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STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.

Objective To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet’s disease. Methods In this systematic review and meta-analysis, the research question was designed using the ‘Population, Intervention, Comparator, and Outcomes’ (PICO) model and the search methodology was developed according to the PRISMA statement. The study was registered on PROSPERO. Web of Science, PubMed, and Cochrane Library databases were searched for articles published in English between January 2000 and January 2020. Data were analysed using Meta-Essentials software, version 10.12. Treatment effect size was determined by a random effects model. Interstudy heterogeneity was explored using I2 statistics. Cumulative meta-analysis was conducted to assess the temporal trend for accumulating evidence. Results Twenty-one studies, comprising 64 patients (mean age, 38 .21 years and mean disease duration, 84.76 months) were included. Effect-size analysis showed that 93.7% of the treated patients in the analysis were responders to infliximab therapy (95% confidence interval 0.88, 0.993). There was no significant inter-study heterogeneity (I2 = 0%). Cumulative analysis showed accumulating evidence favoring increasing effectiveness over the last 20 years. Conclusion Infliximab showed considerable therapeutic effectiveness in the treatment of refractory neuro-Behçet’s disease.

The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1–2 week) in the clinical, public health, and health systems fields. We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group. A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan. An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest. •The proposed approach for developing trustworthy recommendations as part of urgent responses (1–2 week) builds on the general principles of trustworthy guideline development.•The approach proposes the following steps: (1) assess the level of urgency; (2) clarify and focus the scope of question(s); (3) prioritize and collect the information needed; (4) assess the adequacy of identified information; and then (5) develop recommendations;•Developing recommendations can consist of (1) adopting existing recommendations; (2) adapting existing recommendations; (3) developing new recommendations using existing systematic reviews; or (4) developing new recommendations using identified information and panel input.

Background: The authors aimed to explore carpal tunnel syndrome (CTS) among electronic sports (esports) athletes, to compare hand symptoms and their severity between esports athletes and the control group and within the esports athletes, and to study the relationship between esports athletes' variables. Material and Methods: A cross-sectional survey study via telephone with systematic randomized approach was used for esport athletes sampling. Control group were non-esports athletes who do not use computer for prolonged duration. The survey consisted of sports athletes' characteristics, hand symptoms and functions, and the Boston Carpal Tunnel Questionnaire (BCTQ). The unpaired student's t-test, Mann-Whitney U test, and [chi square] test were utilised for statistical comparison, with p < 0.05. Pearson's and Spearman's correlation coefficient tests were used for relationship analyses. Results: Eligible participants were 198 out of 229. Compared to control group, esport athletes reported more CTS (p = 0.01), and radiated pain and numbness in their hands (p = 0.05). Males complained of hand symptoms (p < 0.01) and its radiation (p < 0.01) more than females among esports athletes. Higher BCTQ Symptom Severity Scale (BCTQ-SSS) scores were reported for esports athletes who had been playing esports for prolonged periods compared to those who had playing recently (p = 0.003), with a moderate positive correlation (+0.59, p = 0.004). A significant moderate positive correlation was reported for BCTQ Functional Severity Symptoms (BCTQ-FSS) scores in terms of hours of playing (+0.44, p = 0.04). Esports athletes who used armrests and a PC with a controller for gaming reported less hand symptoms and had milder BCTQ scores than those who used a PC with a keyboard/mouse. Generally, esports athletes spend 5-10 h/day on gaming. Conclusions: Esports athletes might be at risk of developing upper-extremity nerve compression and CTS. Prolonged playing, hours of playing, type of esports device, and using armrests are possible risk factors. Key words: carpal tunnel syndrome, upper extremity, esports athletes, computer games, neuropathies, hand symptoms

The objective of the study was to clarify how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept of certainty of evidence applies to certainty ratings of test accuracy. After initial brainstorming with GRADE Working Group members, we iteratively refined and clarified the approaches for defining ranges when assessing the certainty of evidence for test accuracy within a systematic review, health technology assessment, or guideline. Ranges can be defined both for single test accuracy and for comparative accuracy of multiple tests. For systematic reviews and health technology assessments, approaches for defining ranges include some that do not require value judgments regarding downstream health outcomes. Key challenges arise in the context of a guideline that requires ranges for sensitivity and specificity that are set considering possible effects on all critical outcomes. We illustrate possible approaches and provide an example from a systematic review of a direct comparison between two test strategies. This GRADE concept paper provides a framework for assessing, presenting, and making decisions based on the certainty of evidence for test accuracy. More empirical research is needed to support future GRADE guidance on how to best operationalize the candidate approaches.

This study investigated a severe foodborne outbreak in Ain Al-Basha, Jordan, linked to a fast-food restaurant offering chicken shawarma meals. The outbreak highlighted systemic lapses in food safety, particularly in handling and preparing poultry products, underscoring the need for immediate public health intervention. Outbreak data collected by rapid response teams from the Jordan Ministry of Health (MOH), were analyzed. A case was defined as any individual who visited healthcare centers within the Al-Balqa Governorate between July 27 and August 2, 2020, presenting with two or more of the following symptoms: fever, diarrhea, vomiting, abdominal pain, or headache. Descriptive statistics were used to summarize demographic, clinical, and exposure characteristics. A total of 472 confirmed cases were identified, with a mean (standard deviation [SD]) age of 20.8 (13.4) years. The most frequently reported symptoms were fever (98.3%), abdominal pain (96.8%) and vomiting (96.0%). Most cases reported consuming chicken shawarma (86.0%), garlic sauce (83.1%), or French fries (79.9%). Of the 56 stool specimens tested, 100% tested positive for . Food samples revealed and . contamination in marinated raw chicken, indicating cross-contamination and improper cooking. was not detected in food items. This outbreak underscores critical gaps in food safety practices related to shawarma preparation in Jordan. These findings call for stronger regulations, regular inspections, and focused public education on safe food handling, particularly for vulnerable populations. Timely action to enforce stricter protocols is vital to prevent further outbreaks and protect public health.

The world is experiencing a life-altering and extraordinary situation in response to the COVID-19 pandemic. There are limited data and controversies regarding the relationship between vitamin D (Vit D) status and COVID-19 disease. Thus, this study was designed to investigate the association between Vit D levels and the severity or outcomes of COVID-19 disease. A cross-sectional observational study was conducted in the Eastern province of Saudi Arabia from January to August 2021. All the admitted patients who were diagnosed with COVID-19 infection were distributed into three groups depending on their Vit D levels: normal, insufficiency, and deficiency. For the three groups, demographic data, and laboratory investigations as well as data regarding the severity of COVID-19 were collected and analysed. A total of 203 diagnosed cases of COVID-19 were included in this study. The Vit D level was normal (>30) in 31 (15.3%) cases, insufficient in 45 (22.2%) cases and deficient in 127 (62.6%) cases. Among the included cases, 58 (28.6%) were critical cases, 109 (53.7%) were severe and 36 (17.7%) had a mild-moderate COVID-19 infection. The most prevalent comorbidity of patients was diabetes mellitus 117 (57.6%), followed by hypertension 70 (34.5%), cardiac disease 24 (11.8%), chronic kidney disease 19 (9.4%) and chronic respiratory disease in 17 (8.4%) cases. Importantly, the current study did not detect any significant association between Vit D status and COVID-19 severity (p-value=0.371) or outcomes (hospital stay, intensive care units admission, ventilation, and mortality rate) (p-value > 0.05), even after adjusting the statistical model for the confounders. In hospital settings, Vit D levels are not associated with the severity or outcomes of COVID-19 disease. Further, well-designed studies are required to determine whether Vit D status provides protective effects against worse COVID-19 outcomes.

Graphene has piqued the interest of many researchers due to its superior mechanical, thermal, and physiochemical properties. Graphene nanoplatelets with covalently functionalized surfaces (CF-GNPs) were employed in turbulent-heated pipes to undertake thermal and economic studies. CF-GNPs and distilled water were used to make the current nanofluids at various mass percentages, such as 0.025, 0.05, 0.075%, and 0.1 wt.%. In the range of 6,401 Re 11,907, the thermal system was heated up to 11,205 W/m2 under fully developed turbulent flow conditions. Field emission scanning electron microscopy (FE-SEM), zeta potential, nanoparticle sizer, and field emission transmission electron microscopy (FE-TEM) were used to examine the morphological features and characterise the particles. In addition, the current thermal system’s economic performance was assessed to estimate its price-to-operate ratio. There was a 16.10% reduction in heat exchanger size for 0.025 weight percent, 0.05 weight percent, 0.075 weight percent, and 0.1 weight percent. In addition, the power needed for the base fluid was 422 W, which was then lowered to 354 W, 326 W, 315 W, and 298 W for 0.025 wt.%, 0.05 wt.%, 0.075 wt.%, and 0.1 wt.%, respectively.