tbuckley/cabot-search huggingface dataset:
Krüppel-Like Factor 6 Induces RNA Polymerase II Subunit RPB1 to Promote Kidney Injury
Authors: Sian E. Piret, Samaneh DiMartino, Maanasa Hanubal, Merin Davis, Jiakang Wang, Tej Bahadur, Asha Rath, Nehaben A. Gujarati, Bismark O. Frimpong, Robert Bronstein, Monica P. Revelo, Yiqing Guo, Sandeep K. Mallipattu
Journal: Journal of the American Society of Nephrology (2025)

Background: Initial proximal tubule cell injury and dedifferentiation contribute to acute kidney injury (AKI), and persistent dedifferentiation drives fibrosis and chronic kidney disease (CKD). Proximal tubule-specific knockdown of zinc-finger transcription factor Krüppel-like factor 6 ( Klf6 ) attenuates the AKI to CKD transition. Our aim was to study the early transcriptional mechanisms by which KLF6 induction exacerbates proximal tubular injury and eventual fibrosis. Methods: Aristolochic acid I-treated wild-type and KLF6 overexpression mice underwent single nucleus (sn)RNA-seq and snATAC-seq (acute phase) and assessment of kidney function, injury, and fibrosis (remodeling phase). POLR2A was knocked down in human kidney cells, and cell number, gene expression, differentiation, DNA damage, and cell cycle assessed. Kidney sections from fibrotic mouse models and human CKD secondary to aristolochic acid and diabetes were assessed for RPB1 expression. Results: snRNA-seq identified an injured proximal tubule cluster with high expression of Klf6 and RNA polymerase II subunit a ( Polr2a ) encoding RPB1. After injury, RPB1-positive cells accumulated and were associated with dedifferentiated proximal tubules. POLR2A knockdown in injured cells increased cell death, but reduced inflammatory and fibrotic gene expression, dedifferentiation, DNA damage, and G2/M cell cycle arrest, with a transcriptional switch from long genes to short genes. snATAC-seq demonstrated an open chromatin region in Polr2a intron 1 in injured proximal tubule cells, containing a KLF6 binding site. Knockdown of KLF6 reduced POLR2A induction, whilst proximal tubule-specific KLF6 further increased Polr2a levels after injury. Mice with tubule-specific KLF6 induction had more RPB1-positive proximal tubules and more injury post-AKI. Human kidney samples with DNA-damage induced CKD and diabetic kidney disease also had high POLR2A /RPB1 expression in dedifferentiated proximal tubule cells. Conclusions: Prolonged high expression of RPB1 is associated with dedifferentiated proximal tubule cells. Mice overexpressing KLF6 had higher expression of RPB1 and worse kidney injury after DNA damage.
Moxidectin combination therapies for lymphatic filariasis: an open-label, observer-masked, randomised controlled trial
Authors: Guibehi Benjamin Koudou, Catherine M Bjerum, Foungoye Allassane Ouattara, Toki Pascal Gabo, Charles W Goss, Daphne Lew, N'Goran N Dje, Christopher L King, Peter U Fischer, Gary J Weil, Philip J Budge
Journal: The Lancet Infectious Diseases (2025)
PD-L1 Antibody-Modified Plant-Derived Nanovesicles Carrying a STING Agonist for the Combinational Immunotherapy of Melanoma
Authors: Zhanxue Xu, Xinrui Yang, Xingyu Lu, Dandan Su, Yidan Wang, Huixing Wu, Zhenhua Zhang, Changrui Long, Liqian Su, Yanyu Wang, Hongbo Chen, Shijian Xiang, Benjie Zhou
Journal: Biomaterials (2025)
Confirmation of endoscopic injection sclerotherapy by mucosal whitening in the treatment of hemorrhage of refractory recurrent tiny esophageal varices
Authors: Kazunori Nagashima, Shintaro Yamaguchi, Ryuichi Maki, Fumihiko Urushibara, Tsunehiro Suzuki, Toshimitu Murohisa, Atsushi Irisawa
Journal: Endoscopy (2025)
Evidence of Coxiella burnetii and Bartonella species infections among patients with persistent febrile illness in four low- and middle-income countries
Authors: Carl Boodman, Sophie Edouard, Johan van Griensven, Kanika Deshpande Koirala, Basudha Khanal, Suman Rijal, Narayan Raj Bhattarai, Sayda El Safi, Thong Phe, Kruy Lim, Pascal Lutumba, François Chappuis, Cédric P Yansouni, Barbara Barbé, Marjan van Esbroeck, Tine Verdonck, Marleen Boelaert, Pierre-Édouard Fournier, Emmanuel Bottieau
Journal: Clinical Microbiology and Infection (2025)

This study investigated whether infections due to Coxiella burnetii, Bartonella species or Tropheryma whipplei could be identified among biobanked samples associated with persistent fever in four low- or middle-income countries (LMICs). The NIDIAG consortium prospectively investigated in 2013-2014 the etiological spectrum of 1922 patients with persistent febrile illness (fever greater than 7 days) in Cambodia, Nepal, Sudan and the Democratic Republic of Congo (DRC). Our study retrospectively tested serum and blood samples from the 745 patients (38.8%) who remained without an identified cause of fever. Indirect immunofluorescent antibody assays (IFA) were performed (except in the DRC) to assess immunoglobulin response to C. burnetii and Bartonella antigens. DNA extracts from whole blood samples were tested for Coxiella burnetii, Bartonella genus, Bartonella quintana, Bartonella henselae and Tropheryma whipplei by quantitative polymerase chain reaction (qPCR). Evidence of infection with C. burnetii or Bartonella sp. was found in 124 persistent fever cases (16.6%). IFA for IgG to C. burnetii phase I and II antigens identified 59 (7.9%) positive sera: 31/333 (9.3%) from Sudan, 16/278 (5.8%) from Nepal, and 12/54 (22.2%) from Cambodia. Eight individuals had C. burnetii anti-phase I IgG titers ≥ 1:800. Bartonella IFA identified 60 (8.1%) IgG positive sera, with 49/278 (17.6%) positive samples from Nepal, 7/333 (2.1%) from Sudan and 4/54 (7.4%) from Cambodia. One serum from Sudan had anti-Bartonella IgG titers of 1:800. C. burnetii DNA was detected from blood in 3 individuals from Sudan and one individual from the DRC, whereas B. quintana DNA was present in a blood sample from a Nepalese individual. All qPCR tests for T. whipplei were negative. Direct and indirect evidence of C. burnetii or Bartonella sp. infections was observed in persistent fever cases. Further studies are necessary to elucidate the burden of these diseases in LMICs.
Transpancreatic precut sphincterotomy with a novel highly rotatable sphincterotome in balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography
Authors: Tadahisa Inoue, Rena Kitano, Tomoya Kitada, Kazumasa Sakamoto, Satoshi Kimoto, Jun Arai, Kiyoaki Ito
Journal: Endoscopy (2025)
Size-dependent penetration depth of colloidal nanoparticles into cell spheroids
Authors: Dingcheng Zhu, Dennis Brückner, Martin Sosniok, Marvin Skiba, Neus Feliu, Marta Gallego, Yang Liu, Florian Schulz, Gerald Falkenberg, Wolfgang J Parak, Carlos Sanchez-Cano
Journal: Advanced Drug Delivery Reviews (2025)
Mucosal carcinoma arising in a colon diverticulum: endoscopic submucosal dissection using the novel “clip-band-tent” traction method
Authors: Felipe Ramos-Zabala, Marian García-Mayor, Alejandra Alzina-Pérez, Raúl José Díaz-Molina, Luis Moreno-Almazán
Journal: Endoscopy (2025)
Targeting RBP4–STRA6 retinol signaling disrupts adipose–prostate crosstalk: A novel strategy to suppress basal cell plasticity in androgen deprivation
Authors: Huan Xu, Dajun Gao, Yanting Shen, Jianqing Wang, Junduo Wang, Jun Zhu, Miao Ren, Lai Wei, Hailiang Hu, Ming Zhan, Zhong Wang, Fubo Wang, Bin Xu
Journal: Metabolism (2025)
Eosinophilic Esophagitis (EoE): Allergy &amp; Immunology Perspective on the Updated Guidelines
Authors: Emily C McGowan, Benjamin L Wright, Melanie A Ruffner, Robert D Pesek, Marc E Rothenberg, Jonathan M Spergel, Evan S Dellon, Seema S Aceves
Journal: Journal of Allergy and Clinical Immunology (2025)
Core GRADE 3: rating certainty of evidence—assessing inconsistency
Authors: Gordon Guyatt, Stefan Schandelmaier, Romina Brignardello-Petersen, Hans De Beer, Manya Prasad, M Hassan Murad, Prashanti Eachempati, Derek K Chu, Rohan D'Souza, Alfonso Iorio, Thomas Agoritsas, Liang Yao, Reem A Mustafa, Sameer Parpia, Pasqualina Santaguida, Per Olav Vandvik, Monica Hultcrantz, Victor M Montori
Journal: BMJ (2025)
A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities
Authors: Hadi Alizadeh, Parastoo Akbarabadi, Alireza Dadfar, Mohammad Reza Tareh, Bahram Soltani
Journal: Molecular Cancer (2025)

Ovarian cancer is one of the most lethal gynecological malignancies, with a recurrence rate of 70-80%, particularly in patients diagnosed at advanced stages (stage III or IV), where the five-year survival rate falls below 30%. A key driver of this recurrence is the presence of cancer stem cells (CSCs), which exhibit resistance to chemotherapy and possess the capacity for self-renewal, plasticity, and tumor regeneration. The tumor microenvironment (TME) plays a crucial role in maintaining ovarian cancer stem cells (OCSCs) by providing nutrient and oxygen gradients, extracellular matrix (ECM) interactions, immune cell modulation, and support from cancer-associated fibroblasts (CAFs). CAFs secrete growth factors, cytokines, and ECM components that create a pro-tumorigenic niche, promoting CSC maintenance, invasion, and chemoresistance. Additionally, dysregulation of critical signaling pathways, including WNT, NOTCH, PI3K/AKT/mTOR, TGF-β, JAK/STAT, Hedgehog, NF-κB, and Hippo, supports CSC stemness, plasticity, maintenance, and adaptability, thereby increasing their survival and progression. Numerous inhibitors targeting these pathways have shown promise in preclinical studies. This review discusses the molecular mechanisms underlying CSC-mediated recurrence in ovarian cancer and highlights emerging therapeutic strategies. Particular emphasis is placed on the potential of combination therapies involving routine platinum or taxane based regimens with OCSC inhibitors to overcome chemoresistance, reduce recurrence rates, and improve survival outcomes for patients with advanced-stage ovarian cancer.
Selective Recognition of Bacterial Phospholipids by Antimicrobial Peptides: Employing a Host-Guest-Mediated Competitive Inhibition Strategy
Authors: Xinshuang Zhang, Dong Luo, Jie Hu, Kangxiu Wu, Shuyi Jia, Xueyi Li, Songyin Huang, Houbing Zhang, Dokyun Kim, Yuzhi Hong, Liping Zhao, Menghua Xiong, Yan Bao
Journal: Biomaterials (2025)
Human-machine co-adaptation to automated insulin delivery: a randomised clinical trial using digital twin technology
Authors: Boris P Kovatchev, Patricio Colmegna, Jacopo Pavan, Jenny L Diaz Castañeda, Maria F Villa-Tamayo, Chaitanya L K Koravi, Giulio Santini, Carlene Alix, Meaghan Stumpf, Sue A Brown
Journal: npj Digital Medicine (2025)
Redefining respiratory sinus arrhythmia as respiratory heart rate variability: an international Expert Recommendation for terminological clarity
Authors: Clément Menuet, Alona Ben-Tal, Ambre Linossier, Andrew M Allen, Benedito H Machado, Davi J A Moraes, David G S Farmer, David J Paterson, David Mendelowitz, Edward G Lakatta, Edwin W Taylor, Gareth L Ackland, Irving H Zucker, James P Fisher, James S Schwaber, Julia Shanks, Julian F R Paton, Julie Buron, K Michael Spyer, Kalyanam Shivkumar, Mathias Dutschmann, Michael J Joyner, Neil Herring, Paul Grossman, Robin M McAllen, Rohit Ramchandra, Song T Yao, Thomas Ritz, Alexander V Gourine
Journal: Nature Reviews Cardiology (2025)
Heart failure and obesity: Translational approaches and therapeutic perspectives. A scientific statement of the Heart Failure Association of the <scp>ESC</scp>
Authors: Gianluigi Savarese, Gabriele G. Schiattarella, Felix Lindberg, Markus S. Anker, Antoni Bayes‐Genis, Magnus Bäck, Frieder Braunschweig, Chiara Bucciarelli‐Ducci, Javed Butler, Antonio Cannata, Federico Capone, Ovidiu Chioncel, Emilia D'Elia, Arantxa González, Gerasimos Filippatos, Nicolas Girerd, Jean‐Sébastien Hulot, Carolyn S.P. Lam, Lars H. Lund, Christoph Maack, Brenda Moura, Mark C. Petrie, Massimo Piepoli, Abdullah Shehab, Mehmet B. Yilmaz, Peter Seferovic, Carlo G. Tocchetti, Giuseppe M.C. Rosano, Marco Metra
Journal: European Journal of Heart Failure (2025)

Abstract Obesity and heart failure (HF) represent two growing pandemics. In the general population, obesity affects one in eight adults and is linked with an increased risk for HF. Obesity is even more common in patients with HF, where it complicates the diagnosis of HF and is linked with worse symptoms and impaired exercise capacity. Over the past few years, new evidence on the mechanisms linking obesity with HF has been reported, particularly in relation to HF with preserved ejection fraction. Novel therapies inducing weight loss appear to have favourable effects on health status and cardiovascular risk. Against the backdrop of this rapidly evolving evidence landscape, HF clinicians are increasingly required to tailor their preventive, diagnostic, and therapeutic approaches to HF in the presence of obesity. This scientific statement by the Heart Failure Association of the European Society of Cardiology provides an up‐to‐date summary on obesity in HF, covering key areas such as epidemiology, translational aspects, diagnostic challenges, therapeutic approaches, and trial design.
Reporting of sociodemographic characteristics of trial participants in infectious diseases clinical trials – a systematic review
Authors: Sean W X Ong, Christina Blagojevic, Aliya Bryce, Aaron Ovadia, Matthew Slater, Daire Pryal, Rodrigo Escobar Careaga, Hadrien Moffroid, Arvind Yerramilli, Esmita Charani, Nick Daneman, Steven Y C Tong
Journal: Clinical Microbiology and Infection (2025)

Reporting of demographic characteristics in randomised clinical trials (RCT) is recommended to facilitate assessment of generalisability to other populations. However, there is a lack of consensus as to what variables should be reported, and there are limited data describing current research practice. We aimed to evaluate reporting of sociodemographic characteristics of participants in infectious diseases RCTs and identify gaps in current practice. We conducted a systematic review of all infectious diseases-related RCTs published between January 2014 to August 2023 in ten selected high impact journals by searching the Ovid MEDLINE database. Outcomes of interest were the reporting of five patient-level sociodemographic characteristics, as recommended by the CONSORT-Equity 2017 extension to the CONSORT reporting guidelines: (a) ethnicity, (b) sex and/or gender, (c) education level, (d) socioeconomic status (SES), and (e) rurality. We summarised descriptive results for the reporting of each characteristic overall, by trial type (health equity-related vs non-health equity-related), subject area, and year of publication. We fitted multivariable logistic regression models to identify trial characteristics associated with the reporting of each characteristic. Risk of bias of trials was not assessed as our objective was to assess trial reporting and not results. We screened 4234 articles and included 1343. Almost all trials (1201/1233, 97.4%) reported sex and/or gender. In contrast, less than half (654/1326, 49.3%) reported ethnicity, and only a minority reported education level (113/1252, 9.0%), SES (120/1340, 9.0%), and rurality (45/1269, 3.9%). There was no improvement in reporting of each characteristic over the 10-year period. Subject area, funding source, whether a trial was health-equity related, use of a medical writer, and trial setting (high vs low/middle-income country) were significantly associated with the reporting of ethnicity, education level, and SES. Reporting of sociodemographic characteristics in infectious diseases RCTs is inconsistent and has not improved over time.
Nanogel encapsulation improves pharmacokinetics and biodistribution of antimicrobial peptide LL37 upon lung deposition: In vivo evaluation by SPECT/CT
Authors: Sylvia N Kłodzińska, Tullio V F Esposito, Monica Agnoletti, Cristina Rodríguez-Rodríguez, Colin Blackadar, Lan Wu, Aneesh Thakur, Jessica Nahrstedt, Thomas Rades, Katayoun Saatchi, Urs O Häfeli, Hanne Mørck Nielsen
Journal: Journal of Controlled Release (2025)
Drugs and Toxic-Associated Pulmonary Arterial Hypertension, Prognosis, and Management in the Current Era of Treatment: Results From the REHAP Registry
Authors: J.A. Tenes Mayen, L. Lago Laguna, S. Del Prado Diaz, E. Gutierrez, J.A. Barbera, R. Lopez-Reyes, M. Lazaro Salvador, None Aurtenetxe, P. Escribano Subías, I. Blanco, None on behalf of the REHAP investigators
Journal: American Journal of Respiratory and Critical Care Medicine (2025)
Variation of eGFR Wait Time Modifications for Black Kidney Transplant Candidates in the United States
Authors: Jesse D. Schold, Susana Arrigain, S. Ali Husain, Miko Yu, Rocio Lopez, Deena Brosi, Ryan LaVanchy, Sumit Mohan
Journal: Journal of the American Society of Nephrology (2025)

Background: In 2023, kidney transplant programs in the United States were mandated by the Organ Procurement and Transplantation Network (OPTN) to identify all Black candidates on their kidney waiting lists and evaluate potential modifications of waiting time. This mandate was the result of established differences in eligibility for candidates to receive priority for donor offers based on race-neutral and race-inclusive estimated Glomerular Filtration Rates (eGFR). The policy went into effect on January 5 th ,2023and required submission of appropriate modifications with a deadline of January 3 rd , 2024. Methods: We included OPTN data for adult Black candidates on the kidney and kidney/pancreas transplant waiting lists in the US between January 6 th ,2023 to December 31 st ,2023. We evaluated incidence of wait-time modifications based on eGFR, characterized candidates with and without modifications, heterogeneity in center-level implementation of eGFR modifications and the association of modification with time to deceased donor transplantation using multivariable generalized estimating equations and Cox models. Results: Overall, 32% (14,419/44,912) of Black candidate listings received an eGFR modification of waiting time priority. In multivariable analysis, candidates with modifications were older (compared with candidates aged 18-49, ages 65-69 and 70+ had adjusted odds ratio (AOR)=1.60 (95% C.I. 1.49-1.72) and 1.52 (95% C.I. 1.40-1.66) respectively), female (AOR=1.09,95% C.I. 1.04-1.14), and preemptively placed on the waiting list (AOR=2.58,95% C.I. 2.46-2.72). Kidney alone candidates (versus kidney-pancreas candidates), higher body mass index and prior transplant recipients also had higher adjusted likelihood of waiting time modification. The median increase in qualifying priority days for candidates was 610 [interquartile range (IQR)= 330-1049]. Waitlist modification was associated with a significantly higher rate of deceased donor transplantation (adjusted hazard ratio=2.85 [95% CI: 2.70, 3.02]). There was significant variation by transplant center in the proportion of prevalent patients with modifications (median=31%, IQR=11-45%). Conclusions: There is significant patient and center-level variation in the implementation of eGFR modifications and a higher rate of transplantation for candidates who received modifications.
HRProfiler Detects Homologous Recombination Deficiency in Breast and Ovarian Cancers Using Whole-Genome and Whole-Exome Sequencing Data
Authors: Ammal Abbasi, Christopher D. Steele, Erik N. Bergstrom, Azhar Khandekar, Akanksha Farswan, Rana R. McKay, Nischalan Pillay, Ludmil B. Alexandrov
Journal: Cancer Research (2025)

Abstract Breast and ovarian cancers harboring homologous recombination deficiency (HRD) are sensitive to PARP inhibitors and platinum chemotherapy. Conventionally, detecting HRD involves screening for defects in BRCA1, BRCA2, and other relevant genes. Recent analyses have shown that HRD cancers exhibit characteristic mutational signatures due to the activities of HRD-associated mutational processes. At least three machine learning tools exist for detecting HRD based on mutational patterns. Here, using sequencing data from 1,043 breast and 182 ovarian cancers, we trained Homologous Recombination Proficiency Profiler (HRProfiler), a machine learning method for detecting HRD using six mutational features. The performance of HRProfiler was assessed against prior approaches using additional independent datasets of 417 breast and 115 ovarian cancers, including retrospective data from a clinical trial involving patients treated with PARP inhibitors. Individual HRD-associated mutational signatures alone did not consistently detect HRD or predict clinical response across datasets. Notably, while all tools performed comparably for whole-genome sequenced cancers, HRProfiler was the only approach that consistently identified HRD in whole-exome sequenced breast and ovarian cancers, offering clinically relevant insights. Retrospective analyses provided strong evidence that HRProfiler could serve as a valuable tool for predicting HRD and clinical response in breast and ovarian cancers. This study provides the rational for large-scale prospective clinical trials to validate the potential of HRProfiler as a routine predictive and/or prognostic HRD biomarker to guide clinical decision-making.
The Integrated Stress Response Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer
Authors: Shayna Thomas-Jardin, Shruthy Suresh, Ariana Arce, Nicole Novaresi, Qing Deng, Emily Stein, Lisa Thomas, Cheryl Lewis, Chul Ahn, Bret M. Evers, Esra A. Akbay, Maria E. Salvatierra, Wei Lu, Khaja Khan, Luisa M. Solis Soto, Ignacio I. Wistuba, John D. Minna, Kathryn A. O'Donnell
Journal: Cancer Research (2025)

Abstract The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces PD-L1, leading to suppression of anti-tumor immunity. Here, we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. ISR coordinately induced CD155 and PD-L1, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames in their 5' UTRs. Analysis of primary human lung tumors identified a significant correlation between expression of PD-L1 and CD155. ISR activation accelerated tumorigenesis and inhibited T cell function, which could be overcome by combining PD-1 and TIGIT blockade with the ISR inhibitor ISRIB. This study uncovers a mechanism by which two immune checkpoint proteins are coordinately regulated and suggests a therapeutic strategy for lung cancer patients.