tbuckley/cabot-search huggingface dataset:
Successful hemostasis with red dichromatic imaging for bleeding rectal dieulafoy’s lesion
Authors: Chih-Wen Huang, Hsu-Heng Yen, Yang-Yuan Chen
Journal: Endoscopy (2024)

A 74-year-old man with a history of type 2 diabetes mellitus and hemodialysis suffered from bloody stool for 2 days and underwent a colonoscopy. Laboratory data showed a drop in hemoglobin to 7.2 g/dL. During the colonoscopy, fresh blood was observed in the rectum, where a Dieulafoy's lesion was actively bleeding. Under the white light image, the intestinal wall was coated with fresh blood, making it difficult to clearly identify the bleeding point ([Fig. 1], [Video 1]). We switched to the red dichromatic imaging (RDI) mode for further examination, which allowed us to accurately locate the bleeding point and perform hemostasis ([Fig. 2]). In the end, the hemostasis of Dieulafoy's lesion was successfully achieved ([Fig. 3]).
Successful cholangioscopy-guided cannulation using a novel slim cholangioscope in a patient with Roux-en-Y gastrectomy
Authors: Yuki Tanisaka, Masafumi Mizuide, Akashi Fujita, Takahiro Shin, Kei Sugimoto, Ryuhei Jinushi, Shomei Ryozawa
Journal: Endoscopy (2024)

Selective biliary cannulation in patients with Roux-en-Y gastrectomy is technically challenging [1] [2]. Peroral cholangioscopy (POCS) is beneficial for direct visualization of intraductal bile duct lesions [3]. Recent studies have confirmed the viability of cholangioscopy-guided cannulation [4]. We report a successful cholangioscopy-guided cannulation achieved using a novel slim cholangioscope in a patient with Roux-en-Y gastrectomy.
Through-the-cholangioscope metal biliary stent placement as a novel endoscopic technique for bile duct strictures
Authors: Carlos Robles-Medranda, Maria Egas-Izquierdo, Juan Alcívar-Vásquez, Miguel Puga-Tejada, Martha Arevalo-Mora, Domenica Cunto, Jorge Baquerizo-Burgos
Journal: Endoscopy (2024)

The management of biliary strictures remains challenging. Biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are the currently preferred approaches [1] [2] [3], but advances in cholangioscopy are allowing new tools to be considered [4]. We present our experience using a novel through-the-cholangioscope self-expandable metal stent (TTC-SEMS; Micro-Tech, Nanjing, China) ([Video 1]).
Gravity-assisted opacification method for confirming hilar biliary obstruction
Authors: Yuzo Shimokawa, Hirotada Akiho, Nao Fujimori
Journal: Endoscopy (2024)

Regardless of various strategies for draining malignant hilar obstructions [1] [2], clear guidelines on which biliary branches should be drained are lacking. Branches that are not drained and opacified are at high risk for segmental cholangitis and a poor prognosis [3]. We propose a novel, simple method based on the principle "heavier objects tend to flow downward" for identifying branches to be drained by leveraging the gravitational movement of the contrast medium.
Cholangioscopy-assisted endoscopic mucosal resection for a mildly dysplastic lesion of the common bile duct: a pilot exploration for super minimally invasive surgery
Authors: Wengang Zhang, Ningli Chai, Yujie Feng, Jiafeng Wang, Qingzhen Wu, Bo Zhang, Enqiang Linghu
Journal: Endoscopy (2024)

A 61-year-old man underwent endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct (CBD) stones in our hospital. We performed peroral cholangioscopy to confirm whether any remnant stones were left after basket extraction; however, a polypoid lesion with a wide base was found in the CBD ([Fig. 1] a). We performed biopsy under cholangioscopic guidance, with pathology results revealing mild dysplasia. This patient faced a dilemma: surgical treatment would be accompanied by relatively major trauma; however, follow-up observation carries a risk of lesion progression. Therefore, our team developed a kind of injection needle and a snare with electrocision function, which can be passed through the working channel of the cholangioscope. Subsequently, we confirmed the safety and feasibility of cholangioscopy-assisted endoscopic mucosal resection (CA-EMR) in the CBD in a porcine model [1]. In this study, we performed CA-EMR for the aforementioned patient and successfully resected the CBD lesion.
Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma
Authors: Suzanne I.M. Neppelenbroek, Yvonne M. Geurts, Berthe M.P. Aleman, Pieternella J. Lugtenburg, Saskia E. Rademakers, Roel J. de Weijer, Maaike G.A. Schippers, Bastiaan D.P. Ta, Wouter J. Plattel, Josée M. Zijlstra, Richard W.M. van der Maazen, Marten R. Nijziel, Francisca Ong, Erik C. Schimmel, Eduardus F.M. Posthuma, Marie José Kersten, Lara H. Böhmer, Karin Muller, Harry R. Koene, Liane C.J. te Boome, Yavuz M. Bilgin, Eva de Jongh, Cécile P.M. Janus, Flora E. van Leeuwen, Michael Schaapveld
Journal: Journal of Clinical Oncology (2024)

Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages.
Needle puncture fistulotomy: a new technique for needle-knife fistulotomy as a primary biliary access method for biliary cannulation
Authors: Ahmed Sadek, Kazuo Hara, Nozomi Okuno, Shin Haba, Takamichi Kuwahara
Journal: Endoscopy (2024)

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is a serious complication, occurring in 2%–10% of cases, with frequent cannulation attempts and precutting being the primary risk factors [1].
Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review
Authors: Taija M. Hahka, Rebecca A. Slotkowski, Anum Akbar, Matt C. VanOrmer, Lawrence Fred Sembajwe, Abdul M. Ssekandi, Agnes Namaganda, Haruna Muwonge, Josephine N. Kasolo, Annettee Nakimuli, Naome Mwesigwa, Jeanne A. Ishimwe, Robert Kalyesubula, Annet Kirabo, Ann L. Anderson Berry, Kaushik P. Patel
Journal: Circulation Research (2024)

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.
ASCL1 Drives Tolerance to Osimertinib in <i>EGFR</i> Mutant Lung Cancer in Permissive Cellular Contexts
Authors: Bomiao Hu, Marc Wiesehöfer, Fernando J. de Miguel, Zongzhi Liu, Lok-Hei Chan, Jungmin Choi, Mary Ann Melnick, Anna Arnal Estape, Zenta Walther, Dejian Zhao, Francesc Lopez-Giraldez, Anna Wurtz, Guoping Cai, Rong Fan, Scott Gettinger, Andrew Xiao, Qin Yan, Robert Homer, Don X. Nguyen, Katerina Politi
Journal: Cancer Research (2024)

The majority of EGFR mutant lung adenocarcinomas respond well to EGFR tyrosine kinase inhibitors (TKI). However, most of these responses are partial, with drug-tolerant residual disease remaining even at the time of maximal response. This residual disease can ultimately lead to relapses, which eventually develop in most patients. To investigate the cellular and molecular properties of residual tumor cells in vivo, we leveraged patient-derived xenograft (PDX) models of EGFR mutant lung cancer. Subcutaneous EGFR mutant PDXs were treated with the third-generation TKI osimertinib until maximal tumor regression. Residual tissue inevitably harbored tumor cells that were transcriptionally distinct from bulk pretreatment tumor. Single-cell transcriptional profiling provided evidence of cells matching the profiles of drug-tolerant cells present in the pretreatment tumor. In one of the PDXs analyzed, osimertinib treatment caused dramatic transcriptomic changes that featured upregulation of the neuroendocrine lineage transcription factor ASCL1. Mechanistically, ASCL1 conferred drug tolerance by initiating an epithelial-to-mesenchymal gene-expression program in permissive cellular contexts. This study reveals fundamental insights into the biology of drug tolerance, the plasticity of cells through TKI treatment, and why specific phenotypes are observed only in certain tumors.
Application of New Lineage Tracing Techniques in Cardiovascular Development and Physiology
Authors: MingJun Zhang, Kathy O. Lui, Bin Zhou
Journal: Circulation Research (2024)

Cardiovascular disease has been the leading cause of mortality and morbidity worldwide in the past 3 decades. Multiple cell lineages undergo dynamic alternations in gene expression, cell state determination, and cell fate conversion to contribute, adapt, and even modulate the pathophysiological processes during disease progression. There is an urgent need to understand the intricate cellular and molecular underpinnings of cardiovascular cell development in homeostasis and pathogenesis. Recent strides in lineage tracing methodologies have revolutionized our understanding of cardiovascular biology with the identification of new cellular origins, fates, plasticity, and heterogeneity within the cardiomyocyte, endothelial, and mesenchymal cell populations. In this review, we introduce the new technologies for lineage tracing of cardiovascular cells and summarize their applications in studying cardiovascular development, diseases, repair, and regeneration.
AI-based diabetes care: risk prediction models and implementation concerns
Authors: Serena C. Y. Wang, Grace Nickel, Kaushik P. Venkatesh, Marium M. Raza, Joseph C. Kvedar
Journal: npj Digital Medicine (2024)

The utilization of artificial intelligence (AI) in diabetes care has focused on early intervention and treatment management. Notably, usage has expanded to predict an individual's risk for developing type 2 diabetes. A scoping review of 40 studies by Mohsen et al. shows that while most studies used unimodal AI models, multimodal approaches were superior because they integrate multiple types of data. However, creating multimodal models and determining model performance are challenging tasks given the multi-factored nature of diabetes. For both unimodal and multimodal models, there are also concerns of bias with the lack of external validations and representation of race, age, and gender in training data. The barriers in data quality and evaluation standardization are ripe areas for developing new technologies, especially for entrepreneurs and innovators. Collaboration amongst providers, entrepreneurs, and researchers must be prioritized to ensure that AI in diabetes care is providing quality and equitable patient care.
Patient‐Derived Organoids as Therapy Screening Platforms in Cancer Patients
Authors: Danial Khorsandi, Jia‐Wei Yang, Samuel Foster, Safoora Khosravi, Negar Hosseinzadeh Kouchehbaghi, Fahimeh Zarei, Yun Bin Lee, Farhana Runa, Ankit Gangrade, Leon Voskanian, Darbaz Adnan, Yangzhi Zhu, Zhaohui Wang, Vadim Jucaud, Mehmet Remzi Dokmeci, Xiling Shen, Faraz Bishehsari, Jonathan A. Kelber, Ali Khademhosseini, Natan Roberto de Barros
Journal: Advanced Healthcare Materials (2024)

Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs-on-a-chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. Furthermore, this work introduces tools for data processing and analysis of organoids, along with their microenvironment. These tools aim to achieve enhanced readouts. Finally, this work explores the challenges and future perspectives of using PDOs in drug development and personalized screening for cancer patients.
TR(i)P Goes On: Auxiliary TRP Channel Subunits?
Authors: Veit Flockerzi, Bernd Fakler
Journal: Circulation Research (2024)

Transient receptor potential (TRP) cation channels are a diverse family of channels whose members play prominent roles as cellular sensors and effectors. The important role of TRP channels (and mechanosensitive piezo channels) in the complex interaction of our senses with the environment was underlined by the award of the Nobel Prize in Physiology or Medicine to 2 pioneers in this field, David Julius and Ardem Patapoutian. There are many competent and comprehensive reviews on many aspects of the TRP channels, and there is no intention to expand on them. Rather, after an introduction to the nomenclature, the molecular architecture of native TRP channel/protein complexes in vivo will be summarized using TRP channels of the canonical transient receptor potential subfamily as an example. This molecular architecture provides the basis for the signatures of native canonical transient receptor potential currents and their control by endogenous modulators and potential drugs.
Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling
Authors: Ruyi Zhang, Shanshan Li, Kelly Schippers, Yunlong Li, Boaz Eimers, Marla Lavrijsen, Ling Wang, Guofei Cui, Xin Chen, Maikel P. Peppelenbosch, Joyce H.G. Lebbink, Ron Smits
Journal: Cancer Research (2024)

Abstract AXIN1 is a major component of the β-catenin destruction complex and is frequently mutated in various cancer types, particularly liver cancers. Truncating AXIN1 mutations are recognized to encode a defective protein that leads to β-catenin stabilization, but the functional consequences of missense mutations are not well characterized. Here, we first identified the GSK3β, β-catenin, and RGS/APC interaction domains of AXIN1 that are the most critical for proper β-catenin regulation. Analysis of 80 tumor-associated variants in these domains identified 18 that significantly affected β-catenin signaling. Coimmunoprecipitation experiments revealed that most of them lost binding to the binding partner corresponding to the mutated domain. A comprehensive protein structure analysis predicted the consequences of these mutations, which largely overlapped with the observed effects on β-catenin signaling in functional experiments. The structure analysis also predicted that loss-of-function mutations within the RGS/APC interaction domain either directly affected the interface for APC binding or were located within the hydrophobic core and destabilized the entire structure. In addition, truncated AXIN1 length inversely correlated with the β-catenin regulatory function, with longer proteins retaining more functionality. These analyses suggest that all AXIN1-truncating mutations at least partially affect β-catenin regulation, whereas this is only the case for a subset of missense mutations. Consistently, most colorectal and liver cancers carrying missense variants acquire mutations in other β-catenin regulatory genes such as APC and CTNNB1. These results will aid the functional annotation of AXIN1 mutations identified in large-scale sequencing efforts or in individual patients. Significance: Characterization of 80 tumor-associated missense variants of AXIN1 reveals a subset of 18 mutations that disrupt its β-catenin regulatory function, whereas the majority are passenger mutations.
Human ASXL1-Mutant Hematopoiesis Is Driven by a Truncated Protein Associated with Aberrant Deubiquitination of H2AK119
Authors: Thomas Köhnke, Kevin A. Nuno, Catherine C. Alder, Eric J. Gars, Paul Phan, Amy C. Fan, Ravindra Majeti
Journal: Blood Cancer Discovery (2024)

Mutations in additional sex combs like 1 (ASXL1) confer poor prognosis both in myeloid malignancies and in premalignant clonal hematopoiesis (CH). However, the mechanisms by which these mutations contribute to disease initiation remain unresolved, and mutation-specific targeting has remained elusive. To address this, we developed a human disease model that recapitulates the disease trajectory from ASXL1-mutant CH to lethal myeloid malignancy. We demonstrate that mutations in ASXL1 lead to the expression of a functional, truncated protein and determine that truncated ASXL1 leads to global redistribution of the repressive chromatin mark H2AK119Ub, increased transposase-accessible chromatin, and activation of both myeloid and stem cell gene-expression programs. Finally, we demonstrate that H2AK119Ub levels are tied to truncated ASXL1 expression levels and leverage this observation to demonstrate that inhibition of the PRC1 complex might be an ASXL1-mutant-specific therapeutic vulnerability in both premalignant CH and myeloid malignancy.
Protective effect of height on long-term survival of resectable lung cancer: a new feature of the lung cancer paradox
Authors: Elisa Daffré, Raphaël Porcher, Antonio Iannelli, Mathilde Prieto, Laurent Brouchet, Pierre Emmanuel Falcoz, Françoise Le Pimpec Barthes, Pierre Benoit Pages, Pascal Alexandre Thomas, Marcel Dahan, Marco Alifano
Journal: Thorax (2024)

Introduction Unlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders. Methods We extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV 1 ), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis. Results The study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV. Conclusions Our study shows that height is an independent prognostic factor of resectable lung cancer.
Sintilimab plus bevacizumab combined with radiotherapy as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter, single-arm, phase 2 study
Authors: Meiyan Zhu, Zelong Liu, Shuling Chen, Zhenhua Luo, Jianfei Tu, Liangliang Qiao, Jian Wu, Wenzhe Fan, Zhenwei Peng
Journal: Hepatology (2024)

Systemic treatments are listed as first-line therapies for HCC with portal vein tumor thrombus (PVTT), resulting in modest efficacy. We aimed to evaluate the efficacy and safety of sintilimab plus bevacizumab combined with radiotherapy in HCC with PVTT and to identify prognostic biomarkers.
Response to 2 Induction Courses of Bacillus Calmette-Guèrin Therapy Among Patients With High-Risk Non–Muscle-Invasive Bladder Cancer
Authors: Andrew B. Katims, Jacob Tallman, Emily Vertosick, Shaun Porwal, Guido Dalbagni, Eugene K. Cha, Robert Smith, Nicole Benfante, Harry W. Herr
Journal: JAMA Oncology (2024)

With the ongoing bacillus Calmette-Guèrin (BCG) shortage, alternate therapeutic options for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are needed.