tbuckley/cabot-search huggingface dataset:
Universal statistics of hippocampal place fields across species and dimensionalities
Authors: Nischal Mainali, Rava Azeredo da Silveira, Yoram Burak
Journal: Neuron (2025)

Hippocampal place cells have single, bell-shaped place fields in small environments. Recent experiments, however, reveal that, in large environments, place cells have multiple fields with heterogeneous shapes and sizes. We show that this diversity is explained by a surprisingly simple mathematical model, in which place fields are generated by thresholding a realization of a random Gaussian process. The model captures the statistics of field arrangements and generates new quantitative predictions about the statistics of field shapes and topologies. These predictions are quantitatively verified in bats and rodents, in one, two, and three dimensions, in both small and large environments. These results imply that common mechanisms underlie the diverse statistics observed in different experiments and further suggest that synaptic projections to CA1 are predominantly random.
Association Between Physiological Significance and Vulnerable Plaque Characteristics in Patients With Myocardial Infarction
Authors: Ketina Arslani, Thomas Engstrøm, Michael Maeng, Lars Kjøller-Hansen, Akiko Maehara, Zhipeng Zhou, Ori Ben-Yehuda, Hans Erik Bøtker, Mitsuaki Matsumura, Gary S Mintz, Ole Fröbert, Jonas Persson, Rune Wiseth, Alf I Larsen, Lisette O Jensen, Jan E Nordrehaug, Øyvind Bleie, Elmir Omerovic, Claes Held, Stefan K James, Ziad A Ali, David Erlinge, Gregg W Stone
Journal: JACC. Cardiovascular imaging (2025)
Clinical Behavior of Breast Cancer in Young <i>BRCA</i> Carriers and Prediagnostic Awareness of Germline <i>BRCA</i> Status
Authors: Matteo Lambertini, Eva Blondeaux, Loredana M. Tomasello, Elisa Agostinetto, Anne-Sophie Hamy, Hee Jeong Kim, Maria Alice Franzoi, Rinat Bernstein-Molho, Florentine Hilbers, Katarzyna Pogoda, Hans Wildiers, Jyoti Bajpai, Michail Ignatiadis, Halle C.F. Moore, Ann H. Partridge, Kelly-Anne Phillips, Angela Toss, Christine Rousset-Jablonski, Carmen Criscitiello, Tiphaine Renaud, Alberta Ferrari, Shani Paluch-Shimon, Robert Fruscio, Wanda Cui, Stephanie M. Wong, Claudio Vernieri, Kathryn J. Ruddy, Maria Vittoria Dieci, Alexios Matikas, Mariya Rozenblit, Cynthia Villarreal-Garza, Laura De Marchis, Fabio Puglisi, Kenny A. Rodriguez-Wallberg, Francois P. Duhoux, Luca Livraghi, Marco Bruzzone, Luca Boni, Judith Balmaña
Journal: Journal of Clinical Oncology (2025)

PURPOSE To investigate the clinical behavior of breast cancer in young BRCA carriers according to the specific BRCA gene ( BRCA1 v BRCA2 ) and the association of the timing of genetic testing (before v at diagnosis) with prognosis. METHODS This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in BRCA1 or BRCA2 , who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306 ). RESULTS Compared with BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) had more frequently hormone receptor–negative (74.4% v 15.5%) and high-grade (77.5% v 49.1%) tumors. Similar outcomes were observed in BRCA1 and BRCA2 carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for BRCA at diagnosis (ie, between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1: 61.3% v 32.4%), less nodal involvement (N0: 65.9% v 50.8%), less frequently received chemotherapy (84.4% v 92.9%), and axillary dissection (37.5% v 47.4%). Patients tested before diagnosis had better overall survival (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 to 0.92]); however, this result lost statistical significance after adjustment for potential confounders including tumor stage (adjusted HR, 0.74 [95% CI, 0.47 to 1.15]). CONCLUSION This global study provides evidence on the different clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers. Identifying a BRCA PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.
Development of Prompt Templates for Large Language Model–Driven Screening in Systematic Reviews
Authors: Christian Cao, Jason Sang, Rohit Arora, David Chen, Robert Kloosterman, Matthew Cecere, Jaswanth Gorla, Richard Saleh, Ian Drennan, Bijan Teja, Michael Fehlings, Paul Ronksley, Alexander A. Leung, Dany E. Weisz, Harriet Ware, Mairead Whelan, David B. Emerson, Rahul K. Arora, Niklas Bobrovitz
Journal: Annals of Internal Medicine (2025)

Systematic reviews (SRs) are hindered by the initial rigorous article screen, which delays access to reliable information synthesis. To develop generic prompt templates for large language model (LLM)-driven abstract and full-text screening that can be adapted to different reviews. Diagnostic test accuracy. 48 425 citations were tested for abstract screening across 10 SRs. Full-text screening evaluated all 12 690 freely available articles from the original search. Prompt development used the GPT4-0125-preview model (OpenAI). None. Large language models were prompted to include or exclude articles based on SR eligibility criteria. Model outputs were compared with original SR author decisions after full-text screening to evaluate performance (accuracy, sensitivity, and specificity). Optimized prompts using GPT4-0125-preview achieved a weighted sensitivity of 97.7% (range, 86.7% to 100%) and specificity of 85.2% (range, 68.3% to 95.9%) in abstract screening and weighted sensitivity of 96.5% (range, 89.7% to 100.0%) and specificity of 91.2% (range, 80.7% to 100%) in full-text screening across 10 SRs. In contrast, zero-shot prompts had poor sensitivity (49.0% abstract, 49.1% full-text). Across LLMs, Claude-3.5 (Anthropic) and GPT4 variants had similar performance, whereas Gemini Pro (Google) and GPT3.5 (OpenAI) models underperformed. Direct screening costs for 10 000 citations differed substantially: Where single human abstract screening was estimated to require more than 83 hours and $1666.67 USD, our LLM-based approach completed screening in under 1 day for $157.02 USD. Further prompt optimizations may exist. Retrospective study. Convenience sample of SRs. Full-text screening evaluations were limited to free PubMed Central full-text articles. A generic prompt for abstract and full-text screening achieving high sensitivity and specificity that can be adapted to other SRs and LLMs was developed. Our prompting innovations may have value to SR investigators and researchers conducting similar criteria-based tasks across the medical sciences. None.
Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes
Authors: Huilin Tang, Ying Lu, William T. Donahoo, Sarah C. Westen, Yong Chen, Jiang Bian, Jingchuan Guo
Journal: Annals of Internal Medicine (2025)

Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential antidepressant effects, population studies yield inconsistent results. To compare the risk for depression in older adults with type 2 diabetes (T2D) initiating treatment with GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is). Target trial emulation study. U.S. National Medicare administrative data from January 2014 to December 2020. Adults aged 66 years or older with T2D initiating treatment with a GLP-1RA were matched 1:1 on propensity score with those initiating treatment with either an SGLT2i or a DPP4i. The primary end point was incident depression. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) with 95% CI within matched groups. A total of 14 665 matched pairs of older adults were included in the cohort for GLP-1RAs versus SGLT2is; the rate difference of depression between GLP-1RA users and SGLT2i users was 3.48 (95% CI, -0.81 to 7.78) per 1000 person-years, with an HR of 1.07 (CI, 0.98 to 1.18). In the cohort for GLP-1RAs versus DPP4is (13 711 matched pairs), the rate difference was -5.78 (CI, -10.49 to -1.07) per 1000 person-years, with an HR of 0.90 (CI, 0.82 to 0.98). Unmeasured confounders (such as hemoglobin A1c levels and body mass index), outcome misclassification, and limited generalizability to all GLP-1RA users (for example, younger populations or those without T2D receiving the drug for obesity treatment). Among older adults with T2D, the incidence of depression was relatively low. Use of GLP-1RAs was associated with a modestly lower risk for depression compared with use of DPP4is, but not SGLT2is. National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
Prevalence of Chronic Medical Conditions Among Medicare Advantage and Traditional Medicare Beneficiaries
Authors: Andrew S. Oseran, Rahul Aggarwal, Jose Figueroa, Karen E. Joynt Maddox, Bruce E. Landon, Rishi K. Wadhera
Journal: Annals of Internal Medicine (2025)

The federal government spends billions of dollars per year on payments to Medicare Advantage (MA) plans based, in part, on beneficiaries' risk scores. Despite this, little is known about the true burden of chronic medical conditions among MA beneficiaries compared with those in fee-for-service (FFS) Medicare. To determine whether the prevalence of chronic medical conditions is higher among MA compared with FFS beneficiaries. Cross-sectional. Population based. Adults aged 65 years or older enrolled in MA or FFS Medicare. Using direct physical examination and laboratory data from the National Health and Nutrition Examination Survey (2015 to 2018), we compared the age- and sex-standardized prevalence of obesity, hypertension, hyperlipidemia, diabetes, and chronic kidney disease between MA and FFS beneficiaries. The unweighted study population included 2446 respondents corresponding to a weighted total of 45 426 711 adults (34.4% MA, 65.6% FFS Medicare). The prevalence of obesity (41.1% vs. 40.6%; standardized difference [SDiff], 0.48 percentage points [pp] [95% CI, -5.2 to 6.2 pp]), hypertension (70.9% vs. 71.0%; SDiff, -0.05 pp [CI, -5.8 to 5.7 pp]), hyperlipidemia (79.4% vs. 82.3%; SDiff, -2.86 pp [CI, -7.0 to 1.3 pp]), and chronic kidney disease (19.2% vs. 22.8%; SDiff, -3.48 pp [CI, -9.2 to 2.3 pp]) was not higher among MA beneficiaries compared with FFS beneficiaries. However, the prevalence of diabetes was higher in MA (33.3% vs. 26.3%; SDiff, 7.00 pp [CI, 3.3 to 10.7 pp]). Differences in the severity of specific medical conditions between groups could not be assessed. In this nationally representative study from 2015 to 2018, the prevalence of obesity, hypertension, hyperlipidemia, and chronic kidney disease was not higher among MA compared with FFS beneficiaries; however, the prevalence of diabetes was higher among MA beneficiaries. National Heart, Lung, and Blood Institute (NHLBI) and American Heart Association (AHA).
TL1A: a novel alarmin in airway, intestinal, and autoimmune disorders
Authors: Gilda Varricchi, Remo Poto, Gjada Criscuolo, Caterina Strisciuglio, Parameswaran Nair, Gianni Marone
Journal: Journal of Allergy and Clinical Immunology (2025)

The term alarmin denotes a broad class of molecules rapidly released to alert the immune system through the engagement of specific receptors on immune cells. Three alarmin cytokines, thymic stromal lymphopoietin (TSLP), IL-33, IL-25), are released from epithelial and certain stromal cells. TNF-like cytokine 1A (TL1A) is a member of the TNF cytokine superfamily, first identified in human endothelial cells. TL1A is now considered a novel alarmin expressed by human and mouse bronchial and intestinal epithelial cells. TL1A exerts its biological activities by binding to a trimeric receptor DR3 (death receptor-3), expressed on a wide spectrum of immune and structural cells (e.g., lung fibroblasts, endothelial cells, and bronchial epithelial cells). TL1A has been implicated in experimental and human inflammatory bowel diseases (IBD), airway inflammation and remodeling in severe asthma. A monoclonal antibody anti-TL1A (tulisokibart) is effective in inducing clinical remission in ulcerative colitis patients. Increasing evidence suggests that TL1A is also involved in certain autoimmune disorders (e.g., rheumatoid arthritis, psoriasis). These emerging findings broaden the role of TL1A in various human inflammatory conditions. Several clinical trials are currently evaluating the safety and efficacy of monoclonal antibodies targeting TL1A in asthma or IBD patients.
DCLK1-mediated regulation of invadopodia dynamics and matrix metalloproteinase trafficking drives invasive progression in head and neck squamous cell carcinoma
Authors: Levi Arnold, Marrion Yap, Nathan Farrokhian, Laura Jackson, Michael Barry, Thuc Ly, Pachiappan Arjunan, Angela Kaczorowski-Worthley, Carter Tews, Avisha Pandey, Austin Morrison, Michael P. Washburn, David Standing, Juan P. Gomez, Nanda Kumar Yellapu, David Johnson, Linheng Li, Shahid Umar, Shrikant Anant, Sufi Mary Thomas
Journal: Molecular Cancer (2025)

HNSCC presents a significant health challenge due to its high mortality resulting from treatment resistance and locoregional invasion into critical structures in the head and neck region. Understanding the invasion mechanisms of HNSCC has the potential to guide targeted therapies, improving patient survival. Previously, we demonstrated the involvement of doublecortin like kinase 1 (DCLK1) in regulating HNSCC cell invasion. Here, we investigated the hypothesis that DCLK1 modulates proteins within invadopodia, specialized subcellular protrusions that secrete matrix metalloproteinases to degrade the ECM. We employed tandem mass tag (TMT)-based proteomics to identify the role of DCLK1 in regulating proteins involved in HNSCC invasion and validated the findings using immunoblotting. The Cancer Genome Atlas (TCGA) database was interrogated to correlate DCLK1 expression with tumor stage, grade, and invasion-associated proteins. In vitro invasion was assessed using a Boyden chamber assay, and immunohistochemistry on patient samples determined DCLK1's distribution within tumors. Gelatin invadopodia assay was used to establish DCLK1 localization to invadopodia related gelatin degradation. Super-resolution confocal microscopy demonstrated colocalization of DCLK1 with invadopodia markers and MMP trafficking proteins. ECM degradation by MMPs in HNSCC cells with wild-type and knockdown DCLK1 was evaluated using a dye-quenched tracer, while gel zymography and MMP array identified secreted proteases. Proximity ligation assay (PLA) and co-immunoprecipitation assays were used to confirm interactions between DCLK1, MMP9, KIF16B, and RAB40B. Proteomic analysis demonstrate DCLK1's role in regulating proteins involved in cytoskeletal and ECM remodeling. Clinically, rising DCLK1 levels correlate with higher histological grade and lymph node metastasis, with heightened expression observed at the leading edge of HNSCC patient tissue. DCLK1 is localized with markers of mature invadopodia including TKS4, TKS5, cortactin, and MT1-MMP. Knockdown of DCLK1 led to reductions in invadopodia numbers and decreased in vitro invasion and ECM degradation. MMP9 colocalizes with DCLK1 within invadopodia structures and its secretion is disrupted by DCLK1 knockdown. Further, PLA and co-immunoprecipitations studies demonstrate DLCK1 complexes with KIF16B and RAB40B enabling trafficking of degradative MMP9 cargo along the invadopodia to degrade local ECM. This work unveils a novel function of DCLK1 in regulating KIF16B and RAB40B to traffic matrix degrading MMP9 cargo to the distal end of the invadopodia facilitating HNSCC invasion.
Correction: Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone
Authors: Jianping Jiang, Astrid V Cienfuegos-Gallet, Tengfei Long, Gisele Peirano, Tingyu Chu, Johann D. D. Pitout, Barry N. Kreiswirth, Liang Chen
Journal: Genome Medicine (2025)
Corrigendum to “Enhanced antitumor and anti-metastasis efficiency via combined treatment with CXCR4 antagonist and liposomal doxorubicin” [Journal of Controlled Release, Volume 196 (2014), Pages 324–331].
Authors: Ling Mei, Yayuan Liu, Qianyu Zhang, Huile Gao, Zhirong Zhang, Qin He
Journal: Journal of Controlled Release (2025)
Discussing expected long-term quality of life in the ICU: effect on experiences and outcomes of patients, family, and clinicians—a randomized clinical trial
Authors: Lucy L. Porter, Koen S. Simons, Johannes G. van der Hoeven, Mark van den Boogaard, Marieke Zegers
Journal: Intensive Care Medicine (2025)

To evaluate the effect of discussing personalized predictions of long-term quality of life (QoL) on patient and family experiences and outcomes, and on experiences of ICU clinicians. We conducted a randomized clinical trial in two Dutch hospitals, assigning adult ICU patients to receive usual care or the intervention: discussing the expected long-term QoL based on a validated prediction model, during a family meeting in the ICU. Primary outcome was patient and family experience with shared decision-making (CollaboRATE, range 0–100), evaluated < 3 days after the family meeting. Secondary outcomes included ICU professionals' experiences (Collaboration and Satisfaction about Care Decisions [CSACD] and Ethical Decision-Making Climate Questionnaire [EDMCQ]), symptoms of anxiety and depression among patients and family, and patients' QoL 3 months and 1 year post-ICU. 160 patients were included, of whom 81 were randomized to receive the intervention and 79 to receive usual care. No significant differences were seen in patients' and family members' experiences (median CollaboRATE score 89 [IQR 85–100] in the intervention arm vs 93 [IQR 85–100] in the usual care arm, p = 0.6). The outcomes of patients did not differ, whereas at 1 year post-ICU family members in the usual care group reported a larger increase in depression symptoms (mean 2.3 [SD 4.2] vs 0.2 [SD 3.9], p = 0.04). Regarding ICU professionals' experiences, an improvement in CSACD score was observed post-intervention (median 40 [IQR 34–45] vs 37 [IQR 32–43], p = 0.01), while no significant change in EDMCQ was found. Incorporating personalized predictions of long-term QoL in family meetings had no measurable effect on patients' and family members' experiences. However, a positive effect on family members' symptoms of depression and ICU professionals' experienced collaboration was observed. This study was registered at ClinicalTrials.gov: NCT05155150.
A coding single nucleotide polymorphism in the interleukin-6 receptor enhances IL-6 signalling in CD4 T cells and predicts treatment response to tocilizumab in giant cell arteritis
Authors: Robert Zorc, Christopher Redmond, McKella Sylvester, Mary Maclean, Luciana Yamamoto de Almeida, Kaitlin A Quinn, Alessandro Tomelleri, Corrado Campochiaro, Lorenzo Dagna, Fernanda Gutierrez-Rodrigues, Kristina V Wells, Cameron Rankin, Sabrina Helmold Hait, Chloe Palmer, Robert Corty, Alexander Bick, Kathi Lambert, Jane H Buckner, John J O'Shea, Jin Kyun Park, Massimo Gadina, Peter C Grayson
Journal: Annals of the Rheumatic Diseases (2025)

The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, p.Asp358Ala) predicted treatment response to tocilizumab in giant cell arteritis (GCA). Genetic sequencing of the rs2228145 locus was performed in 2 independent cohorts of patients with GCA. Peripheral blood mononuclear cells (PBMCs) from patients and controls were evaluated for expression of the interleukin 6 receptor (IL-6R) and its coreceptor, gp130, using flow cytometry. The same PBMCs were stimulated with IL-6 and evaluated for downstream targets of IL-6: STAT3 phosphorylation (pSTAT3) and IL-17A expression. In total, 100 patients with GCA were included (derivation cohort n = 58; validation cohort n = 42). The rs2228145 variant predicted tocilizumab response in each cohort. In the derivation cohort, a gene dose-dependent response was observed with a 36% response rate in the homozygous patients and 95% response rate in patients without the variant (P = .003). In the validation cohort, tocilizumab response rates were 50% for homozygotes and 85% for patients without the variant (P = .04). pSTAT3 levels were significantly increased in response to IL-6 stimulation in a gene dose-dependent manner in CD4 T cells from patients with GCA but not controls. CD4 T cells from patients with GCA had significantly higher membrane expression of gp130 than healthy controls, and response to IL-6 correlated with gp130 expression. IL-17 producing CD4 T cells were increased in a gene dose-dependent response to IL-6 (P < .01). The rs2228145 variant is associated with decreased treatment response to tocilizumab and worse outcomes in GCA by enhancing CD4 T cell response to IL-6.
Inflammation in cancer: therapeutic opportunities from new insights
Authors: Yifei Xie, Fangfang Liu, Yunfei Wu, Yuer Zhu, Yanan Jiang, Qiong Wu, Zigang Dong, Kangdong Liu
Journal: Molecular Cancer (2025)

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, and extracellular matrix are discussed. Since FDA-approved anti-inflammation drugs like aspirin show obvious anti-tumor effects, these drugs have unique advantages due to their relatively fewer side effects with long-term use compared to chemotherapy drugs. The characteristics make them promising candidates for cancer chemoprevention. Overall, this review discusses the role of these inflammatory molecules in carcinogenesis of cancer and new inflammation molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that have already been or are expected to be applied in clinical practice, as well as recent discoveries of the anti-tumor effect of non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. The advantages and disadvantages of their application in cancer chemoprevention are also discussed.
Teclistamab in relapsed systemic sclerosis after autologous haematopoietic stem cell transplantation
Authors: Elise Siegert, Robert Biesen, Maria Dzamukova, Christian Furth, Meike Probst, Felix Doellinger, Thula Walter-Rittel, Anja Fleischmann, Artur Wilhelm, Anne Elisabeth Beenken, Edgar Wiebe, Ann-Christin Pecher, Jörg Henes, Stefan Florian, David Simon, Arnd Kleyer, Gerd-Rüdiger Burmester, Ulrich Keller, Jan Krönke, Gerhard Krönke, Tobias Alexander
Journal: Annals of the Rheumatic Diseases (2025)
Associations between moderate-to-vigorous physical activity, p-tau181, and cognition in healthy older adults with memory complaints: a secondary analysis from the MAPT
Authors: Jérémy Raffin, Kaj Blennow, Yves Rolland, Christelle Cantet, Sophie Guyonnet, Bruno Vellas, Philipe de Souto Barreto
Journal: The Lancet Healthy Longevity (2025)