tbuckley/cabot-search huggingface dataset:
Erratum. 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes—2025. Diabetes Care 2025;48(Suppl. 1):S86–S127
Authors: Nuha A. ElSayed, Rozalina G. McCoy, Grazia Aleppo, Kirthikaa Balapattabi, Elizabeth A. Beverly, Kathaleen Briggs Early, Dennis Bruemmer, Justin B. Echouffo-Tcheugui, Barbara Eichorst, Laya Ekhlaspour, Rajesh Garg, Mohamed Hassanein, Kamlesh Khunti, Rayhan Lal, Ildiko Lingvay, Glenn Matfin, Roeland J.W. Middelbeek, Naushira Pandya, Elizabeth J. Pekas, Scott J. Pilla, Sarit Polsky, Alissa R. Segal, Jane Jeffrie Seley, Robert C. Stanton, Molly L. Tanenbaum, Patti Urbanski, Raveendhara R. Bannuru
Journal: Diabetes Care (2025)

In Table 5.4, “Elements for risk calculation and suggested risk score for people with diabetes who seek to fast during Ramadan,” of the article cited above, the risk score for type 2 diabetes was mistakenly given as 2; the correct risk score is 0. The online version of the article (https://doi.org/10.2337/dc25-S005) has been updated with the correct risk score. Figure 5.2 has also been revised to better delineate the columns for blood pressure and A1C within the table detailing the impact of physical behaviors on cardiometabolic health in people with type 2 diabetes.
Neonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice
Authors: Chunling Chen, Yukun Yuan, Heather A. O'Malley, Robert Duba-Kiss, Yan Chen, Karl Habig, Yosuke Niibori, Samantha L. Hodges, David R. Hampson, Lori L. Isom
Journal: Journal of Clinical Investigation (2025)

Dravet syndrome (DS) is a developmental and epileptic encephalopathy (DEE) that begins in the first year of life. While most cases of DS are caused by variants in SCN1A, variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are also linked to DS or to the more severe early infantile DEE. Both disorders fall under the OMIM term DEE52. Scn1b null mice model DEE52, with spontaneous generalized seizures and death in 100% of animals in the third postnatal week. Scn1b null cortical parvalbumin-positive interneurons and pyramidal neurons are hypoexcitable. The goal of this study was to develop a proof-of-principle gene replacement strategy for DEE52. We tested an adeno-associated viral vector encoding β1 subunit cDNA (AAV-Navβ1) in Scn1b null mice. We demonstrated that AAV-Navβ1 drives β1 protein expression in excitatory and inhibitory neurons in mouse brain. Bilateral intracerebroventricular administration of AAV-Navβ1 in Scn1b null mice at postnatal day (P) 2, but not at P10, reduced spontaneous seizure severity and duration, prolonged life span, prevented hyperthermia-induced seizures, and restored cortical neuron excitability. AAV-Navβ1 administration to WT mice resulted in β1 overexpression in brain but no obvious adverse effects. This work lays the foundation for future development of a gene therapeutic strategy for SCN1B-linked DEE patients.
ReFORM synthesis of the 6th International Consensus Statement on Concussion in Sport
Authors: Géraldine Martens, Jon S Patricios, Kathryn J Schneider, Gavin A Davis, Cheri Blauwet, Nina Feddermann-Demont, Camille Tooth, Aurore Thibaut, Jean-François Kaux, Suzanne Leclerc
Journal: British Journal of Sports Medicine (2025)
Six-month safety and efficacy outcomes from the randomized-controlled arm of the WRAPSODY Arteriovenous Access Efficacy (WAVE) trial
Authors: Mahmood K Razavi, Saravanan Balamuthusamy, Angelo N Makris, Jeffrey G Hoggard, Leonardo O Harduin, Prabir Roy-Chaudhury, Robert G Jones
Journal: Kidney International (2025)
Metabolic dysfunction-associated steatotic liver disease in children
Authors: Nidhi P Goyal, Stavra Xanthakos, Jeffrey B Schwimmer
Journal: Gut (2025)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in children. MASLD encompasses a spectrum of liver disease and can be severe, with 10% of affected children presenting with advanced fibrosis. While biopsy remains the most accurate method for diagnosing and staging the disease, MRI proton density fat fraction and magnetic resonance elastography are the most reliable non-invasive measures for assessing steatosis and fibrosis, respectively. MASLD is associated with multiple comorbidities including type 2 diabetes, hypertension, dyslipidaemia, decreased bone mineral density, obstructive sleep apnoea, anxiety and depression. Currently, there are no pharmacological treatments available for children, highlighting the urgent need for paediatric clinical trials. A diet low in free sugars is promising for reducing steatosis and decreasing alanine aminotransferase, a surrogate marker for hepatic inflammation. Emerging data indicate that steatosis can be present in children under 6 years of age, which was previously considered rare. The intricate interplay of genetics may inform future therapeutics and prognostication, with the PNPLA3 gene showing the most evidence for association with the risk and severity of steatotic liver disease and steatohepatitis. MASLD is a complex disease affecting one in ten children and is associated with increased early mortality risk. More dedicated studies are needed in children to advance our understanding of this disease and find effective treatments.
N-acetyl-tryptophan in Acute Kidney Injury after Cardiac Surgery
Authors: Ning Shi, Ji-Wen Wang, Gengchen Su, Gaoxiang Ma, Feng-Qing Huang, Si-Jia Jin, Hua-Mei Xie, Wen-Xin Ge, Jiang-Ping Song, Xiaodong Luan, Lei Zhang, Lian-Wen Qi
Journal: Journal of the American Society of Nephrology (2025)

Cardiac surgery-associated acute kidney injury is a common serious complication after cardiac surgery. Currently, there are no specific pharmacological therapies. Our understanding of its pathophysiology remains preliminary. A total of 2504 patients with and without acute kidney injury (AKI) following cardiac surgery were enrolled. High-performance liquid chromatography coupled with mass spectrometry was used for untargeted analysis of metabolites in plasma, identifying significant differential metabolites. Subsequently, a tandem liquid chromatography-mass spectrometry-based approach using isotope-labeled standard addition was performed for targeted analysis of the metabolic marker N-acetyl-tryptophan. The function of N-acetyl-tryptophan was determined using different kidney injury mouse models and epithelial cellular models. Transcriptome sequencing, surface plasmon resonance and protein mutation were employed to explore the mechanism of N-acetyl-tryptophan on the kidney. We identified a total of 32 differential metabolites related to AKI occurrence based on a cohort of 1042 patients. Among them, N-acetyl-tryptophan was elevated in plasma of patients with cardiac surgery-associated acute kidney injury compared with those who do not develop AKI after cardiac surgery. The higher level of N-acetyl-tryptophan in plasma was confirmed by accurate targeted quantification. N-acetyl-tryptophan exhibited kidney protective effects in ischemia/reperfusion-, cisplatin-, and unilateral ureteral obstruction-induced kidney injury mouse models. Mechanistically, N-acetyl-tryptophan exerted kidney protective effects by interacting with KEAP1 at 483 and 508 sites, resulting in Nrf2 nuclear translocation and the transcription of proteasome genes. N-acetyl-tryptophan plays a key role in kidney protection.
Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC
Authors: Ryan J Corbett, Cricket C Gullickson, Zhuangzhuang Geng, Miguel A Brown, Bo Zhang, Chuwei Zhong, Nicholas Van Kuren, Antonia Chroni, Christopher Blackden, Ammar S Naqvi, Alexa Plisiewicz, Sean McHugh, Emmett Drake, Kaitlin Lehmann, Tom B Davidson, Michael Prados, Phillip B Storm, Adam C Resnick, Angela J Waanders, Sebastian M Waszak, Sabine Mueller, Jo Lynne Rokita, Cassie Kline
Journal: Neuro-Oncology (2025)

Abstract Background Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited. Methods We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment. Results Predicted superpopulations included African (AFR, N=153), Admixed American (AMR, N=222), East Asian (EAS, N=67), European (EUR, N=968), and South Asian (SAS, N=42). Reported race and ethnicity and ancestry-based genetic superpopulations were non-randomly associated (p&amp;lt;0.001). Patients with an atypical teratoid rhabdoid tumor or meningioma were enriched for AFR ancestry (OR=2.6, FDR=0.01; OR=2.9, FDR=0.01, respectively). Among KIAA1549::BRAF fusion-positive low-grade glioma (LGG) diagnoses, EAS and SAS patients disproportionately harbored exon 15:09 breakpoints (FDR&amp;lt;0.05), and AMR patients demonstrated rare breakpoints, which were associated with lesser degree of surgical resection and worse event free survival (EFS) versus other breakpoints (HR=4.6, p=0.03). Non-EUR and AMR patients with germ cell tumors and SHH-activated medulloblastoma, respectively, exhibited worse EFS relative to EUR patients (HR=12.1, p&amp;lt;0.01; HR=5.2, p=0.03) and AFR patients with LGG (HR=16.4, p&amp;lt;0.01) or ependymoma (HR=5.5, p=0.02) had worse overall survival compared to EUR patients. We observed higher frequency of clinical trial enrollment among AMR patients across tumor histologies (OR=2.0, p=&amp;lt;0.01), but increased utilization of photon versus proton radiation relative to other superpopulations (OR=0.55, p=0.04). Conclusions Genetic ancestry-associated differences exist across pediatric CNS tumor histological and molecular subtypes from PBTA and PNOC. Further investigation into genetic and socioeconomic factors contributing to these observed inequities is needed.
Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors
Authors: Juliane Bremer, Pamela Franco, Joelle Aline Menstell, Shelisa Tey, Kamil Kajetan Zajt, Klimentina Popzhelyazkova, Kay Nolte, Jürgen Schlegel, Maria Teresa Pedro, Anja Osterloh, Daniel Delev, Marc Hohenhaus, Christoph Scholz, Oliver Schnell, Juergen Beck, Joachim Weis, Dieter Henrik Heiland
Journal: Neuro-Oncology (2025)

Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells. Here, we aimed at determining the spatial and biological heterogeneity of PNSTs. We performed spatial transcriptomics on formalin-fixed paraffin-embedded diseased peripheral nerve tissue. We used spatial clustering and weighted correlation network analysis to construct niche-similarity networks and gene expression modules. We determined differential expression in primary pathologies, analysed pathways to investigate the biological significance of identified meta-signatures, integrated the transcriptional data with histological features and existing single cell data, and validated expression data by immunohistochemistry. We identified distinct transcriptional signatures differentiating PNSTs. Immune cell infiltration, APOD and perineurial fibroblast marker expression highlighted the neurofibroma component of hybrid PNSTs (HPNSTs). While APOD was evenly expressed in neurofibromatous tumor tissue in both, HPNST and pure neurofibromas, perineurial fibroblast markers were evenly expressed in HPNST, but restricted to the periphery in plexiform neurofibromas. Furthermore, we provide a spatial cellular differentiation map for MPNST, locating Schwann cell precursors, neural crest-like cells and those with mesenchymal transition. This pilot study shows that applying spatial transcriptomics to PNSTs provides important insight into their biology. It helps establishing new markers and provides spatial information about cellular composition and distribution of cellular differentiation states. By integrating morphological and high-dimensional molecular data it can improve PNSTs classification in the future.
Tuberculosis in the US Kidney Failure Population
Authors: Kimberly R. Schildknecht, Molly Deutsch-Feldman, Jason Cummins, Divia P. Forbes, Maryam B. Haddad, Ibironke W. Apata, Jonathan M. Wortham
Journal: Journal of the American Society of Nephrology (2025)

Background: People with chronic kidney disease (CKD) have a higher risk for progression to tuberculosis disease following infection with Mycobacterium tuberculosis. We produced a nationwide incidence estimate and description of tuberculosis among people with kidney failure. Methods: We completed a cross-sectional descriptive analysis of people with a reported case of tuberculosis in the United States between 2010 and 2021. We stratified all people with tuberculosis by reported kidney failure status. The primary outcome was tuberculosis incidence among people with kidney failure. We also compared characteristics of people with tuberculosis by reported kidney failure status. Results: Approximately 3% of people (2,892 of 111,155) diagnosed with tuberculosis between 2010 and 2021 also had kidney failure. Annual tuberculosis incidence ranged from 26.1 to 45.4 per 100,000 people with kidney failure and 2.1 to 3.5 per 100,000 people without kidney failure. Among people with kidney failure, 924 (32%) had extrapulmonary tuberculosis only, and nearly 40% died: 286 were diagnosed with tuberculosis after death, and 792 died during treatment. People with tuberculosis and kidney failure had approximately twice the prevalence of a false-negative tuberculin skin test result (39%) compared to people with tuberculosis alone (20%). Conclusions: Tuberculosis incidence among people with kidney failure between 2010 and 2021 in the United States was 10-fold that among people without kidney failure.
Modeling Biases from Low-Pass Genome Sequencing to Enable Accurate Population Genetic Inferences
Authors: Emanuel M Fonseca, Linh N Tran, Hannah Mendoza, Ryan N Gutenkunst
Journal: Molecular Biology and Evolution (2025)

Abstract Low-pass genome sequencing is cost-effective and enables analysis of large cohorts. However, it introduces biases by reducing heterozygous genotypes and low-frequency alleles, impacting subsequent analyses such as model-based demographic history inference. Several approaches exist for inferring an unbiased allele frequency spectrum (AFS) from low-pass data, but they can introduce spurious noise into the AFS. Rather than correcting the AFS, here, we developed an approach that incorporates low-pass biases into the demographic modeling and directly analyzes the AFS from low-pass data. Our probabilistic model captures biases from the Genome Analysis Toolkit multisample calling pipeline, and we implemented it in the population genomic inference software dadi. We evaluated the model using simulated low-pass datasets and found that it alleviated low-pass biases in inferred demographic parameters. We further validated the model by downsampling 1000 Genomes Project data, demonstrating its effectiveness on real data. Our model is widely applicable and substantially improves model-based inferences from low-pass population genomic data.
Single-cell analysis of neoplastic plasma cells identifies myeloma pathobiology mediators and potential targets
Authors: Luz Yurany Moreno Rueda, Hua Wang, Keiko Akagi, Minghao Dang, Amishi Vora, Li Qin, Hans C Lee, Krina K Patel, Pei Lin, David E Mery, Fenghuang Zhan, John D Shaughnessy, Qing Yi, Yang Song, Bo Jiang, Maura L Gillison, Sheeba K Thomas, Donna M Weber, Lixia Diao, Jing Wang, Isere Kuiatse, Elisabet E Manasanch, David E Symer, Robert Z Orlowski
Journal: Cell Reports Medicine (2025)

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models. Moreover, functional studies show a role of lysosomal-associated membrane protein family member-5 (LAMP5), which is uniquely expressed in neoplastic PCs, in tumor progression and aggressiveness via interactions with c-MYC. Finally, a monoclonal antibody recognizing cell-surface LAMP5 shows efficacy as an antibody-drug conjugate and in a chimeric antigen receptor-guided T-cell format. These studies provide additional insights into myeloma biology and identify potential targeted therapeutic approaches that can be applied to reverse myeloma progression.
WHO guidelines on waist circumference and physical activity and their joint association with cancer risk
Authors: Patricia Bohmann, Michael J Stein, Amina Amadou, Hansjörg Baurecht, Béatrice Fervers, Emma Fontvieille, Heinz Freisling, Christine Friedenreich, Julian Konzok, Laia Peruchet-Noray, Michael F Leitzmann, Anja M Sedlmeier, Andrea Weber
Journal: British Journal of Sports Medicine (2025)

Low body fat and high physical activity levels are key lifestyle factors in cancer prevention, but the interplay of abdominal obesity and physical activity on cancer risk remains unknown. We explored individual and joint associations of waist circumference and physical activity with cancer risk. Using UK Biobank data (n=315 457), we categorised individuals according to WHO guideline thresholds for waist circumference and self-reported physical activity levels. Multivariable-adjusted Cox regression was used to estimate HRs and 95% CIs of total cancer. The reference group comprised individuals with recommended levels of waist circumference (<88 cm for women and <102 cm for men) and physical activity (>10 metabolic equivalent of task hours/week). Furthermore, we estimated the proportion of cancers attributable to abdominal obesity and insufficient physical activity. During a median follow-up period of 11 years (3 321 486 person-years), 29 710 participants developed any type of cancer. Participants not meeting the WHO guideline on waist circumference had increased cancer risk, even when sufficiently physically active according to the WHO (HR 1.11, 95% CI 1.08 to 1.15). Similarly, individuals not achieving the WHO guideline for physical activity showed an elevated risk, even if they were abdominally lean (HR 1.04, 95% CI 1.01 to 1.07). Not adhering to either guideline yielded the strongest increase in risk (HR 1.15, 95% CI 1.11 to 1.19). We estimated that abdominal obesity coupled with insufficient physical activity could account for 2.0% of UK Biobank cancer cases. Adherence to both WHO guidelines for waist circumference and physical activity is essential for cancer prevention; meeting just one of these guidelines is insufficient.
Synthetic Bilirubin‐Based Nanomedicine Protects Against Renal Ischemia/Reperfusion Injury Through Antioxidant and Immune‐Modulating Activity
Authors: Ji‐Jing Yan, Hyunjin Kim, Bomin Kim, Honglin Piao, Joon Young Jang, Tae Kyeom Kang, Wook‐Bin Lee, Dohyeon Kim, Seunghyun Jo, Duckhyang Shin, Sharif MD Abuzar, Myung L. Kim, Jaeseok Yang, Sangyong Jon
Journal: Advanced Healthcare Materials (2025)

Abstract Renal ischemia/reperfusion injury (IRI) is a common form of acute kidney injury. The basic mechanism underlying renal IRI is acute inflammation, where oxidative stress plays an important role. Although bilirubin exhibits potent reactive oxygen species (ROS)‐scavenging properties, its clinical application is hindered by problems associated with solubility, stability, and toxicity. In this study, BX‐001N, a synthetic polyethylene glycol‐conjugated bilirubin 3α nanoparticle is developed and assessed its renoprotective effects in renal IRI. Intravenous administration of BX‐001N led to increase uptake in the kidneys with minimal migration to the brain after IRI. Peri‐IRI BX‐001N administration improves renal function and attenuates renal tissue injury and tubular apoptosis to a greater extent than free bilirubin on day 1 after IRI. BX‐001N suppressed renal infiltration of inflammatory cells and reduced expression of TNF‐α and MCP‐1. Furthermore, BX‐001N increases renal tubular regeneration on day 3 and suppresses renal fibrosis on day 28. BX‐001N decreases the renal expressions of dihydroethidium, malondialdehyde, and nitrotyrosine after IRI. In conclusion, BX‐001N, the first Good Manufacturing Practice‐grade synthetic bilirubin‐based nanomedicine attenuates acute renal injury and chronic fibrosis by suppressing ROS generation and inflammation after IRI. It shows adequate safety profiles and holds promise as a new therapy for renal IRI.
The blood transcriptional response in patients developing intensive care unit-acquired pneumonia
Authors: Justin de Brabander, Erik H.A. Michels, Joe M. Butler, Tom D.Y. Reijnders, Tjitske S.R. van Engelen, Giuseppe G.F. Leite, Fleur P. Paling, Augustijn M. Klarenbeek, Daoud L.S. Sie, Roxane E. Boyer, Timothy E. Sweeney, Marc J.M. Bonten, Leen Timbermont, Surbhi Malhotra-Kumar, Jan A.J.W. Kluytmans, Hessel Peters-Sengers, Tom van der Poll
Journal: European Respiratory Journal (2025)

Introduction Immune response dysregulation has been implicated in the development of intensive care unit (ICU)-acquired pneumonia. We aimed to determine differences in the longitudinal blood transcriptional response between patients who develop ICU-acquired pneumonia (cases) and those who do not (controls). Methods We performed a case-cohort study in mechanically ventilated trauma and surgery patients with ICU stays &gt;2 days, enrolled in 30 hospitals across Europe. We collected blood for RNA sequencing at baseline, day 7 and (in cases) the day of pneumonia diagnosis. We performed gene set enrichment analysis and analysed longitudinal gene expression changes using linear mixed models. External validation was performed using an independent trauma cohort. Results We enrolled 113 cases and 115 controls, with similar baseline characteristics. At baseline (median 2 days after ICU admission), cases showed upregulated gene pathways relating to innate immunity, hemostasis and metabolism, and downregulated adaptive immune pathways. These changes persisted at the day of pneumonia diagnosis (median 6 days, compared to day 7 in controls). In the longitudinal comparison, cases exhibited enhanced upregulation of innate immunity, adaptive immunity and hemostasis pathways, along with enhanced downregulation of metabolism pathways relative to controls (all p&lt;0.00001, except hemostasis p&lt;0.05). These findings were largely externally validated. Cases had higher quantitative sepsis response signature scores (p&lt;0.001), reflective of immune dysregulation. Conclusion Patients developing ICU-acquired pneumonia exhibit distinct blood transcriptional responses shortly after ICU admission and in the subsequent path to pneumonia, suggestive of broad immune dysfunction with both immunosuppressive and inflammatory features.