tbuckley/cabot-search huggingface dataset:
Lumen-apposing metal stent-induced perforation during endoscopic ultrasound-directed transgastric retrograde cholangiopancreaticography managed with an endoscopic suturing device
Authors: Enrico Palmeri, Pieter Hindryckx
Journal: Endoscopy (2024)

A 37-year-old woman was referred to our unit because of typical biliary colic with transient cholestasis. Her relevant medical history included a cholecystectomy and a sleeve gastrectomy, which was subsequently converted to a gastric bypass. After multidisciplinary team (MDT) discussion, we opted for an endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) using a 20/10 lumen-apposing metal stent (LAMS).
Decompression alone or with fusion for degenerative lumbar spondylolisthesis (Nordsten-DS): five year follow-up of a randomised, multicentre, non-inferiority trial
Authors: Eric Loratang Kgomotso, Christian Hellum, Morten Wang Fagerland, Tore Solberg, Jens Ivar Brox, Kjersti Storheim, Erland Hermansen, Eric Franssen, Clemens Weber, Helena Brisby, Knut Robert Hector Algaard, Håvard Furunes, Hasan Banitalebi, Inger Ljøstad, Kari Indrekvam, Ivar Magne Austevoll
Journal: BMJ (2024)

To assess whether decompression alone is non-inferior to decompression with instrumented fusion five years after primary surgery in patients with degenerative lumbar spondylolisthesis.
Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy
Authors: Victor Ng, Sonali Sinha, Ardijana Novaj, Jennifer Ma, Niamh McDermott, Xin Pei, Ana Leda F. Longhini, Helen Grimsley, Rui Gardner, Ezra Rosen, Simon N. Powell, Fresia Pareja, Diana Mandelker, Atif Khan, Jeremy Setton, Anne Roulston, Stephen Morris, Maria Koehler, Nancy Lee, Jorge Reis-Filho, Nadeem Riaz
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The importance of the DNA damage response in mediating effects of radiotherapy (RT) has galvanized efforts to target this pathway with radiosensitizers. Yet early clinical trials of this approach have failed to yield a benefit in unselected populations. We hypothesized that ataxia–telangiectasia mutated (Atm)–null tumors would demonstrate genotype-specific synergy between RT and an inhibitor of the DNA damage response protein ataxia–telangiectasia and Rad3-related (ATR) kinase. Experimental Design: We investigated the synergistic potential of the ATR inhibitor (ATRi) RP-3500 and RT in two Atm-null and isogenic murine models, both in vitro and in vivo. Staining of γ-H2AX foci, characterization of the immune response via flow cytometry, and tumor rechallenge experiments were performed to elucidate the mechanism of interaction. To examine genotype specificity, we tested the interaction of ATRi and RT in a Brca1-null model. Finally, patients with advanced cancer with ATM alterations were enrolled in a phase I/II clinical trial to validate preclinical findings. Results: Synergy between RP-3500 and RT was confirmed in Atm-null lines in vitro, characterized by an accumulation of DNA double-strand breaks. In vivo, Atm-null tumor models had higher rates of durable control with RT and ATRi than controls. In contrast, there was no synergy in tumors lacking Brca1. Analysis of the immunologic response indicated that efficacy is largely mediated by cell-intrinsic mechanisms. Lastly, early results from our clinical trial showed complete responses in patients. Conclusions: Genotype-directed radiosensitization with ATRi and RT can unleash significant therapeutic benefit and could represent a novel approach to develop more effective combinatorial synthetic cytotoxic RT-based treatments.
Targeted radionuclide therapy for gliomas: emerging clinical trial landscape
Authors: Michael Weller, Nathalie L Albert, Norbert Galldiks, Andrea Bink, Matthias Preusser, Erik P Sulman, Valerie Treyer, Patrick Y Wen, Joerg C Tonn, Emilie Le Rhun
Journal: Neuro-Oncology (2024)

Abstract According to the new WHO classification of 2021, gliomas are a heterogeneous group of tumors with very different histology, molecular genetics, and prognoses. In addition to glioblastomas, the most common gliomas, there are also numerous less common gliomas, some of which have a very favorable prognosis. Targeted radionuclide therapy is a therapeutic option that can be attractive if a tumor can be targeted based on its molecular characteristics. It is particularly useful when tumors cannot be completely resected or when conventional imaging does not fully capture the extent of the tumor. Numerous approaches to radionuclide therapy for gliomas are in early development. The most advanced approaches for patients with gliomas in the clinic employ L-type amino acid transporter 1 as an uptake mechanism for radiolabeled amino acids or target somatostatin receptor 2 or gastrin-releasing peptide receptor. Here, we discuss the various target structures of radionuclide therapy in gliomas and provide an outlook for which glioma entities radionuclide therapy could most likely provide a therapeutic alternative.
Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis
Authors: Patrick Howlett, Jeffrey Gan, Maia Lesosky, Johanna Feary
Journal: Thorax (2024)

Silicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship.
What Structural Biology Tells Us About the Mode of Action and Detection of Toxicants
Authors: Albane le Maire, William Bourguet
Journal: The Annual Review of Pharmacology and Toxicology (2024)

The study of the adverse effects of chemical substances on living organisms is an old and intense field of research. However, toxicological and environmental health sciences have long been dominated by descriptive approaches that enable associations or correlations but relatively few robust causal links and molecular mechanisms. Recent achievements have shown that structural biology approaches can bring this added value to the field. By providing atomic-level information, structural biology is a powerful tool to decipher the mechanisms by which toxicants bind to and alter the normal function of essential cell components, causing adverse effects. Here, using endocrine-disrupting chemicals as illustrative examples, we describe recent advances in the structure-based understanding of their modes of action and how this knowledge can be exploited to develop computational tools aimed at predicting properties of large collections of compounds.
Association Between Cardiovascular Health and Lifetime Risk of Heart Failure
Authors: Neela D. Thangada, Arjun Sinha, Hongyan Ning, Amanda Paluch, Victor W. Zhong, Norrina B. Allen, Mercedes R. Carnethon, John T. Wilkins, Donald M. Lloyd-Jones, Sadiya S. Khan
Journal: JACC Heart Failure (2024)
Optimal Medical Therapy and Outcomes Among Patients With Chronic Heart Failure With Reduced Ejection Fraction
Authors: Vishal N. Rao, Anne S. Hellkamp, Laine E. Thomas, Gregg C. Fonarow, Mona Fiuzat, Christopher M. O’Connor, John A. Spertus, Akshay S. Desai, Nancy M. Albert, Javed Butler, Adrian F. Hernandez, Adam D. DeVore
Journal: JACC Heart Failure (2024)
Differential Association of Transthyretin Stability with Variant and Wild-Type Transthyretin Amyloid Cardiomyopathy
Authors: Manuel Urina-Jassir, Sergio Teruya, William S. Blaner, Pierre-Jacques Brun, Tatiana Prokaeva, Felix J. Tsai, Jeffery W. Kelly, Mathew S. Maurer, Frederick L. Ruberg
Journal: JACC Heart Failure (2024)
The Impact of Bariatric Surgery on Coronary Microvascular Function Assessed Using Automated Quantitative Perfusion CMR
Authors: James D Crane, George Joy, Kristopher D Knott, João B Augusto, Clement Lau, Anish N Bhuva, Andreas Seraphim, Timothée Evain, Louise A E Brown, Amrit Chowdhary, Tushar Kotecha, Marianna Fontana, Sven Plein, Sasindran Ramar, Francesco Rubino, Peter Kellman, Hui Xue, Iain Pierce, Rhodri H Davies, James C Moon, J Kennedy Cruickshank, Barbara M McGowan, Charlotte Manisty
Journal: JACC. Cardiovascular imaging (2024)
Heart Failure Specialist Care and Long-Term Outcomes for Patients Admitted With Acute Heart Failure
Authors: Antonio Cannata, Mehrdad A. Mizani, Daniel I. Bromage, Susan E. Piper, Suzanna M.C. Hardman, Cathie Sudlow, Mark de Belder, Paul A. Scott, John Deanfield, Roy S. Gardner, Andrew L. Clark, John G.F. Cleland, Theresa A. McDonagh
Journal: JACC Heart Failure (2024)

For patients with acute heart failure (HF), specialist HF care during admission improves diagnosis and treatments. The authors aimed to investigate the association of HF specialist care with in-hospital and longer term prognosis. The authors used data from the National Heart Failure Audit from January 1, 2018, to December 31, 2022, linked to electronic records for hospitalization and deaths. All-cause mortality was the primary outcome measure and in-hospital mortality the secondary outcome measure. Data for 227,170 patients admitted to hospital with HF (median age: 81 years; IQR: 72-88 years), were analyzed. Approximately 80% of acute HF admissions received support from HF specialists. Thirty-nine percent of patients (n = 70,720) were seen by a multidisciplinary team (HF physicians and HF specialist nurses [HFSNd]), 22% (n = 40,330) were seen by HFSNs alone, and the remaining 39% (n = 71,700) were seen exclusively by specialist HF physicians. At discharge, more patients who received HF specialist care were prescribed medical therapy for HF and had specialized follow-up. Conversely, diuretic agents were prescribed to fewer patients. HF specialist care was independently associated with a higher rate of prescribing HF therapies at discharge and a lower likelihood of receiving diuretic therapy (OR: 0.90 [95% CI: 0.86-0.95]; P < 0.001). HF specialist care was associated with better long-term survival (HR: 0.89 [95% CI: 0.87-0.90]; P < 0.001) and lower in-hospital mortality (OR: 0.92 [95% CI: 0.0.88-0.97]; P < 0.001). Receiving HF specialist care during admission for HF is associated with a higher rate of implementation of medical therapy, fewer discharges on diuretic therapy, and lower in-hospital and long-term mortality across the left ventricular ejection fraction spectrum, especially for patients with heart failure with reduced ejection fraction.
Risk Stratification in Cardiac Sarcoidosis With Cardiac Positron Emission Tomography
Authors: Tahir S. Kafil, Omar M. Shaikh, Yehia Fanous, Joseph Benjamen, Muhammad M. Hashmi, Abdulazeez Jawad, Tahir Dahrouj, Rami M. Abazid, Mina Swiha, Jonathan Romsa, Rob S.B. Beanlands, Terrence D. Ruddy, Lisa Mielniczuk, David H. Birnie, Nikolaos Tzemos
Journal: JACC. Cardiovascular imaging (2024)

Although positron emission tomography (PET) imaging is well established for its diagnostic role in cardiac sarcoidosis, less is known about the prognostic value of PET and its use in risk stratification for major adverse cardiac events (MACE). The goal of this study was to perform a systematic review and meta-analysis looking at the prognostic value of PET imaging in patients with cardiac sarcoidosis. Study investigators systematically searched EMBASE (Excerpta Medica dataBASE), MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ClinicalTrials.gov, and the European Union Clinical Trial Registry for cardiac sarcoidosis and PET imaging. The primary outcome of interest was MACE. The search revealed 3,010 records, of which 55 studies were included. This represented 5,250 patients. Factors associated with MACE included the following: the combination of abnormal fluorodeoxyglucose (FDG) uptake and perfusion defect, which had an OR of 2.86 (95% CI: 1.74-4.71; P < 0.0001); abnormal perfusion or FDG uptake, which had an OR of 2.69 (95% CI: 1.67-4.33); abnormal FDG uptake, which had an OR of 2.61 (95% CI: 1.51-4.50); focal abnormal right ventricular uptake, which had an OR of 6.27 (95% CI: 3.19-12.32; P < 0.00001); and a lack of response to immunosuppression on serial PET, which had an OR of 8.43 (95% CI: 3.25-21.85; P < 0.0001). A QUIPS (Quality in Prognostic Studies) tool analysis found a low to moderate risk of bias, particularly given the small sample sizes in the individual studies. Multiple cardiac PET parameters provide risk stratification value in cardiac sarcoidosis. Focal right ventricular uptake and a lack of response to immunosuppressive therapy on serial PET imaging were particularly predictive of MACE.
Drug and biomarker tissue levels in a randomized presurgical trial on exemestane alternative schedules
Authors: Davide Serrano, Harriet Johansson, Bjørn-Erik Bertelsen, Sara Gandini, Gunnar Mellgren, Parijatham Thomas, Katherine D Crew, Nagi B Kumar, Debora Macis, Valentina Aristarco, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Mauro D’Amico, Tania Buttiron-Webber, Irene Maria Briata, Stefano Spinaci, Viviana Galimberti, Lana A Vornik, Eduardo Villar-Sanchez, Powel H Brown, Brandy M Heckman-Stoddard, Eva Szabo, Bernardo Bonanni, Andrea DeCensi
Journal: JNCI Journal of the National Cancer Institute (2024)

The drug's activity at the target tissue could help to define the minimal effective dose to promote cancer preventive therapy. Here we present exemestane and sex hormone concentrations within breast tissue from a presurgical study of alternative exemestane schedules. Postmenopausal women candidates for breast surgery for estrogen receptor-positive breast cancer were randomly assigned to exemestane 25 mg once daily (QD), 25 mg 3 times/week (TIW), or 25 mg per week (QW) for 4-6 weeks before surgery. Drug and sex hormones were analyzed from homogenized frozen tissue using a QTRAP 6500+ LC-MS/MS System. Tissue drug concentrations were detectable only in the QD arm with higher concentrations in nonmalignant tissue. Estradiol was nearly suppressed in all groups in the nonmalignant tissue (QD vs TIW P = .364 and QD vs QW P = .693). In contrast, a dose-response trend was observed in cancer tissue. Based on estradiol suppression in nonmalignant tissue, lower exemestane schedules should be explored for breast cancer preventive therapy. Trial Registration: Clinical Trials.gov NCT02598557 and EudraCT 2015-005063-1.
Antibody mechanisms of protection against malaria in RTS,S-vaccinated children: a post-hoc serological analysis of phase 2 trial
Authors: Liriye Kurtovic, Gaoqian Feng, Alessia Hysa, Ali Haghiri, Katherine O’Flaherty, Bruce D Wines, Rebeca Santano, Laura D’Andrea, Heidi E Drummer, P Mark Hogarth, Jahit Sacarlal, Freya J I Fowkes, Julie A Simpson, Carlota Dobaño, James G Beeson
Journal: The Lancet Microbe (2024)
Lipoprotein(a) and Progression of Coronary Artery Calcification in a Pooled U.S. Cohort
Authors: Nathan D. Wong, Wenjun Fan, Xingdi Hu, Christie Ballantyne, Ron Hoogeveen, Michael Y. Tsai, Auris Browne, Matthew J. Budoff
Journal: JACC. Cardiovascular imaging (2024)
Quantitative Computed Tomography Angiography for the Evaluation of Valvular Fibrocalcific Volume in Aortic Stenosis
Authors: Maria Lembo, Shruti S Joshi, Jolien Geers, Rong Bing, Lorenzo Carnevale, Tania A Pawade, Mhairi K Doris, Evangelos Tzolos, Kajetan Grodecki, Sebastien Cadet, Neil Craig, Trisha Singh, Piotr J Slomka, Audrey White, Andrea Guala, Jose F Rodriguez-Palomares, Aroa Ruiz-Muñoz, Lydia Dux-Santoy, Gisela Teixido-Tura, Laura Galian-Gay, Michelle C Williams, David E Newby, Soongu Kwak, Seung-Pyo Lee, Andreanne Powers, Marie-Annick Clavel, Damini Dey, Marc R Dweck
Journal: JACC. Cardiovascular imaging (2024)

Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods. The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression. In 136 patients with AS, fibrocalcific volume was calculated on CT angiograms at baseline and after 1 year. CT attenuation distributions were analyzed using Gaussian-mixture-modeling to derive thresholds for tissue types enabling the quantification of calcific, noncalcific, and fibrocalcific volumes. Scan-rescan reproducibility was assessed and validation provided against histology and in an external cohort. Fibrocalcific volume measurements took 5.8 ± 1.0 min/scan, demonstrating good correlation with ex vivo valve weight (r = 0.51; P < 0.001) and excellent scan-rescan reproducibility (mean difference −1%, limits of agreement −4.5% to 2.8%). Baseline fibrocalcific volumes correlated with mean gradient on echocardiography in both male and female participants (rho = 0.64 and 0.69, respectively; both P < 0.001) and in the external validation cohort (n = 66, rho = 0.58; P < 0.001). The relationship was driven principally by calcific volume in men and fibrotic volume in women. After 1 year, fibrocalcific volume increased by 17% and correlated with progression in mean gradient (rho = 0.32; P = 0.003). Baseline fibrocalcific volume was the strongest predictor of subsequent mean gradient progression, with a particularly strong association in female patients (rho = 0.75; P < 0.001). The aortic valve fibrocalcific volume provides an anatomic assessment of AS severity that can track disease progression precisely. It correlates with disease severity and hemodynamic progression in both male and female patients.
Association Between Coronary Artery Spasm and Atherosclerotic Disease
Authors: Denise Peeters, Eva Woelders, Tijn Jansen, Regina Konst, Caïa Crooijmans, Tim van de Hoef, Frans Mensink, Jonathan Los, Dario Pellegrini, Jan Hein Cornel, Peter Ong, Niels van Royen, Aukelien Leen, Suzette Elias-Smale, Robert Jan van Geuns, Peter Damman
Journal: JACC. Cardiovascular imaging (2024)

In at least one-half of the patients with angina or ischemia and nonobstructive coronary arteries undergoing coronary function testing, coronary artery spasm (CAS) is detected. CAS is associated with an adverse prognosis regarding recurrent complaints and ischemic events. Current treatment options are mainly focused on the complaints, not on the underlying pathophysiological process. In this review we discuss available evidence regarding the presence, amount, and morphology of atherosclerosis in CAS patients. The reviewed evidence confirmed that atherosclerosis and vulnerable plaque characteristics are often detected in patients with CAS. The amount of atherosclerosis is higher in patients with focal CAS compared with patients with diffuse CAS. Severity of atherosclerosis is associated with the presence of CAS and the prognosis in CAS patients with atherosclerotic stenosis is worse. Therefore, CAS patients with atherosclerosis might benefit from targeted atherosclerotic treatment. Longitudinal studies are needed to elucidate the exact relation between atherosclerosis and CAS.
Multiparametric Cardiac Magnetic Resonance Imaging to Discriminate Endomyocardial Biopsy-Proven Chronic Myocarditis From Healed Myocarditis
Authors: Jan M. Brendel, Karin Klingel, Christoph Gräni, Ron Blankstein, Jens Kübler, Florian Hagen, Meinrad Gawaz, Konstantin Nikolaou, Patrick Krumm, Simon Greulich
Journal: JACC. Cardiovascular imaging (2024)

Detecting ongoing inflammation in myocarditis patients has prognostic relevance, but there are limited data on the detection of chronic myocarditis and its differentiation from healed myocarditis.
Prognostic Impact of Culprit Lesion Calcified Nodule After Emergency Coronary Intervention
Authors: Masahiro Hada, Tsunekazu Kakuta, Tomoyo Sugiyama, Masahiro Hoshino, Taishi Yonetsu, Eisuke Usui, Yoshihiro Hanyu, Tatsuhiro Nagamine, Kai Nogami, Hiroki Ueno, Kazuki Matsuda, Kodai Sayama, Mirei Setoguchi, Tomohiro Tahara, Tatsuya Sakamoto, Takashi Mineo, Nobuaki Kobayashi, Masamichi Takano, Seita Kondo, Kohei Wakabayashi, Satoru Suwa, Tomotaka Dohi, Hiroyoshi Mori, Shigeki Kimura, Satoru Mitomo, Sunao Nakamura, Takumi Higuma, Junichi Yamaguchi, Makoto Natsumeda, Yuji Ikari, Jun Yamashita, Takuya Mizukami, Myong Hwa Yamamoto, Tetsuo Sasano, Toshiro Shinke
Journal: JACC. Cardiovascular imaging (2024)
Piplartine attenuates aminoglycoside-induced TRPV1 activity and protects from hearing loss in mice
Authors: Marisa Zallocchi, Sarath Vijayakumar, Jonathan Fleegel, Lyudmila Batalkina, Katyarina E. Brunette, Dhaval Shukal, Zhiyong Chen, Olivier Devuyst, Huizhan Liu, David Z. Z. He, Ali Sajid Imami, Abdul-Rizaq Ali Hamoud, Robert McCullumsmith, Martin Conda-Sheridan, Luana Janaína De Campos, Jian Zuo
Journal: Science Translational Medicine (2024)

Hearing loss is a major health concern in our society, affecting more than 400 million people worldwide. Among the causes, aminoglycoside therapy can result in permanent hearing loss in 40% to 60% of patients receiving treatment, and despite these high numbers, no drug for preventing or treating this type of hearing loss has yet been approved by the US Food and Drug Administration. We have previously conducted high-throughput screenings of bioactive compounds, using zebrafish as our discovery platform, and identified piplartine as a potential therapeutic molecule. In the present study, we expanded this work and characterized piplartine’s physicochemical and therapeutic properties. We showed that piplartine had a wide therapeutic window and neither induced nephrotoxicity in vivo in zebrafish nor interfered with aminoglycoside antibacterial activity. In addition, a fluorescence-based assay demonstrated that piplartine did not inhibit cytochrome C activity in microsomes. Coadministration of piplartine protected from kanamycin-induced hair cell loss in zebrafish and protected hearing function, outer hair cells, and presynaptic ribbons in a mouse model of kanamycin ototoxicity. Last, we investigated piplartine’s mechanism of action by phospho-omics, immunoblotting, immunohistochemistry, and molecular dynamics experiments. We found an up-regulation of AKT1 signaling in the cochleas of mice cotreated with piplartine. Piplartine treatment normalized kanamycin-induced up-regulation of TRPV1 expression and modulated the gating properties of this receptor. Because aminoglycoside entrance to the inner ear is, in part, mediated by TRPV1, these results suggested that by regulating TRPV1 expression, piplartine blocked aminoglycoside’s entrance, thereby preventing the long-term deleterious effects of aminoglycoside accumulation in the inner ear compartment.