Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

ABSTRACT Background The present study aimed to evaluate the effects of concomitant proton pump inhibitor (PPI) use on immune checkpoint inhibitor (ICI) efficacy among advanced cancer patients. Methods and Materials A systematic literature search of electronic database was performed to identify all potential reports. Then, meta-analyses were conducted to obtain pooled HRs with 95% CIs, which reveal the influence of PPI use on PFS and OS in patients receiving ICI treatment. Results A total of 7 studies with 3,647 advanced cancer patients fulfilled the inclusion criteria. The impact of PPI use was then evaluated on 3,340 patients for PFS and 3,647 patients for OS. Concomitant PPI use has a detrimental effect on the efficacy of ICIs that PPI use increased the risk of progression by 28% (HR = 1.28, 95% CI 1.17–1.40; I2 = 31.3%, Q test P = .21) when compared to those not receiving PPIs. Similarly, the meta-analysis showed that PPI use was also associated with shorter OS of advanced cancer patients receiving ICIs that PPI use increased risk of death by 39% (HR = 1.39, 95% CI 1.26–1.54; I2 = 36.5%, Q test P = .16). Sensitivity analysis showed that the pooled HRs were constant after excluding one study at a time, and no significant publication biases were detected. Conclusion The meta-analysis suggested that concomitant PPI use is significantly associated with low clinical benefit in ICI treatment, revealing a significantly reduced PFS and OS in advanced cancer patients receiving ICIs who are also exposed to PPI.
Associations of Serum Uric Acid with Clustering of Cardiovascular Risk Factors and a 10-Year Atherosclerotic Cardiovascular Disease Risk Score in Jiangsu Adults, China

Purpose The relationship between serum uric acid (SUA) and Chinese characteristic 10-year atherosclerotic cardiovascular disease (ASCVD) risk score has not been well evaluated in Chinese populations. Aims of this cross-sectional study were to describe the correlation between SUA level and clustering of prevalent cardiovascular risk factors (CRFs) including overweight, central obesity, hypertension, diabetes and dyslipidemia, as well as the Chinese 10-year ASCVD risk score in adults from Jiangsu Province located in Eastern China. Patients and Methods A total of 7700 adults from 12 cities in Jiangsu Province were selected through multi-stage stratified cluster random sampling method in 2015. Face-to-face interviews, physical examinations and laboratory examinations were carried out to collect the information of the participants. Multivariate logistic analysis was used to analyze the relationship between SUA quartiles and various CVD risk factors. The nonlinear analysis was conducted to evaluate the relationship between SUA levels and the China-PAR 10-year ASCVD risk scores. Results The prevalence of hyperuricemia was 13.3% in all of the participants. By adjusting potential confounders, significant correlations were found between the SUA level and the overweight, central obesity, hypertension and dyslipidemia in both males and females. The clustering of CRFs was different across SUA quantiles (χ2=607.685, P<0.001). After Gamma trend test (P < 0.001) and ordered logistic regression analysis, it was found out that with the increase of SUA quantiles, prevalent CRFs gradually gathered in both males and females. Furthermore, sex-specific difference was identified between SUA and 10-year ASCVD risk scores. Conclusion The accumulation of CRFs increased with elevated SUA levels, whereas it was different between genders in the relationship between SUA and 10-year ASCVD risk scores. Tailored strategies should be taken when it came to males and females in managing SUA.
Health-Related Quality of Life and Health Utilities of Mild, Moderate, and Severe Asthma: Evidence from the Medical Expenditure Panel Survey

Background Little information is known about the health-related quality of life (HRQOL) and the patient’s preference values by the severity of asthma. We evaluated the HRQOL and health utility impairment associated with asthma severity using the SF-12 and SF-6D. Methods We conducted a cross-sectional analysis of 2010–2016 Medical Expenditure Panel Survey database of asthma patients aged ≥18 years and categorized them into mild, moderate, and severe asthma. Study outcomes included the SF-12 physical component summary (PCS) and mental component summary (MCS) for measuring HRQOL and SF-6D for health utility. Survey regression models were used to estimate HRQOL and utilities for mild, moderate, and severe asthma. Results Of 10,222 patients with asthma, 75.4%, 23.9%, and 0.8% had mild, moderate and severe asthma. We observed that the greater the severity, the lower the SF-6D scores: 0.731 in mild, 0.723 in moderate, and 0.659 in severe asthma (P < 0.001). Patients with severe asthma had a significantly lower PCS compared to those with mild asthma (−5.3; P < 0.001) but there was no significant difference in MCS (−1.9; P = 0.309) controlling for socioeconomic and clinical variables. Asthma severity, women, older age, and having a lower level education and public insurance were significantly associated with lower PCS (P < 0.01). Conclusion Asthma patients had worse physical HRQOL than mental health, especially patients with severe asthma. These data suggest that the management of physical health of female, older aged, and low education patients with asthma should be focused on improving HRQOL.
Modeling the effect of reduced traffic due to COVID-19 measures on air quality using a chemical transport model: impacts on the Po Valley and the Swiss Plateau regions

The spread of COVID-19 has posed serious challenges for the global communities. To reduce the circulation of the infection, governmental bodies have imposed different lockdown measures at various levels of complexity and duration. As a result, a substantial reduction in mobility might have important, yet unknown, implications for air quality. In this study, we applied the Comprehensive Air quality Model with eXtensions (CAMx) to investigate potential changes in air quality and its chemical composition over northern Italy and Switzerland during periods when lockdown measures were enforced. Our results indicated that lockdown measures reduced nitrogen dioxide (NO2) air concentrations by up to 46% and 25% in the Po Valley and Swiss Plateau regions, respectively, whereas fine particulate matter (PM2.5) air concentrations were reduced only by up to 10% and 6%. This highlights the importance of other emission categories other than traffic for the total PM2.5 levels. The analysis of the PM2.5 components indicated that elemental carbon (EC) and particulate nitrate (NO3−) were the species most affected by the lockdown measures, whereas a mild increase in the secondary organic aerosol (SOA) concentrations occurred in the Po Valley, and specifically over the metropolitan area of Milan. Our results indicated that an increase in the oxidation capacity of the atmosphere, i.e. in the ˙OH and ˙NO3 radicals, was mainly responsible for the mild increase in SOA concentrations.
Germline soma communication mediated by gap junction proteins regulates epithelial morphogenesis

Gap junction (GJ) proteins, the primary constituents of GJ channels, are conserved determinants of patterning. Canonically, a GJ channel, made up of two hemi-channels contributed by the neighboring cells, facilitates transport of metabolites/ions. Here we demonstrate the involvement of GJ proteins during cuboidal to squamous epithelial transition displayed by the anterior follicle cells (AFCs) from Drosophila ovaries. Somatically derived AFCs stretch and flatten when the adjacent germline cells start increasing in size. GJ proteins, Innexin2 (Inx2) and Innexin4 (Inx4), functioning in the AFCs and germline respectively, promote the shape transformation by modulating calcium levels in the AFCs. Our observations suggest that alterations in calcium flux potentiate STAT activity to influence actomyosin-based cytoskeleton, possibly resulting in disassembly of adherens junctions. Our data have uncovered sequential molecular events underlying the cuboidal to squamous shape transition and offer unique insight into how GJ proteins expressed in the neighboring cells contribute to morphogenetic processes.
Overweight, obesity, and thinness among a nationally representative sample of Norwegian adolescents and changes from childhood: Associations with sex, region, and population density

Objective To estimate the prevalence of overweight, obesity, and thinness among Norwegian 13-year-olds and the changes from childhood (age 8 years) to adolescence (age 13 years); and to explore associations with sex, region, and population density from childhood to adolescence. Design We used longitudinal, anthropometric data collected by school health nurses conducted in Norway. Weight status was classified according to the International Obesity Task Force cut-offs for overweight, obesity, and thinness, and according to mean body mass index (kg/m2). Participants The Norwegian Youth Growth Study, consisting of a nationally representative sample of Norwegian 13-year-olds (n = 1852; 50.7% girls), which is a part of The Norwegian Growth Cohort. Results Among 13-year-old Norwegians, the prevalence of overweight (including obesity), obesity, and thinness was 15.8%, 2.5%, and 7.3%, respectively. There was little evidence that these had changed from 8 to 13 years. From 8 to 13 years, the odds of obesity was highest in the Northern region of Norway compared to the South-East (odds ratio (OR): 3.78 (95% confidence interval (CI): 1.13, 12.65; p = 0.036) and in rural areas (OR: 4.76 (95% CI: 1.52, 14.90; p = 0.027). Over the same age period, girls had a trend towards a higher odds of thinness compared to boys (OR: 1.65 (95% CI: 0.98, 2.78; p = 0.057). Conclusions In Norway, the prevalence of overweight, obesity, and thinness among 13-year-olds seem to be established by age 8 years. The prevalence of obesity was higher in the North and in rural areas. The results indicate the continued need for early prevention and treatment, and targeted interventions to certain areas.
The road to conception for women with multiple sclerosis

Objective The objective of this prospective “real world” study is to gain insight into the different “roads to conception” that women with MS take as part of the prospective Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS). Methods Participants are women with MS who are planning a pregnancy. Data cut-off for analyses was April 30, 2020. Results We believe this is the first prospective National study of women with MS planning pregnancies. The data are for the first 44 women enrolled of whom 26 achieved pregnancy by cut-off date. Seven women used assisted reproductive technologies (ARTs); 6 stopped disease modifying therapy (DMT) against their neurologists’ recommendations; 6 had an interruption(s) in trying to conceive due to MS relapses, MRI-detected inflammation, or limited “windows of opportunity” between DMT courses. Conclusion The study illustrates the roads that women take to conception, even if they are on the same therapy and have similar clinical expression of MS. Advice given by treating neurologists on washout periods show discrepancies. This paper highlights the real problem that there is no definitive, international consensus on managing these women due to the lack of “real world” data and thus the goal of CANPREG-MS is to provide such real world data.
Alopecia Areata: An Autoimmune Disease of Multiple Players

Abstract Alopecia areata (AA) is an autoimmune disease of the hair follicles. It is characterized by a well-defined non-scarring alopecic patch or patches that may extend to the entire scalp or lead to total body hair loss. Due to its unpredictable clinical course, AA causes substantial psychological harm. Despite the high prevalence of this disease and extensive research, its exact pathomechanism is unclear, and current treatments have a high relapse rate that has deemed AA incurable. Over the past few decades, researchers have investigated multiple potential factors that may help alleviate its pathogenesis and provide effective treatment. Given its complex immunopathogenesis, AA is considered an autoimmune disease with multiple factors. This review gathers current evidence that emphasizes molecular mechanisms, possible causative etiologies, and targeted immunotherapies for AA. Understanding its underlying mechanisms may shed light on new strategies to effectively manage AA in the future.
Factors of surface thermal variation in high-mountain lakes of the Pyrenees

Thermal variables are crucial drivers of biological processes in lakes and ponds. In the current context of climate change, determining which factors better constrain their variation within lake districts become of paramount importance for understanding species distribution and their conservation. In this study, we describe the regional and short-term interannual variability in surface water temperature of high mountain lakes and ponds of the Pyrenees. And, we use mixed regression models to identify key environmental factors and to infer mean and maximum summer temperature, accumulated degree-days, diel temperature ranges and three-days’ oscillation. The study is based on 59 lake-temperature series measured from 2001 to 2014. We found that altitude was the primary explicative factor for accumulated degree-days and mean and maximum temperature. In contrast, lake area showed the most relevant effect on the diel temperature range and temperature oscillations, although diel temperature range was also found to decline with altitude. Furthermore, the morphology of the catchment significantly affected accumulated degree-days and maximum and mean water temperatures. The statistical models developed here were applied to upscale spatially the current thermic conditions across the whole set of lakes and ponds of the Pyrenees.
Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis

Introduction Newborn sepsis accounts for more than a third of neonatal deaths globally and one in five neonatal deaths in Ethiopia. The first-line treatment recommended by WHO is the combination of gentamicin with ampicillin or benzylpenicillin. Gram-negative bacteria (GNB) are increasingly resistant to previously effective antibiotics. Objectives Our goal was to estimate the prevalence of antibiotic-resistant gram-negative bacteremia and identify risk factors for antibiotic resistance, among newborns with GNB sepsis. Methods At a tertiary hospital in Ethiopia, we enrolled a cohort pregnant women and their newborns, between March and December 2017. Newborns who were followed up until 60 days of life for clinical signs of sepsis. Among the newborns with clinical signs of sepsis, blood samples were cultured; bacterial species were identified and tested for antibiotic susceptibility. We described the prevalence of antibiotic resistance, identified newborn, maternal, and environmental factors associated with multidrug resistance (MDR), and combined resistance to ampicillin and gentamicin (AmpGen), using multivariable regression. Results Of the 119 newborns with gram-negative bacteremia, 80 (67%) were born preterm and 82 (70%) had early-onset sepsis. The most prevalent gram-negative species were Klebsiella pneumoniae 94 (79%) followed by Escherichia coli 10 (8%). Ampicillin resistance was found in 113 cases (95%), cefotaxime 104 (87%), gentamicin 101 (85%), AmpGen 101 (85%), piperacillin-tazobactam 47 (39%), amikacin 10 (8.4%), and Imipenem 1 (0.8%). Prevalence of MDR was 88% (n = 105). Low birthweight and late-onset sepsis (LOS) were associated with higher risks of AmpGen-resistant infections. All-cause mortality was higher among newborns treated with ineffective antibiotics. Conclusion There was significant resistance to current first-line antibiotics and cephalosporins. Additional data are needed from primary care and community settings. Amikacin and piperacillin-tazobactam had lower rates of resistance; however, context-specific assessments of their potential adverse effects, their local availability, and cost-effectiveness would be necessary before selecting a new first-line regimen to help guide clinical decision-making.
Breast Self-Examination Practice and Associated Factors Among Women Attending Family Planning Service in Modjo Public Health Facilities Southwest Ethiopia

Purpose Breast cancer is the leading cause of cancer death worldwide and the second common cancer overall. Breast self-examination is one of the cheapest methods used for the early detection of breast cancer in asymptomatic women. However, the practice of breast self-examination remains low in Ethiopia. Therefore, this study aimed to assess breast self-examination practice and associated factors among women attending family planning services in Modjo public health facilities in southwest Ethiopia. Patient and Methods Facility-based cross-sectional study was conducted in Modjo public health facilities from October 01, 2020, to October 30, 2020. Data were collected from 420 women by using an interviewer-administered structured questionnaire. Variables with a P-value ≤0.2 in the bivariate analysis were included in the multivariable logistic regression model. Results of regression analysis were shown as odds ratio (OR) and confidence intervals (95% CI). Results Overall 86 (20.5%) of the participants had ever performed breast self-examination. The odds of breast self-examination practice among women with tertiary level of education were 2.14 [AOR: 2.14; 95% CI: (1.45, 6.74)] times higher compared to those with secondary education. Women who knew breast self-examination were 4.32 [AOR: 4.32; 95% CI: (1.81, 10.81)] times higher odds of breast self-examination practice compared to their counterparts. The odds of breast self-examination practice among women who had a positive attitude were 2.7 [AOR: 2.7; 95% CI: (1.03, 6.91)] times higher compared to women with a negative attitude towards breast self-examination. Conclusion Breast self-examination practice was low within the study area. Tertiary level of education, having Knowledge on breast self-examination and a positive attitude towards breast self-examination were found to have a significant association with breast self-examination practice. Breast self-examination should be promoted by improving awareness and providing special health education for women that had low educational level.
Overemphasis of USMLE and Its Potential Impact on Diversity in Otolaryngology

Objective Applicant demographics during the 2019-2020 residency cycle were evaluated to determine if strict utilization of United States Medical Licensing Examination (USMLE) scores in applicant selection could lead to a restriction in diversity. Study Design Cross-sectional study. Setting Otolaryngology residency applicants to a single institution. Methods A total of 381 applicants were analyzed by age, gender, applicant type, race/ethnicity, USMLE scores, permanent zip code, and graduating medical school. Results Among applicants, 37% were women; 9% were ≥30 years of age; 12% were underrepresented minorities (URMs); 71% to 81% had above-average socioeconomic surrogate markers; 22% were from a top 25 US News & World Report–ranked institution; and 81% were from an institution with an otolaryngology residency program. There was no increase in applicants who identified as URM from the 2015-2020 cycles. Multivariable regression analysis showed that applicants who were international medical graduates, URMs, and ≥30 years of age had lower Step 1 and Step 2 scores (P < .05). Applicants who identified as women had a lower Step 1 score, and those from top 25 National Institutes of Health–funded institutions had a higher Step 1 score; however, there was no difference when Step 2 scores were compared (P > .05). Conclusion Our data suggest that in the pre–USMLE Step 1 pass/fail setting, strict adherence to USMLE scores may lead to disproportionally low recruitment of applicants who are women, ≥30 years of age, URMs, and from institutions without an otolaryngology residency program. We must implement measures against overemphasizing the absolute values of USMLE scores for a true holistic review of applicants, specifically to prevent an overemphasis on the USMLE Step 2 score.
ESC 2019 guidelines on chronic coronary syndromes: could calcium scoring improve detection of coronary artery disease in patients with low risk score. Findings from a retrospective cohort of patients in a district general hospital

Background The European Society of Cardiology (ESC) published an updated stable chest pain guideline in 2019, recommending the use of an updated pre-test probability (PTP) risk score (RS) to assess the likelihood of coronary artery disease (CAD). We sought to compare the 2019 and 2013 PTPRS in a contemporary cohort of patients. Methods 612 patients who were investigated with computed tomography coronary angiography (CTCA) for stable chest pain were included in a retrospective analysis. Results There were 255 patients with 2019 PTPRS 15–50% with a 9% yield of severe CAD on CTCA, compared with 402 patients and a 4% yield using the 2013 PTPRS (p = 0.01). 355 patients had a 2019 PTPRS of <15%, with 3% found to have severe CAD, compared with 67 patients and none with severe CAD using the 2013 PTPRS (p = 0.14). 336 of patients with 2019 PTPRS of <15% had a calcium score as part of the CTCA. 223 of these had a zero calcium score and only one had severe CAD. In comparison, 113 patients had a positive calcium score, and 10 (9%) had severe CAD (p < 0.001). Discussion The ESC 2019 PTPRS classifies more patients as at lower risk of CAD and hence reduces the risk overestimation associated with the 2013 PTPRS. However, in patients with a 2019 PTPRS of <15%, who would not be investigated, the use of the calcium score detected the majority of patients with significant CAD, who may benefit from secondary prevention and an associated mortality benefit as per the SCOT-Heart trial.
In-hospital mortality among immunosuppressed patients with COVID-19: Analysis from a national cohort in Spain

Background Whether immunosuppressed (IS) patients have a worse prognosis of COVID-19 compared to non-IS patients is not known. The aim of this study was to evaluate the clinical characteristics and outcome of IS patients hospitalized with COVID-19 compared to non-IS patients. Methods We designed a retrospective cohort study. We included all patients hospitalized with laboratory-confirmed COVID-19 from the SEMI-COVID-19 Registry, a large multicentre national cohort in Spain, from March 27th until June 19th, 2020. We used multivariable logistic regression to assess the adjusted odds ratios (aOR) of in-hospital death among IS compared to non-IS patients. Results Among 13 206 included patients, 2 111 (16.0%) were IS. A total of 166 (1.3%) patients had solid organ (SO) transplant, 1081 (8.2%) had SO neoplasia, 332 (2.5%) had hematologic neoplasia, and 570 (4.3%), 183 (1.4%) and 394 (3.0%) were receiving systemic steroids, biological treatments, and immunosuppressors, respectively. Compared to non-IS patients, the aOR (95% CI) for in-hospital death was 1.60 (1.43–1.79) for all IS patients, 1.39 (1.18–1.63) for patients with SO cancer, 2.31 (1.76–3.03) for patients with haematological cancer and 3.12 (2.23–4.36) for patients with SO transplant. The aOR (95% CI) for death for patients who were receiving systemic steroids, biological treatments and immunosuppressors compared to non-IS patients were 2.16 (1.80–2.61), 1.97 (1.33–2.91) and 2.06 (1.64–2.60), respectively. IS patients had a higher odds than non-IS patients of in-hospital acute respiratory distress syndrome, heart failure, myocarditis, thromboembolic disease and multiorgan failure. Conclusions IS patients hospitalized with COVID-19 have a higher odds of in-hospital complications and death compared to non-IS patients.