tbuckley/cabot-search huggingface dataset:
Risk of Adverse Pregnancy Outcomes Among Asian Individuals With Gestational Diabetes Mellitus in the U.S., 2016–2021
Authors: Kartik K. Venkatesh, Xiaoning Huang, Nilay S. Shah,, Mark B. Landon, William A. Grobman, Sadiya S. Khan
Journal: Diabetes Care (2025)

OBJECTIVE The risk of adverse pregnancy outcomes (APOs) differs among race and ethnic groups with gestational diabetes mellitus (GDM). Heterogeneity in APOs may be masked by aggregating these groups. We assessed whether the frequency and risk of APOs differed among Asian groups with GDM. RESEARCH DESIGN AND METHODS This is a serial cross-sectional analysis of U.S. birth certificate data (2016–2021) from individuals with a singleton first livebirth. The exposure was self-reported maternal race and ethnicity stratified by Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese versus non-Hispanic White as the reference. Maternal outcomes included: primary cesarean delivery, hypertensive disorders of pregnancy (HDP), intensive care unit admission, and transfusion. Neonatal outcomes included large-for-gestational-age (LGA), small-for-gestational-age (SGA), preterm birth, and neonatal intensive care unit (NICU) admission. RESULTS The study population included 29,370 Indian, 16,146 Chinese, 9,082 Filipino, 6,497 Vietnamese, 3,754 Korean, and 1,253 Japanese individuals, and 254,433 White individuals. Between 2016 and 2021, the frequency of HDP, but not other APOs, increased among most Asian groups. In multivariable analyses, individuals in all Asian groups had higher likelihood of SGA and lower likelihood of LGA compared with White individuals. Findings for other APOs were heterogeneous. The risk of APOs was generally highest among Filipino individuals, followed by Indian individuals, and lowest among Chinese individuals among Asian groups. CONCLUSIONS There was significant heterogeneity in the frequency and risk of APOs among Asian individuals with GDM in the U.S. Disaggregation of the Asian population in diabetes and pregnancy research and surveillance is necessary to identify opportunities for intervention.
Coordinated Regulation of Renal Glucose Reabsorption and Gluconeogenesis by mTORC2 and Potassium
Authors: John Demko, Bidisha Saha, Enzo Takagi, Anna Mannis, Robert Weber, Hermann Koepsell, David Pearce
Journal: Journal of the American Society of Nephrology (2025)

Background: The kidney is uniquely responsible for reabsorption of filtered glucose and gluconeogenesis. Insulin stimulates glucose transport and suppresses gluconeogenesis in the proximal tubule, however, the signaling mechanisms and coordinated regulation of these processes are poorly understood. The kinase complex mTORC2 is critical for regulation of growth, metabolism, solute transport, and electrolyte homeostasis in response to a wide array of inputs. Here we examined its role in the regulation of renal glucose reabsorption and gluconeogenesis. Methods: Rictor, an essential component of mTORC2, was knocked out using the Pax8-LC1 system to generate inducible tubule Rictor knockout (KO) mice. A second Rictor KO model was generated using Cre-loxP technology and a proximal tubule-specific promoter. Animals were fasted and refed on normal or high K + diets. Metabolic parameters including glucose homeostasis and kidney function were assessed. Kidneys and livers were harvested for molecular analysis of gluconeogenic enzymes, glucose transporters, and mTORC2-regulated signaling targets. Results: On a normal K + diet, mTORC2 KO mice had marked glycosuria despite normal blood glucose. Immunofluorescence microscopy and immunostaining of plasma membrane protein fractions showed lower proximal tubule apical membrane SGLT2 and SGLT1 in the fed state of KO mice. Metabolic testing showed elevated fasting insulin, impaired pyruvate tolerance, and elevated hemoglobin A1c. In addition, renal gluconeogenic enzymes were increased, consistent with abnormal renal gluconeogenesis in KO mice. These effects correlated with reduced downstream phosphorylation of Akt and the transcription factor FOXO4, identifying a novel role of FOXO4 in the kidney tubules. Interestingly, high dietary K + rapidly lowered glycosuria and gluconeogenesis, despite persistent reduction in mTORC2 substrate phosphorylation. Conclusions: Renal tubule mTORC2 is critical for coordinated regulation of sodium-glucose cotransporter membrane localization and renal gluconeogenesis. In the absence of mTORC2, dietary K + promotes glucose reabsorption and suppresses gluconeogenesis independent of insulin signaling.
Correction: Importance of Donor- and Recipient-Derived Selectins in Cardiac Allograft Rejection
Authors: Atsushi Izawa, Takuya Ueno, Mollie Jurewicz, Toshiro Ito, Katsunori Tanaka, Masafumi Takahashi, Uichi Ikeda, Olga Sobolev, Paolo Fiorina, Rex Neal Smith, Richard O. Hynes, Reza Abdi
Journal: Journal of the American Society of Nephrology (2025)
Effect of Marked Weight Loss on Adipose Tissue Biology in People With Obesity and Type 2 Diabetes
Authors: Dmitri Samovski, Gordon I. Smith, Hector Palacios, Terri Pietka, Anja Fuchs, Gary J. Patti, Allah Nawaz, C. Ronald Kahn, Samuel Klein
Journal: Diabetes Care (2025)

OBJECTIVE Weight loss improves insulin sensitivity in people with obesity and type 2 diabetes. However, the mechanisms responsible for this effect are unclear. We hypothesized that alterations in adipose tissue biology and adipose tissue-related factors in plasma are involved in mediating the systemic metabolic benefits of weight loss. RESEARCH DESIGN AND METHODS We evaluated blood and adipose tissue samples obtained from 10 adults with obesity and type 2 diabetes before and after marked (16–20%) weight loss and &amp;gt;50% increase in whole-body insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure. RESULTS Weight loss 1) decreased adipose tissue expression of genes related to extracellular matrix remodeling; 2) decreased adipose tissue expression of SERPINE 1, which encodes plasminogen activator inhibitor 1 (PAI-1); 3) did not decrease adipose tissue immune cell content or expression of genes involved in inflammation; 4) decreased adipose tissue ceramide content; 5) decreased plasma PAI-1 and leptin concentrations and increased plasma high-molecular weight (HMW) adiponectin; and 6) decreased plasma small extracellular vesicle (sEV) concentration and the sEV content of microRNAs proposed to inhibit insulin action, and completely reversed the inhibitory effect of plasma sEVs on insulin signaling in myotubes. CONCLUSIONS These findings suggest that weight loss increases insulin sensitivity in people with obesity and type 2 diabetes by modifying adipose tissue biology, with concomitant alterations in circulating PAI-1, leptin, HMW adiponectin, and sEV microRNAs.
Change in cT1 following interventions in MASLD: A systematic review and meta-analysis
Authors: Anneli Andersson, Rohit Loomba, Cayden Beyer, Sofia Mouchti, Raj Vuppalanchi, Mukesh Harisinghani, Saima Ajaz, Amreen Dinani, Amitava Banerjee, Mark Muthiah, Andrea Dennis, Michele Pansini
Journal: Clinical Gastroenterology and Hepatology (2025)

Liver corrected T1 (cT1), measured with multiparametric magnetic resonance imaging (mpMRI), offers an alternative to liver biopsy to monitor treatment response and liver disease activity. We aim to perform a systematic evaluation of change in cT1 following a treatment intervention in adults with metabolic dysfunction-associated steatotic liver disease (MASLD). We searched the Cochrane Library, PubMed Central, and MEDLINE from 2014 to September 2024 for studies that examined cT1 responses following intervention in MASLD. Two authors independently screened records, assessed risk of bias and extracted data. Meta-analyses were performed to explore the mean change in cT1 between baseline and end of study. A total of 16 studies (n = 1134 individuals) were analysed (13 randomized controlled trials [n = 1077] and 3 prospective diet, lifestyle and bariatric surgery studies [n = 57]). The mean change in cT1 was -57ms [95% CI: -62, -52] over a median 17 weeks (Q1-Q3: 12 - 24). By treatment type, fibroblast growth factor (FGF) analogues, glucagon-like peptide (GLP)-1 receptor agonists and farnesoid X receptor (FXR) agonists, cT1 had a mean change of -79ms [95% CI: -90, -68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively. In contrast, the placebo arms showed a mean change in cT1 of 0ms [95% CI: -8, 8]. Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform study designs for investigational therapies and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice.
Effects of Inflammatory Endotypes on Disease Trajectory in Chronic Rhinosinusitis with Nasal Polyps
Authors: Christina Dorismond, Yash Trivedi, Mason R Krysinski, Rory J Lubner, Li-Ching Huang, Sandeep Goswami, Quanhu Sheng, Rakesh K Chandra, Naweed I Chowdhury, Justin H Turner
Journal: Journal of Allergy and Clinical Immunology (2025)
Inherited predisposition to pneumothorax: estimating the frequency of Birt-Hogg-Dubé syndrome from genomics and population cohorts
Authors: Bryndis Yngvadottir, Lucy Richman, Avgi Andreou, Jessica Woodley, Anita Luharia, Derek Lim, Eamonn R Maher, Stefan J Marciniak
Journal: Thorax (2025)

Birt-Hogg-Dubé syndrome (BHDS) is the most common monogenic cause of pneumothorax. Most affected families have pathogenic variants in the FLCN gene. Using large genomic registries (UK Biobank (UKB), 100,000 Genomes Project and East London Genes &amp; Health) including &gt;550 000 individuals, we demonstrate that the frequency of clinically validated loss-of-function FLCN variants is 1 in 2710 to 4190. While the lifetime risk of pneumothorax in FLCN mutation carriers in the UKB and a BHDS clinical cohort was substantial (28.4% and 37.3%, respectively, to age 65 years), the lifetime risk of renal cancer was significantly lower in UKB than in BHDS patients (1% vs 32.1%). These findings highlight the importance of clinical context in managing individuals with FLCN mutations.
LRBA functional deficiency caused by biallelic LRBA missense variants characterized by Evans syndrome or colitis
Authors: Samuel Cc Chiang, Li Yang, Erika Owsley, Ammar Husami, Nagako Akeno, Cristina Cobb, Nicholas L Hartog, Araceli Elizalde, Christine M Seroogy, Geraldine Blanchard-Rohner, Xiao P Peng Md, Rae Brager, David Buchbinder, Eleanor Cook, Lindsay Phillips, Snezana Maricic, Tatiana Kalashnikova, Beata Derfalvi, Victoria R Dimitriades, Luis E Murguía-Favela, Maria J Gutierrez, Anitha Shrikhande, MacGregor Steele, Jo L Wilson, Nicola Am Wright, Rebecca Marsh, Jack Bleesing, Michael B Jordan, Ashish K Marwaha BMBch
Journal: Journal of Allergy and Clinical Immunology (2025)
Endotypes of Chronic Spontaneous Urticaria and Angioedema
Authors: Dennis Wong, Susan Waserman, Gordon L Sussman
Journal: Journal of Allergy and Clinical Immunology (2025)

The current understanding of chronic spontaneous urticaria (CSU) suggests that a complex network of inflammatory pathways is involved in its pathogenesis. Recent development highlighted autoimmunity as one of the key pathogenic mechanisms of CSU. Two endotypes, type I autoallergic (associated with IgE antibodies against autoantigens) and type IIb autoimmune (mediated by IgG autoantibodies against IgE or its high affinity receptor (FcεRI), have been characterized. A subpopulation of the patients has an overlap of the two endotypes. About 10% of patients with CSU presents with angioedema only. Patients with isolated mast-cell mediated angioedema have distinct clinical and demographic features and should be distinguished from bradykinin-mediated angioedema. Multiple potential biomarkers such as total IgE level and IgG anti-thyroid peroxidase have been identified, and together with the corresponding endotypes, have been linked to disease severity, duration and response to treatments. Currently, the utility of these biomarkers is limited in clinical settings given the few options of therapy. However, with the advent of novel treatments, endotyping CSU might help with tailoring treatment approach.
Fibril fuzzy coat is important for α-synuclein pathological transmission activity
Authors: Yuliang Han, Juan Li, Wencheng Xia, Qintong Li, Zihan Sun, Wen Zeng, Yingxin Hu, Kelvin C Luk, Cong Liu, ShengQi Xiang, Zhuohao He
Journal: Neuron (2025)
Perceptual and technical barriers in sharing and formatting metadata accompanying omics studies
Authors: Yu-Ning Huang, Viorel Munteanu, Michael I Love, Cynthia Flaire Ronkowski, Dhrithi Deshpande, Annie Wong-Beringer, Russell Corbett-Detig, Mihai Dimian, Jason H Moore, Lana X Garmire, T B K Reddy, Atul J Butte, Mark D Robinson, Eleazar Eskin, Malak S Abedalthagafi, Serghei Mangul
Journal: Cell Genomics (2025)
Stigma Experiences of Sexual and Gender Minority Parents and Offspring Mental Health
Authors: Qimin Liu, Mingcong Tang, Violeta J. Rodriguez
Journal: JAMA Network Open (2025)

Importance Nearly 40% of sexual and gender minority individuals become parents. Research has highlighted the intergenerational outcomes of parental psychopathology associated with child psychiatric symptoms, yet how stigma and parental mental health influence child outcomes in sexual and gender minority families remains unclear. Objective To examine associations between parental stigma experiences and psychiatric symptoms and children’s mental health and emotional and behavioral well-being. Design, Setting, and Participants This survey study recruited a community-based sample of sexual and gender minority parents (aged ≥18 years) between October 12 and December 1, 2023. Parents reported stigma experiences, internalizing and externalizing psychopathology, and their children’s emotional and conduct problems. Exposure Parental stigma defined as discrimination and internalized stigma. Main Outcomes and Measures Parental externalizing and internalizing psychopathology and child emotional and conduct problems were analyzed using structural equation modeling with bifactor measurement models. Results The sample included 551 sexual and gender minority parents (mean [SD] age, 34.5 [8.7] years, 268 identifying as cisgender women [48.6%]). Parental psychiatric symptoms were significantly associated with children’s psychiatric symptoms (β [SE], 9.35 [3.44]; 95% CI, 2.61-16.09). Parental externalizing symptoms were associated with child conduct problems (β [SE], 0.67 [0.32]; 95% CI, 0.03-1.30), while internalizing symptoms were associated with child emotional problems (β [SE], 2.05 [0.77]; 95% CI, 0.54-3.55). General stigma was associated with both child psychiatric symptoms (β [SE], 3.53 [1.20]; 95% CI, 1.18-5.89) and emotional problems (β [SE], 2.13 [0.45]; 95% CI, 1.25-3.01). Discrimination, was also significantly associated with child emotional problems (β [SE], 0.22 [0.11]; 95% CI, 0.00-0.44). Conclusions and Relevance This survey study found that parental stigma experiences in sexual and gender minority families are associated with both parental and child psychopathology. These findings highlight the need for longitudinal, multi-informant research to guide interventions supporting sexual and gender minority family mental health.
Childcare Barriers and Appointment Nonadherence Among Women in a Safety-Net Health System
Authors: Anisha P. Ganguly, Robert Martin, Erin Barnett, Jillian Smartt, Michael Harms, Kimberly A. Kho, Michael E. Bowen, Bijal A. Balasubramanian, Kavita P. Bhavan
Journal: JAMA Network Open (2025)

Importance Health-related social needs (HRSNs) contribute to appointment nonadherence. Childcare needs are an underrecognized HRSN that particularly affect women. Objective To determine whether self-reported childcare barriers were associated with appointment nonadherence among women. Design, Setting, and Participants This cross-sectional study used linked survey and electronic health record (EHR) data. Survey data were collected from November 2023 to May 2024 and EHR data were extracted for the 1 year prior to the survey date for each participant. Data were analyzed between June and September 2024. This single-center study was conducted in a safety-net health system in Dallas County, Texas. EHR data included ambulatory care encounters. Eligible participants included women aged 18 years or older referred to gynecology for abnormal cervical cancer screening who reported having childcare responsibilities. Exposure Self-reported childcare barriers to appointments in the past year. Main Outcomes and Measures Regression analysis was used to evaluate the primary outcome of appointment nonadherence rate during the year prior to survey date. Results Of 1264 women eligible for the survey, 836 were successfully reached by telephone, of whom 671 women (53.1% of eligible sample) were included in the sample. Among the 671 initial respondents, 486 women reported having childcare responsibilities (72.4%). The mean (SD) age of the study sample was 34.8 (8.6) years, 405 (83.3%) identified as Hispanic, and 349 (71.8%) preferred Spanish. Additionally, 105 women reported childcare barriers to attending appointments in the past year (21.6%). Women with self-reported childcare barriers were mean 2.9 years younger and more likely to receive Medicaid (38 [36.2%]) than women without childcare barriers (89 [23.4%]). Women with self-reported childcare barriers were more likely to care for an increased number of children and younger children than women without. The mean (SD) appointment nonadherence rate was 25.1% (21.8%) among women with self-reported childcare barriers compared with 15.2% (22.1%) among women without. The adjusted difference in appointment nonadherence was 8.8 (95% CI, 3.6-14.0) percentage points ( P = .001) higher among women with self-reported childcare barriers. Conclusions and Relevance In this cross-sectional study of women in a safety-net health system, self-reported childcare barriers were associated with increased appointment nonadherence. Younger women with younger children were most likely to report childcare barriers to appointments. These findings highlight the importance of childcare needs as a HRSN that warrants screening and intervention.
Neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma
Authors: Xin An, Sheng Jie Guo, Ru Yan, Ting Xue, Long Bin Xiong, Hua Li Ma, Cong Xue, Ying Chun Zhang, Ji Bin Li, Mei Ting Chen, Zai Shang Li, Ting Yu Liu, Zhi Ling Zhang, Pei Dong, Yong Hong Li, Kai Yao, Zhi Quan Hu, Xiao Feng Chen, Jie Xin Luo, Yong Hong Lei, Pei Yu Liang, Zhi Zhong Liu, Lin Qi, Wen Feng Xu, Zheng Guo Cao, Nan Hui Chen, Xiang Li, Xi Nan Sheng, Guang Heng Luo, Ben Kang Shi, Qun Xie, Zhuo Wei Liu, Fang Jian Zhou, Philippe E Spiess, Yan Xia Shi, Hui Han
Journal: Cancer Cell (2025)
Economic Evaluation of Enhanced Cleaning and Disinfection of Shared Medical Equipment
Authors: David Brain, Nirmali Sivapragasam, Katrina Browne, Nicole M. White, Philip L. Russo, Allen C. Cheng, Andrew J. Stewardson, Georgia Matterson, Peta E. Tehan, Kirsty Graham, Maham Amin, Martin Kiernan, Jennie King, Brett G. Mitchell
Journal: JAMA Network Open (2025)

Importance The economic value of cleaning and disinfection of shared medical equipment is currently unknown. Objective To evaluate whether or not better environmental cleaning and disinfection of shared medical equipment would be cost-effective compared with usual care. Design, Setting, and Participants This economic evaluation study was a within-trial cost-effectiveness analysis of a stepped-wedge cluster randomized clinical trial: the Cleaning and Enhanced Disinfection (CLEEN) study. The trial included 5002 inpatients and was conducted in 10 adult acute-care wards at a tertiary hospital in Australia between March 20, 2023, and November 24, 2023. The evaluation takes a hospital costing perspective. A decision-tree model was developed to evaluate the intervention; costs are presented in Australian dollars. Statistical analysis was performed from May to October 2024. Interventions A multimodal cleaning intervention was introduced during the intervention, focusing on additional cleaning hours, education, audit, and feedback. The control group received usual care, including routine cleaning by clinical staff. Main Outcomes and Measures Incremental cost-effectiveness ratio, where the mean change to costs associated with the intervention is divided by the mean change in outcomes. Results This study assessed 5002 patients (2478 [49.5%] male, 2524 [50.5%] female [50.5%]; mean [SD] age, 71.6 [16.1] years). For a cohort of 1000 patients at risk of health care–associated infection (HAI), the estimated total costs associated with the intervention were $1 513 300, compared with $2 155 310 for usual care. The estimated number of HAIs was 100 in the intervention group, compared with 130 for the usual care group. Compared with usual care, the intervention was associated with reduced HAIs and costs, with a 90.5% chance that intervention adoption was cost-saving. This probability increased to 99.9% if a decision-maker was willing to pay $20 000 to avoid an infection. Conclusions and Relevance In this economic evaluation study of enhanced cleaning and disinfection of shared medical equipment, the intervention resulted in reduced HAIs and a $642 010 reduction in costs per 1000 patients, compared with the control group. These results suggest that the CLEEN intervention is a cost-saving initiative.