeding the death of microbes.

Robust and Transparent Silver Oxide Coating Fabricated at Room Temperature Kills Clostridioides difficile Spores, MRSA, and Pseudomonas aeruginosa.

Antimicrobial coatings can inhibit the transmission of infectious diseases when they provide a quick kill that is achieved long after the coating application. Here, we describe the fabrication and testing of a glass coating containing Ag2O microparticles that was prepared from sodium silicate at room temperature. The half-lives of both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa on this coating are only 2-4 min. The half-life of Clostridioides difficile spores is about 9-12 min, which is extremely short for a spore. Additional tests on MRSA demonstrate that the coating retains its antimicrobial activity after abrasion and that an increased loading of Ag2O leads to a shorter half-life. This coating combines the properties of optical transparency, robustness, fast kill, and room temperature preparation that are highly desirable for an antimicrobial coating.

Normal spirometry prediction equations for the Iranian population.

BACKGROUND: This study aimed to establish normative spirometric equations in a healthy population of Iranian children and adults, and compare these equations with those developed by the Caucasian Global Lung Initiative (GLI) for the first time. METHODS: Spirometric data from healthy Iranian aged 4-82 years sampled in 2019 were used to derive reference equations using the generalized additive model for location (mu), shape (lambda), and scale (sigma). RESULTS: A total of 418 females and 204 males were included in the study. Applying the GLI standards for the Iranian population resulted from the Z scores of FEV1, FVC, FEV1/FVC, and FEF25-75% was not different from zero. Based on the newly calculated LLN, eleven individuals showed significant values below the LLN for FEV1/FVC. In all age groups, this frequency was less than 5%, except for men over 70 years of age, which was 12.5%. There are significant differences between new data and GLI for Caucasian data. CONCLUSION: It is recommended that the values and equations generated from this study should be used by physicians and technicians in their routine practice for the diagnosis and assessment of pulmonary disorders.

Game-based vs. Case-based Training for Increasing Knowledge and Behavioral Fluency of Nurse Students Regarding Crisis and Disaster Management; a Quasi-Experimental Study.

Introduction: Nurses play an active role in disaster response, and the ability of nurses to appropriately apply management principles during large-scale disasters or mass casualty incidents is of critical importance. This study aimed to compare the effect of game-based Training (GBT) and case-based training (CBT) on nursing students' knowledge and behavioral fluency regarding Crisis and Disaster Management. Methods: This is a quasi-experimental study with a pretest-posttest design. Convenience sampling was used to select third-year nursing students who had completed their clinical clerkship at the time of the study (n=60). In the intervention group, disaster-themed games were used, while in the control group, CBT was used. The emergency and crisis management course consisted of this study's theoretical and clinical training phases. After completion of the theoretical phase (five weeks), the practical part (four weeks) is completed as an internship. The data was collected from the disaster Nurses' Knowledge Questionnaire, demographic survey, and measurement checklists for disasters and crises at five stations. Results: GBT students achieved significantly higher knowledge scores than CBT students after training (p< 0.001). CBT and GBT groups had no significant differences in Objective Structured Clinical Examination (OSCE)1 pretest scores. Posttest1-OSCE2 and posttest2-OSCE3 scores showed significant differences after one week (P < 0.001) and one month (P < 0.001). The mean pretest and posttest1 scores were statistically significant in both groups. A comparison of posttest scores between one month after GBT training (69.03 ± 6.09) and one week after it (69.23 ± 6.14) revealed no statistical significance (p = 0.056). Conclusion: Nursing students' knowledge and behavioral fluency regarding crisis management were more effectively improved by using the disaster and crisis game than by using a case-based method.

Targeting STAT5 Signaling Overcomes Resistance to IDH Inhibitors in Acute Myeloid Leukemia through Suppression of Stemness.

Mutant isocitrate dehydrogenase 1 (IDH1) and IDH2 block the differentiation of acute myeloid leukemia (AML) cells through production of R-2-hydroxyglutarate (R-2-HG). IDH inhibitors can induce differentiation of AML cells by lowering R-2-HG but have limited clinical efficacy as single agents. Here, we performed a genome-wide CRISPR knockout screen in an Idh1-mutated hematopoietic progenitor cell line to identify genes that increased the differentiation response to ivosidenib, an IDH1 inhibitor. The screen identified C-type lectin member 5a (Clec5a), which encodes a spleen tyrosine kinase (SYK)-coupled surface receptor, as one of the top hits. Knockout of Clec5a and Syk rendered cells more sensitive to ivosidenib-induced differentiation through a reduction in STAT5-dependent expression of stemness-related genes, including genes in the homeobox (HOX) family. Importantly, direct inhibition of STAT5 activity was sufficient to increase the differentiation response to IDH inhibitors in primary human IDH1- and IDH2-mutated AML cells, including those harboring mutations in receptor tyrosine kinase (RTK) and MAPK genes that have been linked to drug resistance. In patient-derived xenograft models of IDH1-mutated AML, combination treatment with ivosidenib and the STAT5 inhibitor pimozide was superior to each agent alone in inducing differentiation in leukemic cells without compromising normal hematopoiesis. These findings demonstrate that STAT5 is a critical mediator of resistance to IDH inhibitors and provide the rationale for combining STAT5 and IDH inhibitors in the treatment of IDH-mutated AML. SIGNIFICANCE: A CRISPR knockout screen identifies a mechanism of resistance to IDH inhibitors in AML involving activated STAT5 signaling, suggesting a potential strategy to improve the clinical efficacy of IDH inhibitors.

Effect of Selenium on Triglyceride and Total Cholesterol, Weight Gain, and Physical Activity on Hemodialysis Patients: A Randomized Double-Blinded Controlled Trial.

Background: End-stage renal disease is one of the most important chronic diseases. Selenium is one of the so-called rare elements which are essential for our body functions. Here, we aimed to investigate and the effects of selenium supplement therapy on weight gain, physical activity, and triglyceride (TG) and total cholesterol in patients under hemodialysis. Methods: The current study is a double-blinded clinical trial performed on patients with ESRD under hemodialysis in 2019. In the beginning, serum selenium levels were assessed. All patients were randomly divided into two groups. The first group was under treatments with tablets of selenium 400 µg. Patients received selenium tablets three times after each hemodialysis session (3 times a week) and the other group received placebo tablets. 3 months after the beginning of the study, blood selenium levels, TG and total cholesterol, and weight and physical activities of patients were evaluated again and compared with the beginning. Results: A total of 78 patients were included. Serum selenium levels at the beginning of our study were 40.06 ± 8.50 in the intervention group and 45.00 ± 8.16 in control groups. Selenium levels and physical activities of patients were increased significantly in intervention group compared to baseline (P < 0.001 for both). Weight, physical activity, total cholesterol, and TG in both intervention and control groups did not change significantly after interventions (P > 0.05). Conclusions: We showed that selenium supplement therapies have beneficial effects in patients under hemodialysis. Furthermore, we showed that selenium supplement therapies have positive effects on serum selenium levels but no effects on total cholesterol and TG.