tbuckley/cabot-search huggingface dataset:
Epidemiology, genetic etiology and intervention of premature ovarian insufficiency
Authors: Ting Guo, Hongyuan Liu, Bingying Xu, Yu Qi, Keyan Xu, Xinyi Wu, Xinmiao He, Yingying Qin, Zi-Jiang Chen
Journal: Endocrine Reviews (2025)

Abstract Premature ovarian insufficiency (POI) is a highly heterogeneous reproductive disorder in both its etiology and clinical presentation. The epidemiological characteristics of POI suggest that its occurrence likely involves a combination of genetic and environmental factors. Deciphering the pathogenic mechanisms of POI is crucial for improving reproductive outcomes as well as managing the long-term complications associated with ovarian dysfunction. Recent studies expand the list of POI-causal genes and promote the viability of genetic diagnosis. However, whole exome sequencing studies in large-scale POI cohorts and genome-wide association studies on the age at natural menopause have uncovered a complex genetic architecture underlying POI that includes monogenic and oligogenic inheritance modes, emphasizing the difficulties in genetic diagnosis, especially for the isolated cases. Moreover, our understanding of the physiology of ovarian aging has greatly benefited from recent advances in multi-omics analysis, expanding our perspective on the pathogenic mechanisms and potential targeted therapeutic strategies for POI. In this review, we summarize the epidemiological characteristics of POI, as well as progress in genetic and epigenetic etiologies, and discuss advances in pharmacology and material science that will likely contribute to new interventions for ovarian aging. Finally, this review offers new insights into prospects for early diagnosis and treatment of POI, while identifying persistent challenges and potential solutions to be addressed through future research.
Clinical factors associated with pneumocystis pneumonia despite its primary prophylaxis: When to stop prophylaxis?
Authors: Ju Yeon Kim, Se Rim Choi, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Jun Won Park
Journal: Arthritis & Rheumatology (2025)

Objective Although previous studies show that primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is effective in patients with rheumatic diseases receiving immunosuppressive treatment, there is limited evidence regarding the optimal timing for prophylaxis withdrawal. This study aimed to identify the risk factors for PJP despite prophylaxis and provide evidence for an optimal prophylaxis schedule. Methods This case‐control study included 1,294 prophylactic episodes in 1,148 patients with rheumatic disease who received immunosuppressants and prophylactic trimethoprim‐sulfamethoxazole (TMP‐SMX). The primary outcome was a one‐year incidence of PJP. A Cox proportional hazards model with LASSO was used to evaluate clinical factors associated with outcomes. Results During 1,174 person‐years of observation, 10 cases of PJP were identified, with an incidence rate of 0.85 per 100 person‐years. The mean (standard deviation [SD]) duration of TMP‐SMX prophylaxis was 181.9 (128.7) days. Except in one case, PJP occurred after discontinuation of TMP‐SMX, with a median (interquartile range [IQR]) interval of 117.0 (86.0‐161.0) days. The dose of glucocorticoids at the time of TMP‐SMX discontinuation was significantly higher in the PJP group relative to the control group (median [IQR]: 22 [20‐40] vs 10 [5‐15] mg). Discontinuing TMP‐SMX while on a glucocorticoid dose &gt;12.5 mg/day of prednisone equivalent significantly increased the risk of PJP (adjusted hazard ratio: 13.84 [95% confidence interval, 1.71‐111.80]). There were 63 cases of adverse events during the observation period, and seven (11.1%) were attributed to TMP‐SMX with probable causality. Conclusion Tapering glucocorticoids with 12.5 mg/day of prednisone equivalent could be a reasonable timepoint to initiate the withdrawal of PJP prophylaxis in patients with rheumatic diseases. image
ERS “IMPORTANCE” Clinical Research Collaboration: Implications of Positive Airway Pressure and Home Mechanical Ventilation: TowArds optimal patient CarE
Authors: Jiali Cai, Sophia Schiza, Esther Irene Schwarz, Raphael Heinzer, Jacek Nasilowski, Winfried Randerath, Maxime Patout, Carla Ribeiro, Michael Cheng, Aileen Kharat, Andreas Palm, Claudia Crimi, Rebecca D'Cruz, Manuel Sánchez-de-la-Torre, Marieke Duiverman
Journal: European Respiratory Journal (2025)
Schoolchildren with asthma face different risks at different ages
Authors: Helen Saul, Brendan Deeney, Laura Swaithes, Chloe Bloom
Journal: BMJ (2025)

The study Khalaf Z, Bush A, Saglani S, et al. Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma. Thorax 2024;79:112-119. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/schoolchildren-with-asthma-face-different-risks-at-different-ages/
An alternative self-splicing intron lifecycle revealed by dynamic intron turnover in <i>Epichloë</i> endophyte mitochondrial genomes
Authors: Jennie Chan, Mauro Truglio, Christopher L Schardl, Murray P Cox, Carolyn A Young, Austen R D Ganley
Journal: Molecular Biology and Evolution (2025)

Self-splicing group I and II introns are selfish genetic elements that are widely yet patchily distributed across the tree of life. Their selfish behavior comes from super-Mendelian inheritance behaviors, collectively called 'homing', that allow them to rapidly spread within populations to the specific genomic sites they home into. Observations of self-splicing intron evolutionary dynamics have led to the formulation of an intron 'lifecycle' model where, once fixed in a population, the introns lose selection for homing and undergo an extensive period of degradation until their eventual loss. Here, we find that self-splicing introns are common in the mitochondrial genomes of Epichloë species, endophytic fungi that live in symbioses with grasses. However, these introns show substantial intron presence-absence polymorphism, with our analyses suggesting that this results from a combination of vertical intron inheritance coupled with multiple invasion and loss events over the course of Epichloë evolution. Surprisingly, we find little evidence for the extensive intron degradation expected under the existing intron lifecycle model. Instead, these introns in Epichloë appear to be lost soon after fixation, suggesting that Epichloë self-splicing introns have a different lifecycle. However, rapid intron loss alone cannot explain our results, indicating that additional factors, such as the evolution of homing suppressors, also contribute to Epichloë self-splicing intron dynamics. This work shows that self-splicing introns have more diverse evolutionary dynamics than previously appreciated.
Pharmacologic Agents Used in the Assessment or Correction of Blepharoptosis
Authors: Seanna R Grob, Jeremiah P Tao, Vinay K Aakalu, Jill A Foster, Lora R Dagi Glass, Timothy J McCulley, M Reza Vagefi, Michael Yoon, Stephen J Kim, Edward J Wladis
Journal: Ophthalmology (2025)
Enhanced PDMS Functionalization for Organ‐on‐a‐Chip Platforms Using Ozone and Sulfo‐SANPAH: A Simple Approach for Biomimetic Long‐Term Cell Cultures
Authors: Mitzi Pérez‐Calixto, Cindy Peto‐Gutiérrez, Alyssa Shapiro, Lazaro Huerta, Mathieu Hautefeuille, Marina Macías‐Silva, Daniel Pérez‐Calixto, Genaro Vázquez‐Victorio
Journal: Advanced Healthcare Materials (2025)

Surface modification of polydimethylsiloxane (PDMS) for organ-on-a-chip (OOC) systems is fundamental for the success of cell physiological assays. Although UV light is commonly used for this purpose, surface chemical modifications are only temporary. To overcome these limitations, an alternative approach is proposed: a physicochemical modification using ozone and the heterofunctional crosslinker sulfo-SANPAH (SS). This simple one-step approach is carried out on PDMS microchannels of OOC platforms. A broad physicochemical characterization based on spectroscopy and microscopy techniques confirms successful modification of the PDMS surface. The PDMS surface contact angle decreases after addition of SS (from 101.4° to 79.9°) but decreases as low as 20.8° after extracellular matrix deposition, demonstrating successful transition of the surface from hydrophobic to hydrophilic. For biological characterization, human liver sinusoidal endothelial cells (LSEC) and murine primary hepatocytes are cultured in OOC channels for up to 7 days. LSECs and hepatocytes establish strong cell adhesions under laminar flow and form a well-established canaliculi network, respectively. This one-step method of PDMS surface modification for OOC is simpler than others reported in the literature (e.g., based on 3-aminopropyltriethoxysilane) and ideal for beginners interested in using microfluidic platforms for cell culture.
Survival and Cost-Effectiveness of Bariatric Surgery Among Patients With Obesity and Cirrhosis
Authors: Shalini Bansal, Amanda Bader, Nadim Mahmud, David E. Kaplan
Journal: JAMA Surgery (2025)

Obesity and steatotic liver disease are associated with excess morbidity and mortality from cardiovascular, pulmonary, metabolic, and hepatic causes. Bariatric surgery has demonstrated long-term benefits in terms of weight loss and mortality rates, but barriers to its utilization persist. To evaluate the impact of bariatric surgery on outcomes and cost-effectiveness among patients with obesity, focusing on those with cirrhosis. This economic evaluation was a retrospective cohort study including US veterans older than 18 years with a body mass index (BMI) higher than 35 or with a BMI higher than 30 and more than 1 major metabolic comorbidity. These veterans were referred to a structured lifestyle modification program (MOVE!), and a subset proceeded to bariatric surgery, including sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) from 2008 to 2020. Risk set matching was used to match bariatric surgery cases 1:5 with nonsurgical controls. Data were analyzed from September 2008 to September 2023. Bariatric surgery (SG or RYGB) or structured lifestyle intervention (MOVE!). The primary outcomes were the incremental cost-effectiveness ratio (ICER) of SG or RYGB vs MOVE! over 10 years. Secondary outcomes included overall survival, quality-adjusted survival, and weight loss achieved. The final cohort included 4301 SG, 1906 RYGB, and 31 055 MOVE! participants, among whom 64, 8, and 354, respectively, had cirrhosis. The median (IQR) age of the cohort was 52 (44-59) years; there were 25 581 male patients (68.7%) and 11 681 female (31.3%). Compared with MOVE!, bariatric surgery was associated with longer observed survival (9.67 years vs 9.46 years overall; 9.09 years vs 8.23 years in cirrhosis). The ICER was $132 207 for SG and $159 027 for RYGB in the overall cohort, and $18 679 for SG and $44 704 for RYGB in the cirrhosis cohorts. Bariatric surgery was cost-effective at a willingness-to-pay threshold of $100 000 per quality-adjusted life-year among patients with cirrhosis. Bariatric surgery was associated with improved survival and expected weight loss and was cost-effective. These findings support the expanded use of bariatric surgery in appropriately selected patients, including those with cirrhosis, to improve outcomes and reduce long-term health care costs.
Risk of New-Onset Type 2 Diabetes Among Vaccinated Adults After Omicron or Delta Variant SARS-CoV-2 Infection
Authors: Liang En Wee, Jue Tao Lim, Enoch Xueheng Loy, Calvin J. Chiew, E. Shyong Tai, Su Chi Lim, Yong Mong Bee, Sock Hwee Tan, Charmaine Qing Fei Chan, Wai Leng Chow, James Wei Luen Yip, Khung Keong Yeo, Benjamin Ong, David Chien Boon Lye, Mark Yan Yee Chan, Derek J. Hausenloy, Kelvin Bryan Tan
Journal: JAMA Network Open (2025)

This cohort study estimates the risk of new-onset type 2 diabetes after Delta or Omicron variant SARS-CoV-2 infection among vaccinated adults in Singapore.
Transcriptomic skin niches in systemic sclerosis underpins a role for mitochondrial dysfunction
Authors: Junqin Wang, Dylan Hennessey, Aishwarya Iyer, Sandra O’Keefe, Lamia Khan, Desiree Redmond, Mohammed Osman, Robert Gniadecki
Journal: British Journal of Dermatology (2025)

Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by fibrosis, vasculopathy, and immune dysregulation. Using spatial transcriptomics on the dermis of 11 SSc patients, we identified distinct transcriptomic niches associated with fibrosis, immune activation, and mitochondrial dysfunction. Our findings highlight mitochondrial dysfunction as a central mechanism in SSc pathogenesis, ranging from adaptive remodeling in immune zones to metabolic collapse in fibrotic zones, underscoring mitochondria as a therapeutic target.
Recurrence Risk in Pediatric Non‐Infectious Uveitis during Adalimumab Tapering: An International Multicenter Retrospective Study
Authors: Achille Marino, Maria Vittoria Cicinelli, Elisabetta Miserocchi, Stefania Costi, Francesco Baldo, Maurizio Virgilio Gattinara, Pierluigi Scandale, Scott D Smith, Debra A Goldstein, Dina Baddar, Terese KA Gerges, Timothy M Janetos, Matilde Ruiz‐Cruz, Kazuichi Maruyama, Massimiliano Serafino, Paola Camicione, Vishali Gupta, Radgonde Amer, Emilio M Dodds, Sebastian Inchauspe, Marion R Munk, Ester Carreño, Soon‐Phaik Chee, Aniruddha Agarwal, Ariel Schlaen, Ramiro A Gómez, Cristobal A. Couto, Moncef Khairallah, Piergiorgio Neri, Cecilia B Chighizola, Roberto F Caporali, Francesco Pichi
Journal: Arthritis & Rheumatology (2025)

This study aims to assess the risk of non-infectious uveitis (NIU) relapse in pediatric patients undergoing Adalimumab (ADA) tapering, evaluating potential predictors of such risk METHODS: We conducted a multicenter retrospective cohort study involving pediatric NIU patients who underwent ADA tapering due to inactive uveitis. Cox proportional hazards regression was used to analyze risk factors for NIU recurrence. The study cohort comprised 114 patients (65 girls; 57%). Most commonly, patients presented juvenile idiopathic arthritis-associated uveitis (JIA-U) (52/114; 46%) or idiopathic uveitis (IU) (46/114; 40%). At ADA tapering, 46% (53/114) experienced NIU recurrence after an overall median time of 30 weeks [interquartile range (IQR) 15-58 weeks)] from the start of ADA tapering. Patients without recurrences were followed for a median of 70 weeks (IQR 48-98 weeks). Multivariate Cox regression analysis showed that a slower ADA tapering schedule was associated with a lower recurrence rate during the waning (hazard ratio [HR] 0.40; 95% CI 0.21-0.74; p < 0.01). Subgroup analysis of patients with juvenile idiopathic arthritis-associated uveitis (JIA-U) indicated that beginning ADA tapering after at least two years of disease inactivity significantly reduced recurrence risk (HR 0.65; 95% CI 0.43-0.95; p = 0.05). Among 59 patients (52%) who discontinued ADA, recurrence rates were similar between fast and slow tapering groups (21% vs. 33%; p=0.6), but median time to recurrence was shorter with fast tapering (10 weeks vs. 37 weeks; p=0.05). This study highlights the significant clinical impact of ADA tapering on uveitis recurrence risk, recommending a gradual, slow tapering approach with close monitoring.
Increased Utilization of Overtime and Agency Nurses and Patient Safety
Authors: Patricia Pittman, Hong-Lun Tiunn, Qian Luo, Michael Herron, Drew Tatum, John Martin
Journal: JAMA Network Open (2025)

The use of nurse overtime and agency nurses has increased in recent years, making it important to understand the opportunities and limits of these alternative staffing strategies on patient safety outcomes. To examine the association between overtime and agency nurse staffing hours and hospital patient safety. This quality improvement study used data from 70 US hospitals, from January 2019 through December 2022. Participants included patients and nurse staff across the 70 hospitals. The use of overtime and agency nursing. The main outcomes were 10 of the US Agency for Healthcare Research and Quality's patient safety indicators and their associations with regular, overtime, and agency nursing hours per patient day: pressure ulcers, iatrogenic pneumothorax, in-hospital fall with hip fracture, perioperative hemorrhage or hematoma, postoperative acute kidney injury requiring dialysis, postoperative respiratory failure, perioperative thromboembolism, postoperative sepsis, postoperative wound dehiscence, and accidental puncture or laceration. A baseline Poisson regression model and a structural breakpoint analysis were used to identify safety thresholds. Pairwise interactions between staffing intensity variables and hospital bed size were also included. Adjustments were made for the COVID-19 hospital census, patient case mix, and hospital characteristics. The sample included 46 hospitals in the South, 20 in the West, and 4 in the Northeast; 48 hospitals were urban, 32 hospitals had fewer than 200 beds, 26 had between 200 and 399 beds, and 12 had 400 or more beds. The average use of nurse overtime and agency nurse hours exceeded safe thresholds for pressure ulcers by 140.0% for agency staffing and by 63.6% for overtime, representing a 6.44% increase associated with excess agency nurse hours and a 2.09% increase for excess use of overtime. There also was a statistically significant association of agency hours with postsurgery hemorrhage or hematoma rates, but no breakpoint threshold. There were no significant associations with other outcomes. These findings suggest that both nurse overtime and nurse agency hours are associated with increased rates of pressure ulcers, a measure that is one of the most sensitive to nursing care. In future research, hospitals could use their own data to track safe thresholds.
<scp>TOP10</scp>‐<scp>SCAR</scp>: A Global Pharmacovigilance Study on Medications Most Frequently Related to Severe Cutaneous Adverse Reactions
Authors: Jaehyeong Cho, Hyesu Jo, Jaeyu Park, Jeongseon Oh, Tae Hyeon Kim, Kyeongmin Lee, Hayeon Lee, Jinyoung Jeong, Sooji Lee, Michael Miligkos, Nikolaos G Papadopoulos, Dong Keon Yon
Journal: Allergy (2025)
Early-Life Ozone Exposure and Asthma and Wheeze in Children
Authors: Logan C. Dearborn, Marnie F. Hazlehurst, Allison R. Sherris, Adam A. Szpiro, Drew B. Day, Christine T. Loftus, Magali N. Blanco, Margaret A. Adgent, Aileen R. Andrade-Torres, Yu Ni, Mary E. Crocker, Jianzhao Bi, Joel D. Kaufman, Ruby H. N. Nguyen, Kaja Z. LeWinn, Paul E. Moore, Kecia N. Carroll, Catherine J. Karr
Journal: JAMA Network Open (2025)

Ozone (O3) is the most frequently exceeded air pollutant standard in the US. While short-term exposure is associated with acute respiratory health, the epidemiologic evidence linking postnatal O3 exposure to childhood asthma and wheeze is inconsistent and rarely evaluated as a mixture with other air pollutants. To determine associations between ambient O3 and subsequent asthma and wheeze outcomes both independently and in mixture with fine particulate matter and nitrogen dioxide in regions with low annual O3 concentrations. This cohort study consisted of a pooled, multisite analysis across 6 US cities using data from the prospective ECHO-PATHWAYS consortium (2007-2023). Included children had complete airway surveys, complete address histories from age 0 to 2 years, and a full term birth (≥37 weeks). Logistic regression and bayesian kernel machine regression (BKMR) mixture analyses were adjusted for child anthropomorphic, socioeconomic, and neighborhood factors. Exposure to ambient O3 in the first 2 years of life derived from a validated point-based spatiotemporal model using residential address histories. The primary outcome was asthma and wheeze at ages 4 to 6 years; the secondary outcome was asthma and wheeze at ages 8 to 9 years. Outcomes were based on caregiver reports derived from a validated survey. The analytic sample of 1188 participants had a mean (SD) age of 4.5 (0.6) years at the age 4 to 6 years visit and consisted of 614 female participants (51.7%) and 663 mothers who had a bachelor's degree or higher (55.8%). The mean (SD) O3 concentration was 26.1 (2.9) parts per billion (ppb). At age 4 to 6 years, 148 children had current asthma (12.3%) and 190 had current wheeze (15.8%). The odds ratio per 2 ppb higher O3 concentration was 1.31 (95% CI, 1.02-1.68) for current asthma and 1.30 (95% CI, 1.05-1.64) for current wheeze at age 4 to 6 years; null associations were observed for outcomes at age 8 to 9 years, and for sensitivity covariate adjustment. BKMR suggested that higher exposure to O3 in mixture was associated with current asthma and wheeze in early childhood. In this cohort study with relatively low ambient O3 exposure, early-life O3 was associated with asthma and wheeze outcomes at age 4 to 6 years and in mixture with other air pollutants but not at age 8 to 9 years. Regulating and reducing exposure to ambient O3 may help reduce the significant public health burden of asthma among US children.
Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance
Authors: Tingting Zhang, Zhang Li, Jiao Li, Yong Peng
Journal: Molecular Cancer (2025)

The human genome harbors approximately twenty thousand protein-coding genes, and a significant portion of life science research focuses on elucidating their functions and the underlying mechanisms. Recent studies have revealed that small open reading frame (sORF), originating from non-coding RNAs or the 5' leader sequences of messenger RNAs, can be translated into small peptides called microproteins through cap-dependent or cap-independent mechanisms. These microproteins interact with diverse molecular partners to modulate gene expression at multiple regulatory levels, thereby playing critical roles in various biological processes. Notably, sORF-encoded microproteins exhibit aberrant expression patterns in cancer and are implicated in tumor initiation and progression, expanding our understanding of cancer biology. In this review, we introduce the translational mechanisms and identification methods of microproteins, summarize their dysregulation in cancer and their biological functions in regulating gene expression, and emphasize their roles in driving hallmark events of cancer. Furthermore, we discuss their clinical significance as diagnostic and prognostic biomarkers, as well as therapeutic targets.