tbuckley/cabot-search huggingface dataset:
Sustained software development, not number of citations or journal choice, is indicative of accurate bioinformatic software
Authors: Paul P. Gardner, James M. Paterson, Stephanie McGimpsey, Fatemeh Ashari-Ghomi, Sinan U. Umu, Aleksandra Pawlik, Alex Gavryushkin, Michael A. Black
Journal: Genome biology (2022)

Computational biology provides software tools for testing and making inferences about biological data. In the face of increasing volumes of data, heuristic methods that trade software speed for accuracy may be employed. We have studied these trade-offs using the results of a large number of independent software benchmarks, and evaluated whether external factors, including speed, author reputation, journal impact, recency and developer efforts, are indicative of accurate software.We find that software speed, author reputation, journal impact, number of citations and age are unreliable predictors of software accuracy. This is unfortunate because these are frequently cited reasons for selecting software tools. However, GitHub-derived statistics and high version numbers show that accurate bioinformatic software tools are generally the product of many improvements over time. We also find an excess of slow and inaccurate bioinformatic software tools, and this is consistent across many sub-disciplines. There are few tools that are middle-of-road in terms of accuracy and speed trade-offs.Our findings indicate that accurate bioinformatic software is primarily the product of long-term commitments to software development. In addition, we hypothesise that bioinformatics software suffers from publication bias. Software that is intermediate in terms of both speed and accuracy may be difficult to publish-possibly due to author, editor and reviewer practises. This leaves an unfortunate hole in the literature, as ideal tools may fall into this gap. High accuracy tools are not always useful if they are slow, while high speed is not useful if the results are also inaccurate.
Clinical, genomic, and transcriptomic correlates of response to immune checkpoint blockade-based therapy in a cohort of patients with angiosarcoma treated at a single center
Authors: Evan Rosenbaum, Cristina R Antonescu, Shaleigh Smith, Martina Bradic, Daniel Kashani, Allison L Richards, Mark Donoghue, Ciara M Kelly, Benjamin Nacev, Jason E Chan, Ping Chi, Mark A Dickson, Mary L Keohan, Mrinal M Gounder, Sujana Movva, Viswatej Avutu, Katherine Thornton, Ahmet Zehir, Anita S Bowman, Samuel Singer, William Tap, Sandra D’Angelo
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Angiosarcoma is a histologically and molecularly heterogeneous vascular neoplasm with aggressive clinical behavior. Emerging data suggests that immune checkpoint blockade (ICB) is efficacious against some angiosarcomas, particularly cutaneous angiosarcoma of the head and neck (CHN). Methods Patients with histologically confirmed angiosarcoma treated with ICB-based therapy at a comprehensive cancer center were retrospectively identified. Clinical characteristics and the results of targeted exome sequencing, transcriptome sequencing, and immunohistochemistry analyses were examined for correlation with clinical benefit. Durable clinical benefit was defined as a progression-free survival (PFS) of ≥16 weeks. Results For the 35 patients included in the analyses, median PFS and median overall survival (OS) from the time of first ICB-based treatment were 11.9 (95% CI 7.4 to 31.9) and 42.5 (95% CI 19.6 to 114.2) weeks, respectively. Thirteen patients (37%) had PFS ≥16 weeks. Clinical factors associated with longer PFS and longer OS in multivariate analyses were ICB plus other therapy regimens, CHN disease, and white race. Three of 10 patients with CHN angiosarcoma evaluable for tumor mutational burden (TMB) had a TMB ≥10. Five of six patients with CHN angiosarcoma evaluable for mutational signature analysis had a dominant mutational signature associated with ultraviolet (UV) light. No individual gene or genomic pathway was significantly associated with PFS or OS; neither were TMB or UV signature status. Analyses of whole transcriptomes from nine patient tumor samples found upregulation of angiogenesis, inflammatory response, and KRAS signaling pathways, among others, in patients with PFS ≥16 weeks, as well as higher levels of cytotoxic T cells, dendritic cells, and natural killer cells. Patients with PFS &lt;16 weeks had higher numbers of cancer-associated fibroblasts. Immunohistochemistry findings for 12 patients with baseline samples available suggest that neither PD-L1 expression nor presence of tumor-infiltrating lymphocytes at baseline appears necessary for a response to ICB-based therapy. Conclusions ICB-based therapy benefits only a subset of angiosarcoma patients. Patients with CHN angiosarcoma are more likely to have PFS ≥16 weeks, a dominant UV mutational signature, and higher TMB than angiosarcomas arising from other primary sites. However, clinical benefit was seen in other angiosarcomas also and was not restricted to tumors with a high TMB, a dominant UV signature, PD-L1 expression, or presence of tumor infiltrating lymphocytes at baseline.
Abstract P3-09-06: Targeting tumor subpopulations based on single-cell transcriptomics
Authors: Jacqueline M Grible, Tess Leftwich, Amy L Olex, Alex K Duong, Nicole Hairr, Narmeen S Rashid, Timothy M Smith, Lia Signaevskaia, David C Boyd, Mikhail G Dozmorov, Joshua C Harrell
Journal: Cancer Research (2022)

Abstract Breast cancers that are hormone receptor negative, such that they do not express the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), are known as triple-negative breast cancer (TNBC), and are predominantly of the basal-like subtype. These tumors aggressively metastasize, have limited effective therapeutic options, and are prevalent in patients of African descent. In these studies, we utilized a racially diverse set of 21 breast cancer patient-derived xenografts (PDXs) and 6 cell lines to identify new therapeutic combinations that may exhibit increased efficacy for patients based on ancestral heritage. Tumor subpopulation abundance was measured by single-cell RNA-sequencing (scRNAseq) a set of 13 PDXs, including some that had been subjected to long term carboplatin treatment or endocrine therapy in vivo. We identified two to four major cell types per PDX and sought to integrate this information with cytotoxic high throughput screens (HTS) of 516 clinically actionable agents. Among several interesting and overlapping findings from these multiscale models, BIRC5 (Survivin) was identified as a readily actionable target in the proliferative component of all TNBC models assayed. Analysis of public datasets found that BIRC5 expression in TNBC patient tumors was significantly correlated with reduced metastasis-free survival. In vitro and in vivo studies from our group and others found that YM155, which targets Survivin, was highly cytotoxic towards breast cancer cells. YM155 has been previously safely administered in Phase I/II clinical trials. To uncover putative dependency pathways that may be exploited to prevent acquired resistance to BIRC5 (Survivin) inhibition, we performed synergistic HTS assays whereby the efficacy of our 516 therapeutic library was assessed in the presence versus absence of YM155. Those drugs which were found to be more highly effective when given in combination with YM155 were then selected for ongoing in vitro and in vivo applications. Grant ID: 1R01CA246182-01A1 (NIH/NCI), CCR19608826 (Susan G. Komen Foundation), VCU School of Medicine VETAR, the Jeffress Trust, UL1TR002649 (CTSA/NCATS) Citation Format: Jacqueline M Grible, Tess Leftwich, Amy L Olex, Alex K Duong, Nicole Hairr, Narmeen S Rashid, Timothy M Smith, Lia Signaevskaia, David C Boyd, Mikhail G Dozmorov, Joshua C Harrell. Targeting tumor subpopulations based on single-cell transcriptomics [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 P3-09-06.
Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression
Authors: Zhenzhen Pan, Kai Wang, Xiniao Wang, Zhirong Jia, Yuqi Yang, Yalei Duan, Lianzhan Huang, Zhuo-Xun Wu, Jian-ye Zhang, Xuansheng Ding
Journal: Molecular Cancer (2022)

Abstract Background The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) brings remarkable benefits for the survival of patients with advanced NSCLC harboring EGFR mutations. Unfortunately, acquired resistance seems to be inevitable and limits the application of EGFR-TKIs in clinical practice. This study reported a common molecular mechanism sustaining resistance and potential treatment options to overcome EGFR-TKIs resistance. Methods EGFR-TKIs resistant NSCLC cells were established and confirmed by MTT assay. Cholesterol content was detected and the promotional function of cholesterol on NSCLC growth was determined in vivo. Then, we identified ERRα expression as the downstream factor of cholesterol-mediated drug resistance. To dissect the regulatory mechanism, we conducted experiments, including immunofluorescence, co-immunoprecipitation, luciferase reporter assay and chromatin immunoprecipitation assay. Results Long-term exposure to EGFR-TKIs generate drug resistance with the characteristic of cholesterol accumulation in lipid rafts, which promotes EGFR and Src to interact and lead EGFR/Src/Erk signaling reactivation-mediated SP1 nuclear translocation and ERRα re-expression. Further investigation identifies ERRα as a target gene of SP1. Functionally, re-expression of ERRα sustains cell proliferation by regulating ROS detoxification process. Lovastatin, a drug used to decrease cholesterol level, and XCT790, an inverse agonist of ERRα, overcome gefitinib and osimertinib resistance both in vitro and in vivo. Conclusions Our study indicates that cholesterol/EGFR/Src/Erk/SP1 axis-induced ERRα re-expression promotes survival of gefitinib and osimertinib-resistant cancer cells. Besides, we demonstrate the potential of lowing cholesterol and downregulation of ERRα as effective adjuvant treatment of NSCLC.
2P Sitravatinib + tislelizumab in patients with metastatic non-small cell lung cancer (NSCLC)
Authors: Q. Zhou, X. Yu, B. Gao, Z. Ma, Q. Chu, D. Huang, J. Zhao, D. Day, A.L. Body, H. Pan, J. Cui, H. Li, J. Sun, J. Zhang, C. Fei, Y-L. Wu
Journal: Annals of Oncology (2022)
AGAINST ALL ODDS: A CASE OF REFRACTORY IDIOPATHIC VENTRICULAR TACHYCARDIA TREATED WITH ECMO AND ABLATION
Authors: George Prousi, Christopher Salmon, William Lorson, James Davis, Meer Fakhry, William Meeks, Ninad M. Zaman, Sultan M. Siddique
Journal: Journal of the American College of Cardiology (2022)
RATE AND CAUSES OF 30-DAY READMISSION AFTER IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR PLACEMENT: ANALYSIS OF NATIONAL INPATIENT SAMPLE
Authors: Bharosa Sharma, Mukunthan Murthi, Ramtej Atluri, Sujitha Velagapudi, Hafeez Shaka
Journal: Journal of the American College of Cardiology (2022)
Anti-SARS-CoV-2 antibody response after 2 and 3 doses of BNT162b2 mRNA vaccine in patients with lymphoid malignancies
Authors: Simon B. Gressens, Slim Fourati, Anne Le Bouter, Fabien Le Bras, Jehan Dupuis, Mohammad Hammoud, Taoufik El Gnaoui, Romain Gounot, Louise Roulin, Karim Belhadj, Corinne Haioun, Sébastien Gallien, Giovanna Melica, François Lemonnier
Journal: Clinical Microbiology and Infection (2022)
Assessment of Vitiligo Area Scoring Index (VASI), Facial-VASI and Vitiligo Extent Score using standardized photography of patients with vitiligo
Authors: Ribal Merhi, Dorine Canu, Thomas Barnetche, Elodie Duchez, Aurélia Gey, Nicolas Andreu, Alain Taieb, Katia Boniface, Julien Seneschal
Journal: British Journal of Dermatology (2022)

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RANOLAZINE ADMINISTRATION EFFECTIVELY ALLEVIATES TRASTUZUMAB-INDUCED CARDIOTOXICITY THROUGH MODULATION OF MITOCHONDRIAL FUNCTION IN RATS
Authors: Apiwan Arinno, Chayodom Maneechote, Thawatchai Khuanjing, Titikorn Chunchai, Nanthip Prathumsap, Busarin Arunsak, Krekwit Shinlapawittayatorn, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Journal of the American College of Cardiology (2022)
Diagnostic Dilemma of Pericarditis Concurrent With ST Elevation Myocardial Infarction
Authors: Mochammad Yusuf Alsagaff, Yudi Her Oktaviono, Terrence Timothy Evan Lusida
Journal: JAMA Internal Medicine (2022)

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Insurance Coverage Mandates and the Adoption of Digital Breast Tomosynthesis
Authors: Ilana B. Richman, Jessica B. Long, Kelly A. Kyanko, Xiao Xu, Cary P. Gross, Susan H. Busch
Journal: JAMA Network Open (2022)

Digital breast tomosynthesis (DBT) is a breast cancer screening modality that has gained popularity in recent years. Although insurance coverage for DBT is not mandated under the Patient Protection and Affordable Care Act, several states have required coverage without cost sharing for private insurers.To evaluate the association between state-level insurance coverage mandates for DBT and changes in DBT use, price, and out-of-pocket payments.This cohort study used an event-study design with repeated cross-sectional observations of US states. Data were obtained from the Blue Cross Blue Shield Axis database for commercially insured women aged 40 to 64 years who underwent screening mammography between January 1, 2015, and June 30, 2019. Data were analyzed between January 14, 2021, and January 20, 2022.Passage of state-level legislation requiring insurance coverage of DBT.Change in DBT use among women screened for breast cancer, overall DBT price, and out-of-pocket payments for DBT in states with mandates for coverage of DBT compared with states that did not pass legislation.This study included 9 604 084 screening mammograms from 5 754 123 women (mean [SD] age, of 53 [6.7] years). During the study period, 15 states enacted DBT coverage mandates and 34 states did not. In states with coverage mandates, DBT use increased by 9.0 percentage points (95% CI, 1.8-16.3 percentage points; P = .02) 2 years after the mandate compared with states without coverage mandates. Coverage mandates were also associated with a net $38.7 (95% CI, $13.4-$63.9; P = .003) decrease in the mean price of DBT compared with no coverage mandates. There was no association between coverage mandates and out-of-pocket payments 2 years after mandate passage ($-2.1; 95% CI, $-5.3 to $1.0; P = .18).In this cohort study, DBT coverage mandates were associated with an increase in DBT use but not with any change in out-of-pocket payments. The findings suggest that coverage mandates for DBT may have been associated with broader use but were not associated with changes in direct costs to patients.
Sodium–Glucose Cotransporter 2 Inhibitor–Linked Pericolonoscopy Hyperketonemia: A Retrospective Study
Authors: Venkatesan Thiruvenkatarajan, Georgia Smithson-Tomas, Arvind Jothin, Emily Meyer, Brianna Lindley, David Jesudason, Nagesh Nanjappa, Roelof Van Wijk
Journal: Diabetes Care (2022)
COST-EFFECTIVENESS OF INCLISIRAN IN ATHEROSCLEROTIC CARDIOVASCULAR PATIENTS WITH ELEVATED LOW-DENSITY LIPOPROTEIN CHOLESTEROL DESPITE STATIN USE: A THRESHOLD ANALYSIS
Authors: Caresse Campbell, Nihar R. Desai, Batul Electricwala, Margaret Constanti, David Trueman, Fionn Woodcock, Joaquim Cristino
Journal: Journal of the American College of Cardiology (2022)
KOUNIS SYNDROME: A RARE MEDIATOR OF ACUTE CORONARY SYNDROME
Authors: Amogh M. Joshi, Chun Siu, Zeel J. Patel, Mirza Ali, Amy Lam, Tarick Sheikh, Sagar Vadhar, Akhil Kher, Apurva Vijay Vyas
Journal: Journal of the American College of Cardiology (2022)
A RANDOMIZED CLINICAL TRIAL OF SCREENING FOR ATRIAL FIBRILLATION WITH A 14-DAY PATCH MONITOR: ANALYSIS OF ECG RECORDINGS FROM THE GUARD-AF STUDY
Authors: Daniel E. Singer, Steven Atlas, Alan S. Go, Renato D. Lopes, Steven Lubitz, David McManus, James H. Revkin, Donna Mills, Lori Crosson, Judith C. Lenane, Ronald S. Aronson
Journal: Journal of the American College of Cardiology (2022)
TIE BREAKING PHYSICAL EXAMINATION: ACUTE LEFT MAIN DISEASE VERSUS TYPE A AORTIC DISSECTION
Authors: Shoaib Ashraf, Jeirym Miranda, David Song, Kelmendi Fatjona, Sulejman Celaj, Alaa Omar, Jonathan N. Bella, Muhammad Saad, Shrivastav Rishi, Krim Nassim
Journal: Journal of the American College of Cardiology (2022)
Socioeconomic Diversity of the Matriculating US Medical Student Body by Race, Ethnicity, and Sex, 2017<b>-</b>2019
Authors: Arman A. Shahriar, Vikram V. Puram, Jonathan M. Miller, Varun Sagi, Lorenzo Adolfo Castañón-Gonzalez, Shailendra Prasad, Renée Crichlow
Journal: JAMA Network Open (2022)

health and the accumulation of unexpected expenses, given that they do not have the family support of their peers from high-income households. 6is study has limitations.Reliability and validity of self-reported parental income are unknown, subject to response biases, and may differ between groups.Furthermore, AAMC-MSQ nonrespondent characteristics were unavailable, potentially introducing sampling variance.Future work should explore temporal trends and examine factors resulting in such a broad range of representation among the lowest-income students of various racial and ethnic groups.
The contribution of altered neuronal autophagy to neurodegeneration
Authors: Alessia Filippone, Emanuela Esposito, Deborah Mannino, Nicholas Lyssenko, Domenico Praticò
Journal: Pharmacology & Therapeutics (2022)

Defects in cellular functions related to altered protein homeostasis and associated progressive accumulation of pathological intracellular material is a critical process involved in the pathogenesis of many neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Autophagy is an essential mechanism that ensures neuronal health by removing long-lived proteins or defective organelles and by doing so prevents cell toxicity and death within the central nervous system. Abundant evidence has shown that neuronal autophagy pathways are altered in Alzheimer's disease, Parkinson's disease and traumas of the central nervous system including Spinal Cord Injury and Traumatic Brain Injury. In this review, we aimed to summarize the latest studies on the role that altered neuronal autophagy plays in brain health and these pathological conditions, and how this knowledge can be leveraged for the development of novel therapeutics against them.
CHARACTERISTICS AND MANAGEMENT OF PATIENTS AGED ≥ 80 YEARS PRESENTING WITH ST ELEVATION MYOCARDIAL INFARCTIONS IN THE UNITED STATES: A NATIONWIDE INPATIENT SAMPLE COHORT STUDY
Authors: Alejandro Sanchez, Efehi Igbinomwanhia, Antonio Lewis, Abdullah Sarkar, Jose Sleiman
Journal: Journal of the American College of Cardiology (2022)
Endothelial MEKK3-KLF2/4 signaling integrates inflammatory and hemodynamic signals during definitive hematopoiesis
Authors: Yiqing Yang, Melanie Mumau, Joanna Tober, Qin Zhu, Laura Bennett, Courtney Hong, Derek Sung, Thomas Keller, Yasin Uzun, Peng Gao, Swapnil Shewale, Mei Chen, Jisheng Yang, Xiaowen Chen, Steven A. Thomas, Kai Tan, Nancy A. Speck, Mark L. Kahn
Journal: Blood (2022)
EPR22-114: Acceptance of SARS-CO-2 Vaccination Among Cancer Patients: Experience of Radiation Therapy Center in Tunisia
Authors: Rihab Melliti, R. Melliti, S. Tbessi, A. Chamsi, H. Ouaz, F. Bouguerra, S. Belajouza, N. Bouzid, S. Tebra
Journal: Journal of the National Comprehensive Cancer Network (2022)
Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study
Authors: Jean-Pierre Gangneux, Eric Dannaoui, Arnaud Fekkar, Charles-Edouard Luyt, Françoise Botterel, Nicolas De Prost, Jean-Marc Tadié, Florian Reizine, Sandrine Houzé, Jean-François Timsit, Xavier Iriart, Béatrice Riu-Poulenc, Boualem Sendid, Saad Nseir, Florence Persat, Florent Wallet, Patrice Le Pape, Emmanuel Canet, Ana Novara, Melek Manai, Estelle Cateau, Arnaud W Thille, Sophie Brun, Yves Cohen, Alexandre Alanio, Bruno Mégarbane, Muriel Cornet, Nicolas Terzi, Lionel Lamhaut, Estelle Sabourin, Guillaume Desoubeaux, Stephan Ehrmann, Christophe Hennequin, Guillaume Voiriot, Gilles Nevez, Cécile Aubron, Valérie Letscher-Bru, Ferhat Meziani, Marion Blaize, Julien Mayaux, Antoine Monsel, Frédérique Boquel, Florence Robert-Gangneux, Yves Le Tulzo, Philippe Seguin, Hélène Guegan, Brice Autier, Matthieu Lesouhaitier, Romain Pelletier, Sorya Belaz, Christine Bonnal, Antoine Berry, Jordan Leroy, Nadine François, Jean-Christophe Richard, Sylvie Paulus, Laurent Argaud, Damien Dupont, Jean Menotti, Florent Morio, Marie Soulié, Carole Schwebel, Cécile Garnaud, Juliette Guitard, Solène Le Gal, Dorothée Quinio, Jeff Morcet, Bruno Laviolle, Jean-Ralph Zahar, Marie-Elisabeth Bougnoux
Journal: The Lancet Respiratory Medicine (2021)
Blood-brain barrier delivery for lysosomal storage disorders with IgG-lysosomal enzyme fusion proteins
Authors: William M. Pardridge
Journal: Advanced Drug Delivery Reviews (2022)

The majority of lysosomal storage diseases affect the brain. Treatment of the brain with intravenous enzyme replacement therapy is not successful, because the recombinant lysosomal enzymes do not cross the blood-brain barrier (BBB). Biologic drugs, including lysosomal enzymes, can be re-engineered for BBB delivery as IgG-enzyme fusion proteins. The IgG domain of the fusion protein is a monoclonal antibody directed against an endogenous receptor-mediated transporter at the BBB, such as the insulin receptor or the transferrin receptor. This receptor transports the IgG across the BBB, in parallel with the endogenous receptor ligand, and the IgG acts as a molecular Trojan horse to ferry into brain the lysosomal enzyme genetically fused to the IgG. The IgG-enzyme fusion protein is bi-functional and retains both high affinity binding for the BBB receptor, and high lysosomal enzyme activity. IgG-lysosomal enzymes are presently in clinical trials for treatment of the brain in Mucopolysaccharidosis.
REGIONAL AND TEMPORAL VARIATIONS IN THE INCIDENCE OF SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD): INSIGHTS FROM THE NATIONAL INPATIENT SAMPLE (NIS)
Authors: Mohsin Mughal, Maryam Saleem, Hasan Mirza, Weiyi Xia, Ali Ghani, Hafsa Akbar, Waqar Arshad Mughal, Ammar Nasir, Sundeep Kumar, Ahsan Raza, Mahboob Alam, Mohammed Haris Usman, Najam Wasty, Howard L. Levitt, Sergio Waxman, Julie Master, Fahad Waqar
Journal: Journal of the American College of Cardiology (2022)
The integrated information theory of consciousness: Unmasked and identified
Authors: Bjorn Merker, Kenneth Williford, David Rudrauf
Journal: Behavioral and Brain Sciences (2022)

Abstract In our response to a truly diverse set of commentaries, we first summarize the principal topical themes around which they cluster, then address two “outlier” positions (the problem of consciousness has been solved vs. is intractable). Next, we address ways in which commentaries by non-integrated information theory (IIT) authors engage with the specifics of our IIT critique, turning finally to the four commentaries by IIT authors.