tbuckley/cabot-search huggingface dataset:
A Clinically Annotated Transcriptomic Atlas of Nervous System Tumors
Authors: Chi H Le, Ajai K Nelson, Adam J Berrones, Janki R Naidugari, Robert P Naftel, Eyas M Hattab, Brian J Williams, Akshitkumar M Mistry
Journal: Neuro-Oncology (2025)

Abstract Background While DNA methylation signatures are distinct across nervous system neoplasms, it has not been comprehensively demonstrated whether transcriptomic signatures exhibit similar uniqueness. Additionally, no large-scale dataset for comparative gene expression analyses exists. This study addresses these knowledge and resource gaps. Methods We compiled and harmonized raw transcriptomic and clinical data for neoplastic (n=5,402) and non-neoplastic (n=1,973) nervous system samples from publicly available sources, all profiled on the same microarray platform. After adjusting for surrogate variable effects (‘batch effects’), machine learning methods were used to visualize, cluster, and reclassify samples with uncertain diagnoses (n=2,225). Results We generated the largest clinically annotated transcriptomic atlas of nervous system tumors to date. Sample clustering was primarily driven by diagnosis. We show the utility of the atlas by refining the transcriptional subtypes of pheochromocytoma and paraganglioma (PH/PG), revealing six robust subtypes (Neuronal, Vascular, Metabolic, Steroidal, Developmental, Indeterminate), which were independently validated using TCGA RNA-seq data and that correlated with specific mutational signatures and clinical behaviors of these tumors. Conclusions Like bulk DNA methylation, we demonstrate that bulk transcriptomic signatures are distinct across the diagnostic spectrum of nervous system neoplasms. Our atlas’ broad coverage of diagnoses, including rarely studied entities, spans all ages and includes individuals from diverse geographical regions, enhancing its utility for comprehensive and robust comparative gene expression analyses, as exemplified by our PH/PG analyses. For access visit http://kdph.shinyapps.io/atlas/ or https://github.com/axitamm/BrainTumorAtlas.
Lung cancer risk assessment by prediction model: a global perspective
Authors: Longyao Zhang, Xiang Wang, Qiuyuan Chen, Mengsheng Zhao, Can Ju, David C Christiani, Feng Chen, Ruyang Zhang, Yongyue Wei
Journal: Thorax (2025)

Background Numerous lung cancer risk prediction models have been developed and validated worldwide. It is imperative to offer a comprehensive overview and comparative analysis of their performances. Methods We conducted an extensive literature search to identify studies developing and/or validating lung cancer risk prediction models. Then we summarised and compared the external performance of these models, focusing on discriminative accuracy (C-index) and calibration performance (E:O ratio). Results After an initial screening of 10 210 articles, 35 studies on 21 distinct prediction models were identified, which used 42 different types of predictors spanning seven categories. Notable performance variations were observed in external validations. In North American cohorts, the C-index ranged from 0.60 to 0.87, with E:O ratios from 0.62 to 3.70. Among the European cohorts, the Trøndelag health study HUNT and CanPredict exhibited C-indices surpassing 0.870. Conversely, the Bach, lung cancer risk assessment tool (LCRAT), prostate, lung, colorectal and ovarian cancer screening (PLCO) m2012 and PLCO all2014 performed poorly in electronic health records of the Qresearch database subgroup, with C-indices falling below 0.60. PLCO m2012 reached the best E:O ratio of 1.00 (95% CI: 0.93 to 1.08) in the UK Biobank subgroup. In Asian cohorts, the C-index ranged from 0.54 to 0.87. Only three models, Korean Men, LCRAT and Liverpool lung project incidence risk model (LLPi), achieved a C-index exceeding 0.80. LCRAT demonstrated the best calibration, while Hoggart performed the worst. Conclusions Performance of lung cancer risk prediction models, despite being well developed and validated, varies in diverse populations. Significant regional imbalance persists in the development of these models. Rigorous external validation or recalibration study in the target population is crucial in accordance with the guidance prior to model implementation. PROSPERO registration number CRD42022324602.
Preoperative risk factors for laparoscopic to open appendectomy conversion; a systematic review and meta-analysis
Authors: Arian Mirdamadi, Mona Javid, Ehsan Amini-Salehi, Fatemeh Mohammadyari, Shervin Tavakoli, Mohamadreza Javid, Mohammad-Hossein Keivanlou, Pirouz Samidoust, Ranjan Nayak, Eddy P. Lincango, Rachana Borkar, Sandeep Samethadka NayakA, Soheil Hassanipour
Journal: International Journal of Surgery (2025)

Background: Laparoscopic appendectomy (LA) is a standard treatment for acute appendicitis (AA), offering reduced complications and improved patient outcomes. However, in certain cases, the need for conversion to open appendectomy (OA) may arise. The present systematic review and meta-analysis aimed to identify preoperative risk factors associated with conversion from LA to OA. Method: The global databases of PubMed, Web of Science, Scopus, and Embase were systematically searched from inception to 20 April 2024. Studies evaluating clinical, laboratory, and imaging risk factors of conversion from LA to OA were assessed for inclusion eligibility. Fixed-effects or random-effects models were utilized to calculate pooled Odds ratio (OR) and Standard difference in mean (SMD) with a 95% Confidence interval (CI), using Comprehensive Meta-Analysis software version 3. The Joanna Briggs Institute Critical Appraisal Checklist was employed to assess the quality of the eligible studies. Results: In total, 45 studies with an overall sample size of 3,202,336 were included for meta-analysis. The conversion rate from LA to OA was 8.7% (95% CI: 7.7%, 9.8%). Conversion was associated with older age, male gender, and comorbidities such as obesity, diabetes, hypertension and cardiovascular disease. Previous abdominal surgery, prolonged symptom duration, higher Alvarado score, elevated inflammatory markers, and imaging findings (e.g., larger appendiceal diameter and intra-abdominal fluid) were also significant predictors. Conclusion: The present systematic review and meta-analysis identified the most important clinical, laboratory, and imaging factors associated with the conversion from LA to OA, aiding surgeons in perioperative risk stratification and improving patient outcomes. Despite the inclusion of high-quality studies, the majority were retrospective, and the quality of evidence for many risk factors was moderate to low, representing an important limitation.
Single Anastomosis Sleeve Jejunal (SAS-J) Bypass Vs Single Anastomosis Sleeve Ileal (SASI) bypass, prospective randomized controlled clinical trial
Authors: Alaa Mostafa Sewefy, Mohmed A. AbdElzaher, Karim Sabry, Amr Madyan, Ramy Helmy, Mina Makram Hendy, Taha Hassan Kayed
Journal: International Journal of Surgery (2025)

Background Single anastomosis sleeve ileal (SASI) bypass is a modification of Santoro’s operation. Which aimed to keep normal food pathway and allow endoscopic examination. The procedure was modified to single anastomosis sleeve jejunal (SAS-J) bypass to minimize the nutritional deficiency. The study aimed to compare SASI to SAS-J bypass. Material and Methods This was a prospective randomized controlled trial that included 180 patients. Patients were randomly assigned to 2 equal groups: Group 1, was operated with SASI bypass while Group 2 was operated with SAS-J bypass. All patients complete at least one year follow up. Results 63% of patients were female and 37 % were male. The mean body mass index (BMI) was 47.6. The mean age was 37 years. The total incidence of malnutrition was 58% in Group 1 VS 27.6% in Group 2 (p = .000). Protein malnutrition occurred in 15.9% Group 1 VS 4.6% in Group 2 (p = .014). Anemia occurred in 14.8% in Group 1 VS 5.7% in Group 2 (p = .049). %EWL at one year was 94.8 in Group 1 VS 90.6 in Group 2 (p = .005). Diarrhea occurred in 21.6% in Group 1 VS 8% in Group 2 (p = .012). The incidence of excessive weight loss (EXWL) was 11.4% in Group 1 VS 2.3% in Group 2 (p = .0031). The rat of reoperation was 11.4% in group 1 VS 2.3% in Group 2 (p = .018). Conclusions Both SASI and SAS-J bypass are effective as a metabolic and a weight loss surgery, but, SAS-J bypass is associated with less nutritional deficiency and less complications rate compared to SASI bypass.
Preoperative biliary drainage for patients with malignant obstructive jaundice: an update systematic review and model-based bayesian network meta-analysis
Authors: Peiyan Sun, Yanjie Zhong, Yafei Hu, Sunchuri Diwas, Jianlin Wu, Ruiqi Zou, Aoqiang Zhai, Siqi Yang, Xian Shi, Yanwen Jin, Fuyu Li, Haijie Hu
Journal: International Journal of Surgery (2025)
Erratum: Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64Cu PET/CT study in healthy humans
Authors: Frederik Teicher Kirk, Ditte Emilie Munk, Eugene Scott Swenson, Adam Michael Quicquaro, Mikkel Holm Vendelbo, Michael L. Schilsky, Peter Ott, Thomas Damgaard Sandahl
Journal: Hepatology (2025)
Commentary on “Implications of Portal Vein/superior Mesenteric Vein Involvement in Pancreatic Cancer A Comprehensive Correlation From Preoperative Radiological Assessment to Resection, Pathology, and Long-term Outcomes. A Retrospective Cohort Study”
Authors: Qi Yu, Yanfei Yang, Hui Qiu, Yiqi Wang
Journal: International Journal of Surgery (2025)
Situating governance and regulatory concerns for generative artificial intelligence and large language models in medical education
Authors: Michael Tran, Chinthaka Balasooriya, Jitendra Jonnagaddala, Gilberto Ka-Kit Leung, Neeraj Mahboobani, Subha Ramani, Joel Rhee, Lambert Schuwirth, Neysan Sedaghat Najafzadeh-Tabrizi, Carolyn Semmler, Zoie Sy Wong
Journal: npj Digital Medicine (2025)
AMHY and sex determination in egg-laying mammals
Authors: Linda Shearwin-Whyatt, Jane Fenelon, Hongshi Yu, Andrew Major, Zhipeng Qu, Yang Zhou, Keith Shearwin, James Galbraith, Alexander Stuart, David Adelson, Guojie Zhang, Michael Pyne, Stephen Johnston, Craig Smith, Marilyn Renfree, Frank Grützner
Journal: Genome biology (2025)
Advancing breast, lung and prostate cancer research with federated learning. A systematic review
Authors: Anshu Ankolekar, Sebastian Boie, Maryam Abdollahyan, Emanuela Gadaleta, Seyed Alireza Hasheminasab, Guang Yang, Charles Beauville, Nikolaos Dikaios, George Anthony Kastis, Michael Bussmann, Claude Chelala, Sara Khalid, Hagen Kruger, Philippe Lambin, Giorgos Papanastasiou
Journal: npj Digital Medicine (2025)
Corrigendum to “Light sheet fluorescence microscopy for monitoring drug delivery: unlocking the developmental phases of embryos” [Adv Drug Del. Rev. 218 (2025) 115520]
Authors: Gagan Raju, Aymeric Le Gratiet, Giuseppe Sancataldo, Guan-Yu Zhuo, Yury Kistenev, Subir Das, Ajeetkumar Patil, Soubarno Kundu, Tribikram Patel, Nirmal Mazumder
Journal: Advanced Drug Delivery Reviews (2025)
Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma
Authors: Toshiro Hara, Rony Chanoch-Myers, Nathan D. Mathewson, Chad Myskiw, Lyla Atta, Lillian Bussema, Stephen W. Eichhorn, Alissa C. Greenwald, Gabriela S. Kinker, Christopher Rodman, L. Nicolas Gonzalez Castro, Hiroaki Wakimoto, Orit Rozenblatt-Rosen, Xiaowei Zhuang, Jean Fan, Tony Hunter, Inder M. Verma, Kai W. Wucherpfennig, Aviv Regev, Mario L. Suvà, Itay Tirosh
Journal: Cancer Cell (2025)
Correction: Revised free light chain reference intervals enhance risk stratification in monoclonal gammopathy of undetermined significance and reduce overdiagnosis
Authors: Cecilie Velsoe Maeng, Sæmundur Rögnvaldsson, Thórir Einarsson Long, Christian Brieghel, Emil Hermansen, Carsten Utoft Niemann, Kirsten Grønbæk, Sigurður Yngvi Kristinsson, Sigrún Thorsteinsdóttir
Journal: Blood Cancer Journal (2025)
A wireless device for continuous measurement of brain parenchymal resistance tracks glymphatic function in humans
Authors: Paul Dagum, Laurent Giovangrandi, Swati Rane Levendovszky, Jake J Winebaum, Tarandeep Singh, Yeilim Cho, Robert M Kaplan, Michael S Jaffee, Miranda M Lim, Carla Vandeweerd, Jeffrey J Iliff
Journal: Nature Biomedical Engineering (2025)

Glymphatic function in animal models supports the clearance of brain proteins whose mis-aggregation is implicated in neurodegenerative conditions including Alzheimer's and Parkinson's disease. The measurement of glymphatic function in the human brain has been elusive due to invasive, bespoke and poorly time-resolved existing technologies. Here we describe a non-invasive multimodal device for the continuous measurement of sleep-active changes in parenchymal resistance in humans using repeated electrical impedance spectroscopy measurements in two separate clinical validation studies. Device measurements successfully paralleled sleep-associated changes in extracellular volume that regulate glymphatic function and predicted glymphatic solute exchange measured by contrast-enhanced MRI. We replicate preclinical findings showing that glymphatic function is increased with increasing sleep electroencephalogram (EEG) delta power and is decreased with increasing sleep EEG beta power and heart rate. The present investigational device permits the continuous and time-resolved assessment of parenchymal resistance in naturalistic settings necessary to determine the contribution of glymphatic impairment to risk and progression of Alzheimer's disease and to enable target-engagement studies that modulate glymphatic function in humans.
Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging
Authors: Zhenguo Wang, Zhe Li, Hongyu Liu, Chenghua Yang, Xin Li
Journal: Nature Aging (2025)

Mitochondria rapidly accumulate mutations throughout a lifetime, potentially acting as a molecular clock for aging and disease. We profiled mitochondrial RNA across 47 human tissues from 838 individuals, revealing rapid development of clonal mosaicism with two distinct tissue-specific aging signatures. Tissues with constant cellular turnover such as the gastrointestinal tract or skin exhibit accelerated accumulation of sporadic mutations and clonal expansions, implicating increased susceptibility to age-related tumorigenesis and dysfunction. By contrast, post-mitotic tissues, such as the heart and brain, accumulate mutations at deterministic hotspots (tissue-specific, recurrently mutated sites), reflecting the cumulative burden of high energy demand and mitochondrial turnover independent of cell division. These findings support a biphasic model of the mitochondrial clock: stochastic clonal expansion of sporadic replication errors in proliferative tissues, versus age-dependent heteroplasmy increases at hotspots in high-metabolic tissues. This mutational landscape provides a map of tissue-specific vulnerabilities during aging and offers potential therapeutic targets.
Lutetium-177–PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial
Authors: Edmond M Kwan, Sarah W S Ng, Sofie H Tolmeijer, Louise Emmett, Shahneen Sandhu, James P Buteau, Amir Iravani, Anthony M Joshua, Roslyn J Francis, Vinod Subhash, Sze-Ting Lee, Andrew M Scott, Andrew J Martin, Martin R Stockler, Gráinne Donnellan, Matti Annala, Cameron Herberts, Ian D Davis, Michael S Hofman, Arun A Azad, Alexander W Wyatt
Journal: Nature Medicine (2025)
GABA-dependent microglial elimination of inhibitory synapses underlies neuronal hyperexcitability in epilepsy
Authors: Zhang-Peng Chen, Xiansen Zhao, Suji Wang, Ruolan Cai, Qiangqiang Liu, Haojie Ye, Meng-Ju Wang, Shi-Yu Peng, Wei-Xuan Xue, Yang-Xun Zhang, Wei Li, Hua Tang, Tengfei Huang, Qipeng Zhang, Liang Li, Lixia Gao, Hong Zhou, Chunhua Hang, Jing-Ning Zhu, Xinjian Li, Xiangyu Liu, Qifei Cong, Chao Yan
Journal: Nature Neuroscience (2025)
The cerebellum shapes motions by encoding motor frequencies with precision and cross-individual uniformity
Authors: Chia-Wei Liu, Yi-Mei Wang, Shun-Ying Chen, Liang-Yin Lu, Ting-Yu Liang, Ke-Chu Fang, Peng Chen, I-Chen Lee, Wen-Chuan Liu, Ami Kumar, Sheng-Han Kuo, Jye-Chang Lee, Chung-Chuan Lo, Shun-Chi Wu, Ming-Kai Pan
Journal: Nature Biomedical Engineering (2025)

Understanding brain behaviour encoding or designing neuroprosthetics requires identifying precise, consistent neural algorithms across individuals. However, cerebral microstructures and activities are individually variable, posing challenges for identifying precise codes. Here, despite cerebral variability, we report that the cerebellum shapes motor kinematics by encoding dynamic motor frequencies with remarkable numerical precision and cross-individual uniformity. Using in vivo electrophysiology and optogenetics in mice, we confirm that deep cerebellar neurons encode frequencies using populational tuning of neuronal firing probabilities, creating cerebellar oscillations and motions with matched frequencies. The mechanism is consistently presented in self-generated rhythmic and non-rhythmic motions triggered by a vibrational platform or skilled tongue movements of licking in all tested mice with cross-individual uniformity. The precision and uniformity allowed us to engineer complex motor kinematics with designed frequencies. We further validate the frequency-coding function of the human cerebellum using cerebellar electroencephalography recordings and alternating current stimulation during voluntary tapping tasks. Our findings reveal a cerebellar algorithm for motor kinematics with precision and uniformity, the mathematical foundation for a brain-computer interface for motor control.
Early detection of multiple cancer types using multidimensional cell-free DNA fragmentomics
Authors: Hua Bao, Shanshan Yang, Xiaoxi Chen, Guangqiang Dong, Yuan Mao, Shuyu Wu, Xi Cheng, Xuxiaochen Wu, Wanxiangfu Tang, Min Wu, Shiting Tang, Wenhua Liang, Zheng Wang, Liu Yang, Jiaqi Liu, Tao Wang, Bingzhong Zhang, Kuirong Jiang, Qin Xu, Jierong Chen, Hairong Huang, Junjie Peng, Xiaomeng Xia, Yumei Wu, Shun Xu, Ji Tao, Li Chong, Dongqin Zhu, Ruowei Yang, Shuang Chang, Peng He, Xiuxiu Xu, JinPeng Zhang, Yi Shen, Ya Jiang, Sisi Liu, Xian Zhang, Xue Wu, Xiaonan Wang, Yang Shao
Journal: Nature Medicine (2025)
Conservation of regulatory elements with highly diverged sequences across large evolutionary distances
Authors: Mai H Q Phan, Tobias Zehnder, Fiona Puntieri, Andreas Magg, Blanka Majchrzycka, Milan Antonović, Hannah Wieler, Bai-Wei Lo, Damir Baranasic, Boris Lenhard, Ferenc Müller, Martin Vingron, Daniel M Ibrahim
Journal: Nature Genetics (2025)

Abstract Developmental gene expression is a remarkably conserved process, yet most cis -regulatory elements (CREs) lack sequence conservation, especially at larger evolutionary distances. Some evidence suggests that CREs at the same genomic position remain functionally conserved independent of sequence conservation. However, the extent of such positional conservation remains unclear. Here, we profiled the regulatory genome in mouse and chicken embryonic hearts at equivalent developmental stages and found that most CREs lack sequence conservation. To identify positionally conserved CREs, we introduced the synteny-based algorithm interspecies point projection, which identifies up to fivefold more orthologs than alignment-based approaches. We termed positionally conserved orthologs ‘indirectly conserved’ and showed that they exhibited chromatin signatures and sequence composition similar to sequence-conserved CREs but greater shuffling of transcription factor binding sites between orthologs. Finally, we validated indirectly conserved chicken enhancers using in vivo reporter assays in mouse. By overcoming alignment-based limitations, we revealed widespread functional conservation of sequence-divergent CREs.
Lemborexant ameliorates tau-mediated sleep loss and neurodegeneration in males in a mouse model of tauopathy
Authors: Samira Parhizkar, Xin Bao, Wei Chen, Nicholas Rensing, Yun Chen, Michal Kipnis, Sihui Song, Grace Gent, Eric Tycksen, Melissa Manis, Choonghee Lee, Javier Remolina Serrano, Megan E Bosch, Emily Franke, Carla M Yuede, Eric C Landsness, Michael Wong, David M Holtzman
Journal: Nature Neuroscience (2025)
Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity
Authors: Shiyi Zhou, Katherine E Novak, Rachel Kaletsky, Yifei Weng, Jonathan St Ange, Morgan E Stevenson, Erik Toraason, Yanping Zhang, Wenhong Zhang, Meng-Qiu Dong, Coleen T Murphy
Journal: Nature Aging (2025)

While memory regulation is predominantly understood as autonomous to neurons, factors outside the brain can also affect neuronal function. In Caenorhabditis elegans, the insulin/IGF-1-like signaling (IIS) pathway regulates longevity, metabolism and memory: long-lived daf-2 insulin/IGF-1 receptor mutants more than double memory duration after a single training session, and it was assumed that memory regulation was strictly neuronal. However, here we show that degradation of DAF-2 in the hypodermis also greatly extends memory, via expression of the diffusible Notch ligand, OSM-11, which in turn activates Notch signaling in neurons. Single-nucleus RNA sequencing of neurons revealed increased expression of CREB and other memory genes. Furthermore, in aged animals, activation of the hypodermal IIS-Notch pathway as well as OSM-11 overexpression rescue both memory and learning via CREB activity. Thus, insulin signaling in the liver-like hypodermis non-autonomously regulates neuronal function, providing a systemic connection between metabolism and memory through IIS-Notch-CREB signaling from the body to the brain.
Patient-centered integration of tumor and germline genetic results can improve cancer care
Authors: Alanna J Church, Oindrila Bhattacharyya, Julie O Culver, Yonatan Amzaleg, Erin Linnenbringer, Maeve Smart, Christina Ip-Toma, Adan Reinosa Rivera, Bethany Davis, Charité Ricker, Heinz-Josef Lenz, Stacy W Gray, Heather Hampel, David W Craig
Journal: Nature Medicine (2025)