tbuckley/cabot-search huggingface dataset:
Chromoanagenesis Is Frequently Associated With Highly Complex Karyotypes, Extensive Clonal Heterogeneity, and Treatment Refractoriness in Acute Myeloid Leukemia
Authors: Qing Wei, Shimin Hu, Sanam Loghavi, Gokce A. Toruner, Farhad Ravandi‐Kashani, Zhenya Tang, Shaoying Li, Jie Xu, Naval Daver, L. Jeffrey Medeiros, Guilin Tang
Journal: American Journal of Hematology (2025)

ABSTRACT Chromoanagenesis (CAG) encompasses a spectrum of catastrophic genomic events, including chromothripsis, chromoanasynthesis, and chromoplexy. We studied CAG in 410 patients with a diagnosis of acute myeloid leukemia (AML), 292 newly diagnosed (ND), and 118 refractory/relapsed, using optical genome mapping. CAG was identified by the presence of clusters (with 10 or more breakpoints) of structural abnormalities and/or segmental copy number alterations within one or more chromosomal regions. CAG was detected in 65 (16%) patients. Compared with patients without CAG, those with CAG showed significantly ( p &lt; 0.0001) higher frequencies of highly complex karyotype (92% vs. 11%), monosomal karyotype (88% vs. 12%), extensive clonal heterogeneity (75% vs. 7%), gene amplification (49% vs. 1%), and TP53 deletion/mutation (92% vs. 9%). Overall, CAG was detected in about two‐thirds of AML patients who exhibited the abovementioned high‐risk cytogenetic abnormalities/karyotype. Among the 42 patients with ND AML and CAG, 36 received treatments and follow‐ups, and 28 (78%) had no or only partial response to therapy. Among patients with ND AML, those with CAG had a shorter overall survival than those without CAG (median survival: 5 vs. 14 months, p &lt; 0.0001). However, in multivariate analysis, CAG did not appear to be an independent risk factor for survival. These results indicate that CAG is frequently associated with high‐risk chromosomal alterations and genomic instability in AML and may contribute to treatment refractoriness and inferior survival in this subset of AML patients.
Rescue from Stx2-Producing E. coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice
Authors: Ryo Ozuru, Shohei Wakao, Takahiro Tsuji, Naoya Ohara, Takashi Matsuba, Muhammad Y. Amran, Junko Isobe, Morio Iino, Naoki Nishida, Sari Matsumoto, Kimiharu Iwadate, Noriko Konishi, Kaori Yasuda, Kosuke Tashiro, Misato Hida, Arisato Yadoiwa, Shinsuke Kato, Eijiro Yamashita, Sohkichi Matsumoto, Yoichi Kurozawa, Mari Dezawa, Jun Fujii
Journal: Molecular Therapy (2025)
Cancer evolution: from Darwin to the Extended Evolutionary Synthesis
Authors: Thomas Savy, Lucy Flanders, Thaneswari Karpanasamy, Min Sun, Marco Gerlinger
Journal: Trends in cancer (2025)

The fundamental evolutionary nature of cancer has been recognized for decades. Increasingly powerful genetic and single cell sequencing technologies, as well as preclinical models, continue to unravel the evolution of premalignant cells, and progression to metastatic stages and to drug-resistant end-stage disease. Here, we summarize recent advances and distil evolutionary principles and their relevance for the clinic. We reveal how cancer cell and microenvironmental plasticity are intertwined with Darwinian evolution and demonstrate the need for a conceptual framework that integrates these processes. This warrants the adoption of the recently developed Extended Evolutionary Synthesis (EES).
Corticosteroids in severe alcohol-associated hepatitis? Not so fast: A systematic review of randomized controlled trials
Authors: Michael A. Shi, Prisca Pungwe, Lauren LM. Comer, Maya Balakrishnan, Tzu-Hao Lee, George Cholankeril, Kavish R. Patidar, Avegail G. Flores, Vijay H. Shah, Ramon Bataller, Sumeet K. Asrani, Juan P. Arab, Fasiha Kanwal, Ruben Hernaez
Journal: Hepatology (2025)

Background: Severe alcohol-associated hepatitis (AH) is rising in incidence with a high mortality burden. While corticosteroids are recommended for eligible patients with severe AH, no guidance exists for the timing of steroid initiation, tapering regimens, and surveillance of adverse events. Objective: We aim to systematically review these variables and provide evidence-based recommendations for the inpatient and outpatient management of severe AH. Design: We performed a literature search from inception to 5/30/2024 to include clinical trials published in full form and assessed the quality of evidence using the Cochrane Risk of Bias tool. Data were collected on the timing of initiation, rate, and complications following steroid therapy, and taper regimens in the setting of severe AH. Results: Of 28 studies that fulfilled our inclusion criteria, median time from admission to steroid initiation was 6.5 days. The most common steroid dosing regimen was prednisolone 40 mg daily for 28 days. Twenty-five studies containing 3,196 subjects reported adverse events, with exactly 50% in the steroid arm and the other half in the comparison arm. Infections, gastrointestinal bleeds, and renal impairment were the most frequently reported adverse events. Most infections occurred within the first month of the study. A two-week steroid taper was the most frequently reported regimen. Conclusion: We recommend taking up to a week to systematically and thoroughly evaluate patients before initiating steroids, and vigilant monitoring in the first month of treatment. We also recommend the lowest possible steroid exposure with a two-week steroid taper and close outpatient follow-up.
Deep Learning–Powered CT-Less Multitracer Organ Segmentation From PET Images
Authors: Yazdan Salimi, Zahra Mansouri, Isaac Shiri, Ismini Mainta, Habib Zaidi
Journal: Clinical Nuclear Medicine (2025)

Purpose The common approach for organ segmentation in hybrid imaging relies on coregistered CT (CTAC) images. This method, however, presents several limitations in real clinical workflows where mismatch between PET and CT images are very common. Moreover, low-dose CTAC images have poor quality, thus challenging the segmentation task. Recent advances in CT-less PET imaging further highlight the necessity for an effective PET organ segmentation pipeline that does not rely on CT images. Therefore, the goal of this study was to develop a CT-less multitracer PET segmentation framework. Patients and Methods We collected 2062 PET/CT images from multiple scanners. The patients were injected with either 18 F-FDG (1487) or 68 Ga-PSMA (575). PET/CT images with any kind of mismatch between PET and CT images were detected through visual assessment and excluded from our study. Multiple organs were delineated on CT components using previously trained in-house developed nnU-Net models. The segmentation masks were resampled to coregistered PET images and used to train 4 different deep learning models using different images as input, including noncorrected PET (PET-NC) and attenuation and scatter-corrected PET (PET-ASC) for 18 F-FDG (tasks 1 and 2, respectively using 22 organs) and PET-NC and PET-ASC for 68 Ga tracers (tasks 3 and 4, respectively, using 15 organs). The models’ performance was evaluated in terms of Dice coefficient, Jaccard index, and segment volume difference. Results The average Dice coefficient over all organs was 0.81 ± 0.15, 0.82 ± 0.14, 0.77 ± 0.17, and 0.79 ± 0.16 for tasks 1, 2, 3, and 4, respectively. PET-ASC models outperformed PET-NC models ( P &lt; 0.05) for most of organs. The highest Dice values were achieved for the brain (0.93 to 0.96 in all 4 tasks), whereas the lowest values were achieved for small organs, such as the adrenal glands. The trained models showed robust performance on dynamic noisy images as well. Conclusions Deep learning models allow high-performance multiorgan segmentation for 2 popular PET tracers without the use of CT information. These models may tackle the limitations of using CT segmentation in PET/CT image quantification, kinetic modeling, radiomics analysis, dosimetry, or any other tasks that require organ segmentation masks.
Atorvastatin and Myocardial Extracellular Volume Expansion During Anthracycline-Based Chemotherapy
Authors: Vencel Juhasz, Thiago Quinaglia, Zsofia D Drobni, Julius C Heemelaar, Donna S Neuberg, Yuchi Han, Bonnie Ky, Raymond Y Kwong, James L Januzzi, Aarti Asnani, Robert A Redd, Negareh Mousavi, Michael Jerosch-Herold, Marielle Scherrer-Crosbie, Tomas G Neilan
Journal: JACC CardioOncology (2025)

In the STOP-CA (Statins to Prevent the Cardiotoxicity From Anthracyclines) trial, atorvastatin preserved the left ventricular ejection fraction among patients with lymphoma treated with anthracyclines. The protective mechanisms are currently unclear. The aim of this study was to test the effect of atorvastatin on the anthracycline-associated increase in myocardial extracellular volume (ECV) using cardiac magnetic resonance imaging (MRI). Cardiac MRI with mapping was performed at baseline and at 12-month follow-up. ECV was calculated, and the primary endpoint was a ≥3% increase. Increases of ≥1 SD in native T1 and T2 times and ECV were secondary endpoints. The subgroup included 171 participants with paired cardiac MRI scans, and 127 had contrast scans of appropriate quality (median age 52 years, 47% women). The proportion of participants with ≥3% increases in ECV was lower in the atorvastatin compared with the placebo group (8% vs 29%; P = 0.002; OR: 0.20; 95% CI: 0.06 to 0.59). A ≥3% increase in ECV was associated with an 8.4% decrease in left ventricular ejection fraction at follow-up (95% CI: -6.31 to -10.38; P < 0.001). The proportion of participants with ≥1-SD increases in T1 and T2 times was statistically similar between groups at 12 months. At 24 months, there were fewer heart failure events among those without ≥3% increases in ECV (8% vs 24%; P = 0.054), though not statistically significantly. Compared with placebo, atorvastatin limited ECV expansion among participants with lymphoma undergoing anthracycline chemotherapy. This study is the first to provide mechanistic insight into statins' cardioprotective effects with anthracyclines. (Statins to Prevent the Cardiotoxicity From Anthracyclines [STOP-CA]; NCT02943590).
Targeted modulation of intestinal barrier and mucosal immune-related microbiota attenuates IgA nephropathy progression
Authors: Ran Zhang, Yuyan Tang, Xiangru Feng, Xiaoxuan Lu, Mengyao Zhao, Jiayang Jin, Xiaoguo Ji, Haidong He, Liming Zhao
Journal: Gut Microbes (2025)

IgA nephropathy (IgAN) is related to the balance of gut microbiota. However, it is unclear whether changes in the gut microbiota can cause IgAN or attenuate its progression. This study employed IgAN and human microbiota-associated (HMA)-IgAN models to investigate the impact of IgAN on gut microbiota alteration and the mechanisms by which gut microbiota might trigger IgAN. Furthermore, this study examined the effects of chitooligosaccharides (COS) and COS formulation (COSF) with microbiota-targeting function on enhancing intestinal barrier and renal functions. These results revealed that IgAN led to a reduction in α-diversity and structural alterations in the gut microbiota, characterized by an increase in Shigella sonnei, Streptococcus danieliae, Desulfovibrio fairfieldensis, and a decrease in Bifidobacterium pseudolongum and Clostridium leptum. There was also an imbalance in intestinal B-cell immunity and a decrease in the level of tight junction proteins (ZO-1 and Occludin). Intestinal barrier and mucosal immune-related microbiota (Clostridium leptum, unclassified Lachnospiraceae NK4Al36 group, unclassified Clostridia vadinBB60 group, unclassified Oscillospiraceae, and unclassified Roseburia) were enriched through targeted modulation with COS/COSF, enhancing intestinal ZO-1 expression and reducing APRIL/BAFF overexpression, thereby reducing renal damage in IgAN. In conclusion, this study clarified the kidney-gut crosstalk between gut microbiota and IgAN, providing scientific evidence for developing microbiota-targeted food interventions to improve IgAN outcomes.
Pharmacomicrobiomics: a new field contributing to optimizing drug therapy in Parkinson’s disease
Authors: Yi Zhang, Chengjun Mo, Penghui Ai, Xiaoqin He, Qin Xiao, Xiaodong Yang
Journal: Gut Microbes (2025)

Gut microbiota, which act as a determinant of pharmacokinetics, have long been overlooked. In recent years, a growing body of evidence indicates that the gut microbiota influence drug metabolism and efficacy. Conversely, drugs also exert a substantial influence on the function and composition of the gut microbiota. Pharmacomicrobiomics, an emerging field focusing on the interplay of drugs and gut microbiota, provides a potential foundation for making certain advances in personalized medicine. Understanding the communication between gut microbiota and antiparkinsonian drugs is critical for precise treatment of Parkinson's disease. Here, we provide a historical overview of the interplay between gut microbiota and antiparkinsonian drugs. Moreover, we discuss potential mechanistic insights into the complex associations between gut microbiota and drug metabolism. In addition, we also draw attention to microbiota-based biomarkers for predicting antiparkinsonian drug efficacy and examine current state-of-the-art knowledge of microbiota-based strategies to optimize drug therapy in Parkinson's disease.
Cell-specific transcriptional signatures of vascular cells in Alzheimer’s disease: perspectives, pathways, and therapeutic directions
Authors: Soumilee Chaudhuri, Minyoung Cho, Julia C. Stumpff, Paula J. Bice, Özkan İş, Nilüfer Ertekin-Taner, Andrew J. Saykin, Kwangsik Nho
Journal: Molecular Neurodegeneration (2025)

Abstract Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances in high throughput single-cell transcriptomics technology have enabled the study of the human brain vasculature at an unprecedented depth. Additionally, the understudied niche of cerebrovascular cells, such as endothelial and mural cells, and their subtypes have been scrutinized for understanding cellular and transcriptional heterogeneity in AD. Here, we provide an overview of rich transcriptional signatures derived from recent single-cell and single-nucleus transcriptomic studies of human brain vascular cells and their implications for targeted therapy for AD. We conducted an in-depth literature search using Medline and Covidence to identify pertinent AD studies that utilized single-cell technologies in human post-mortem brain tissue by focusing on understanding the transcriptional differences in cerebrovascular cell types and subtypes in AD and cognitively normal older adults. We also discuss impaired cellular crosstalk between vascular cells and neuroglial units, as well as astrocytes in AD. Additionally, we contextualize the findings from single-cell studies of distinct endothelial cells, smooth muscle cells, fibroblasts, and pericytes in the human AD brain and highlight pathways for potential therapeutic interventions as a concerted multi-omic effort with spatial transcriptomics technology, neuroimaging, and neuropathology. Overall, we provide a detailed account of the vascular cell-specific transcriptional signatures in AD and their crucial cellular crosstalk with the neuroglial unit. Graphical Abstract Endothelial and mural cell types mediate dysregulated transcriptional pathways and cell-cell interactions in AD. The neurovascular unit (NVU) is composed of various cell types, including endothelial cells, mural cells (pericytes, smooth muscle cells), fibroblast neurons, microglia, and astrocytes. Dysregulated transcriptional pathways in AD involve multiple pathways, notably immune responses, and angiogenesis common to both endothelial and mural cells. Additionally, pathways involving neuroinflammation and amyloid clearance are prominent in endothelial cell types, while mural cells exhibit pathways related to growth factors, cytoskeletal remodeling and synaptic function. In addition, crosstalk within the NVU and gliovascular unit (GVU) is altered in AD, with altered cell-cell communication evident, with increased interactions between endothelial cells, pericytes, neurons, and microglia, and decreased interactions between endothelial cells, fibroblasts, astrocytes, and neurons. Figure created with BioRender.com. Abbreviations: AD, Alzheimer's disease; NVU, Neurovascular unit; CNS, Central Nervous System.
Magnetic compression anastomosis for recanalization of anastomotic stenosis after radical surgery for esophageal cancer
Authors: Miaomiao Zhang, Huanchen Sha, Guifang Lu, Mudan Ren, Shuixiang He, Yi Lv, Xiaopeng Yan
Journal: Endoscopy (2025)

A 67-year-old man who had previously undergone radical surgery for esophageal cancer had experienced dysphagia over the past year. Gastroscopy revealed esophageal anastomotic stenosis. Multiple endoscopic balloon dilation and esophageal stent placement procedures were carried out, with limited success. Following reconfirmation of the stenosis through gastroscopy and esophagography ([Fig. 1]), a treatment plan utilizing magnetic compression anastomosis (MCA) was devised ([Fig. 2]).
A case of gallstone pancreatitis with a history of choledochojejunostomy treated by the endoscopic ultrasound rendezvous technique and stone removal from the residual bile duct
Authors: Fumiya Kataoka, Mitsuru Okuno, Atsushi Tagami, Hiroshi Araki, Eiichi Tomita, Hisataka Moriwaki, Masahito Shimizu
Journal: Endoscopy (2025)

Gallstone pancreatitis necessitates emergency endoscopic removal of the responsible stone [1]. We report a case highlighting three significant clinical characteristics: 1) recurrent stone in the residual bile duct of the pancreatic head 13 years after choledochojejunostomy; 2) a challenging transpapillary approach to the buried papilla within a diverticulum; and 3) use of the endoscopic ultrasound rendezvous (EUS-RV) technique to access the bile duct. Successful stone removal alleviated the pancreatitis ([Video 1]).
Modified anchor traction method allows safe colorectal endoscopic submucosal dissection: the T-shaped traction method
Authors: Keisaku Yamada, Masahiro Tajika, Tsutomu Tanaka, Nobuhito Ito, Akihiro Takagi, Yasumasa Niwa
Journal: Endoscopy (2025)

Using a traction device can reduce the procedure time and complications associated with colorectal endoscopic submucosal dissection (ESD) [1] [2]. We developed a novel traction technique using a multi-loop traction device (MLTD; Boston Scientific, Tokyo, Japan) that enables traction at three locations; we termed this the "anchor traction method" [3]. However, with this traction method, attachment to the opposite side of the intestinal tract may be difficult in places where the lumen is wide, such as in the cecum and ascending colon, because of the shortness of the traction device, and there may be a risk of perforation caused by elevation of the muscle layer due to excessive traction force (pulling too hard). Here, we report a useful traction method that overcomes these points by combining two MLTDs in colorectal ESD.
Endoscopic retrieval of a proximally migrated pancreatic stent utilizing a basket through a catheter in surgically altered anatomy: “Basket-through-the-catheter” technique
Authors: Haruka Toyonaga, Takuya Takayama, Tatsuya Nakagawa, Masahiro Orino, Ryosuke Tonozuka, Takao Itoi, Masaaki Shimatani
Journal: Endoscopy (2025)

Endoscopic retrieval of proximally migrated pancreatic duct stents (PDSs) is challenging due to the narrow and winding pancreatic duct (PD), the presence of PD stenosis, lack of optimal retrieval devices, and potential of severe adverse events. In cases with surgically altered anatomy, scope maneuverability is compromised, and device options are restricted. While various retrieval methods have been reported [1] [2] [3] [4] [5], we successfully retrieved a migrated PDS employing the "basket-through-the-catheter" technique ([Fig. 1], [Video 1]).
Pre-incision traction method using clip-and-thread for gastric endoscopic submucosal dissection
Authors: Eisuke Nakao, Satoshi Asai, Ayumu Chaen, Tomoya Hashimura, Yuma Fujita, Eisuke Akamine
Journal: Endoscopy (2025)

Gastric endoscopic submucosal dissection (G-ESD) has become a widely accepted and well-established treatment modality [1]. However, G-ESD can be technically challenging depending on the lesion's location owing to the difficulty in creating a mucosal flap. This can increase procedure time and lead to unintentional bleeding during mucosal incision and submucosal dissection. To address these challenges, we present a new method called the "pre-incision traction method" for G-ESD.
Effective conservative management of late-onset post-endoscopic retrograde cholangiopancreatography pancreatitis due to biodegradable stent fragments retention
Authors: Irma Valeria Albergati, Andrea Anderloni, Pietro Fusaroli, Graziella Masciangelo, Fabio Monica, Andrea Lisotti
Journal: Endoscopy (2025)

In the last decade, biodegradable stents have been proposed to spare subsequent endoscopic retrograde cholangiopancreatography (ERCP) procedures required for stent removal [1] [2]. Main adverse events in this field were migration and post-ERCP pancreatitis (PEP) [3] [4]; anecdotally, failure of stent degradation has been reported [5].
Peroral cholangioscopy-guided basket extraction of intrahepatic bile duct stones, using a novel thin cholangioscope under balloon enteroscopy, in a patient with Roux-en-Y anatomy
Authors: Yuki Tanisaka, Shomei Ryozawa, Masafumi Mizuide, Akashi Fujita, Ryuhei Jinushi, Ryuichi Watanabe, Ryo Sato
Journal: Endoscopy (2025)

Endoscopic stone extraction using a balloon enteroscope in patients with a Roux-en-Y anastomosis is challenging due to the difficulty in aligning the axis between retrieval devices and stones, which often results in failure of stone capture [1] [2]. Recently, it has been reported that a novel thin cholangioscope (EyeMax; Micro-Tech, China), with a length of 219 cm and a diameter of 9 Fr, enables peroral cholangioscopy (POCS)-guided procedures using a balloon enteroscope with a 3.2-mm forceps channel ([Fig. 1]) [3] [4]. Furthermore, it also enables POCS-guided basket extraction. We report a case of successful POCS-guided basket extraction of intrahepatic bile duct stones using a novel thin cholangioscope under balloon enteroscopy in a patient who had undergone a Roux-en-Y procedure.
Whole slide image based deep learning refines prognosis and therapeutic response evaluation in lung adenocarcinoma
Authors: Tao Chen, Jialiang Wen, Xinchen Shen, Jiaqi Shen, Jiajun Deng, Mengmeng Zhao, Long Xu, Chunyan Wu, Bentong Yu, Minglei Yang, Minjie Ma, Junqi Wu, Yunlang She, Yifan Zhong, Likun Hou, Yanrui Jin, Chang Chen
Journal: npj Digital Medicine (2025)

Existing prognostic models are useful for estimating the prognosis of lung adenocarcinoma patients, but there remains room for improvement. In the current study, we developed a deep learning model based on histopathological images to predict the recurrence risk of lung adenocarcinoma patients. The efficiency of the model was then evaluated in independent multicenter cohorts. The model defined high- and low-risk groups successfully stratified prognosis of the entire cohort. Moreover, multivariable Cox analysis identified the model defined risk groups as an independent predictor for disease-free survival. Importantly, combining TNM stage with the established model helped to distinguish subgroups of patients with high-risk stage II and stage III disease who are highly likely to benefit from adjuvant chemotherapy. Overall, our study highlights the significant value of the constructed model to serve as a complementary biomarker for survival stratification and adjuvant therapy selection for lung adenocarcinoma patients after resection.