tbuckley/cabot-search huggingface dataset:
Preliminary analysis of the impact of lab results on large language model generated differential diagnoses
Authors: Balu Bhasuran, Qiao Jin, Yuzhang Xie, Carl Yang, Karim Hanna, Jennifer Costa, Cindy Shavor, Wenshan Han, Zhiyong Lu, Zhe He
Journal: npj Digital Medicine (2025)

Differential diagnosis (DDx) is crucial for medicine as it helps healthcare providers systematically distinguish between conditions that share similar symptoms. This study evaluates the influence of lab test results on DDx accuracy generated by large language models (LLMs). Clinical vignettes from 50 randomly selected case reports from PMC-Patients were created, incorporating demographics, symptoms, and lab data. Five LLMs-GPT-4, GPT-3.5, Llama-2-70b, Claude-2, and Mixtral-8x7B-were tested to generate Top 10, Top 5, and Top 1 DDx with and without lab data. Results show that incorporating lab data enhances accuracy by up to 30% across models. GPT-4 achieved the highest performance, with Top 1 accuracy of 55% (0.41-0.69) and lenient accuracy reaching 79% (0.68-0.90). Statistically significant improvements (Holm-adjusted p values < 0.05) were observed, with GPT-4 and Mixtral excelling. Lab tests, including liver function, metabolic/toxicology panels, and serology, were generally interpreted correctly by LLMs for DDx.
Mirvetuximab soravtansine: current and future applications
Authors: Beihua Kong, Wenxin Zheng
Journal: Journal of Hematology & Oncology (2025)

Ovarian epithelial cancer (OEC), particularly high-grade serous carcinoma (HGSC), remains a clinical challenge due to its late-stage diagnosis, high recurrence rates, and poor survival outcomes. Mirvetuximab soravtansine (MIRV), an antibody-drug conjugate targeting folate receptor alpha (FRα), has demonstrated promising efficacy in platinum-resistant OEC, particularly in high FRα-expressing populations, as evidenced by key clinical trials such as FORWARD I, FORWARD II, SORAYA, and MIRASOL. These trials highlight MIRV's ability to improve progression-free survival, response rates, and quality of life in advanced disease settings. Emerging data suggest that FRα is also highly expressed in serous tubal intraepithelial carcinoma (STIC), a non-invasive precursor lesion to HGSC. Although MIRV has not yet been studied for STIC management, we propose its potential application in this context to prevent progression to invasive carcinoma, particularly in high-risk populations undergoing risk-reducing bilateral salpingo-oophorectomy. This novel use could bridge the gap between prevention and treatment, offering a proactive strategy for hereditary cancer management. Furthermore, MIRV's therapeutic versatility extends to other FRα-positive tumors, such as endometrial and breast cancers, broadening its clinical relevance. Despite challenges such as accessibility and cost, MIRV represents a significant advancement in precision medicine, with potential to redefine prevention and treatment strategies for hereditary and sporadic cancers.
A structured coalescent model reveals deep ancestral structure shared by all modern humans
Authors: Trevor Cousins, Aylwyn Scally, Richard Durbin
Journal: Nature Genetics (2025)

Abstract Understanding the history of admixture events and population size changes leading to modern humans is central to human evolutionary genetics. Here we introduce a coalescence-based hidden Markov model, cobraa, that explicitly represents an ancestral population split and rejoin, and demonstrate its application on simulated and real data across multiple species. Using cobraa, we present evidence for an extended period of structure in the history of all modern humans, in which two ancestral populations that diverged ~1.5 million years ago came together in an admixture event ~300 thousand years ago, in a ratio of ~80:20%. Immediately after their divergence, we detect a strong bottleneck in the major ancestral population. We inferred regions of the present-day genome derived from each ancestral population, finding that material from the minority correlates strongly with distance to coding sequence, suggesting it was deleterious against the majority background. Moreover, we found a strong correlation between regions of majority ancestry and human–Neanderthal or human–Denisovan divergence, suggesting the majority population was also ancestral to those archaic humans.
Prognostic Biomarkers in MCL: Insights from the SHINE Trial on the impact of MCL35 score and TP53 Mutation Status
Authors: Ciara L Freeman, Srimathi Srinivasan, Brendan Hodkinson, Sanjay Deshpande, Todd Henninger, Merrill Boyle, Michael L Wang, Martin Dreyling, David W. Scott
Journal: Blood (2025)
Leveraging artificial intelligence for neoantigen prediction
Authors: Jing Zeng, Zhengjun Lin, Xianghong Zhang, Tao Zheng, Haodong Xu, Tang Liu
Journal: Cancer Research (2025)

Abstract Neoantigens represent a class of antigens within tumor microenvironments that arise from diverse somatic mutations and aberrations specific to tumorigenesis, holding substantial promise for advancing tumor immunotherapy. However, only a subset of neoantigens effectively elicits anti-tumor immune responses, and the specific neoantigens recognized by individual T cell receptors (TCRs) remain incompletely characterized. Therefore, substantial research has focused on screening immunogenic neoantigens, mainly through their major histocompatibility complex (MHC) presentation and TCR recognition specificity. Given the resource-intensiveness and inefficiency of experimental validation, predictive models based on artificial intelligence (AI) have gradually become mainstream methods to discover immunogenic neoantigens. Here, we provided a comprehensive summary of current AI methodologies for predicting neoantigens, with a particular focus on their capability to model peptide-MHC (pMHC) and pMHC-TCR binding. Furthermore, a thorough benchmarking analysis was conducted to assess the performance of antigen presentation predictors for scoring the immunogenicity of neoantigens. AI models have potential applications in the treatment of clinical diseases, although several limitations must first be overcome to realize their full potential. Anticipated advancements in data accessibility, algorithmic refinement, platform enhancement, and comprehensive validation of immune processes are poised to enhance the precision and utility of neoantigen prediction methodologies.
STAT1-driven interferon signatures are associated with JAK inhibitor sensitivity in T-ALL
Authors: Jason Xu, Jonathan H Sussman, Austin Yang, Satoshi Yoshimura, Jianzhong Hu, Changya Chen, Tiffaney L Vincent, Shovik Bandyopadhyay, Elizabeth Y Li, Tristan Lee Lim, Omar Elghawy, Adam Barsouk, Damjan Karanfilovski, Shira L Wald, Gregory M Chen, David Wei Wu, Haley Newman, Alexander Li, Chia-Hui Chen, Kathrin Maria Bernt, Brent L. Wood, Stuart Sheldon Winter, Kimberly P. Dunsmore, Elizabeth A. Raetz, Meenakshi Devidas, Stanley B Pounds, Mignon L. Loh, Stephen P Hunger, Mark Chiang, Caroline Diorio, Danika Di Giacomo, Petri Pölönen, Charles G. Mullighan, Jun J Yang, Kai Tan, Yusha Sun, David Trent Teachey
Journal: Blood (2025)
Single Cell Expression Analysis of Ductal Carcinoma in Situ Identifies Complex Genotypic-Phenotypic Relationships Altering Epithelial Composition
Authors: Xiaodi Qin, Siri H. Strand, Marissa R. Lee, Aashrith Saraswathibhatla, David G.P. van IJzendoorn, ChunFang Zhu, Sujay Vennam, Sushama Varma, Allison Hall, Rachel E. Factor, Lorraine King, Lunden Simpson, Xiaoke Luo, Graham A. Colditz, Shu Jiang, Ovijit Chaudhuri, E. Shelley Hwang, Jeffrey R. Marks, Kouros Owzar, Robert B. West
Journal: Cancer Research (2025)

Abstract Ductal carcinoma in situ (DCIS) is a risk factor for subsequent invasive breast cancer. To identify events in DCIS that lead to invasive cancer, we performed single-cell RNA-sequencing (scRNA-seq) on DCIS lesions and matched normal breast tissue. Inferred copy number variation (CNV) was used to identify neoplastic epithelial cells from clinical specimens, which contained a mixture of DCIS and normal ducts. Phylogenetic analysis demonstrated intratumoral clonal heterogeneity that was associated with significant gene expression differences. Classification of epithelial cells into mammary cell states revealed that subclones contained a mixture of cell states, suggesting an ongoing pattern of differentiation after neoplastic transformation. Cell state proportions were significantly different based on estrogen receptor (ER) expression with ER-negative DCIS more closely resembling the distribution in the normal breast, particularly with respect to cells with basal characteristics. Specific alterations in cell state proportions were associated with progression to invasive cancer in a cohort of DCIS with longitudinal outcome. Ongoing transcription of key basement membrane (BM) genes occurred in specific subsets of epithelial cell states, including basal/myoepithelial, which are diminished in DCIS. In the transition to invasive breast cancer, the BM protein laminin, but not COL4, was altered in DCIS adjacent to invasion. Loss of COL4, but not laminin, in an in vitro DCIS model led to an invasive phenotype. These findings suggest that the process of invasion is a loss-of-function event due to an imbalance in critical cell populations essential for BM integrity rather than a gain of an invasive phenotype by neoplastic cells.
Fate of revision total ankle arthroplasty: a meta-analysis of 999 cases
Authors: Ning Sun, Hua Li, Xing Li, Heng Li, Liangpeng Lai, Yong Wu, Hui Du
Journal: International Journal of Surgery (2025)

Background: Revision total ankle arthroplasty (reTAA) is becoming more common. This meta-analysis aimed to evaluate its re-revision rate and factors affecting longevity. Methods: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guideline, we searched PubMed, Embase, Web of Science, and Cochrane Library databases from 1 January 2010 to 1 October 2024. Studies reporting survivorship of reTAA were included. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). The primary outcome was the re-revision rate. Pooled estimates with 95% confidence intervals (CIs) were calculated using a random-effects model. The annual re-revision rate was introduced for time-adjusted analysis. Heterogeneity was explored using meta-regression and subgroup analyses. Results: The analysis included 22 retrospective studies (cohort studies and case series) and one prospective cohort study. The NOS scores indicated moderate to high quality. A total of 999 reTAAs with a mean follow-up of five years were identified. The pooled re-revision rate was 9.9% (95% CI: 5.9% to 13.9%). The annual re-revision rate was 2.6% (95% CI: 1.8% to 3.6%). Subgroup analysis indicated that stemmed tibial components were potentially associated with a lower re-revision rate (5.5%) versus unstemmed tibial components (13.2%) (P = 0.077). However, meta-regression model identified follow-up duration as the only significant factor influencing re-revision rates. The pooled complication rate following reTAA was 18.2%. Among those failed reTAAs, 64.9% underwent conversion to ankle fusion and 5.3% received below-knee amputation. Conclusion: Although most included studies were low-level evidence, our meta-analysis revealed an overall re-revision rate of 9.9% at five-year follow-up, with an annual rate of 2.6% for reTAA. Limited evidence suggested that revision systems using stemmed tibial components might reduce the risk of re-revision.
Surgical Treatment of Synchronous Liver-only Oligometastatic Pancreatic Adenocarcinoma: a Systematic Review and Meta-analysis of Long-term Outcomes
Authors: Claudio Fiorillo, Lodovica Langellotti, Edoardo Panza, Giuseppe Daloiso, Beatrice Biffoni, Chiara Lucinato, Maria Carmen Puzzangara, Giuseppe Massimiani, Teresa Mezza, Davide De Sio, Roberta Menghi, Vincenzo Tondolo, Sergio Alfieri, Giuseppe Quero
Journal: International Journal of Surgery (2025)

Background The potential long-term survival benefits of surgical resection for synchronous liver-only metastases of pancreatic ductal adenocarcinoma (liver oligo-PDAC) remain controversial. This systematic review and meta-analysis aim to compare the current evidence on long-term survival outcomes between surgical treatment of liver oligo-PDAC and conventional systemic chemotherapy. Materials and Methods A systematic review and meta-analysis were conducted using the PubMed and Scopus databases to identify studies comparing surgery and systemic chemotherapy in terms of long-term survival in oligo-PDAC patients. The search included studies published up to October 2024. The meta-analysis was performed using the Jamovi software. Results Eleven retrospective studies were selected for a total of 897 patients: 565(63%) underwent synchronous resection of liver metastases and the primary tumor, while 332(37%) received conventional chemotherapy. The majority of patients presented a pancreatic head tumor, and the median number of liver metastases ranged between 1 and 3 in the surgical cohort and 1 and 2 in the non-surgical cohort. The rate of major surgical complications was 14.4% while the cumulative incidence of post-operative mortality was 2.8%. The median overall survival(OS) in the surgical group ranged from 7.6 to 18.4 months, while a lower value comprised between 6 and 9.9 months was evidenced in the non-surgical cohort. Six studies were included in the meta-analysis for the OS evaluation, showing significantly better survival outcomes in the surgical group (OR: 0.286, 95% CI: 0.100–0.409; p &lt;0.0001). According to the Q-test, there was no significant heterogeneity in the true outcomes (Q = 4.063, p = 0.541, I 2 = 0 %). A sensitivity analysis, conducted by excluding one study at a time, confirmed the robustness of the meta-analysis findings. Conclusions Surgical resection of oligo-PDAC may represent a valuable treatment option with potential long-term survival benefits. However, prospective randomized trials are required to further validate these findings.
Identification of blood-secreted proteins as potential biomarkers for early perinatal depression
Authors: Sainan Duan, Xiaoqin Jiang
Journal: International Journal of Surgery (2025)

aDepartment of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, China bKey Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education c Department of Anesthesiology, West China Hospital, Sichuan university, Chengdu, Sichuan, China d Department of Anesthesiology, Chengdu Hi-Tech Zone Hospital for Women and Children, Chengdu, China *Corresponding author. Address: Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education; Department of Anesthesiology, Chengdu Hi-Tech Zone Hospital for Women and Children, Chengdu, China. E-mail address: [email protected] (X. Jiang). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website,www.journalsurgery.net. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Association of chronic musculoskeletal pain, APOE Ɛ4 genotype, and analgesics with the risk of dementia: a population-based prospective cohort study
Authors: Yuan Zhang, Jiangtao Feng, Hongxi Yang, Shu Li
Journal: International Journal of Surgery (2025)

Chronic musculoskeletal pain (CMP) is associated with the risk of dementia, yet little is known about whether this association is modified by APOE genotype and whether analgesics may mitigate the risk effect of CMP on dementia. This prospective cohort study, included 415,072 participants from UK Biobank, found that CMP was associated with a higher risk of dementia, and this association may be modified by the APOE genotype. Analgesics may not mitigate the risk effect of CMP on dementia.
Editorial commentary on “urological age and mortality risk: an investigation of urological age acceleration”
Authors: Cyrille Guillot-Tantay, Mikolaj Przydacz
Journal: International Journal of Surgery (2025)

aDepartment of Urology, Hopital Foch, Suresnes, France bDepartment of Urology, Jagiellonian University, Krakow, Poland *Corresponding Author. Address: Department of Urology, Hopital Foch, 40, rue Worth, Suresnes, 92150 France. Tel: 00 33 1 46 25 36 82; Fax: 00 33 1 46 25 21 06. E-mail: [email protected] (C. Guillot-Tantay). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Erratum: Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab in a Treatment-Naïve Chronic Lymphocytic Leukemia Population Enriched for High-Risk Disease
Authors: Matthew S. Davids, Christine E. Ryan, Benjamin L. Lampson, Yue Ren, Svitlana Tyekucheva, Stacey M. Fernandes, Jennifer L. Crombie, Austin I. Kim, Matthew Weinstock, Josie Montegaard, Heather A. Walker, Claire Greenman, Victoria Patterson, Caron A. Jacobson, Ann S. LaCasce, Philippe Armand, David C. Fisher, Steve Lo, Adam J. Olszewski, Jon E. Arnason, Inhye E. Ahn, Jennifer R. Brown
Journal: Journal of Clinical Oncology (2025)
Correction: myCAF-derived Exosomal PWAR6 accelerates CRC liver metastasis via altering glutamine availability and NK cell function in the tumor microenvironment
Authors: Hongsheng Fang, Weixing Dai, Ruiqi Gu, Yanbo Zhang, Jin Li, Wenqin Luo, Shanyou Tong, Lingyu Han, Yichao Wang, Chengyao Jiang, Xue Wang, Renjie Wang, Guoxiang Cai
Journal: Journal of Hematology & Oncology (2025)
Enhanced α2-3 linked sialylation determines the extended half-life of CHO-rVWF
Authors: Ciara Byrne, Soracha Ward, Jamie M O'Sullivan, Alain Chan Kwo Chion, Patricia Lopes, Bogdan Baci, Caoimhe Dowd, Darragh Jordan, Ross Ian Baker, Roger . Preston, Marco Monopoli, Peter L Turecek, Maximilianos Kotsias, Jack Cheeseman, Alan Moran, Richard A Gardner, Daniel I R Spencer, Ferdows Atiq, James S. O'Donnell
Journal: Blood (2025)

The half-life of recombinant VWF (rVWF) expressed in CHO cells (CHO-rVWF; Vonicog alfa, VonvendiÒ / VeyvondiÒ) is significantly longer than plasma-derived (pd) VWF concentrates. This finding is intriguing since CHO cells do not generate α2-6 sialylation, which constitutes the majority of human pdVWF sialylation. We hypothesized that glycan differences might regulate the longer half-life of CHO-rVWF. In lectin plate binding assays and liquid chromatography mass spectrometry analysis, we confirmed that CHO-rVWF lacked α2-6 linked sialylation. Conversely, however, α2-3 linked sialylation was significantly increased on CHO-rVWF, which also had reduced exposed β-Gal compared to pdVWF. Consistent with human data, CHO-rVWF clearance was significantly (p&amp;lt;0.001) reduced in VWF-/- mice compared to pdVWF. However, clearance of asialo-pdVWF and asialo-CHO-rVWF were identical. In keeping with the in vivo half-life prolongation, CHO-rVWF binding to murine macrophages (p=0.012) and HepG2 cells (p=0.001) was significantly decreased compared to pdVWF. Furthermore, CHO-rVWF binding to purified MGL and ASGPR receptors was also significantly reduced. In contrast to pdVWF, in vivo studies in MGL1-/- mice and Asgr1-/- mice demonstrated that neither MGL nor ASGPR play significant roles in regulating CHO-rVWF clearance. Together, our findings demonstrate that enhanced α2-3 linked sialylation on CHO-rVWF is responsible for its extended in vivo half-life.
Cerebrospinal fluid biomarkers of neuroinflammation and postoperative neurocognitive disorders in patients undergoing orthopedic surgery
Authors: Huiru Feng, Yang Liu, Xue Wang, Chunxiu Wang, Tianlong Wang
Journal: International Journal of Surgery (2025)

Introduction: Postoperative neurocognitive disorders (PNDs) are common postoperative complications that can hinder patients’ postoperative recovery. Various studies have investigated the correlations between PNDs and cerebrospinal fluid (CSF) neuroinflammatory biomarkers in orthopedic patients. However, combined evidence is required to confirm the homogeneity and robustness of these findings. Methods: Observational studies were searched to explore the associations between PNDs and these biomarkers in orthopedic patients. A comprehensive study retrieval was performed in MEDLINE (via OVID), EMBASE, and the Cochrane Library without any restrictions on language or date. Subgroup and sensitivity analyses were performed to confirm robustness of the results. Result: A total of 27 articles were included in this study. Significant concentration differences were found between PNDs and non-PNDs groups in the majority of preoperative CSF neuroinflammatory biomarkers, particularly in patients with postoperative delirium (POD) and delayed neurocognitive recovery (dNCR). Moderate quality evidence identified that increased preoperative CSF levels of t-Tau (OR: 1.008, 95%CI: 1.005–1.010) and p-Tau (OR: 1.077, 95%CI: 1.042–1.078), along with decreased Aβ42 level (OR: 0.998, 95% CI: 0.997–0.999), were risk factors for POD in orthopedic patients. Low quality evidence suggested that preoperative CSF level of Aβ42/t-Tau was a valuable predictive biomarker for dNCR. Conclusion: Different subtypes of PNDs after orthopedic surgery have different CSF biomarkers, with POD having the most and postoperative neurocognitive disorder (POCD) having the fewest. Studies concerning dNCR and POCD are needed to investigate their correlations with these biomarkers. Meanwhile, studies concerning diagnostic tests are also highly needed to help screen for practical biomarkers and analyze these biomarkers from a more comprehensive perspective.
Early Fasting Serum Glucose or Weight Reduction With Tirzepatide and Metabolic Outcomes in People With Type 2 Diabetes: A Post Hoc Analysis of the SURPASS Trials
Authors: Francesco Giorgino, Ildiko Lingvay, Luc F. Van Gaal, Palash Sharma, Ángel Rodríguez, Jacek Kiljański, Amelia Torcello-Gómez, Joshua A. Levine
Journal: Diabetes Care (2025)

OBJECTIVE To evaluate late (week 40 or 42; hereafter, week 40/42) metabolic outcomes by early glycemic response (&amp;lt;20% or ≥20% fasting serum glucose [FSG] reduction at week 4) or weight response (&amp;lt;5% or ≥5% weight reduction at week 8), respectively, in tirzepatide-treated participants with type 2 diabetes in the SURPASS trials. RESEARCH DESIGN AND METHODS This post hoc analysis used pooled data across trials. Baseline characteristics, change from baseline to week 40/42 for efficacy parameters, and gastrointestinal (GI) adverse events (AEs) were described and analyzed by early response in terms of FSG (SURPASS-1 to -4; n = 3,676) or weight (SURPASS-1 to -5; n = 4,121) in the efficacy and safety analysis set, respectively. RESULTS Early responders in FSG (50%) were younger, with higher glycemic parameters and lower weight at baseline. Early responders in weight (31%) had lower glycemic parameters and weight at baseline, and a greater percentage were women and White. Early versus nonearly responders in FSG or weight achieved better HbA1c (−2.6% vs. −2.0% or −2.5% vs. −2.2%, respectively) and weight (−11% vs. −10% or −15% vs. −8%, respectively) responses at week 40/42 and greater improvements in blood pressure and lipids profile. Nonearly responders also had clinically meaningful HbA1c and weight reductions with all tirzepatide doses. The incidence of GI AEs (generally mild to moderate events) decreased over time and was, in general, comparable between early and nonearly responders. CONCLUSIONS Both early glucose and weight responses with tirzepatide were associated with better longer-term metabolic outcomes. Early response may be a good clinical indicator that could help inform treatment individualization to achieve therapeutic goals.