Tag: nevin manimala

Science. 2025 Sep 4;389(6764):1016-1023. doi: 10.1126/science.adp4629. Epub 2025 Sep 4.

ABSTRACT

The global burden of kidney disease displays marked sexual dimorphism. Lineage tracing and single-cell RNA-sequencing revealed that starting from puberty, estrogen signaling in female mice supports self-renewal and differentiation of renal progenitors to increase filtration capacity, reducing sensitivity to glomerular injury compared with that of males. This phenomenon accelerated as female kidneys adapted to the workload of pregnancy. Deletion of estrogen receptor α in renal progenitors disrupted this adaptation, leading to preeclampsia, fetal growth restriction, and increased maternal risk of hypertension and chronic kidney disease. Offspring from affected mothers had fewer nephrons, resulting in early-life hypertension and greater susceptibility to kidney disease. These results highlight the fundamental role of kidney fitness and renal progenitors for pregnancy and preeclampsia and as a determinant of sexual dimorphism in kidney disease.

PMID:40906846 | DOI:10.1126/science.adp4629

PLoS One. 2025 Sep 4;20(9):e0330998. doi: 10.1371/journal.pone.0330998. eCollection 2025.

ABSTRACT

BACKGROUND: The consumption of sorghum-based foods has been associated with reduced postprandial blood glucose levels and increased satiety in previous studies. Sorghum’s low glycemic index, high fiber content, and rich profile of bioactive compounds may contribute to improved health outcomes. Nutritional strategies incorporating sorghum could serve as a valuable tool for the prevention of diabetes, obesity, as well as other non-communicable diseases.

PURPOSE: To identify and evaluate the evidence on the effectiveness of the sorghum-based foods in modulating blood glucose levels and promoting satiety in adults.

METHODS AND EXPECTED OUTPUTS: This systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. We will include randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) published through February 2025 that assess the effects of sorghum-based food consumption. Qualitative studies, guidelines, and reviews will be excluded. Six electronic databases-MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and ScienceDirect-will be systematically searched. Additional sources will include ClinicalTrials.gov, The British Library, Google Scholar, International Diabetes Federation, and American Diabetes Association (ADA). No restrictions on language or publication date will be applied. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment according to the study design. A qualitative synthesis will be presented. Statistical heterogeneity will be assessed using the I² statistic. If appropriate, a meta-analysis will be conducted using a random-effects model.

EXPECTED OUTCOMES: To the best of our knowledge, this will be the first systematic review to specifically address the impact of sorghum-based food consumption on glycemic response and satiety. The findings are expected to provide robust evidence to inform future research and support nutritional strategies involving sorghum-based products for health promotion.

PROSPERO REGISTRATION ID: CRD42023431520.

PMID:40906791 | DOI:10.1371/journal.pone.0330998

PLoS One. 2025 Sep 4;20(9):e0329451. doi: 10.1371/journal.pone.0329451. eCollection 2025.

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic has highlighted the critical deficiency of infectious disease (ID) specialists, a subspecialty that remains underrepresented among Japanese medical students.

METHODS: This nationwide cross-sectional survey was administered between April and August 2024 via an online questionnaire distributed to medical students throughout Japan. The survey assessed awareness of and interest in ID specialization, categorizing students by academic year: lower (first- and second-year students), middle (third- and fourth-year students), and upper grades (fifth- and sixth-year students).

RESULTS: Of 502 respondents, data for 492 medical students were eligible, of whom 69.7% demonstrated awareness of ID specialists, with recognition rates increasing proportionally with academic progression. Regarding career aspirations, 9.8% of respondents expressed interest in pursuing ID specialization, with the highest proportion observed among upper-grade students (19.4%). Male students (14.8%) expressed greater interest in ID specialization than female students (5.2%). The pandemic positively influenced 5.5% of students to consider ID specialization as a future career, whereas only 0.6% reported a negative impact.

CONCLUSIONS: These findings underscore the necessity of enhanced educational initiatives to promote ID specialization among medical students, addressing current shortages and future infectious disease preparedness.

PMID:40906766 | DOI:10.1371/journal.pone.0329451

Biology (Basel). 2025 Aug 13;14(8):1043. doi: 10.3390/biology14081043.

ABSTRACT

Novel infection control practices are necessary to reduce the incidence of healthcare-associated infections (HAIs). Since 2007, probiotic-based cleaning solutions have been proposed as an alternative to traditional methods using disinfectants and detergents in healthcare settings, including hospitals. We conducted a comprehensive search across Google Scholar, PubMed, Scopus, and Web of Science resources. Studies that assessed the reduction in pathogens on surfaces and the emergence of HAIs after the use of probiotic-based cleaning solutions were eligible for evaluation. A total of 16 studies (13 in clinical settings and 3 on experimental surfaces) were included. The Staphylococcus species were most commonly identified before and after the use of probiotic-based cleaning solutions. All studies showed numerically lower pathogen counts and fewer HAIs after using probiotic-based cleaning solutions compared to disinfectants and detergents. Three studies indicated a reduction in antimicrobial resistance genes after use of probiotic-based cleaning solutions. One of these showed statistically significant differences compared to traditional disinfectants (alcohol, amines, and quaternary ammonium compounds) and detergents (non-ionic and anionic surfactants). The results of the included studies suggest the consideration of probiotic-based cleaning solutions for infection control in healthcare systems. However, given the novelty of this approach, further studies are needed to verify the evaluated findings and investigate the short- and long-term effectiveness, and safety of probiotic-based cleaning solutions on infection control practices in healthcare settings.

PMID:40906379 | DOI:10.3390/biology14081043

Dermatol Ther (Heidelb). 2025 Sep 4. doi: 10.1007/s13555-025-01503-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Atopic dermatitis (AD) is a chronic, highly pruritic, relapsing inflammatory disease associated with high quality-of-life burden. Topical 1.5% ruxolitinib cream is a selective Janus kinase (JAK)1/JAK2 inhibitor that is well tolerated and effective in improving itch and lesion clearance in patients ≥ 12 years old. This analysis estimates comparative efficacy for 1.5% ruxolitinib cream relative to systemic therapies for treatment of patients ≥ 12 years with AD.

METHODS: A systematic literature review (SLR) identified randomized controlled trials evaluating 1.5% ruxolitinib cream, oral JAK inhibitors, monoclonal antibodies, phosphodiesterase 4 inhibitors, and systemic immunosuppressants. A feasibility assessment evaluated whether indirect treatment comparison (ITC) was appropriate and determined appropriate ITC methods. This network meta-analysis (NMA) assessed the comparative efficacy of 1.5% ruxolitinib cream against systemic therapies in a “systemic-eligible moderate AD” subgroup defined as ≥ 12 years old and eligible for topical and systemic therapies (Investigator’s Global Assessment [IGA] = 3, Eczema Area and Severity Index [EASI] ≥ 16, and body surface area ≥ 10%); an ITC with the full study populations was not feasible. A frequentist framework using a penalized likelihood NMA included outcomes of IGA 0/1 with at least a 2-point improvement from baseline, EASI-75, and Itch Numerical Rating Scale 4 (NRS4).

RESULTS: The SLR identified 25 studies, of which 12 reported outcomes for the relevant subgroup for four interventions: 1.5% ruxolitinib cream, dupilumab 300 mg, upadacitinib (15 mg, 30 mg), and abrocitinib (100 mg, 200 mg), which were compared against placebo or placebo + topical corticosteroids. There were no statistically significant differences between active comparators for IGA 0/1, EASI-75, and Itch NRS4, although point estimates numerically favored 1.5% ruxolitinib cream for IGA 0/1 and EASI‑75.

CONCLUSION: For patients with moderate AD who are eligible for systemic therapies, 1.5% ruxolitinib cream might provide disease control comparable to systemic treatments, such as dupilumab, regarding IGA 0/1, EASI-75, and Itch NRS4.

PMID:40906354 | DOI:10.1007/s13555-025-01503-1

Dermatol Ther (Heidelb). 2025 Sep 4. doi: 10.1007/s13555-025-01505-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Interleukin-1 receptor-associated kinase 4 (IRAK4) is expressed in various immune cells and regulates proinflammatory cytokine production. Its inhibition represents a novel, promising therapeutic option in the treatment of atopic dermatitis (AD). Zabedosertib (BAY1834845) is a potent, selective IRAK4 inhibitor that suppresses markers of local and systemic immune responses. This study aimed to evaluate the efficacy and safety of zabedosertib in adults with moderate-to-severe AD.

METHODS: DAMASK was a randomized, double-blind, 12-week, placebo-controlled, phase 2a, proof-of-concept study. Patients were randomized 2:1 to receive oral zabedosertib 120 mg twice daily or placebo. The primary efficacy endpoint was a composite of 75% reduction from baseline on the Eczema Area and Severity Index (EASI-75), no discontinuation of study medication for lack of efficacy, no rescue medication during the 4 weeks before Day 84, and no initiation of systemic AD treatment. Other efficacy assessments included validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD), Peak Pruritus numerical rating scale score, and affected body surface area (BSA); for safety, it included frequency and severity of treatment-emergent adverse events (TEAEs).

RESULTS: Of 77 randomized patients, 69 were included in the primary efficacy analysis (zabedosertib, n = 47; placebo, n = 22); 55 patients completed treatment. At Week 12, there was no significant difference between zabedosertib and placebo in the primary efficacy endpoint (32.3% vs. 37.4%) or percentage change in EASI from baseline (- 44.6% vs. – 55.9%). There were also no significant differences between zabedosertib and placebo at Week 12 in vIGA-AD response (15.9% vs. 28.5%), Peak Pruritus response (16.4% vs. 25.0%), percentage change in Peak Pruritus (- 20.7% vs. – 27.3%), or percentage change in BSA affected by AD (- 13.3% vs. – 20.3%). No severe or serious TEAEs were reported throughout the study.

CONCLUSIONS: Zabedosertib was safe and well tolerated in adults with moderate-to-severe AD but showed no evidence of efficacy in reducing disease severity or pruritus in this placebo-controlled study.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05656911.

PMID:40906353 | DOI:10.1007/s13555-025-01505-z

J Nephrol. 2025 Sep 4. doi: 10.1007/s40620-025-02380-9. Online ahead of print.

ABSTRACT

BACKGROUND: Kidney function decline is associated with cardiovascular disease and various other morbidities. Previous studies regarding polygenic risk scores of estimated glomerular filtration rate (eGFR) change were generally based on individuals of European ancestry and not validated on populations of East Asian ancestry.

METHODS: We conducted a genome-wide association study for eGFR slope among 26,755 non-diabetic individuals from the Taiwan Biobank. We developed an eGFR slope polygenic risk score and validated its prediction power on chronic kidney disease (CKD) in another sample with 58,777 non-diabetic individuals.

RESULTS: Eight candidate loci associated with eGFR slope (P-value ranging from 1.56 × 10^-6 to 8.73 × 10^-6) located in the SLC9A9, SLC26A8, DEPTOR, OBP2B, PRMT8, C19orf44 genes and an intergenic locus between MTMR12-ZFR genes were identified and a polygenic risk score for eGFR slope was constructed. The polygenic risk score was validated externally to be significantly associated with CKD in another set of individuals (P-value = 0.0182; odds ratio = 0.753; 95% confidence interval: 0.5936-0.9504).

CONCLUSIONS: We constructed a genome-wide polygenic risk score for eGFR decline and externally validated its use in predicting CKD in another Taiwan population. Our eGFR slope polygenic risk score might be useful for clinical CKD risk assessment in future, especially for East Asians.

PMID:40906351 | DOI:10.1007/s40620-025-02380-9

Clin Rheumatol. 2025 Sep 4. doi: 10.1007/s10067-025-07670-y. Online ahead of print.

ABSTRACT

OBJECTIVES: This study compared the incidence and time-to-event outcomes of ocular extraintestinal manifestations (O-EIMs) and EIMs among patients with human leukocyte antigen (HLA)-B27-associated diseases receiving different classes of immunotherapy.

METHODS: A retrospective cohort study was conducted using aggregated electronic health records from the TriNetX network between January 1, 2014, and December 31, 2024. Patients with HLA-B27-associated diseases were included if they were newly prescribed tumor necrosis factor (TNF), janus kinase (JAK), or interleukin (IL) inhibitors on or after their initial diagnosis. The cumulative incidence of O-EIMs and EIMs was calculated per 100 person-years. Kaplan-Meier estimates were used to graph time-to-event outcomes using R Studio (version 4.4.1).

RESULTS: We identified 22,287 patients [mean age 47.2 (16.8) years; 13,132 (58.9) % women]. The cumulative incidence of anterior uveitis from the index date was 0.11 cases per 100 person-years. According to first medication prescribed, the incidence of anterior uveitis was lowest in patients prescribed IL inhibitors, followed by JAK and TNF inhibitors (0.07%, 0.10%, and 0.20%, cases per 100 person-years respectively). Time-to-event analysis showed a higher likelihood of anterior uveitis with initial TNF inhibitor use, although the difference was not statistically significant. Regarding EIMs, incident sacroiliitis was highest with TNF (0.91%), followed by JAK (0.72%) and IL (0.37%). Psoriatic dermatitis incidence was highest with JAK inhibitors (2.85%), compared to TNF (2.19%) and IL (2.17%).

CONCLUSION: In this cohort study of patients with HLA-B27-associated diseases, the lack of statistical significance indicates similar effectiveness across immunotherapy classes in preventing O-EIMs and EIMs. Key Points • Large-scale comparative study assessing time-to-incident O-EIMs and EIMs in patients with HLA-B27-associated diseases treated with TNF, JAK, or IL inhibitor therapies using real-world data from the TriNetX network. • Low overall incidence of O-EIMs and EIMs was observed across all immunotherapy classes, with no statistically significant difference in time-to-event outcomes, indicating similar effectiveness in preventing these manifestations.

PMID:40906344 | DOI:10.1007/s10067-025-07670-y

Sleep Breath. 2025 Sep 4;29(5):280. doi: 10.1007/s11325-025-03448-3.

ABSTRACT

PURPOSE: Armodafinil has been approved for treating excessive daytime sleepiness (EDS) in OSA patients who still experience EDS after adequately treated with CPAP. However, the effectiveness of armodafinil administration in OSA patients with suboptimal CPAP usage and persistent EDS remains unexplored.

METHOD: A 12-week prospective cohort study enrolled 33 moderate to severe OSA patients with suboptimal CPAP usage (2- < 4 h/night) who experienced EDS and were naïve to armodafinil. Patients received daily 150 mg of armodafinil and continued using CPAP. Efficacy and adverse events were evaluated.

RESULTS: A total of 30 patients with mean age of 45.10 ± 10.74 years and Epworth sleepiness scale (ESS) of 13.93 ± 3.16 completed the study; however, one participant completed only the 8-week follow-up. After 12 weeks, ESS was significantly decreased by 5.03 ± 4.22 (p < 0.001). Clinical global impression (CGI) rated by investigators and by participants was significantly decreased by 1.79 ± 0.72 (p < 0.001) and 1.93 ± 0.75 (p < 0.001); respectively. Pittsburgh sleep quality index (PSQI) was significantly decreased by 5.27 ± 2.93 (p < 0.001). The OSLER error index did not significantly improved (p = 0.61); however, a trend toward improvement was observed in patients with baseline psychomotor vigilance impairment (p = 0.17). While CPAP adherence showed no statistically significant change, there was a trend toward improvement from 2.99 ± 0.63 h/night at baseline to 3.47 ± 1.38 h/night (p = 0.09). No serious side effects were observed.

CONCLUSION: In moderate to severe OSA patients with suboptimal CPAP usage who still experience EDS, administering armodafinil over 12 weeks period significantly improved EDS and sleep quality subjectively without compromising CPAP adherence. Armodafinil demonstrated excellent tolerability with self-limiting side effects.

PMID:40906339 | DOI:10.1007/s11325-025-03448-3

Sleep Breath. 2025 Sep 4;29(5):281. doi: 10.1007/s11325-025-03455-4.

ABSTRACT

PURPOSE: The objectives of this study were to monitor transcutaneous and end-tidal partial pressures of CO₂ simultaneously during polysomnography, determine the advantages and disadvantages of each method, and identify relevant factors that can affect the results.

METHODS: This cross-sectional study enrolled 55 adults who underwent polysomnography at the Ajou University Hospital Sleep Center between February 2021 and September 2022. They were volunteers who spontaneously breathed room air. Polysomnography reports, including those of CO₂ monitoring, of all participants were reviewed and analyzed by sleep experts. Generalized Estimation Evaluation, Bon Ferroni Post Hoc and multivariable regression analysis were used for statistical analysis.

RESULTS: Throughout all sleep stages, the mean, highest, and lowest values of end-tidal and transcutaneous partial pressure of CO₂ showed significant differences. The mean transcutaneous partial pressure was higher than the mean end-tidal partial pressure by 2.53 mmHg. The apnea index, apnea-hypopnea index, and height were significant factors affecting the difference between the mean transcutaneous and end-tidal partial pressure of CO₂. As the obstructive sleep apnea grade increased, the mean end-tidal CO₂ partial pressure value decreased. Two patients had hypoventilation; one met the criteria based on the transcutaneous partial pressure of CO₂ and the other met those based on the end-tidal partial pressure of CO₂.

CONCLUSION: During diagnostic sleep studies, the application of both transcutaneous and end-tidal measurements is suggested for stable and accurate monitoring of partial pressure of CO₂ and complementary analysis.

PMID:40906334 | DOI:10.1007/s11325-025-03455-4