tbuckley/cabot-search huggingface dataset:
Hepatic encephalopathy - We are no longer those who believe that reality is what we perceive
Authors: Sara Montagnese, Andres Duarte-Rojo
Journal: Hepatology (2025)

1Professor of Medicine, Department of Medicine Padova University Hospital Via Giustiniani, 2 – 35128 Padova, Italy 2Professor of Medicine and Surgery, Division of Gastroenterology and Hepatology and Comprehensive Transplant Center, Northwestern Medicine, Feinberg School of Medicine, 676 N. St. Clair St., Room 1900, Chicago, IL 60611, USA Correspondence Professor of Medicine, Department of Medicine Padova University Hospital Via Giustiniani, 2 – 35128 Padova, Italy. Email: [email protected]
Epidemiology of Coronary Atherosclerosis Among People Living With HIV in Uganda
Authors: Mark J. Siedner, Brian Ghoshhajra, Geoffrey Erem, Rita Nassanga, Mangun Randhawa, Andrew Ochieng, Moses Acan, Michael T. Lu, Vikas Thondapu, Angelo Takigami, Zahra Reynolds, Flavia Atwiine, Edna Tindimwebwa, Rebecca F. Gilbert, Eliza Passell, Shruti Sagar, Yao Tong, Ntobeko A.B. Ntusi, Alexander C. Tsai, Prossy Bibangambah, Thomas Gaziano, Susanne S. Hoeppner, Christopher T. Longenecker, Samson Okello, Stephen Asiimwe
Journal: Annals of Internal Medicine (2025)

Data on the prevalence of coronary atherosclerotic disease (CAD) in the African region among people with and without HIV are lacking.
CAD manipulates tumor intrinsic DHO/UBE4B/NF-κB pathway and fuels macrophage cross-talk, promoting hepatocellular carcinoma metastasis
Authors: Jiaomeng Pan, Mao Zhang, Dongning Rao, Junjie Ma, Xia Shen, Haokai Qin, Kun Gan, Jian Lin, Yingying Huang, Chen Sang, Juan Zhang, Jiaqiang Ma, Yingcheng Wu, Zheng Tang, Daming Gao, Qiang Gao, Liuxiao Yang, Jia Fan
Journal: Hepatology (2025)

Background and Aims: Portal vein tumor thrombosis (PVTT), an indicator of clinical metastasis, significantly shortens hepatocellular carcinoma (HCC) patients’ lifespan, and no effective treatment has been established. We aimed to illustrate mechanisms underlying PVTT formation and tumor metastasis, and identified potential targets for clinical intervention. Approach and Results: Multi-omics data of 159 HCC patients (including 37 cases with PVTT) was analyzed to identify contributors to PVTT formation and tumor metastasis. In vitro and in vivo experiments were performed to confirm the critical role of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) in HCC metastasis. Metabolomics and transcriptomics techniques, single-cell RNA sequencing, combined with experimental verification were complemented to illustrate mechanisms underlying CAD induced pro-metastatic efficacy. Analysis of proteogenomic data of HCC cohort identified CAD as the key contributor to PVTT formation and tumor metastasis in HCC. Further experiments confirmed that high CAD expression could significantly promote HCC metastasis, and vice versa. Mechanistically, CAD manipulated de novo pyrimidine anabolism, leading to dihydroorotic acid (DHO) accumulation which directly bound to ubiquitination factor E4B (UBE4B). UBE4B subsequently regulated JAK1 ubiquitination and activated the NF-κB pathway to promote epithelial-mesenchymal transition (EMT) of HCC cells. Additionally, CAD generated an immunosuppressive milieu conducive to HCC metastasis by recruiting and reprogramming macrophages into a “pro-tumor” phenotype. Consequently, the metastatic capability of HCC was remarkably enhanced. Conclusion: Therapy targeting CAD may offer a promising approach to curb HCC metastasis by reducing tumor cells’ metastatic potential and also shifting the tumor microenvironment towards a less pro-metastatic state.
Reply: Fiber and whole grain intakes in relation to liver cancer risk: An analysis in 2 prospective cohorts and systematic review and meta-analysis of prospective studies
Authors: Cody Z. Watling, Aika Wojt, Andrea A. Florio, Gisela Butera, Demetrius Albanes, Stephanie J. Weinstein, Wen-Yi Huang, Dominick Parisi, Xuehong Zhang, Barry I. Graubard, Jessica L. Petrick, Katherine A. McGlynn
Journal: Hepatology (2025)

Watling, Cody Z.; Wojt, Aika; Florio, Andrea A.; Butera, Gisela; Albanes, Demetrius; Weinstein, Stephanie J.; Huang, Wen-Yi; Parisi, Dominick; Zhang, Xuehong; Graubard, Barry I.; Petrick, Jessica L.; McGlynn, Katherine A. Author Information
Incidence of Scrub Typhus in Rural South India
Authors: Carol Devamani, Neal Alexander, Daniel Chandramohan, John Stenos, Mary Cameron, Kundavaram P.P. Abhilash, Punam Mangtani, Stuart Blacksell, Huong Thi Thu Vu, Winsley Rose, Wolf-Peter Schmidt
Journal: New England Journal of Medicine (2025)

Hospital studies suggest that scrub typhus is a leading cause of severe undifferentiated fever in regions across Asia where the disease is endemic, but the population-based incidence of infection and illness has been little studied. We conducted a population-based cohort study to assess epidemiologic and clinical characteristics of scrub typhus in 37 villages in Tamil Nadu, India, where the disease is highly endemic. Study participants were visited every 6 to 8 weeks over a period of 2 years; a venous blood sample was obtained from those who had had fever since the last visit. A subcohort of participants underwent blood sampling to estimate the incidence of serologically confirmed Orientia tsutsugamushi infection. We systematically assessed 32,279 participants from 7619 households for acute febrile illness. During 54,588 person-years of follow-up, we observed 6175 episodes of fever. A blood sample was obtained in 4474 episodes (72.5%), of which 328 (7.3%) met the clinical case definition of scrub typhus (detection of IgM against O. tsutsugamushi on enzyme-linked immunosorbent assay [ELISA] or detection of O. tsutsugamushi on polymerase-chain-reaction assay). The incidence of clinical infection was 6.0 cases per 1000 person-years (95% confidence interval [CI], 4.8 to 7.5). A total of 71 clinical cases (21.6%) resulted in hospitalization (incidence, 1.3 events per 1000 person-years; 95% CI, 1.0 to 1.7). A total of 29 clinical cases (8.8%) were severe, as indicated by the presence of organ dysfunction or adverse pregnancy outcomes (incidence, 0.5 cases per 1000 person-years; 95% CI, 0.4 to 0.8). Among 2128 participants in the subcohort who provided samples at the beginning and end of a study year, the incidence of seroconversion independent of any symptoms was 81.2 events per 1000 person-years (95% CI, 70.8 to 91.6). The incidence of clinical infection was higher in older age groups than in younger age groups and higher among female participants than among male participants. By contrast, the age-adjusted rate of severe infection was similar among male and female participants. Among 5602 participants assessed at the start of the first year of the study, the seroprevalence of IgG as assessed with ELISA was 42.8% (95% CI, 35.8 to 50.2). IgG seropositivity at the beginning of years 1 or 2 did not protect against clinical illness during the subsequent year but was associated with less severe disease than IgG seronegativity. We describe the burden of scrub typhus, including the incidence of asymptomatic infection, in a region of Asia where the disease is endemic. (Funded by the U.K. Medical Research Council; ClinicalTrials.gov number, NCT04506944.).
CD105 blockade restores osimertinib sensitivity in drug-resistant EGFR-mutant non-small cell lung cancer
Authors: Manish Thiruvalluvan, Sandrine Billet, Zhenqiu Liu, Joseph Lownik, Barliz Waissengrin, Hyoyoung Kim, Anton L Villamejor, Larry Milshteyn, Xiamo Li, Matthew Gayhart, Manuel Araña, Kamya Sankar, Edwin M Posadas, Jean Lopategui, Sungyong You, Karen L Reckamp, Neil A Bhowmick
Journal: Drug Resistance Updates (2025)

To investigate the role of CD105 in mediating drug resistance to EGFR-targeted therapy in non-small cell lung cancer (NSCLC). Imaging mass cytometry was conducted on 66 NSCLC tumors, 44 of which had EGFR mutations. We correlated clinical variables, including overall survival, with CD105 (endoglin) expression, a co-receptor for bone morphogenetic protein (BMP) signaling. Two osimertinib-resistant EGFR-mutant cell lines were developed to study the effects of EGFR and CD105 disruption. Single cell RNA sequencing of the isogenic parental and osimertinib resistant lines was performed. Additionally, ATAC sequencing and Single Cell ENergetIc metabolism by profiling Translation inHibition analysis (SCENITH) was used to assess promoter chromatin status and glycolytic state. We found a negative correlation between CD105 expression and overall survival in patients. Treatment with osimertinib or EGFR knockdown significantly elevated CD105 expression in EGFR-mutant cell lines. Single-cell RNA sequencing identified a subset of cells with heightened endothelial characteristics and altered pyrimidine metabolism, associated with osimertinib resistance. These cells exhibited a slow-cycling behavior, characterized by elevated chromatin condensation and reduced glycolysis. Combining osimertinib with carotuximab, a CD105 neutralizing antibody, significantly reduced the slow-cycling transcriptomic signature, increased chromatin accessibility, and restored glycolysis compared to osimertinib treatment alone. Mass spectrometry confirmed that carotuximab re-engaged EGFR signaling by coupling it with CD105. Consequently, carotuximab re-sensitized resistant tumors to osimertinib by increasing their mitotic index and ERK signaling in mouse models. Carotuximab effectively reduced the slow-cycling cell population and restored osimertinib sensitivity, offering a promising strategy for managing refractory NSCLC.
Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial
Authors: Miguel R Abboud, Rodolfo D Cançado, Mariane De Montalembert, Wally R Smith, Hala Rimawi, Ersi Voskaridou, Birol Güvenç, Kenneth I Ataga, Deborah Keefe, Kai Grosch, Jimmy Watson, Evgeniya Reshetnyak, Michele L Nassin, Yvonne Dei-Adomakoh
Journal: The Lancet Haematology (2025)
Real-time automated assessment of histological disease activity in patients with ulcerative colitis using single-wavelength endoscopy technology
Authors: Pieter Sinonquel, Matthias Lenfant, Tom Eelbode, Belian Callaerts, Hiroki Watanabe, João Sabino, Bram Verstockt, Frederik Maes, Gert De Hertogh, Séverine Vermeire, Raf Bisschops
Journal: Endoscopy (2025)

Abstract Single-wavelength endoscopy (SWE) has shown promising results in assessing histological disease activity in ulcerative colitis. Our objective was to validate the real-time performance of a bedside prototype of SWE computer-aided diagnosis (CAD) as proof of concept. A bedside module for real-time use evaluated histological disease activity when endoscopy was performed in the rectum and sigmoid based on white-light endoscopy and SWE (410 nm monochromatic light). Biopsies were taken for reference and scored using the Geboes score (GBS). SWE-CAD displayed a blue or red indicator, corresponding to histological remission or non-remission, respectively. Simultaneous scoring using the Mayo Endoscopic Score was performed by the endoscopist. In 36 patients, histological disease activity was automatically scored using SWE-CAD. At the section level, SWE-CAD showed an accuracy of 96.4%, sensitivity of 96.1%, and specificity of 85.5%. When differentiating disease activity into mild, moderate, and severe, accuracy was 97.7%, 62.8%, and 95.0%, respectively. At the per-patient level, overall diagnostic accuracy remained high at 94.4%, with only 2/36 underestimations compared with GBS. A novel SWE-CAD system demonstrated clinical accuracy of 94.4% at the per-patient level, potentially aiding physicians in interpreting subtle endoscopic abnormalities and paving the way to more individualized patient management.
Cigarette smoke-induced epithelial cell ferroptosis promotes neutrophilic inflammation in patients with nasal polyps
Authors: Li Pan, Ze Yu, Wen-Xuan Xiang, Shi-Ran Sun, Jing-Xian Li, Yi-Ke Deng, Meng-Chen Wang, Ji-Xin Zhong, Kun Huang, Pei-Song Gao, Li-Ping Zhu, Yin Yao, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2025)
Impact of treatment for adolescent and young adults with essential thrombocythemia and polycythemia vera
Authors: Yan Beauverd, Jean-Christophe Ianotto, Kyaw Htin Thaw, Marta Sobas, Parvis Sadjadian, Natalia Curto-Garcia, Lee-Yung Shih, Timothy Devos, Dorota Krochmalczyk, Serena Galli, Maria Bieniaszewska, Ilona Seferynska, Mary Frances McMullin, Anna Armatys, Adrianna Spalek, Joanna Waclaw, Mihnea Tudor Zdrenghea, Laurence Legros, Francois Girodon, Krzysztof Lewandowski, Beatriz Bellosillo, Jan Samuelsson, Aitor Abuin Blanco, Pascale Cony-Makhoul, Angela Collins, Chloe James, Rajko Kusec, Marie Lauermannova, Maria Soledad Noya, Malgorzata Skowronek, Lukasz Szukalski, Anna Szmigielska-Kaplon, Marielle Wondergem, Iryna Dudchenko, Joanna Gora-Tybor, Kamel Laribi, Anna Kulikowska de Nałęcz, Jean-Loup Demory, Katell Le Dû, Sonja Zweegman, Carlos Besses Raebel, Radek C. Skoda, Stephane Giraudier, Martin Griesshammer, Jean-Jacques Kiladjian, Claire N Harrison
Journal: Leukemia (2025)

Abstract Essential thrombocythemia (ET) and polycythemia vera (PV) are rare in adolescent and young adult (AYA). These conditions, similar to those in older patients, are linked with thrombotic complications and the potential progression to secondary myelofibrosis (sMF). This retrospective study of ET and PV patients diagnosed before age 25 evaluated complication rates and impact of cytoreductive drugs on outcomes. Among 348 patients (278 ET, 70 PV) with a median age of 20 years, the of thrombotic events was 1.9 per 100 patient-years. Risk factors for thrombosis included elevated white blood cell count (&gt;11 × 10 9 /L) (HR: 2.7, p = 0.012) and absence of splenomegaly at diagnosis (HR: 5.7, p = 0.026), while cytoreductive drugs did not reduce this risk. The incidence of sMF was 0.7 per 100 patient-years. CALR mutation (HR: 6.0, p &lt; 0.001) and a history of thrombosis (HR: 3.8, p = 0.015) were associated with sMF risk. Interferon as a first-line treatment significantly improved myelofibrosis-free survival compared to other treatments or the absence of cytoreduction ( p = 0.046). Although cytoreduction did not affect thrombotic event, early interferon use reduced sMF risk. These findings support interferon use to mitigate sMF risk in AYA ET and PV patients.
Comparison of subcutaneous injection versus intravenous infusion of cytarabine for induction therapy in adult acute myeloid leukemia
Authors: Huafeng Wang, Shanshan Suo, Dengju Li, Jianyong Li, Lu Liu, Ying Lu, Jianping Shen, Chunyan Ji, Tong Chen, Kang Yu, Hanyun Ren, Yan Li, Ying Chen, Shaolei Zang, Bin Liang, Sijing Kang, Jinghan Wang, Wei Cheng, Wenjuan Yu, Haitao Meng, Hongyan Tong, Jie Jin
Journal: Leukemia (2025)
VEGF-B is a novel mediator of endoplasmic reticulum stress which induces angiogenesis in the heart without VEGFR1 or NRP activities via RGD-binding integrins
Authors: Rahul Mallick, Ahmed B Montaser, Henna Komi, Greta Juusola, Annakaisa Tirronen, Erika Gurzeler, Maria Barbiera, Petra Korpisalo, Tetsuya Terasaki, Tiina Nieminen, Seppo Ylä-Herttuala
Journal: Molecular Therapy (2025)

Vascular endothelial growth factor B186 (VEGF-B186), a ligand for VEGF receptor 1 (VEGFR1) and neuropilin (NRP), promotes vascular growth in healthy and ischemic myocardium. However, the mechanisms and signaling of VEGF-B186 to support angiogenesis have remained unclear. We studied the effects of VEGF-B186 and its variant, VEGF-B186R127S, which cannot bind to NRPs, using VEGFR1 tyrosine kinase knockout (TK-/-) mice to explore the mechanism of VEGF-B186 in promoting vascular growth. Ultrasound-guided adenoviral VEGF-B186, VEGF-B186R127S, and control vector gene transfers were performed into VEGFR1 TK-/- mice hearts. In vitro studies in cardiac endothelial cells and further validation in normal and ischemic pig hearts, as well as in wild-type mice, were conducted. Both VEGF-B186 forms promoted vascular growth in VEGFR1 TK-/- mouse heart and increased the expression of proangiogenic and hematopoietic factors. Unlike VEGF-A, VEGF-B186 forms induced ER stress via the upregulation of Binding immunoglobulin Protein (BiP) as well as ER stress sensors (ATF6, PERK, IRE1α) through ITGAV and ITGA5 integrins, newly identified receptors for VEGF-B, activating the unfolded protein response (UPR) through XBP1. VEGFR1 and NRP are not essential for VEGF-B186-induced vascular growth. Instead, VEGF-B186 can stimulate cardiac regeneration through RGD-binding integrins and ER stress, suggesting a novel mechanism of action for VEGF-B186.
Redefining Clinical Trial Strategic Design to Support Drug Approval in Medical Oncology
Authors: G Antonarelli, J M Pérez-García, M Gion, H Rugo, P Schmid, A Bardia, S Hurvitz, N Harbeck, S M Tolaney, G Curigliano, A Llombart-Cussac, J Cortés
Journal: Annals of Oncology (2025)
Treatment of a necrotic collection after tangential gastric resection by using an automated endoscopic debridement catheter
Authors: Dario Biasutto, Benedetto Neri, Martina Marrelli, Nicolò Citterio, Serena Stigliano, Francesco Maria Di Matteo
Journal: Endoscopy (2025)

We report the case of a 59-year-old woman who underwent a proximal subtotal gastrectomy for a gastric stromal tumor. At 15 days after surgery, the patient presented at the emergency room with sepsis, fever, and abdominal pain. Contrast-enhanced computed tomography (CT) scan and subsequent esophagogastroduodenoscopy (EGD) showed a semicircumferential anastomotic dehiscence and a large perigastric collection with super-fluid necrotic material ([Fig. 1] a, b).
Direct needle puncture technique using a radial miniature probe for complete anastomotic obstruction after hepaticojejunostomy
Authors: Tomohiro Ishii, Kazuya Sugimori, Michio Ueda, Arisa Omata, Shoichiro Yonei, Takashi Kurosawa, Shin Maeda
Journal: Endoscopy (2025)

Anastomotic stenosis of the hepaticojejunostomy is a major complication following pancreaticoduodenectomy [1]. In cases of complete anastomotic obstruction, drainage has been attempted using a cholangioscope via the percutaneous transhepatic biliary drainage route or a forward-viewing echoendoscope [2] [3]. However, reports of direct puncture of the anastomotic site remain scarce [4]. Here, we present a case of complete hepaticojejunostomy obstruction successfully managed with direct needle puncture drainage using a radial miniature probe (UM-2R; Olympus, Tokyo, Japan).
Flushing ensures vessel presealing in underwater third-space endoscopy
Authors: Antonio Capogreco, Roberta Maselli, Romain Legros, Ludovico Alfarone, Cesare Hassan, Jérémie Jacques, Alessandro Repici
Journal: Endoscopy (2025)

Intraprocedural bleeding due to unintentional cutting of the vessel affects both the safety and efficiency of third-space endoscopy and may be prevented by complete coagulation of the vessel before its cutting, also known as "presealing." In a prospective series, an underwater (saline-immersion) presealing technique achieved with a large-tip knife appeared to minimize intraprocedural bleeding, saving the use and cost of coagulation forceps [1] [2]. Unexpectedly, when applying the same presealing technique with a small-tip knife rather than a large-tip one, we found that the coagulation effect disappeared, with inadvertent cutting of the vessel occurring. The lack of presealing appeared to be associated with the formation of microbubbles around the tip of the knife, which was presumably owing to the different density of current for a large- and small-tip knife. In order to restore the presealing effect, we hypothesized that continuous flushing around the tip of the knife would replace the CO2 bubbles that formed with a new saline interface. In this video, we show the efficacy of this new strategy to optimize the presealing effect while using a small-tip knife ([Video 1]).
Endoscopic ultrasound-guided hepaticojejunostomy using forward-viewing echoendoscope for hepatic duct obstruction due to postoperative bile duct injury
Authors: Kei Yane, Kota Hanada, Kotaro Morita, Koki Yoshida, Sota Hirokawa, Yuki Ikeda, Tetsuya Sumiyoshi
Journal: Endoscopy (2025)

Bile duct injuries can occur at various sites, and the Strasberg classification is useful in considering their treatment strategy [1]. A Strasberg Type B injury is a bile duct obstruction that commonly occurs from the atypical right hepatic duct, and its endoscopic treatment is difficult [2].
Safe and reliable removal of a migrated biliary metal stent with a snare placed over the balloon using the two-devices-in-one-channel method
Authors: Kazuya Sumi, Jun Ushio, Hisaki Kato, Akinori Komagata, Yuki Kawasaki, Takayoshi Ito, Haruhiro Inoue
Journal: Endoscopy (2025)

Metal stents are useful for the palliative treatment of malignant biliary stenosis (MBS); however, they can occasionally migrate, complicating removal. Stent removal is often performed using the rat tooth forceps, snares, basket, and balloon catheter [1] [2] [3], but the efficacy and reliability of these methods are limited. This video demonstrates the successful removal of a migrated stent using the two-devices-in-one-channel method, with a snare positioned over a balloon catheter.
Reintervention technique for endoscopic ultrasound-guided hepaticogastrostomy combined with bridging stent deployment using a novel double-lumen dilator
Authors: Nobu Nishioka, Takeshi Ogura, Yuki Uba, Takafumi Kanadani, Hiroki Nishikawa
Journal: Endoscopy (2025)

Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) can be indicated for failed endoscopic retrograde cholangiopancreatography (ERCP). In cases of hilar biliary obstruction (HBO), the use of a bridging technique under EUS guidance has been reported [1] [2] [3]. However, reintervention for HBO after the bridging technique may be challenging because of complex uncovered self-expandable metal stent (UCSEMS) deployment. Recently, a novel dedicated double-lumen dilation device (Meissa; Japan Life Line, Tokyo, Japan) for dilation of the tract during EUS-HGS has become available ([Fig. 1]). The device has a 2.3-Fr tip and a maximum diameter of 7.4 Fr. There is also a side hole 2 cm from the tip. Contrast medium injection, aspiration of bile juice, and 0.025-inch guidewire insertion can be performed. Therefore, implementing a double-guidewire technique is possible using this device. Successful reintervention for recurrent biliary obstruction after EUS-HGS with bridging technique is described.
A case report of piecemeal submucosal tunnel endoscopic resection for a giant esophageal leiomyoma larger than 8 cm
Authors: Ping Ma, Limei Gu, Tingsheng Ling
Journal: Endoscopy (2025)

A 26-year-old man presented with substernal discomfort. Enhanced computed tomography scans revealed a significant submucosal tumor with dimensions of 8.19×4.55×2.69 cm ([Fig. 1] a). Endoscopy revealed a huge tumor on the posterior wall of the esophagus, protruding into the lumen [Fig. 1] b). Three-dimensional reconstruction demonstrated that the lesion was situated on the posterior wall of the esophagus, in proximity to the thoracic aorta ([Fig. 1] c). After a thorough discussion regarding the risks and benefits, piecemeal submucosal tunnel endoscopic resection (P-STER) was performed to remove the tumor ([Video 1]).
Endoscopic ultrasound-guided hepaticojejunostomy through an endoscopic ultrasound-guided enteroanastomosis
Authors: Luis Araya-Acero, Maria Lynch-Mejia, Fernanda Castro-Gonzalez, Jorge Vargas-Madrigal
Journal: Endoscopy (2025)

Endoscopic retrograde cholangiopancreatography (ERCP) in surgically altered anatomy is a challenging procedure [1]. Transjejunal ERCP through endoscopic ultrasound (EUS)-guided enteroanastomosis appears to be a safe and effective technique [2]. We report a 65-year-old woman with a previous Roux-en-Y hepaticojejunal anastomosis presenting with acute bacterial cholangitis complicated by septic shock. She underwent unsuccessful enteroscopy-assisted ERCP. Given her altered anatomy, an EUS-guided approach was offered ([Video 1]).