tbuckley/cabot-search huggingface dataset:
Stroke Incidence Evolution in People With Newly Diagnosed Diabetes and Impaired Glucose Tolerance: A 34-Year Follow-up of the Da Qing Diabetes Study
Authors: Yanyan Chen, Jinping Wang, Xinxin Feng, Xin Qian, Siyao He, Qier An, Xiang Yin, Xuan Wang, Yali An, Qiuhong Gong, Shuhan Zhou, Hui Li, Xiuwei Zhai, Xiaoping Chen, Guangwei Li
Journal: Diabetes Care (2025)

OBJECTIVE To examine the incidence of stroke in Chinese adults with newly diagnosed type 2 diabetes (NDD), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) over a 34-year follow-up period. RESEARCH DESIGN AND METHODS This cohort study included participants with NDD, IGT, and NGT initially identified in 1986 in the Da Qing Diabetes Prevention Study who were followed up for 34 years. Patients with IGT were randomized into a 6-year lifestyle intervention or control group. The stroke incidence and hazard ratios (HRs) were determined across the three glucose-level groups. RESULTS Over 34 years, the cumulative stroke incidence in the NDD, IGT nonintervention, and IGT intervention groups were 65.4%, 62.8%, and 49.8%, respectively. The annual incidence in the NDD group was significantly higher than that in the NGT group (24.3 vs. 18.5 per 1,000 person-years), after adjusting for age and sex. After adjusting for risk factors, the risk of stroke was significantly higher in the NDD (HR 1.80, 95% CI 1.46–2.21, P &amp;lt; 0.001), IGT nonintervention (HR 1.52, 95% CI 1.11–2.07, P = 0.008), and IGT intervention (HR 1.33, 95% CI 1.17–1.63, P = 0.01) groups than in the NGT group. A reduced stroke risk was observed in the overall IGT intervention group compared with the NDD group (HR 0.77, 95% CI 0.64–0.94, P = 0.009), especially in women (HR 0.64, 95% CI 0.47–0.88, P = 0.006). CONCLUSIONS Over 34 years, ∼50% of Chinese adults with NDD and IGT experienced stroke. Further efforts in diabetes management and intervention are required.
Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target
Authors: Shiekh Tanveer Ahmad, Yiran Li, Jesus Garcia-Lopez, Brian L Gudenas, Jennifer Hadley, Leena Paul, Stephanie C Wu, Alaa Refaat, Marija Kojic, Melissa Batts, Taha Soliman, Aaron Pitre, Frederik Arnskötter, Frederique Zindy, Alun Jones, Nathaniel R Twarog, Anand Mayasundari, Brandon Bianski, Christopher Tinkle, Abbas Shirinifard, Laura Janke, Meifen Lu, Sara A Lewis, Arzu Onar-Thomas, Stefan M Pfister, Amar Gajjar, Suzanne J Baker, Martine F Roussel, Zoran Rankovic, Giles W Robinson, Brent A Orr, Brandon Wainwright, Anang A Shelat, Sebastian M Waszak, Lena M Kutscher, Hong Lin, Paul A Northcott
Journal: Cancer Cell (2025)
Integrative characterization of MYC RNA-binding function
Authors: Sihan Li, Zehua Wang, Xiaofei Wang, Yifei Wang, Dhamotharan Pattarayan, Yu Zhang, Phuong Nguyen, Avishek Bhuniya, Yuang Chen, Haozhe Huang, Yixian Huang, Luxuan Wang, Junmei Wang, Song Li, Min Zhang, Yang Liu, Nara Lee, Da Yang
Journal: Cell Genomics (2025)

Emerging evidence suggests that MYC interacts with RNAs. Here, we performed an integrative characterization of MYC as an RNA-binding protein in six cell lines. We found that MYC binds to a myriad of RNAs with high affinity for guanosine-rich RNAs. Global and specific depletion of RNAs reduces MYC chromatin occupancy. Mechanistically, two highly conserved sequences, amino acids 355-357 KRR and 364-367 RQRR, within the basic region of MYC are necessary for its RNA binding. Notably, alanine substitution of KRR abolishes MYC's RNA-binding ability both in vitro and in vivo, without affecting its ability to bind E-box DNA as part of the MYC:MAX dimer in vitro. The loss of RNA-binding function decreases MYC chromatin binding in vivo and attenuates its ability to promote gene expression, cell-cycle progression, and proliferation. Our study lays a foundation for future investigation into the role of RNAs in MYC-mediated transcriptional activation and oncogenic functions.
Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis
Authors: Derek Dang, Akash Deogharkar, John McKolay, Kyle S Smith, Pooja Panwalkar, Simon Hoffman, Wentao Tian, Sunjong Ji, Ana P Azambuja, Siva Kumar Natarajan, Joanna Lum, Jill Bayliss, Katie Manzeck, Stefan R Sweha, Erin Hamanishi, Matthew Pun, Diya Patel, Sagar Rau, Olamide Animasahun, Abhinav Achreja, Martin P Ogrodzinski, Jutta Diessl, Jennifer Cotter, Debra Hawes, Fusheng Yang, Robert Doherty, Andrea T Franson, Allison R Hanaford, Charles G Eberhart, Eric H Raabe, Brent A Orr, Robert J Wechsler-Reya, Brandon Chen, Costas A Lyssiotis, Yatrik M Shah, Sophia Y Lunt, Ruma Banerjee, Alexander R Judkins, John R Prensner, Carl Koschmann, Sebastian M Waszak, Deepak Nagrath, Marcos Simoes-Costa, Paul A Northcott, Sriram Venneti
Journal: Cancer Cell (2025)
Opioid-driven disruption of the septum reveals a role for neurotensin-expressing neurons in withdrawal
Authors: Rhiana C Simon, Weston T Fleming, Brandy A Briones, Marta Trzeciak, Pranav Senthilkumar, Kentaro K Ishii, Madelyn M Hjort, Madison M Martin, Koichi Hashikawa, Andrea D Sanders, Sam A Golden, Garret D Stuber
Journal: Neuron (2025)
Disparities, trends, and projections of cancer mortality burden related to high body mass index in China from 2005 to 2030
Authors: Yixin Tian, Xue Cao, Chenye Chang, Xin Wang, Congyi Zheng, Xuyan Pei, Xue Yu, Yujie Zhang, Nuerguli Tuerdi, Zhenping Zhao, Limin Wang, Peng Yin, Yuehui Fang, Mei Zhang, Yuna He, Maigeng Zhou, Zengwu Wang
Journal: Cell Reports Medicine (2025)

High body mass index (BMI), defined as a BMI greater than or equal to 20-25 kg/m2, is considered a rapid-increased risk factor for cancer. Based on comparative risk assessment framework, we elaborate the mortality burden of cancers attributable to high BMI in China. In 2018, we estimated that there were 85.19 thousand cancer-related deaths and 2,220.01 thousand cancer-related years of life lost (YLLs) attributable to high BMI in China. Of these, 62.14 thousand deaths and 1,698.81 thousand YLLs were from males. With higher socioeconomic levels, the burden generally increases initially and then decreases. By 2030, the projected age-standardized mortality rate attributable to high BMI in China will be 6.67 per 100,000 people, increased by 3.25% from that in 2005. In summary, the swift increase and substantial disparities in the cancer burden attributable to high BMI underscore the urgent need for evidence-based policies and interventions in China.
Targeting the Dependence on PIK3C3-mTORC1 Signaling in Dormancy-Prone Breast Cancer Cells Blunts Metastasis Initiation
Authors: Islam E. Elkholi, Amélie Robert, Camille Malouf, Joshua L. Wu, Hellen Kuasne, Stanislav Drapela, Graham Macleod, Steven Hébert, Alain Pacis, Virginie Calderon, Claudia L. Kleinman, Ana P. Gomes, James V. Alvarez, Julio A. Aguirre-Ghiso, Morag Park, Stéphane Angers, Jean-François Côté
Journal: Cancer Research (2025)

Abstract Halting breast cancer metastatic relapse following primary tumor removal remains challenging due to a lack of specific vulnerabilities to target during the clinical dormancy phase. To identify such vulnerabilities, we conducted genome-wide CRISPR screens on two breast cancer cell lines with distinct dormancy properties: 4T1 (short-term dormancy) and 4T07 (prolonged dormancy). The dormancy-prone 4T07 cells displayed a unique dependency on class III PI3K (PIK3C3). Unexpectedly, 4T07 cells exhibited higher mechanistic target of rapamycin complex 1 (mTORC1) activity than 4T1 cells due to lysosome-dependent signaling occurring at the cell periphery. Pharmacologic inhibition of PIK3C3 suppressed this phenotype in the 4T1-4T07 models as well as in human breast cancer cell lines and a breast cancer patient-derived xenograft. Furthermore, inhibiting PIK3C3 selectively reduced metastasis burden in the 4T07 model and eliminated dormant cells in a HER2-dependent murine breast cancer dormancy model. These findings suggest that PIK3C3-peripheral lysosomal signaling to mTORC1 may represent a targetable axis for preventing dormant cancer cell–initiated metastasis in patients with breast cancer. Significance: Dormancy-prone breast cancer cells depend on the class III PI3K to mediate peripheral lysosomal positioning and mTORC1 hyperactivity, which can be targeted to blunt breast cancer metastasis.
Proposing an Immune-Inclusive Lens to the New Epidermal Differentiation Disorders Classification
Authors: Rahul Mahajan, Hitaishi Mehta, Dipankar De, Sanjeev Handa
Journal: British Journal of Dermatology (2025)

We commend the structural and mechanistic clarity offered by the new pathogenesis-based classification for inherited epidermal differentiation disorders (EDDs) while proposing a complementary immunological dimension—epidermal differentiation disorders with immune dysregulation (EDDID). Drawing on emerging data from ichthyosis and parallels with inflammatory dermatoses like atopic dermatitis and psoriasis, we suggest that recognizing immune endotypes within this framework may enhance diagnostic precision and expand therapeutic horizons.
Cave-Associated Histoplasmosis Outbreak Among Travelers Returning from Costa Rica — Georgia, Texas, and Washington, December 2024–January 2025
Authors: Ria R. Ghai, Elizabeth T. Sajewski, Mitchell Blass, Hayley Belles, Hope Dishman, Julie Gabel, BreeAnna Dell, Mariah Harper, Hanna N. Oltean, Olivia Smith, Emeka Ogwuegbu, Saad Zaheer, Alexander Jordan, Meghan Lyman, Ian Hennessee, Mitsuru Toda
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Histoplasmosis is a fungal infection that primarily affects the lungs. The condition is caused by Histoplasma organisms, which are often found in soil contaminated with bird or bat droppings. On January 17, 2025, a Georgia infectious disease physician notified CDC of suspected histoplasmosis cases among 12 members of an extended family from households in Georgia, Texas, and Washington. The ill family members included six adults aged 42-49 years and six children aged 8-16 years. They had recently returned from Costa Rica, where they toured a cave linked to a previous histoplasmosis outbreak (1).
<i>Notes from the Field:</i> Multistate Outbreak of <i>Salmonella enterica</i> I 4:I:- Infections Linked to Charcuterie-Style Meats — United States, 2023–2024
Authors: Angelo Lodato, Andrea Cote, Joshua Rounds, Laurie K. Stewart, Anna E. Pickett, Megan E. Cahill, Lorrie L. B. Martin, Jennifer K. Adams, Lauren Gollarza, Zachary D. McCormic
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Gastrointestinal Barrier Disruption in Post‐<scp>COVID</scp> Syndrome Fatigue Patients
Authors: Johanna Rohrhofer, Viktoria Wolflehner, Johannes Schweighardt, Larissa Koidl, Michael Stingl, Sonja Zehetmayer, Joana Séneca, Petra Pjevac, Eva Untersmayr
Journal: Allergy (2025)

ABSTRACT Background Post‐COVID Syndrome (PCS) is the term for a condition with persistent symptoms in a proportion of COVID‐19 patients after asymptomatic, mild, or severe disease courses. Numbers vary, but the current estimate is that after COVID‐19 approximately 10% develop PCS. The aim of our study was to evaluate the impact of SARS‐CoV‐2 infection on the gastrointestinal (GI) tract and associations with the development of PCS with fatigue, post‐exertional malaise (PEM), orthostatic dysregulation, autonomous dysregulation, and/or neurocognitive dysregulation. Methods By combining medical record data from a prospective observational study with symptom analysis before, during, and after SARS‐CoV‐2 infection, we aimed to identify potential risk factors and predictive markers for PCS. Additionally, we analyzed blood, saliva, and stool samples from this well‐characterized PCS patient cohort to biologically validate our findings. Results We identified significant associations between pre‐existing GI complaints and the development of PCS Fatigue. PCS patients showed higher LBP/sCD14 ratios, lower IL‐33 levels, and higher IL‐6 levels compared to control groups. Our results highlight the critical role of the GI tract in PCS development of post‐viral Fatigue. Conclusion We propose that the viral infection disrupts pathways related to the innate immune response and GI barrier function, evidenced by intestinal low‐grade inflammation and GI barrier leakage. Monitoring GI symptoms and markers before, during, and after SARS‐CoV‐2 infection is crucial for identifying predictive clinical phenotypes in PCS. Understanding the interaction between viral infections, immune responses, and gut integrity could lead to more effective diagnostic and treatment strategies, ultimately reducing the burden on PCS patients.
Preclinical Development of <scp>GR2002</scp>, a Novel Anti‐<scp>TSLP</scp> Bispecific Antibody With Potent <scp>TSLP</scp> Inhibitory Effects
Authors: Xueping Zhang, Suya Luo, Xiaobo Hao, Yulan Liu, Junjie Hu, Jiaqian Yang, Hongtao Qin, Zhigang Liu
Journal: Allergy (2025)
The Mutational Landscape in Polycythemia Vera: Phenotype, Genotype, and Prognostic Correlates
Authors: Masooma S. Rana, Moazah Iftikhar, Yamna Jadoon, Maymona Abdelmagid, David S. Viswanatha, Rong He, Kaaren K. Reichard, Animesh D. Pardanani, Naseema Gangat, Ayalew Tefferi
Journal: American Journal of Hematology (2025)

ABSTRACT Polycythemia vera (PV) is invariably associated with a JAK2 mutation, with over 50% of patients harboring additional non‐ JAK2 mutations. In the current study, 319 patients with PV underwent NGS at diagnosis or in chronic phase PV (Group A: N = 270, 85%) or at the time of fibrotic (Group B; N = 37, 12%) or leukemic (Group C; N = 12, 4%) transformation. Mutational frequencies involving TP53/SRSF2/IDH1/U2AF1 were significantly ( p &lt; 0.05) different between patients in the mutually exclusive Groups A (2%/4%/2%/0.4%), B (8%/0%/0%/5%), and C (50%/25%/17%/8%). Analyses on phenotype/genotype associations and prognostic impact on overall (OS), leukemia‐free (LFS), and myelofibrosis‐free (MFFS) survival were limited to Group A patients. ASXL1 MUT was associated with younger age ( p &lt; 0.01), SRSF2 MUT with older age and leukocytosis ( p &lt; 0.01), and TP53 MUT with leukocytosis ( p &lt; 0.01). Mutation co‐segregation was apparent between ASXL1 and IDH2 ( p &lt; 0.01) or SRSF2 ( p &lt; 0.01), SRSF2 and IDH2 ( p &lt; 0.01), and TP53 and NRAS ( p = 0.01). Multivariable analysis identified SRSF2 MUT ( p &lt; 0.01; HR, 4.2, 1.9–9.5), IDH2 MUT ( p = 0.01; HR, 5.3, 1.8–15.3), ASXL1 MUT ( p = 0.04; HR, 2.0, 1.1–3.7), leukocyte count ≥ 15 × 10 9 /L ( p &lt; 0.01; HR 2.0, 1.3–3.1), and advanced age ( p &lt; 0.01) as risk factors for OS. Median OS in the presence ( N = 235; 87%) or absence ( N = 35; 13%) of any adverse mutation (i.e., SRSF2 MUT , ASXL1 MUT , or IDH2 MUT ) was 8.8 versus 17.8 years ( p = 0.01; HR 1.8, 1.1–2.9). In addition, ASXL1 MUT ( p = 0.02; HR, 1.6–24.9), SRSF2 MUT ( p = 0.06; HR, 11.9, 1.1–126.2), and advanced age ( p = 0.04) were associated with inferior LFS, and SRSF2 MUT ( p &lt; 0.01; HR, 24.0, 5.5–103.8) and abnormal karyotype ( p &lt; 0.01; HR 3.8, 1.6–8.9) with inferior MFFS. The number of non‐ JAK2 mutations was significant in predicting outcome in univariate but not multivariable analysis. The observations from the current study highlight the prognostic significance of non‐ JAK2 mutations in PV and the prospect of their inclusion in future prognostic models.
Reducing outpatient visits for FIT-positive participants of colorectal cancer screening programs with home-based digital counselling
Authors: Fleur E Marijnissen, Elyse E C Rijnders, Merel M Tielemans, Désiree van Noord, Leonieke M M Wolters, Jeroen M Jansen, Ingrid Schot, Frank C Bekkering, Agnes N Reijm, Sophia M van Baalen, Tingting Wang, Marijke Melles, Richard Goossens, Sohal Y Ismail, Iris Lansdorp-Vogelaar, Pieter Jan F de Jonge, Manon C W Spaander
Journal: npj Digital Medicine (2025)

Digital counselling can alleviate the burden on healthcare systems and patients. While it has been evaluated as a supplement to standard care or a substitute for follow-up visits, its use for initial triaging and counselling remains unstudied. We developed a Digital Intake Tool (DIT) to facilitate the entire pre-colonoscopy counselling process for FIT-positive participants of a colorectal cancer screening program digitally, replacing the need for physicians. In this multicentre prospective non-inferiority study, we evaluated if the DIT could replace in-person counselling. DIT-counselling resulted in adequately prepared participants in 96.5%, compared to 97.6% after in-person counselling, demonstrating non-inferiority. Outpatient visits were significantly reduced, with only 3.4% requiring face-to-face consultations. Patient experiences were highly positive, without increased psychological distress or anxiety, and effective knowledge transfer. This approach benefits patients and healthcare systems, allowing patients to receive care at home, reducing travel and carbon emissions, while increasing outpatient capacity. ICTRP-registration: NL9315, March 8, 2021.
Urinary Prostaglandin Metabolites as Potential Biomarkers for Differentiating <scp>IgE</scp>‐Mediated Food Allergy and Food Protein‐Induced Enterocolitis Syndrome
Authors: Kotaro Umezawa, Nanae Nagata, Shigenori Kabashima, Yusuke Inuzuka, Hisako Ogasawara, Mami Shimada, Sayaka Hamaguchi, Osamu Natsume, Tatsuki Fukuie, Tatsuo Shimosawa, Yukihiro Ohya, Takahisa Murata, Kiwako Yamamoto‐Hanada
Journal: Allergy (2025)
Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses
Authors: Daan Jansen, Sara Deleu, Clara Caenepeel, Tine Marcelis, Ceren Simsek, Gwen Falony, Kathleen Machiels, João Sabino, Jeroen Raes, Séverine Vermeire, Jelle Matthijnssens
Journal: Gut Microbes (2025)

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.
Network analysis of the cerebrospinal fluid proteome reveals shared and unique differences between sporadic and familial forms of amyotrophic lateral sclerosis
Authors: Adam N Trautwig, Edward J Fox, Eric B Dammer, Anantharaman Shantaraman, Lingyan Ping, Duc M Duong, Caroline M Watson, Fang Wu, Seneshaw Asress, Qi Guo, Allan I Levey, James J Lah, Federico Verde, Alberto Doretti, Antonia Ratti, Nicola Ticozzi, Cindy V Ly, Timothy M Miller, Mark A Garret, James D Berry, Eleanor V Thomas, Christina N Fournier, Zachary T McEachin, Nicholas T Seyfried, Jonathan D Glass
Journal: Molecular Neurodegeneration (2025)

Abstract Background Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease involving loss of motor neurons, typically results in death within 3–5 years of disease onset. Although roughly 10% of cases can be linked to a specific inherited mutation (e.g., C9orf72 hexanucleotide repeat expansion or SOD1 mutation), the cause(s) of most cases are unknown. Consequently, there is a critical need for biomarkers that reflect disease onset and progression across ALS subgroups. Methods We employed tandem mass tag mass spectrometry (TMT-MS) based proteomics on cerebrospinal fluid (CSF) to identify and quantify 2105 proteins from sporadic, C9orf72, and SOD1 ALS patients, asymptomatic C9orf72 expansion carriers, and controls ( N = 101). To verify trends in our Emory University cohort we used data-independent acquisition (DIA-MS) on an expanded, four center cohort. This expanded cohort of 259 individuals included 50 sporadic ALS (sALS), 43 C9orf72 ALS, 22 SOD1 ALS, 72 asymptomatic gene carriers (59 C9orf72 and 13 SOD1) and 72 age-matched controls. We identified 2330 proteins and used differential protein abundance and network analyses to determine how protein profiles vary across disease subtypes in ALS CSF. Results Differential abundance and co-expression network analysis identified proteomic differences between ALS and control, as well as differentially abundant proteins between sporadic, C9orf72 and SOD1 ALS. A panel of proteins differentiated forms of ALS that are indistinguishable in a clinical setting. An additional panel differentiated asymptomatic from symptomatic C9orf72 and SOD1 mutation carriers, marking a pre-symptomatic proteomic signature of genetic forms of ALS. Leveraging this large, multicenter cohort, we validated our ALS CSF network and identified ALS-specific proteins and network modules. Conclusions This study represents a comprehensive analysis of the CSF proteome across sporadic and genetic causes of ALS that resolves differences among these ALS subgroups and also identifies proteins that distinguish symptomatic from asymptomatic gene carriers. These new data point to varying pathogenic pathways that result in an otherwise clinically indistinguishable disease.
Unraveling important outcomes for elderly patients facing critical illness: a vignette-based survey
Authors: Ryohei Yamamoto, Hajime Yamazaki, Hiroaki Nakagawa, Akihiro Ozaka, Kazuharu Harada, Ryohei Yamamoto, Hajime Yamazaki, Hiroaki Nakagawa, Akihiro Ozaka, Kazuharu Harada, Sho Sasaki, Sugihiro Hamaguchi, Shunichi Fukuhara
Journal: Intensive Care Medicine (2025)
Long-term outcomes of depression up to 10-years after stroke in the South London Stroke Register: a population-based study
Authors: Lu Liu, Iain J. Marshall, Xianqi Li, Ajay Bhalla, Lidan Liu, Ruonan Pei, Charles D.A. Wolfe, Matthew D.L. O'Connell, Yanzhong Wang
Journal: The Lancet Regional Health - Europe (2025)