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Comparative Efficacy of Janus Kinase Inhibitors Indicated for Severe Alopecia Areata: A Bayesian Network Meta-Analysis and Matching-Adjusted Indirect Comparison.

Systemic Janus kinase inhibitors (JAKIs) have markedly advanced the therapeutic landscape for alopecia areata (AA). Although baricitinib and ritlecitinib are approved in the United States (US) and Europe, and deuruxolitinib in the US for severe AA, the lack of head-to-head randomized controlled trials (RCTs) limits evidence-based prescribing decisions. Moreover, prior meta-analyses excluded data on certain oral JAKIs or incorporated findings from agents and dosing regimens that were abandoned, investigational, clinically ineffective, or associated with unacceptable safety profiles. To compare the efficacy of oral JAKIs, limited to FDA, EMA, or MHRA approved drugs and doses-baricitinib (2 and 4 mg QD), ritlecitinib (50 mg QD), and deuruxolitinib (8 mg BID)-for severe AA, using advanced indirect comparison methodologies. A systematic review was performed following PRISMA 2020 guidelines (CRD420251116775). Bayesian network meta-analysis (NMA) synthesized data from RCTs reporting Week 24 outcomes on Severity of Alopecia Tool (SALT) ≤ 10 and SALT ≤ 20 thresholds. Multilevel network meta-regression (ML-NMR) evaluated heterogeneity and adjusted for baseline imbalances. Additionally, unanchored matching-adjusted indirect comparisons (MAIC) were conducted using individual patient-level data from THRIVE trials. Surface under the cumulative ranking (SUCRA) values were calculated to rank treatments. Seven RCTs (n = 4560 participants) were included. Deuruxolitinib 8 mg significantly outperformed baricitinib 2 and 4 mg on both SALT endpoints. Differences with ritlecitinib 50 mg were directionally favorable for deuruxolitinib but not statistically significant in NMA and ML-NMR models. MAICs confirmed superior odds for deuruxolitinib versus baricitinib 2 mg (OR = 71.55) and ritlecitinib (OR = 18.27) for SALT ≤ 20. SUCRA rankings also consistently favored deuruxolitinib. Among approved oral JAKIs, deuruxolitinib 8 mg shows the highest short-term efficacy for severe AA. These findings provide preliminary evidence to guide treatment decisions but should be interpreted as exploratory pending confirmation.

Humans

Clustering patterns of behavioral and metabolic risk factors for noncommunicable diseases in Iran: findings from a national STEPS survey.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading cause of mortality in Iran, driven by behavioral and metabolic risk factors that frequently co-occur. OBJECTIVE: To identify patterns of co-occurring behavioral and metabolic NCD risk factors among Iranian adults and characterize their demographic and socioeconomic correlates. METHODS: This cross-sectional study analyzed data from 16,618 adults aged ≥25 years who participated in Iran's 2021 nationally representative STEPS survey. Thirteen behavioral and metabolic variables, including physical activity, nutrition score, smoking frequency, alcohol intake, salt intake, body mass index, blood pressure, fasting plasma glucose, and lipid markers, were entered into a K-means clustering analysis. Clusters were characterized by their risk profiles and demographic/socioeconomic attributes. Multinomial logistic regression examined associations between cluster membership and sociodemographic factors. RESULTS: Five distinct behavioral-metabolic clusters emerged. The smokers-drinkers (SD) cluster (3.1%) comprised mostly older, less-educated men with high smoking and alcohol use. The healthy-low-risk (HLR) cluster (40.3%) showed favorable profiles and included younger, more educated individuals. The physically active (PA) cluster (6.6%) was characterized mainly by younger men with markedly high physical activity levels. The dyslipidemic (DLP) cluster (26.0%) exhibited high dyslipidemia and overweight prevalence, while the hypertensive-diabetic (HTD) cluster (24.0%) had the highest obesity, hypertension, and diabetes rates, common among older urban adults. CONCLUSION: Behavioral and metabolic NCD risk factors in Iran formed five distinct co-occurrence patterns. Nearly half of adults belonged to metabolically high-risk clusters, highlighting the need for targeted prevention strategies that combine lifestyle interventions with screening and management of obesity, hypertension, diabetes, and dyslipidemia.

Humans

Deep learning-based annotation of plant abiotic stress resistance genes for crops.

The declining costs of DNA sequencing have expanded genomic data, crucial for understanding plant abiotic stress responses and crop improvement. However, accurate gene annotation remains challenging. To address this limitation, we propose the PASRGA, a deep learning approach that leverages transfer learning and contrastive learning to annotate genes related to drought, salt, cold, and UV resistance. PASRGA achieves high F1-scores, area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), and Matthews correlation coefficient (MCC) in annotating stress resistance genes, significantly outperforming the general protein annotation model CLEAN, the plant phosphatase gene annotation model PF-NET, the top-ranked model in the CAFA5 challenge NetGO 4.0, and four traditional machine learning methods. Its effectiveness was further validated with a salt stress treatment experiment in Eutrema salsugineum. To facilitate crop breeding practices, we utilized PASRGA to annotate the genomes of 17 major crops. To improve accessibility and utility, we incorporated both manually curated and PASRGA-predicted gene data, together with the PASRGA tool, into the PlantASRG database (https://bioinfor.nefu.edu.cn/PlantASRG/). This comprehensive resource aims to support crop breeding initiatives and ensure food security.

Crops, Agricultural

Inflammatory responses of the rabbit eye to prostaglandins.

A modified Draize scoring procedure has been used to quantify the vascular effects of prostaglandins on the rabbit eye. Topical application of 100 microgram of PGE1 caused conjunctival redness (erythema due to vasodilatation), swelling (oedema due to increased capillary permeability), discharge, lids closure (decrease in palpebral aperture) and occasionally miosis, though no corneal or iridial damage was detected up to three hours. PGE1 and GE2 produced practically identical dose-related increases in scores for most of the inflammation parameters, though oedema responses were consistently lower after PGE2. The neutral, triethanolamine salt of PGE1 was as inflammatory as PG1 itself. PGF2alpha was 10-50 times less inflammatory than PGE1. It produced relatively greater erythema responses than oedema responses, when compared to PGE1. The novel prostaglandins, 19-OH PGE1 and 19-OH PGE2, recently identified as major prostaglandin constituents of human semen, were respectively 71 and 78 times inflammatory than PGE1. The 19-OH PGEs produced much greater erythema responses, relative to oedema, lids closure or discharge responses.

Animals

Admission Gut and Plasma-Derived Signatures Associated With Severity and 90-day Outcome in Hepatitis A-Related and Drug-Induced Acute Liver Failure.

Acute liver failure (ALF) due to hepatitis A (ALF-A) has high mortality, but admission-day markers associated with disease severity and outcome are unknown. We aimed to define gut microbiome and plasma multi-omics signatures associated with severity and 90-day outcomes in ALF-A, compared to drug-induced ALF (ALF-D) as non-viral ALF group. ALF patients (aged 26&#x2009;&#xb1;&#x2009;9&#x2009;years; 50.7% male, 49.3% female) with IgM HAV positive (ALF-A, n&#x2009;=&#x2009;33), ALF-D (n&#x2009;=&#x2009;38) were recruited along with acute viral hepatitis (AVH-A, n&#x2009;=&#x2009;27) and healthy subjects (HC, n&#x2009;=&#x2009;20). Stool bacteria profiling was done at D0; plasma cytokines, metabolites and barrier markers were analysed at D0, 3, 5, 7. Correlations with clinical severity parameters were assessed. Associations with 90-day mortality were assessed using severity-adjusted association analyses. ALF-A patients were more severe at the time of admission than ALF-D. In ALF-A, 90-day mortality was 33% versus 18.4% with increased severity scores like KCH 21% versus 10.5%, SOFA score 7.97&#x2009;&#xb1;&#x2009;2.89 versus 5.87&#x2009;&#xb1;&#x2009;2.32, SIRS 60.6% versus 18.4%, mechanical ventilation 39% versus 21%. At D0, ALF-A was enriched for lactate/ammonia/bile salt hydrolase/histamine-producing pathobionts like Enterococcus, Ruminococcus gnavus, Flavonifractor, Thomasclavelia correlating positively with severity (|r|&#x2009;>&#x2009;0.4, p&#x2009;<&#x2009;0.05) showing higher baseline abundance in ALF-A non-survivors (NS). At D0 in ALF-A, histamine accumulation, reduced tryptophan, butyrate metabolism inversely correlated with severity and worsened in ALF-A_NS by D7. Pro-inflammatory cytokines, IFABP2 were elevated at Day 0 in ALF-A, correlated positively with severity, and remained increased through Day 7 in ALF-A_NS. In contrast, ALF-D_NS retained commensals, showed increased fatty acid, bile acid biosynthesis with low levels of pro-inflammatory cytokines. In ALF-A, gut and plasma integrated multi-omics features were associated with disease severity, 90-day outcomes and identified candidate biomarkers for future validation.

Humans

Modified hemolytic plaque technique for the detection of bluetongue virus antibody-forming cells.

A hemolytic plaque assay was developed for the detection of antibody-forming cells to bluetongue virus (BTV). Sheep erythrocytes (SRBC), onto which BTV had been absorbed, served as the indicator of lysis due to the presence of BTV antibody-forming cells. The ratio of BTV to SRBC was found to be critical for optimum hemolytic plaque formation. For routine use, 50 mul of 12% BTV SRBC, 0.1 ml of a spleen cell suspension, and 0.5 ml of 0.5% agarose in a balanced salt solution were mixed and plated on a microscope slide precoated with 0.1% aqueous agarose. Slides were incubated for 1 h at 37 C in a humidified incubator and subsequently flooded with 0.4 ml of a 1:15 dilution of complement. Incubation was continued for a further 2 h before the hemolytic plaques were scored. It was not possible to establish BTV serotype specificity by this technique.

Animals

Quality of life and gender identity in females with congenital adrenal hyperplasia after genital restoration surgery: A single-center experience.

BACKGROUND: Legislation restricting surgical interventions in children with differences of sex development (DSD) has intensified debate about female genital restoration surgery (FGRS) in patients with congenital adrenal hyperplasia (CAH). Long-term patient-reported outcomes are needed regarding the optimal timing of surgery. OBJECTIVE: We aimed to assess health-related quality of life (HRQoL), gender identity, and family satisfaction regarding surgical timing and outcome in females with CAH following genital restoration surgery. STUDY DESIGN: Cross-sectional survey of CAH patients who underwent surgery between January 2007 to December 2016 at our institution. Validated instruments (KINDL questionnaire for HRQoL, Utrecht Gender Dysphoria Scale, UGDS) and structured telephone interviews were employed. RESULTS: Data on HRQoL was available for 25 patients (self- and/or parent-reported) out of 56 eligible patients (45% response rate). Median age at first surgery was 6 months (range: 3-137 months). Patients' age at time of participation ranged from 2 to 28 years. All had 21-hydroxylase deficiency (92% salt-wasting form) with Prader grades ranging from II-V. Wound dehiscence requiring secondary suturing occurred in 15% of patients with primary surgery at our center, while only one (4%) patient developed vaginal stenosis after early primary vaginoplasty. Two additional patients (8%) with prior outside surgery required vaginal revision after FGRS at age 12. HRQoL scores were comparable to healthy reference populations across most age groups. Children aged 3-6 and adolescents and young adults showed no significant difference from reference values, while children aged 7-13 showed a slight elevation. None of five patients &#x2265;14 years demonstrated gender dysphoria (all UGDS scores <40, threshold &#x2265;40). 14 patients and families were also interviewed by telephone. All preferred early surgical timing. No family expressed regret about the decision or preferred delayed surgery. DISCUSSION: This study provides validated intermediate-term patient- and parent-reported outcomes after FGRS in CAH. Key limitations include the small sample size, single-center design, and young age of most patients. Selection bias may exist, though participating families included those who underwent revision surgery. The absence of a non-operated comparison group reflects current clinical reality, as nearly all CAH patients with urogenital sinus underwent surgical correction. CONCLUSIONS: Females with CAH reported normal HRQoL and a comfortable female gender identity after early FGRS. The patients and their families expressed a preference for early surgery. However, there is need for longer-term follow-up to assess sexual function and reproductive outcomes as well comparison of outcomes with a non-operated group.

Humans

Treating dysmenorrhea with anti-inflammatory agents: a double-blind trial with naproxen sodium.

Thirty-two dysmenorrheic patients participated in a double-blind trial of naproxen sodium for three consecutive menstrual cycles. The women were divided into two groups: 15 women were given naproxen sodium (the sodium salt of d-2-(6-methoxy-2-naphthyl) propionic acid) and 17 women received placebo tablets. The women were prescribed two tablets (550 mg) at the first sign of menstrual pain and one tablet (275 mg) thereafter every six hours, as required. There were no significant differences between the two groups in physical characteristics, obstetric and gynecologic histories, including the character of dysmenorrhea and pretreatment pain intensity scores (p = 0.7). Following intake of the drug or placebo, the participants rated the relief provided by the medication with a six-point scoring system. When the scores for pain relief were tallied for the three treatment cycles, the naproxen sodium group averaged 13.7 +/- 0.65 standard error, while the placebo group averaged 8.8 +/- 0.95 standard error out of a possible maximum relief score of 18. The difference between the two groups was statistically significant at p = 0.0004. Few patients reported side effects.

Clinical Trials as Topic

The nitroblue tetrazolium test in acne vulgaris.

The nitroblue tetrazolium (N.B.T.) test has been studied in 19 patients with moderate or severe acne vulgaris and 18 patients with subclinical or no acne. There was a significant elevation of the N.B.T. score in those patients with moderate or severe acne as compared with the control group. This is probably a result of the inflammatory reaction in and around the involved sebaceous gland follicles.

Acne Vulgaris

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans

Cellular and humoral factors involvement in the enhanced NBT reduction by neutrophil leucocytes of newborn infants.

The histochemical NBT test was performed on blood samples from ten healthy newborn infants. High spontaneous NBT reduction has been confirmed for neutrophils and assessed for monocytes. The stimulation of both neutrophils and monocytes with Escherichia coli endotoxin induces a statistically significant increase of NBT positive cells. The reason for the false positive test results in neonates was investigated by incubating neutrophils from adult donors and for different time periods in either neonatal or adult plasma before the addition of NBT. NBT reduction by adult neutrophils was increased after incubation in neonatal plasma, and this increase was related to the concentration of the plasma used. Maximum NBT reduction was observed after 90 min of incubation, at which time the NBT scores of adult cells incubated in neonatal plasma were similar to the results of tests performed on whole neonatal blood. It is concluded that neonatal leucocytes demonstrate efficient spontaneous and stimulated phagocytosis, and that there are, in the plasma of neonates, humoral factors which stimulated phagocytosis by neutrophils and are thus responsible for the false positive NBT test results observed in these subjects.

Endotoxins

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p&#xa0;<&#xa0;0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p&#xa0;=&#xa0;0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans

The Effect of Colesevelam on the Microbiome in Postoperative Crohn's Disease.

BACKGROUND: While surgery plays a pivotal role in the management of ileal Crohn's disease, the risk of endoscopic recurrence following an ileocaecal resection can be greater than 65% within 12 months of surgery. More than 90% of patients with Crohn's disease have a concomitant diagnosis of bile acid diarrhea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in patients with Crohn's disease who have undergone a primary terminal ileal resection with concomitant bile acid diarrhea can alter the microbiome and prevent disease recurrence. METHODS: Patients with Crohn's disease who underwent a primary terminal ileal resection and had symptoms of diarrhea within 1-3 months of surgery underwent 75SeHCAT testing for bile acid diarrhea. If positive (75SeHCAT&#x2005;&#x2264;&#x2005;15%), patients were treated with colesevelam and stool samples were collected at 4 weeks, 8 weeks, and 6-12 months posttreatment. If negative (75SeHCAT&#x2005;>&#x2005;15%), treatment was not given and were reviewed in the clinic as per local guidelines. All patients underwent a 6-12 month postoperative colonoscopy where further stool samples and mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeert's score <i2 and disease recurrence &#x2265;i2. 16S ribosomal RNA gene analysis was undertaken for the collected fecal and mucosal samples to assess &#x3b1;/&#x3b2;-diversity and microbial composition. RESULTS: A total of 14 patients who completed the study, 10 of whom had a 75SeHCAT positive diagnosis of bile acid diarrhea and were started on treatment with colesevelam. Four patients did not require treatment as 3 were asymptomatic and 1 had a negative 75SeHCAT scan. Three of the fourteen patients had disease recurrence at their 6-12 month postoperative colonoscopy assessment, of which 1 patient was taking colesevelam and 2 patients were not taking colesevelam. A total of 44 fecal samples and 44 mucosal biopsies underwent 16S ribosomal RNA gene analysis to assess &#x3b1;/&#x3b2;-diversity and microbial composition. In the colesevelam treated patients there was no significant difference in &#x3b1;/&#x3b2;-diversity pre- and posttreatment. Pretreatment, the 3 most abundant bacterial classes in all patients were Bacteroidia, Clostridia, and Gammaproteobacteria. Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the 2 patients not given colesevelam, one showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. CONCLUSIONS: This small pilot study demonstrated that patients who were given colesevelam, were more likely to be in disease remission at their 6-12 months colonoscopy review compared with those not treated. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in postoperative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance as well as investigate whether this benefit may be present even in those patients with 75SeHCAT negative disease.

Humans