In the recent JAVELIN Bladder 100 phase 3 trial, avelumab plus best supportive care significantly prolonged overall survival relative to best supportive care alone as first-line maintenance therapy following first-line platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). Discovering biomarkers using genomic profiling to understand potential patient heterogeneity is essential to help improve patient care with precision medicine. For the JAVELIN Bladder 100 trial, it is unclear which variable selection methods can most reliably identify biomarkers to inform patient care because the dataset is characterized by high collinearity and low signal. The aim of this paper was to evaluate available selection methods and their ability to discover prognostic and predictive biomarkers in patients with aUC receiving first-line maintenance therapy. A simulation study evaluated the performance of popular variable selection approaches for high-dimensional data, including penalized regression models, random survival forests, and Bayesian variable selection methods. For Bayesian variable selection methods, a modified Bayesian Information Criterion (BIC) thresholding rule was proposed in addition to the traditional BIC thresholding rule. These methods were applied to the JAVELIN Bladder 100 dataset to investigate potential biomarkers associated with survival benefit. Results from the simulations demonstrated the strengths and limitations of the different methods. The variable selection methods demonstrated low false discovery rates under different conditions. However, their performance declined in the presence of high collinearity. Using the JAVELIN Bladder 100 data, we identified some potentially significant biomarkers across multiple models. Several lasso-related methods were able to identify potentially biologically meaningful variables in the trial. Some variable selection methods (such as stochastic search variable selection and random survival forest) may not be well suited to this type of data due to the presence of extreme collinearity and low signal. Future research should explore novel variable selection methods that may be more suitable for identifying prognostic and predictive biomarkers in this population.Trial registration: ClinicalTrials.gov Identifier: NCT02603432.

Kawasaki Disease (KD) is the most common acquired pediatric heart disease in the developed world. Rapid infusion of high-dose intravenous immunoglobulin is the standard therapy. Different manufacturing processes of IVIG may influence their efficacy. This study aims to conduct a head to head comparison of two IVIGs, TBSF and Privigen, from a nationwide perspective. The main data source was the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 3368 KD cases involving children under 2 years of age were enrolled from January 2015 to November 2020. The primary endpoint was IVIG resistance, which we defined as the total amount exceeding 26 g in one admission. The secondary endpoints encompassed two distinct criteria: coronary involvement, which was defined as the prolonged use of aspirin or anti-coagulation agents between 180 and 360 days after the index date, and recurrence, which was defined as readmission for IVIG therapy occurring more than 30 days after previous KD index day and continuing until the end of the follow-up period. Privigen demonstrated a lower IVIG resistance rate at 9.4% in comparison to TBSF, which exhibited a rate of 9.7% (odds ratio 0.72, 95% CI 0.52–0.99). Privigen had a lower odds of coronary involvement (odds ratio 0.38, 95% CI 0.18–0.82). There is no difference in recurrence rate (odds ratio 0.60, 95% CI 0.22–1.68). Privigen might have a lower rate of IVIG resistance and reduced coronary artery involvement. The discrepancy may be due to the concentration, the stabilizers, or the source of plasma. Further investigation is needed to compare the effectiveness of different IVIGs in the large randomized controlled clinical trial.

To compare fecal level of short-chain fatty acid (SCFA) and some serum inflammatory markers between the low-carbohydrate (LCD) and the habitual (HD) diet, subjects were enrolled from our previous study on the effect of LCD vs. HD on gut microbiota in obese women following an energy-restricted diet. Serum interleukin-6 (IL-6) significantly increased in the HD group (p < 0.001). Adjusted for the baseline parameters, fecal level of butyric, propionic, and acetic acid were significantly different between the LCD and HD groups (p < 0.001, p = 0.02, and p < 0.001, respectively). Increase in serum insulin level correlated with decrease in fecal propionic acid by 5.3-folds (95% CI =  − 2.7,  − 0.15, p = 0.04). Increase in serum high sensitive C-reactive protein (hs-CRP) correlated with decrease in the percentage of fecal butyric acid by 25% (p = 0.04). Serum fasting blood sugar (FBS) and insulin showed a significant effect on fecal acetic acid (p = 0.009 and p = 0.01, respectively). Elevated serum FBS and insulin correlated with increase in fecal acetic acid by 2.8 and 8.9-folds (95%CI = 0.34, 1.9 and 1.2, 9.2), respectively. The LCD increased fecal SCFAs and a significant correlation was seen between serum IL-6 and fecal propionic acid level. More studies are needed to reach a concise correlation.Trial registration number: The trial was registered in Iranian ClinicalTrials.gov IRCT20200929048876N3.

Systemic lupus erythematosus (SLE) in males is rare and poorly understood. Thus, still little is known about sex differences in SLE. We set out to identify sex differences regarding clinical manifestations as well as renal and cardiovascular outcomes of SLE. We analyzed patient data from the Swiss SLE Cohort Study. Cumulative clinical manifestations according to the updated American College of Rheumatology criteria were recorded at inclusion. Cardiovascular events were recorded within Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-SDI). Renal failure was defined as eGFR < 15 ml/min/1.73 m2, initiation of renal replacement therapy or doubling of serum creatinine which were all assessed yearly or documented as end stage renal disease in SLICC-SDI. Risk differences were calculated using logistic regression and cox regression models. We analyzed 93 men and 529 women with a median follow up time of 2 years. Males were significantly older at diagnosis (44.4 versus 33.1 years, p < 0.001) and had less often arthritis (57% versus 74%, p = 0.001) and dermatological disorders (61% versus 76%, p < 0.01). In multivariate analysis female sex remained a significantly associated with arthritis and dermatological disorders. In multivariate analysis men had a significantly higher hazard ratio of 2.3 for renal failure (95% confidence interval (95%-CI) 1.1–5.2, p < 0.04). Total SLICC-SDI Score was comparable. Men had significantly more coronary artery disease (CAD) (17% versus 4%, p < 0.001) and myocardial infarction (10% versus 2%, p < 0.01). In multivariate analysis, male sex remained a significant risk factor for CAD (odds ratio (OR) 5.6, 95%-CI 2.3–13.7, p < 0.001) and myocardial infarction (OR 8.3, 95%-CI 2.1–32.6, p = 0.002). This first sex study in a western European population demonstrates significant sex differences in SLE. Male sex is a risk factor for cardiovascular events and renal failure in SLE. Potential etiological pathomechanisms such as hormonal or X-chromosomal factors remain to be further investigated.

This paper reports a realistic analysis of a region using Grounded Theory (GT) to provide a sustainable model for family farming systems based on the intercropping system in rural communities of Iran. Furthermore, the fuzzy analytic hierarchy process (FAHP) was applied to assign weights to the criteria and sub-criteria of intercropping and monocropping systems. According to the model, the main phenomenon was “sustainability in the family farming system based on intercropping”. In this model, the causal factors were found to include behavioral and attitudinal motivators. Micro- and macro-factors were identified as the interfering factors in family farming systems based on intercropping. Social factors, economic components, and environmental potentials were the contextual factors of this system. Finally, the consequences included the conceptual development and evolution of sustainability, socioeconomic transformation, and ecological-environmental transformation. The results of FAHP showed that the environmental criterion was ranked the first among all criteria underpinning the sustainability of the intercropping system.

Growing prevalence of obesity among youth would have adverse consequences and increased risk of developing chronic diseases at older ages. This study explored the prevalence of obesity and its association with relevant risk factors in the Rafsanjan youth cohort population. This cross-sectional study was done on 3006 individuals from the 15–35-year-old population included in the Rafsanjan youth cohort study. The data were extracted from the youth cohort databases, which had been collected through in-person interview and standard questionnaires. Definition of general obesity was considered as body mass index ≤ 30 and that of central obesity as waist to hip ratio (WHR) ≥ 0.9 for men and ≥ 0.85 for women. Multivariate stepwise proportional odds model and multivariable stepwise logistic regression models were done to explore the factors associated with general obesity and central obesity. The mean age was 25.78 ± 6.06 years with 56% (n = 1683) female. The prevalence of general obesity was 15.80% (95% CI 14.50–17.11) and central obesity was 28.41% (95% CI 26.80–30.02). The risk of general obesity increased with increasing age (OR = 1.053, P < 0.0001), being married (OR = 1.658, P < 0.0001), history of diabetes (OR = 1.609, P = 0.0185), history of hypertension (OR = 1.609, P < 0.0001), elevated triglyceride (OR = 1.007, P < 0.0001) and LDL (OR = 1.015, P < 0.0001), while decreasing with being employed (OR = 0.748, P = 0.0002) and elevated HDL (OR = 0.975, P < 0.0001). Prevalence of obesity was high in study population. Marital status, increasing age, and history of chronic diseases were associated with obesity. Preventing programs should be developed against obesity and for promoting healthy habits in young adult especially during education at schools.