tbuckley/cabot-search huggingface dataset:
Adaptive erasure of spurious sequences in sensory cortical circuits
Authors: Alberto Bernacchia, József Fiser, Guillaume Hennequin, Máté Lengyel
Journal: Neuron (2022)

Sequential activity reflecting previously experienced temporal sequences is considered a hallmark of learning across cortical areas. However, it is unknown how cortical circuits avoid the converse problem: producing spurious sequences that are not reflecting sequences in their inputs. We develop methods to quantify and study sequentiality in neural responses. We show that recurrent circuit responses generally include spurious sequences, which are specifically prevented in circuits that obey two widely known features of cortical microcircuit organization: Dale's law and Hebbian connectivity. In particular, spike-timing-dependent plasticity in excitation-inhibition networks leads to an adaptive erasure of spurious sequences. We tested our theory in multielectrode recordings from the visual cortex of awake ferrets. Although responses to natural stimuli were largely non-sequential, responses to artificial stimuli initially included spurious sequences, which diminished over extended exposure. These results reveal an unexpected role for Hebbian experience-dependent plasticity and Dale's law in sensory cortical circuits.
IMPACT OF ATRIAL FIBRILLATION ON SURVIVAL IN PATIENTS WITH DILATED ATRIUM ACROSS DIFFERENT SEVERITIES OF ATRIAL FUNCTIONAL MITRAL REGURGITATION
Authors: Andrea Amabile, Makoto Mori, Cheryl K. Zogg, Ritu Agarwal, Markus Krane, Lissa Sugeng, ARNAR GEIRSSON
Journal: Journal of the American College of Cardiology (2022)
COST-EFFECTIVENESS OF SACUBITRIL-VALSARTAN IN CHRONIC HEART FAILURE AT EJECTION FRACTION RANGES BELOW NORMAL: A POOLED ANALYSIS FROM PARADIGM-HF AND PARAGON-HF.
Authors: Ankeet Bhatt, Brian Claggett, Muthiah Vaduganathan, Akshay S. Desai, Xian Shen, Joaquim Cristino, John J.V. McMurray, Scott D. Solomon, Thomas Andrew Gaziano
Journal: Journal of the American College of Cardiology (2022)
SPONTANEOUS CORONARY ARTERY DISSECTION AND CORONARY VASOSPASM IN FEMALE-TOMALE TRANSGENDER ON HORMONAL THERAPY
Authors: Todd Nagamine, Horyun Choi, Stephanie Pyskir, Jason Kuniyoshi, Chanavuth Kanitsoraphan, Jihun Yeo, Parthav Shah, Chol Techorueanwiwat, Thiratest Leesutipornchai, Nishant Trivedi, Sandeep Randhawa
Journal: Journal of the American College of Cardiology (2022)
INTRAVASCULAR LITHOTRIPSY FOR THE TREATMENT OF STENT UNDEREXPANSION: THE MULTICENTER IVL-DRAGON REGISTRY
Authors: Wojciech Wanha, Mariusz Tomaniak, Piotr Wańczura, Jacek Bil, Rafał Januszek, Rafał Wolny, Maksymilian P. Opolski, Łukasz Kuźma, Marek Milewski, Lukasz Lewicki, Jan Kulczycki, Sylwia Iwańczyk, Jerzy Sacha, Adam Janas, Milosz Dziarmaga, Milosz Jaguszewski, Lukasz Koltowski, Bartosz Olajossy, Krzysztof Dyrbuś, Robert Gil, Stanisław Bartuś, Krzysztof Reczuch, Janusz Kochman, Maciej Lesiak, Wojciech Wojakowski
Journal: Journal of the American College of Cardiology (2022)
EPR22-119: Cost-Effectiveness of Multi-Cancer Early Detection (MCED) Test in Subgroups With Smoking History or Obesity
Authors: Ali Tafazzoli, Scott D. Ramsey, Alissa Shaul, Weicheng Ye, Ameya Chavan, Karen C. Chung, Anuraag R. Kansal, A. Mark Fendrick
Journal: Journal of the National Comprehensive Cancer Network (2022)
Abstract P1-18-10: A clinical study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced triple negative breast cancer (TNBC)
Authors: Sacha J Howell, Laura M Kenny, Simon Lord, Matthew G Krebs, Tobias Arkenau, Richard Baird, Iain R MacPherson, Ash Bahl, Glen Clack, Edward Ainscow, Anthony GM Barrett, Paul A Dickinson, Matthew J Fuchter, Manfred Lehnert, Simak Ali, Stuart McIntosh, Charles Coombes
Journal: Cancer Research (2022)

Abstract Background: CDK7 inhibition is a promising therapeutic strategy in cancer. CDK7 is a key kinase, regulating cell division, transcription and nuclear receptor function [1]. Although recent advances have been made in the treatment of TNBC this disease is still one of significant unmet need. Materials and Methods: Tolerability and efficacy of Samuraciclib were assessed in a TNBC expansion cohort of the first in human study of Samuraciclib. These patients had metastatic or locally advanced TNBC and had received prior taxane and anthracycline therapy including at least one line of chemotherapy for metastatic or locally advanced disease. Results: From 29th January 2019 to 12th April 2021, 23 women with advanced TNBC were recruited and dosed with Samuraciclib 360mg OD. Treatment has generally been well tolerated with all patients remaining on treatment until disease progression. The most common adverse drug reactions (AE) were: G1-2 Nausea (96%), Vomiting (52%) and Diarrhea (91%). There were 4 dose reductions to manage upper GI adverse events of nausea and/or vomiting. G3 events were as follows: 2 Grade 3 Diarrhea, 1 Grade 3 Vomiting, 1 Grade 3 Fatigue, 1 Grade 3 Stomatitis, 1 Grade 3 Anaemia and 1 Grade 4 Thrombocytopenia21 patients have had follow-up evaluations for assessment of efficacy. Stable disease was achieved in 14 patients, 1 with partial response (being on treatment for 72 weeks) and 7 patients with progressive disease; two additional patients remain on compassionate use treatment, following disease progression by RECIST. 5 patients have been on treatment for at least 24 weeks of whom 3 have exceeded 1 year. Conclusions: Samuraciclib demonstrated an acceptable safety and tolerability profile with evidence of antitumour activity in advanced TNBC. References1.Patel et al. ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol Cancer Ther. 2018. doi: 10.1158/1535-7163.MCT-16-0847. PMID:29545334. Citation Format: Sacha J Howell, Laura M Kenny, Simon Lord, Matthew G Krebs, Tobias Arkenau, Richard Baird, Iain R MacPherson, Ash Bahl, Glen Clack, Edward Ainscow, Anthony GM Barrett, Paul A Dickinson, Matthew J Fuchter, Manfred Lehnert, Simak Ali, Stuart McIntosh, Charles Coombes. A clinical study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-10.
Trends in Use of Single- vs Dual-Chamber Implantable Cardioverter-Defibrillators Among Patients Without a Pacing Indication, 2010-2018
Authors: Ryan T. Borne, Paul Varosy, Zhou Lan, Frederick A. Masoudi, Jeptha P. Curtis, Daniel D. Matlock, Pamela N. Peterson
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Use of dual-chamber implantable cardioverter-defibrillator (ICD) systems among patients without a pacing indication is an example of low-value care given higher procedural risks, higher costs, and little evidence for benefit from an atrial lead. However, variation in the use of dual-chamber systems was present among patients without a pacing indication. <h3>Objective</h3> To examine the temporal trends and hospital variation in use of single- and dual-chamber ICD implantation among patients without a pacing indication undergoing first-time ICD implantation. <h3>Design, Setting, and Participants</h3> A multicenter cross-sectional study was conducted using the US National Cardiovascular Data Registry ICD Registry. A total of 266 182 patients undergoing initial implantation of a single- or dual-chamber transvenous ICD without a bradycardia pacing indication, class I or II cardiac resynchronization therapy indication, or history of atrial fibrillation or atrial flutter were included. The study was conducted from April 1, 2010, to December 31, 2018; data analysis was performed from October 19, 2020, to January 5, 2022. <h3>Exposures</h3> Implantation of a single- or dual-chamber ICD. <h3>Main Outcomes and Measures</h3> Temporal trends among patients undergoing single- vs dual-chamber ICDs were determined using the Cochran-Armitage trend test, and hospital-level variation using adjusted hospital median odds ratios was examined. <h3>Results</h3> A total of 266 182 patients (single-chamber ICD, 134 925; dual-chamber ICD, 131 257) were included in this analysis; mean (SD) age was 58.0 (14.0) years and 91 990 patients (68.2%) were men. The use of dual-chamber ICDs decreased from 64.7% (n = 15 694) in 2010 to 42.2% (n = 9762) in 2018 (<i>P</i> &lt; .001). Adjusted for patient characteristics, the median hospital-level proportion of single-chamber ICDs increased from 42.9% (95% CI, 42.6%-45.0%) in 2010 to 50.0% (95% CI, 47.8%-51.0%) in 2018. The median odds ratio for the use of dual-chamber ICDs, adjusted for patient characteristics, was 1.6 (95% CI, 1.6-1.8) in 2010 and 1.5 (95% CI, 1.5-1.8) in 2018, indicating decreasing but persistent variation in use. <h3>Conclusions and Relevance</h3> In this national study of US patients undergoing first-time ICD implantation without a clinical indication for an atrial lead, the use of dual-chamber devices decreased. However, institutional variability in the use of atrial leads persists, suggesting differences in individual or institutional cultures of real-world practice and opportunity to reduce this low-value practice.
Surveillance and return to work of healthcare workers following SARS-CoV-2 Omicron variant infection, Sheffield, England, 17 January to 7 February 2022
Authors: Mohammed Raza, Prosenjit Giri, Subhashis Basu
Journal: Eurosurveillance (2022)

The SARS-CoV-2 Omicron variant has challenged demands to minimise workplace transmission in healthcare settings while maintaining adequate staffing. Policymakers have shortened COVID-19 isolation periods, although little real-world data have evaluated the utility. Our findings from surveillance of 240 healthcare workers from Sheffield Teaching Hospitals, England, show that 55% of affected staff could return before day 10 of isolation with over 25% eligible on day 6, pending two successive negative antigen tests. This outcome is favourable for continuity of healthcare services.
Bile acid–sensitive tuft cells regulate biliary neutrophil influx
Authors: Claire E. O’Leary, Julia Sbierski-Kind, Maya E. Kotas, Johanna C. Wagner, Hong-Erh Liang, Andrew W. Schroeder, Jeshua C. de Tenorio, Jakob von Moltke, Roberto R. Ricardo-Gonzalez, Walter L. Eckalbar, Ari B. Molofsky, Christoph Schneider, Richard M. Locksley
Journal: Science Immunology (2022)

Inflammation and dysfunction of the extrahepatic biliary tree are common causes of human pathology, including gallstones and cholangiocarcinoma. Despite this, we know little about the local regulation of biliary inflammation. Tuft cells, rare sensory epithelial cells, are particularly prevalent in the mucosa of the gallbladder and extrahepatic bile ducts. Here, we show that biliary tuft cells express a core genetic tuft cell program in addition to a tissue-specific gene signature and, in contrast to small intestinal tuft cells, decreased postnatally, coincident with maturation of bile acid production. Manipulation of enterohepatic bile acid recirculation revealed that tuft cell abundance is negatively regulated by bile acids, including in a model of obstructive cholestasis in which inflammatory infiltration of the biliary tree correlated with loss of tuft cells. Unexpectedly, tuft cell-deficient mice spontaneously displayed an increased gallbladder epithelial inflammatory gene signature accompanied by neutrophil infiltration that was modulated by the microbiome. We propose that biliary tuft cells function as bile acid-sensitive negative regulators of inflammation in biliary tissues and serve to limit inflammation under homeostatic conditions.
Abstract P5-05-08: CXCL16 as a potential therapeutic target of triple-negative breast cancer
Authors: Sun Wook Cho, Mi Gyeong Jang, Hyun Jin Sun, Han Sai Lee, Young Shin Song, Seong Keun Kim
Journal: Cancer Research (2022)

Abstract CXCL16, as a chemotactic cytokine, promotes cancer proliferation, migration, and immune cell infiltration in tumor microenvironment. However, CXCL16 has been shown to play a conflicting role in breast cancer. The aim of this study was to investigate the therapeutic potential of CXCL16 in breast cancer. Breast cancer patients (n=1097) from the TCGA dataset were divided into two group according to the CXCL16 expressions, the CXCL16low (n=548) and the CXCLhigh (n=549) groups. Mean diagnostic ages were similar between groups (59 ± 13.5 vs 58 ± 12.9 years, P=0.233). The ratio of triple-negative breast cancer (TNBC) was significantly higher in the CXCLhigh than that of the CXCL16low groups (24.8 vs 6.8%, P&amp;lt;0.001), while the presence of distant metastasis or overall survivals were not different between groups. Interestingly, gene scoring analysis showed that oncogenic molecules including M2-macrophage- (r=0.36, P&amp;lt;0.001), efferocytosis- (r=0.42, P&amp;lt;0.001), and chemokine- (r=0.46, P&amp;lt;0.001) related gene sets showed significantly strong positive relations with the CXCL16 expressions in all patients including both TNBC (n=924) and non-TNBC (n=173). Additionally, the gene set score from PI3K/Akt pathway showed positive relation with the CXCL16 expressions in the non-TNBC (r=022, P&amp;lt;0.001) but not in the TNBC group. Next, a xenograft mouse model of TNBC was established with MDA-MB-231 cells, and anti-mouse CXCL16 antibody (designated as aCXCL16 group) or control IgG (designated as control group) were intravenously injected (25µg/100µl), twice per week. During 3 weeks, tumor growth was significantly delayed in the aCXCL16 than the control group by 37%. In conclusion, CXCL16 is highly expressed in TNBC and positively correlates with M2-macrophage related genes. Neutralizing CXCL16 by anti-CXCL16 shows therapeutic effects on the xenograft model of TNBC, suggesting that CXCL16 can be a potential therapeutic target for breast cancer. Citation Format: Sun Wook Cho, Mi Gyeong Jang, Hyun Jin Sun, Han Sai Lee, Young Shin Song, Seong Keun Kim. CXCL16 as a potential therapeutic target of triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-05-08.
ZNF384 Fusion Oncoproteins Drive Lineage Aberrancy in Acute Leukemia
Authors: Kirsten M. Dickerson, Chunxu Qu, Qingsong Gao, Ilaria Iacobucci, Zhaohui Gu, Hiroki Yoshihara, Emily A. Backhaus, Yunchao Chang, Laura J. Janke, Beisi Xu, Gang Wu, Evangelia K. Papachristou, Clive S. D'Santos, Kathryn G. Roberts, Charles G. Mullighan
Journal: Blood Cancer Discovery (2022)

Abstract ZNF384-rearranged fusion oncoproteins (FO) define a subset of lineage ambiguous leukemias, but their mechanistic role in leukemogenesis and lineage ambiguity is poorly understood. Using viral expression in mouse and human hematopoietic stem and progenitor cells (HSPC) and a Ep300::Znf384 knockin mouse model, we show that ZNF384 FO promote hematopoietic expansion, myeloid lineage skewing, and self-renewal. In mouse HSPCs, concomitant lesions, such as NRASG12D, were required for fully penetrant leukemia, whereas in human HSPCs, expression of ZNF384 FO drove B/myeloid leukemia, with sensitivity of a ZNF384-rearranged xenograft to FLT3 inhibition in vivo. Mechanistically, ZNF384 FO occupy a subset of predominantly intragenic/enhancer regions with increased histone 3 lysine acetylation and deregulate expression of hematopoietic stem cell transcription factors. These data define a paradigm for FO-driven lineage ambiguous leukemia, in which expression in HSPCs results in deregulation of lineage-specific genes and hematopoietic skewing, progressing to full leukemia in the context of proliferative stress. Significance: Expression of ZNF384 FO early in hematopoiesis results in binding and deregulation of key hematopoietic regulators, skewing of hematopoiesis, and priming for leukemic transformation. These results reveal the interplay between cell of origin and expression of ZNF384 FO to mediate lineage ambiguity and leukemia development. This article is highlighted in the In This Issue feature, p. 171
Epidemiological and clinical insights from SARS-CoV-2 RT-PCR crossing threshold values, France, January to November 2020
Authors: Samuel Alizon, Christian Selinger, Mircea T Sofonea, Stéphanie Haim-Boukobza, Jean-Marc Giannoli, Laetitia Ninove, Sylvie Pillet, Vincent Thibault, Alexis de Rougemont, Camille Tumiotto, Morgane Solis, Robin Stephan, Céline Bressollette-Bodin, Maud Salmona, Anne-Sophie L’Honneur, Sylvie Behillil, Caroline Lefeuvre, Julia Dina, Sébastien Hantz, Cédric Hartard, David Veyer, Héloïse M Delagrèverie, Slim Fourati, Benoît Visseaux, Cécile Henquell, Bruno Lina, Vincent Foulongne, Sonia Burrel
Journal: Eurosurveillance (2022)

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.
Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure
Authors: Gizem Keceli, Ashish Gupta, Joevin Sourdon, Refaat Gabr, Michael Schär, Swati Dey, Carlo G. Tocchetti, Annina Stuber, Jacopo Agrimi, Yi Zhang, Michelle Leppo, Charles Steenbergen, Shenghan Lai, Lisa R. Yanek, Brian O’Rourke, Gary Gerstenblith, Paul A. Bottomley, Yibin Wang, Nazareno Paolocci, Robert G. Weiss
Journal: Circulation Research (2022)

Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF.
In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Authors: Rana Gbyli, Yuanbin Song, Wei Liu, Yimeng Gao, Giulia Biancon, Namrata S. Chandhok, Xiaman Wang, Xiaoying Fu, Amisha Patel, Ranjini Sundaram, Toma Tebaldi, Padmavathi Mamillapalli, Amer M. Zeidan, Richard A. Flavell, Thomas Prebet, Ranjit S. Bindra, Stephanie Halene
Journal: Leukemia (2022)
USE OF SHAPE-HF SYSTEM FOR POINT-OF-CARE CARDIOPULMONARY EXERCISE TESTING OF PATIENTS WITH CTEPH AND CTED; A PRELIMINARY ANALYSIS
Authors: Estefania Oliveros Soles, Kaitlyn Mcsurdy, Rylie Pietrowicz, Vladimir Lakhter, Riyaz Bashir, William Auger, Anjali Vaidya, Paul Forfia
Journal: Journal of the American College of Cardiology (2022)
Development of a TCR-like antibody and chimeric antigen receptor against NY-ESO-1/HLA-A2 for cancer immunotherapy
Authors: Xin Liu, Yixiang Xu, Wei Xiong, Bingnan Yin, Yuqian Huang, Junjun Chu, Changsheng Xing, Chen Qian, Yang Du, Tianhao Duan, Helen Y Wang, Ningyan Zhang, John S. Yu, Zhiqiang An, Rongfu Wang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background The current therapeutic antibodies and chimeric antigen receptor (CAR) T cells are capable of recognizing surface antigens, but not of intracellular proteins, thus limiting the target coverage for drug development. To mimic the feature of T-cell receptor (TCR) that recognizes the complex of major histocompatibility class I and peptide on the cell surface derived from the processed intracellular antigen, we used NY-ESO-1, a cancer-testis antigen, to develop a TCR-like fully human IgG1 antibody and its derivative, CAR-T cells, for cancer immunotherapy. Methods Human single-chain variable antibody fragment (scFv) phage library (~10 ∧11 ) was screened against HLA-A2/NY-ESO-1 (peptide 157–165) complex to obtain target-specific antibodies. The specificity and affinity of those antibodies were characterized by flow cytometry, ELISA, biolayer interferometry, and confocal imaging. The biological functions of CAR-T cells were evaluated against target tumor cells in vitro. In vivo antitumor activity was investigated in a triple-negative breast cancer (TNBC) model and primary melanoma tumor model in immunocompromised mice. Results Monoclonal antibody 2D2 identified from phage-displayed library specifically bound to NY-ESO-1 157-165 in the context of human leukocyte antigen HLA-A*02:01 but not to non-A2 or NY-ESO-1 negative cells. The second-generation CAR-T cells engineered from 2D2 specifically recognized and eliminated A2+/NY-ESO-1+tumor cells in vitro, inhibited tumor growth, and prolonged the overall survival of mice in TNBC and primary melanoma tumor model in vivo. Conclusions This study showed the specificity of the antibody identified from human scFv phage library and demonstrated the potential antitumor activity by TCR-like CAR-T cells both in vitro and in vivo, warranting further preclinical and clinical evaluation of the TCR-like antibody in patients. The generation of TCR-like antibody and its CAR-T cells provides the state-of-the-art platform and proof-of-concept validation to broaden the scope of target antigen recognition and sheds light on the development of novel therapeutics for cancer immunotherapy.