tbuckley/cabot-search huggingface dataset:
Regulation of the cGAS-STING Pathway
Authors: Bing Zhang, Pengbiao Xu, Andrea Ablasser
Journal: Annual Review of Immunology (2025)

The cGAS-cGAMP-STING pathway is essential for immune defense against pathogens. Upon binding DNA, cGAS synthesizes cGAMP, which activates STING, leading to potent innate immune effector responses. However, lacking specific features to distinguish between self and nonself DNA, cGAS-STING immunity requires precise regulation to prevent aberrant activation. Several safeguard mechanisms acting on different levels have evolved to maintain tolerance to self DNA and ensure immune homeostasis under normal conditions. Disruption of these safeguards can lead to erroneous activation by self DNA, resulting in inflammatory conditions but also favorable antitumor immunity. Insights into structural and cellular checkpoints that control and terminate cGAS-STING signaling are essential for comprehending and manipulating DNA-triggered innate immunity in health and disease.
Inhibition of CCT5-mediated asparagine biosynthesis and anti-PD-L1 produce synergistic antitumor effects in colorectal cancer
Authors: Yujie Zhang, Weiyi Zhao, Ling Wu, Tianjing Ai, Jie He, Zetao Chen, Chuangyuan Wang, Hui Wang, Rui Zhou, Chaoqun Liu, Liang Zhao
Journal: Acta Pharmaceutica Sinica B (2025)
Fast and ultra-high shot diffusion MRI image reconstruction with self-adaptive Hankel subspace
Authors: Chen Qian, Mingyang Han, Liuhong Zhu, Zi Wang, Feiqiang Guan, Yucheng Guo, Dan Ruan, Yi Guo, Taishan Kang, Jianzhong Lin, Chengyan Wang, Merry Mani, Mathews Jacob, Meijin Lin, Di Guo, Xiaobo Qu, Jianjun Zhou
Journal: Medical Image Analysis (2025)
EASL-ERN Clinical Practice Guidelines on Wilson’s disease
Authors: Piotr Socha, Wojciech Jańczyk, Alberto Zanetto, Patrizia Burra, Anna Czlonkowska, Dominique Debray, Peter Ferenci, Uta Merle, Emanuele Nicastro, Aurelia Poujois, Hartmut Schmidt, Emmanuel Tsochatzis
Journal: Journal of Hepatology (2025)
VenusMutHub: A systematic evaluation of protein mutation effect predictors on small-scale experimental data
Authors: Liang Zhang, Hua Pang, Chenghao Zhang, Song Li, Yang Tan, Fan Jiang, Mingchen Li, Yuanxi Yu, Ziyi Zhou, Banghao Wu, Bingxin Zhou, Hao Liu, Pan Tan, Liang Hong
Journal: Acta Pharmaceutica Sinica B (2025)
Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum
Authors: Muhammad Ali, Jigyasha Timsina, Daniel Western, Menghan Liu, Aleksandra Beric, John Budde, Anh Do, Gyujin Heo, Lihua Wang, Jen Gentsch, Suzanne E Schindler, John C Morris, David M Holtzman, Agustin Ruiz, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, Jarod Rutledge, Hamilton Oh, Edward N Wilson, Yann Le Guen, Rana R Khalid, Chloe Robins, David J Pulford, Rawan Tarawneh, Laura Ibanez, Tony Wyss-Coray, Yun Ju Sung, Carlos Cruchaga
Journal: Neuron (2025)

Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated in AD. Of these, 865 (43%) were previously reported, and 1,164 (57%) are novel. The identified proteins cluster in four different pseudo-trajectories groups spanning the AD continuum and were enriched in pathways including neuronal death, apoptosis, and tau phosphorylation (early stages), microglia dysregulation and endolysosomal dysfunction (mid stages), brain plasticity and longevity (mid stages), and microglia-neuron crosstalk (late stages). Using machine learning, we created and validated highly accurate and replicable (area under the curve [AUC] > 0.90) models that predict AD biomarker positivity and clinical status. These models can also identify people that will convert to AD.
Centromeric transposable elements and epigenetic status drive karyotypic variation in the eastern hoolock gibbon
Authors: Gabrielle A Hartley, Mariam Okhovat, Savannah J Hoyt, Emily Fuller, Nicole Pauloski, Nicolas Alexandre, Ivan Alexandrov, Ryan Drennan, Danilo Dubocanin, David M Gilbert, Yizi Mao, Christine McCann, Shane Neph, Fedor Ryabov, Takayo Sasaki, Jessica M Storer, Derek Svendsen, William Troy, Jackson Wells, Leighton Core, Andrew Stergachis, Lucia Carbone, Rachel J O'Neill
Journal: Cell Genomics (2025)
Dietary timing enhances exercise by modulating fat-muscle crosstalk via adipocyte AMPKα2 signaling
Authors: Jianghui Chen, Jing Xiang, Meiyu Zhou, Rongfeng Huang, Jianxin Zhang, Yuanting Cui, Xiaoqing Jiang, Yang Li, Runchao Zhou, Haoran Xin, Jie Li, Lihua Li, Sin Man Lam, Jianfang Zhu, Yanxiu Chen, Qingyuan Yang, Zhifu Xie, Guanghou Shui, Fang Deng, Zhihui Zhang, Min-Dian Li
Journal: Cell Metabolism (2025)
Protein profiles predict treatment responses to the PI3K inhibitor umbralisib in patients with chronic lymphocytic leukemia
Authors: Yanping Yin, Haifeng Xu, Liye He, Jennifer R. Brown, Anthony R. Mato, Tero Aittokallio, Sigrid S. Skånland
Journal: Clinical Cancer Research (2025)

Abstract Purpose: The management of chronic lymphocytic leukemia (CLL) has significantly improved with targeted therapies. However, many patients experience a suboptimal response. To optimally select the best therapy, predictive biomarkers are necessary. Here, we used the PI3K inhibitor umbralisib as a model to (i) understand how targeted treatment affects cell signaling and immunophenotypes in responders and non-responders; (ii) identify molecular features that predict individual treatment responses; and (iii) suggest alternative treatment options for the non-responders. Experimental design: We performed functional phenotyping of CLL cells from patients enrolled in two clinical trials with umbralisib, administered either as a monotherapy (NCT02742090, n=55) or in combination with the BTK inhibitor acalabrutinib (NCT04624633, n=12). Results: We found that umbralisib monotherapy led to significant changes in (phospho)protein levels, including AKT (pS473), in responders but not in non-responders. Furthermore, the proportion of cytotoxic natural killer cells increased at the end of study, but only in responders, suggesting a role in the anti-tumor response. To identify molecular predictors of response, we used the baseline levels of 30 (phospho)proteins in the monotherapy cohort as input features for a machine learning model, which achieved a significant prediction accuracy in cross-validation and maintained its predictive power in the combination cohort. Drug sensitivity profiling of the CLL cells at baseline suggested that PI3K + Bcl-2 inhibitors are effective in umbralisib non-responders. Conclusions: Functional phenotyping reveals differential cellular responses to umbralisib treatment in responders and non-responders; predicts treatment response of individual CLL patients; and suggests alternative treatment options for the non-responders.
Retraction: Cell-Permeable NM23 Blocks the Maintenance and Progression of Established Pulmonary Metastasis
Authors: Junghee Lim, Giyong Jang, Seeun Kang, Guewha Lee, Do Thi Thuy Nga, Do Thi Lan Phuong, Hyuncheol Kim, Wael El-Rifai, H. Earl Ruley, Daewoong Jo
Journal: Cancer Research (2025)
HLA-DQB1*03:01 and risk of Hepatitis B virus-related hepatocellular carcinoma
Authors: Ting Zhang, Chih-Jen Huang, Hai-Tao Chen, Yu-Han Huang, Mei-Hung Pan, Mei-Hsuan Lee, Mathias Viard, Allan Hildesheim, Ruth M. Pfeiffer, Mary Carrington, Chien-Jen Chen, Bin Zhu, Tobias L. Lenz, Deke Jiang, Hwai-I Yang, Zhiwei Liu
Journal: Hepatology (2025)

Background &amp; Aims: The human leukocyte antigen (HLA) locus is implicated in hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers. We investigated associations of HLA variants, amino acid polymorphisms, zygosity, and evolutionary divergence (HED) with HBV-related HCC in Han Chinese and explored biological mechanisms. Approach &amp; Results: We examined the associations of HLA variants (imputed 4-digit classical alleles and amino acid polymorphisms), zygosity, and HED with HBV-related HCC in a discovery set (706 HBV-related HCC cases, 6,197 chronic HBV carriers in Taiwan). Significant signals were validated in independent set (636 cases, 560 controls in Qidong, PR China). We used logistic regression adjusted for sex, age, and top 10 genetic principal components, with a Bonferroni-correction for multiple testing ( p &lt;1.6×10 −4 ). We evaluated predicted peptide-binding affinities and control of viral load, viral population diversity, and inflammatory markers for significant signals. HLA-DQB1*03:01 was most significantly associated with HBV-related HCC in discovery and validation sets (OR meta-analysis =1.33, P meta-analysis =2.6×10 −8 ). Three amino acids within DQβ1 peptide-binding region, HLA-DQβ1Ala13, HLA-DQβ1Tyr26, and HLA-DQβ1Glu45, were positively associated with HCC. HLA-DQB1*03:01 was associated with lower binding affinity of HBV nucleocapsid antigen and higher HBV DNA load and serum soluble programmed cell death 1 (sPD-1) ( P &lt;0.05). HLA-DQB1 heterozygosity was inversely associated with HCC independent of HLA-DQB1*03:01 ( P meta-analysis =3.3×10 −3 ). Conclusions: HLA-DQB1*03:01 and its three key amino acids are associated with an increased HBV-related HCC risk. This association may be explained by the low binding affinity to HBV antigen, resulting in poor control of viral load and increased inflammation, as evidenced by sPD-1 levels.
Aged and BRCA mutated stromal cells drive epithelial cell transformation
Authors: Geyon L. Garcia, Taylor Orellana, Grace Gorecki, Leonard Frisbie, Roja Baruwal, Swathi Suresh, Ester Goldfeld, Ian Beddows, Ian P. MacFawn, Ananya K. Britt, Macy M. Hale, Amal Taher. Elhaw, Brian R. Isett, Nadine Hempel, Riyue Bao, Hui Shen, Ronald J. Buckanovich, Toren Finkel, Ronny Drapkin, T  Rinda Soong, Tullia C. Bruno, Huda I. Atiya, Lan G. Coffman
Journal: Cancer Discovery (2025)

Abstract The fundamental steps in high-grade serous ovarian cancer (HGSOC) initiation are unclear presenting critical barriers in prevention and early detection of this deadly disease. Current models propose that fallopian tube epithelial (FTE) cells transform into serous tubal intraepithelial carcinoma (STIC) precursor lesions and subsequently HGSOC. Here we report that an epigenetically altered mesenchymal stem cell niche, termed high risk MSC (hrMSC), exists prior to STIC lesion formation. hrMSCs are enriched in STIC stroma and contribute to a stromal ‘field effect’ extending beyond the borders of STIC lesion. hrMSCs promote DNA damage in FTE cells while also fostering FTE cell survival. hrMSCs induce malignant transformation of FTE resulting in metastatic cancer in vivo, indicating hrMSCs promote cancer initiation. hrMSCs are significantly enriched in BRCA1/2 mutation carriers and increase with age. Combined, these findings indicate that hrMSCs can incite ovarian cancer initiation and have important implications for ovarian cancer detection and prevention.
The Omics Landscape of Long <scp>COVID</scp>—A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery
Authors: Nadia Baalbaki, Elise M. A. Slob, Samuel W. Kazer, Mahmoud I Abdel‐Aziz, Harm Jan Bogaard, Korneliusz Golebski, Anke H. Maitland‐van der Zee
Journal: Allergy (2025)

ABSTRACT An estimated 10% of coronavirus disease (COVID‐19) survivors suffer from persisting symptoms referred to as long COVID (LC), a condition for which approved treatment options are still lacking. This systematic review (PROSPERO: CRD42024499281) aimed to explore the pathophysiological mechanisms underlying LC and potential treatable traits across symptom‐based phenotypes. We included studies with primary data, written in English, focusing on omics analyses of human samples from LC patients with persistent symptoms of at least 3 months. Our search in PubMed and Embase, conducted on January 8, 2024, identified 642 studies, of which 29 met the inclusion criteria after full‐text assessment. The risk of bias was evaluated using the Joanna Briggs Institute appraisal tool. The synthesis of omics data, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, revealed common findings associated with fatigue, cardiovascular, pulmonary, neurological, and gastrointestinal phenotypes. Key findings included mitochondrial dysfunction, dysregulated microRNAs associated with pulmonary dysfunction, tissue impairment, blood–brain barrier disruption, coagulopathy, vascular dysfunction, microbiome disturbances, microbial‐derived metabolite production and persistent inflammation. Limitations include cross‐study heterogeneity and variability in sampling methods. Our review emphasizes the complexity of LC and the need for further longitudinal omics‐integrated studies to advance the development of biomarkers and targeted treatments.
Post-operative Fluid Restriction to Prevent Delayed Hyponatremia after Endoscopic Transsphenoidal Surgery
Authors: Doriann Klassen, Shinghei Mok, Jenie Y Hwang, Sydney L Blount, Kelley J Williams, Brendan M Fong, Michael R Chicoine, Ralph G Dacey Jr., Nyssa F Farrell, Joshua W Osbun, Keith M Rich, Lauren T Roland, John S Schneider, Gregory J Zipfel, Chongliang Luo, Albert H Kim, Julie M Silverstein
Journal: Neuro-Oncology (2025)

Abstract Background Readmission following endoscopic endonasal transsphenoidal surgery (EETS) for pituitary neuroendocrine tumor (PitNET) and other sellar pathology is most commonly due to delayed hyponatremia. Studies suggest post-operative fluid restriction (FR) reduces delayed hyponatremia. We present a prospective randomized controlled study evaluating post-EETS FR. Methods 300 participants were scheduled for EETS (2016-2023) at a single institution. Patients with CKD, CHF, arginine vasopressin deficiency on post-operative day (POD) 3, chronic hyponatremia, and untreated adrenal insufficiency or hypothyroidism were excluded. Groups included control (ad-lib, n=94), moderate FR (1.8 L/day or 2 L/day weight &amp;gt;100 kg, n=39), and strict FR (1 L/day or 1.2 L/day weight &amp;gt;100 kg, n=62) from POD 3-14. Incidence of overall, moderate, and severe hyponatremia (Na &amp;lt;135, 125-129, and &amp;lt;125 mEq/L), readmission rates, fluid intake, and thirst were evaluated. Results The incidence of overall hyponatremia was 31.9%, 28.2%, and 21.0% in control, moderate FR, and strict FR groups, and the incidence of severe hyponatremia was 7.4%, 5.1%, and 0% in control, moderate FR, and strict FR groups. Nadir Na level was higher (1.81 mEq/L; 95% CI, 0.34 to 3.27; P=0.02) and severe hyponatremia occurred less frequently (95% CI, 0.00 to 1.02; P=0.04) in the strict FR vs. control group. Readmission was lower in the strict FR (1.6%, n=1) vs. control group (6.4%, n=6). Conclusion Post-operative FR decreases rates of delayed hyponatremia and related readmission compared to patients drinking ad-lib. Further studies are needed to assess the optimal volume and duration of FR after EETS.
Blocking ITGA5 potentiates the efficacy of anti‐PD‐1 therapy on glioblastoma by remodeling tumor‐associated macrophages
Authors: Rongrong Zhao, Ziwen Pan, Jiawei Qiu, Boyan Li, Yanhua Qi, Zijie Gao, Wei Qiu, Weijie Tang, Xiaofan Guo, Lin Deng, Gang Li, Hao Xue
Journal: Cancer Communications (2025)

Abstract Background Glioblastoma (GBM) is largely refractory to antibodies against programmed cell death 1 (anti‐PD‐1) therapy. Fully understanding the cellular heterogeneity and immune adaptations in response to anti‐PD‐1 therapy is necessary to design more effective immunotherapies for GBM. This study aimed to dissect the molecular mechanisms of specific immunosuppressive subpopulations to drive anti‐PD‐1 resistance in GBM. Methods We systematically analysed single‐cell RNA sequencing and spatial transcriptomics data from GBM tissues receiving anti‐PD‐1 therapy to characterize the microenvironment alterations. The biological functions of a novel circular RNA (circRNA) were validated both in vitro and in vivo. Mechanically, co‐immunoprecipitation, RNA immunoprecipitation and pull‐down assays were conducted. Results Mesenchymal GBM (MES‐GBM) cells, which were associated with a poor prognosis, and secreted phosphoprotein 1 (SPP1) + myeloid‐derived macrophages (SPP1 + MDMs), a unique subpopulation of MDMs with complex functions, preferentially accumulated in non‐responders to anti‐PD‐1 therapy, indicating that MES‐GBM cells and SPP1 + MDMs were the main anti‐PD‐1‐resistant cell subpopulations. Functionally, we determined that circular RNA succinate dehydrogenase complex assembly factor 2 (circSDHAF2), which was positively associated with the abundance of these two anti‐PD‐1‐resistant cell subpopulations, facilitated the formation of a regional MES‐GBM and SPP1 + MDM cell interaction loop, resulting in a spatially specific adaptive immunosuppressive microenvironment. Mechanically, we found that circSDHAF2 promoted MES‐GBM cell formation by stabilizing the integrin alpha 5 (ITGA5) protein through N‐glycosylation. Meanwhile, the N‐glycosylation of the ITGA5 protein facilitated its translocation into exosomes and subsequent delivery to MDMs to induce the formation of SPP1 + MDMs, which in turn maintained the MES‐GBM cell status and induced T‐cell dysfunction via the SPP1‐ITGA5 pathway, ultimately promoting GBM immune escape. Importantly, our findings demonstrated that antibody‐mediated ITGA5 blockade enhanced anti‐PD‐1‐mediated antitumor immunity. Conclusions This work elucidated the potential tissue adaptation mechanism of intratumoral dynamic interactions between MES‐GBM cells, MDMs and T cells in anti‐PD‐1 non‐responders and identified the therapeutic potential of targeting ITGA5 to reduce anti‐PD‐1 resistance in GBM.
Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers
Authors: Dietmar Rudolf Thal, Koen Poesen, Rik Vandenberghe, Steffi De Meyer
Journal: Molecular Neurodegeneration (2025)

Abstract Alzheimer’s disease (AD) is neuropathologically characterized by the extracellular deposition of the amyloid-β peptide (Aβ) and the intraneuronal accumulation of abnormal phosphorylated tau (τ)-protein (p-τ). Most frequently, these hallmark lesions are accompanied by other co-pathologies in the brain that may contribute to cognitive impairment, such as vascular lesions, intraneuronal accumulation of phosphorylated transactive-response DNA-binding protein 43 (TDP-43), and/or α-synuclein (αSyn) aggregates. To estimate the extent of these AD and co-pathologies in patients, several biomarkers have been developed. Specific tracers target and visualize Aβ plaques, p-τ and αSyn pathology or inflammation by positron emission tomography. In addition to these imaging biomarkers, cerebrospinal fluid, and blood-based biomarker assays reflecting AD-specific or non-specific processes are either already in clinical use or in development. In this review, we will introduce the pathological lesions of the AD brain, the related biomarkers, and discuss to what extent the respective biomarkers estimate the pathology determined at post-mortem histopathological analysis. It became evident that initial stages of Aβ plaque and p-τ pathology are not detected with the currently available biomarkers. Interestingly, p-τ pathology precedes Aβ deposition, especially in the beginning of the disease when biomarkers are unable to detect it. Later, Aβ takes the lead and accelerates p-τ pathology, fitting well with the known evolution of biomarker measures over time. Some co-pathologies still lack clinically established biomarkers today, such as TDP-43 pathology or cortical microinfarcts. In summary, specific biomarkers for AD-related pathologies allow accurate clinical diagnosis of AD based on pathobiological parameters. Although current biomarkers are excellent measures for the respective pathologies, they fail to detect initial stages of the disease for which post-mortem analysis of the brain is still required. Accordingly, neuropathological studies remain essential to understand disease development especially in early stages. Moreover, there is an urgent need for biomarkers reflecting co-pathologies, such as limbic predominant, age-related TDP-43 encephalopathy-related pathology, which is known to modify the disease by interacting with p-τ. Novel biomarker approaches such as extracellular vesicle-based assays and cryptic RNA/peptides may help to better detect these co-pathologies in the future.
A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients
Authors: Yered Pita-Juarez, Dimitra Karagkouni, Nikolaos Kalavros, Johannes C. Melms, Sebastian Niezen, Toni M. Delorey, Adam L. Essene, Olga R. Brook, Deepti Pant, Disha Skelton-Badlani, Pourya Naderi, Pinzhu Huang, Liuliu Pan, Tyler Hether, Tallulah S. Andrews, Carly G. K. Ziegler, Jason Reeves, Andriy Myloserdnyy, Rachel Chen, Andy Nam, Stefan Phelan, Yan Liang, Mark Gregory, Shanshan He, Michael Patrick, Tushar Rane, Aster Wardhani, Amit Dipak Amin, Jana Biermann, Hanina Hibshoosh, Molly Veregge, Zachary Kramer, Christopher Jacobs, Yusuf Yalcin, Devan Phillips, Michal Slyper, Ayshwarya Subramanian, Orr Ashenberg, Zohar Bloom-Ackermann, Victoria M. Tran, James Gomez, Alexander Sturm, Shuting Zhang, Stephen J. Fleming, Sarah Warren, Joseph Beechem, Deborah Hung, Mehrtash Babadi, Robert F. Padera, Sonya A. MacParland, Gary D. Bader, Nasser Imad, Isaac H. Solomon, Eric Miller, Stefan Riedel, Caroline B. M. Porter, Alexandra-Chloé Villani, Linus T.-Y. Tsai, Winston Hide, Gyongyi Szabo, Jonathan Hecht, Orit Rozenblatt-Rosen, Alex K. Shalek, Benjamin Izar, Aviv Regev, Yury V. Popov, Z. Gordon Jiang, Ioannis S. Vlachos
Journal: Genome biology (2025)

Abstract Background The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. Results We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell–cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Conclusions Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.