tbuckley/cabot-search huggingface dataset:
The role of phosphorylation in atrial fibrillation: a focus on mass spectrometry approaches
Authors: Sina Safabakhsh, Pankaj Panwar, Scott Barichello, Sarabjit S Sangha, Paul J Hanson, Filip Van Petegem, Zachary Laksman
Journal: Cardiovascular Research (2021)

Abstract Atrial fibrillation (AF) is the most common arrhythmia worldwide. It is associated with significant increases in morbidity in the form of stroke and heart failure, and a doubling in all-cause mortality. The pathophysiology of AF is incompletely understood, and this has contributed to a lack of effective treatments and disease-modifying therapies. An important cellular process that may explain how risk factors give rise to AF includes post-translational modification of proteins. As the most commonly occurring post-translational modification, protein phosphorylation is especially relevant. Although many methods exist for studying protein phosphorylation, a common and highly resolute technique is mass spectrometry (MS). This review will discuss recent evidence surrounding the role of protein phosphorylation in the pathogenesis of AF. MS-based technology to study phosphorylation and uses of MS in other areas of medicine such as oncology will also be presented. Based on these data, future goals and experiments will be outlined that utilize MS technology to better understand the role of phosphorylation in AF and elucidate its role in AF pathophysiology. This may ultimately allow for the development of more effective AF therapies.
Tackling health inequalities: avoid unconscious associations with guilt or disgust
Authors: Woody Caan
Journal: BMJ (2021)

Marteau and colleagues are right to emphasise the impact of growing inequalities on health in England during the present pandemic.1 As a member of the Alcohol Health Alliance, I welcome their suggestions for tackling these inequalities, including increasing alcohol duty and minimum unit pricing.

Alcohol consumption often has delayed effects on physical and mental health, …
Fine-Tuning and training of densenet for histopathology image representation using TCGA diagnostic slides
Authors: Abtin Riasatian, Morteza Babaie, Danial Maleki, Shivam Kalra, Mojtaba Valipour, Sobhan Hemati, Manit Zaveri, Amir Safarpoor, Sobhan Shafiei, Mehdi Afshari, Maral Rasoolijaberi, Milad Sikaroudi, Mohd Adnan, Sultaan Shah, Charles Choi, Savvas Damaskinos, Clinton JV Campbell, Phedias Diamandis, Liron Pantanowitz, Hany Kashani, Ali Ghodsi, H.R. Tizhoosh
Journal: Medical Image Analysis (2021)

Feature vectors provided by pre-trained deep artificial neural networks have become a dominant source for image representation in recent literature. Their contribution to the performance of image analysis can be improved through fine-tuning. As an ultimate solution, one might even train a deep network from scratch with the domain-relevant images, a highly desirable option which is generally impeded in pathology by lack of labeled images and the computational expense. In this study, we propose a new network, namely KimiaNet, that employs the topology of the DenseNet with four dense blocks, fine-tuned and trained with histopathology images in different configurations. We used more than 240,000 image patches with 1000×1000 pixels acquired at 20× magnification through our proposed "high-cellularity mosaic" approach to enable the usage of weak labels of 7126 whole slide images of formalin-fixed paraffin-embedded human pathology samples publicly available through The Cancer Genome Atlas (TCGA) repository. We tested KimiaNet using three public datasets, namely TCGA, endometrial cancer images, and colorectal cancer images by evaluating the performance of search and classification when corresponding features of different networks are used for image representation. As well, we designed and trained multiple convolutional batch-normalized ReLU (CBR) networks. The results show that KimiaNet provides superior results compared to the original DenseNet and smaller CBR networks when used as feature extractor to represent histopathology images.
CLO21-021: Impact on Survival of the Number of Lymph Nodes Resected in Patients With Esophageal Cancer Following Neo-Adjuvant Therapy
Authors: Jordan McDonald, Anupam Rishi, Sabrina Saeed, Rutika Mehta, David Pointer, Jessica Frakes, Sarah Hoffe, Jacques Fontaine, Jose Pimiento
Journal: Journal of the National Comprehensive Cancer Network (2021)

"CLO21-021: Impact on Survival of the Number of Lymph Nodes Resected in Patients With Esophageal Cancer Following Neo-Adjuvant Therapy" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Low Health Literacy is Associated with the Onset of CKD during the Life Course
Authors: Matheus S. Gurgel do Amaral, Sijmen A. Reijneveld, Bas Geboers, Gerjan J. Navis, Andrea F de Winter
Journal: Journal of the American Society of Nephrology (2021)

Health literacy, the ability to deal with information related to one's health, is a predictor of health outcomes in CKD. However, research has not explored whether low health literacy predicts the onset of CKD.
Abstract 10388: Left Atrial Appendage Closure With the Watchman Device Using Intracardiac vs. Transesophageal Echocardiography: Procedural and Cost Considerations
Authors: Majd Hemam, Paul A Schurmann, Amish S Dave, Diego A Rodríguez, Luis C Sáenz, Miguel Valderrábano
Journal: Circulation (2018)

Introduction: Imaging guidance for left atrial appendage (LAA) closure (LAAC), conventionally consists of transesophageal echocardiography (TEE) and fluoroscopy under general anesthesia (GA). Intra...
Iqbal Haroon Master: researched and implemented new drugs and models of care for treating tuberculosis
Authors: Paul Stoffels, Norbert Ndjeka
Journal: BMJ (2021)

Credit: Ikana Media, Johnson & Johnson

“Our job is to do more than administer drugs; it’s to restore hope to people during their darkest hours.” No one quote can summarise any one person, but these words, spoken by Iqbal Haroon Master, provide some perspective into the humanity with which of one of South Africa’s most respected tuberculosis (TB) clinicians and researchers approached his work, which had a transformative effect in his home country.

Master could easily have lost sight of medicine’s human element. In his role as the chief medical officer of one of South Africa’s busiest TB clinics he oversaw the treatment of countless patients for an infectious disease that, until the emergence of covid-19, claimed more lives each year than any other. KwaZulu-Natal province, where his hospital is located, has the highest burden of drug resistant TB in the country, and many of those living with TB also have HIV.

Despite this, Master took a personal interest in every patient in …
Development of a Gestational and Lactational Physiologically Based Pharmacokinetic (PBPK) Model for Perfluorooctane Sulfonate (PFOS) in Rats and Humans and Its Implications in the Derivation of Health-Based Toxicity Values
Authors: Wei-Chun Chou, Zhoumeng Lin
Journal: Environmental Health Perspectives (2021)

There is a great concern on potential adverse effects of exposure to perfluorooctane sulfonate (PFOS) in sensitive subpopulations, such as pregnant women, fetuses, and neonates, due to its reported transplacental and lactational transfer and reproductive and developmental toxicities in animals and humans.This study aimed to develop a gestational and lactational physiologically based pharmacokinetic (PBPK) model in rats and humans for PFOS to aid risk assessment in sensitive human subpopulations.Based upon existing PBPK models for PFOS, the present model addressed a data gap of including a physiologically based description of basolateral and apical membrane transporter-mediated renal reabsorption and excretion in kidneys during gestation and lactation. The model was calibrated with published rat toxicokinetic and human biomonitoring data and was independently evaluated with separate data. Monte Carlo simulation was used to address the interindividual variability.Model simulations were generally within 2-fold of observed PFOS concentrations in maternal/fetal/neonatal plasma and liver in rats and humans. Estimated fifth percentile human equivalent doses (HEDs) based on selected critical toxicity studies in rats following U.S. Environmental Protection Agency (EPA) guidelines ranged from 0.08 to 0.91μg/kg per day. These values are lower than the HEDs estimated in U.S. EPA guidance (0.51-1.6μg/kg per day) using an empirical toxicokinetic model in adults.The results support the importance of renal reabsorption/excretion during pregnancy and lactation in PFOS dosimetry and suggest that the derivation of health-based toxicity values based on developmental toxicity studies should consider gestational/lactational dosimetry estimated from a life stage-appropriate PBPK model. This study provides a quantitative tool to aid risk reevaluation of PFOS, especially in sensitive human subpopulations, and it provides a basis for extrapolating to other per- and polyfluoroalkyl substances (PFAS). All model codes and detailed tutorials are provided in the Supplemental Materials to allow readers to reproduce our results and to use this model. https://doi.org/10.1289/EHP7671.
FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer
Authors: Preeti Narayan, Christy L. Osgood, Harpreet Singh, Haw-Jyh Chiu, Tiffany K. Ricks, Edwin Chiu Yuen Chow, Junshan Qiu, Pengfei Song, Jingyu Yu, Frances Namuswe, Maria Guiterrez-Lugo, Sherry Hou, William F. Pierce, Kirsten B. Goldberg, Shenghui Tang, Laleh Amiri-Kordestani, Marc R. Theoret, Richard Pazdur, Julia A. Beaver
Journal: Clinical Cancer Research (2021)

Abstract On December 20, 2019, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki [DS-8201a; T-DXd; tradename ENHERTU (Daiichi Sankyo)] for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2–based regimens in the metastatic setting. Approval was based on data from study DS8201-A-U201 (DESTINY-Breast01) with supportive safety data from study DS8201-A-J101. The primary efficacy endpoint in DESTINY-Breast01 was overall response rate (ORR) based on confirmed responses by blinded independent central review (ICR) using RECIST v1.1 in all participants who were assigned to receive the recommended dose of 5.4 mg/kg while secondary endpoints included duration of response (DoR). The confirmed ORR based on ICR in these 184 patients was 60.3% [95% confidence interval (CI): 52.9–67.4] and the median DoR was 14.8 months (95% CI: 13.8–16.9). Interstitial lung disease, including pneumonitis, was experienced in patients treated with T-DXd and can be severe, life threatening, or fatal. In addition, neutropenia and left ventricular dysfunction were included as Warnings and Precautions in labeling. Other important common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, diarrhea, and thrombocytopenia. Overall, the totality of efficacy and safety data supported the accelerated approval of T-DXd for the intended indication.
Performance and operational feasibility of antigen and antibody rapid diagnostic tests for COVID-19 in symptomatic and asymptomatic patients in Cameroon: a clinical, prospective, diagnostic accuracy study
Authors: Yap Boum, Karl Njuwa Fai, Birgit Nikolay, Akenji Blaise Mboringong, Lisa M Bebell, Mark Ndifon, Aristide Abbah, Rachel Essaka, Lucrèce Eteki, Francisco Luquero, Céline Langendorf, Nicole Fouda Mbarga, Rene Ghislain Essomba, Bongkiyung Donald Buri, Tchoula Mamiafo Corine, Bertrand Tchualeu Kameni, Nadia Mandeng, Mahamat Fanne, Anne-Cécile Zoung-Kani Bisseck, Clement B Ndongmo, Sara Eyangoh, Achta Hamadou, Jean Patrick Ouamba, Modeste Tamakloé Koku, Richard Njouom, Okomo Marie Claire, Linda Esso, Emilienne Epée, Georges Alain Etoundi Mballa
Journal: The Lancet Infectious Diseases (2021)
The Frequency and Impact of IKZF1 Deletions on Minimal Residual Disease in Adult Ph-Negative B-Cell Acute Lymphoblastic Leukemia Patients Treated in Russian Acute Lymphoblastic Leukemia Study
Authors: Galina Baskhaeva, Bella V. Biderman, Julia O. Davydova, Olga A. Gavrilina, Ksenija I. Zarubina, Elena Stepanova, Irina A. Lukyanova, Vera V. Troitskaya, Andrey Sudarikov, Irina V. Galtseva, Elena N. Parovichnikova, Valery Savchenko
Journal: Blood (2017)
Single-cell analysis can define distinct evolution of tumor sites in follicular lymphoma
Authors: Sarah Haebe, Tanaya Shree, Anuja Sathe, Grady Day, Debra K. Czerwinski, Susan M. Grimes, HoJoon Lee, Michael S. Binkley, Steven R. Long, Brock Martin, Hanlee P. Ji, Ronald Levy
Journal: Blood (2021)
Abstract 13127: Cardiac Metastasis of Lingual Squamous Cell Carcinoma, A Systematic Review of Presentation, Management, and Outcomes
Authors: Connor C Kerndt, Trevor Nessel, John A Bills, Zaid A Shareef, Alexander Balinski, Devin Mistry
Journal: Circulation (2020)

Introduction: Cardiac metastasis of lingual squamous cell carcinoma (LSCC) describes a rare oncologic progression of oral disease currently ill-defined by medical literature. In this systematic review, we aim to characterize the presentation, management, and outcomes associated with LSCC cardiac metastases. Methods: A comprehensive search of PubMed, Embase, and Cochrane Library databases was performed from inception until December 2019. Inclusion criteria included a histologically diagnosed LSCC, definitive location of cardiac metastasis, and Oxford evidence level of 4. Duplicate, non-English, animal studies, and non-original research were excluded. Patient demographics, presenting symptomology, imaging findings, interventions, and outcomes were collected and analyzed. Results: Twenty-seven articles containing 31 cases met the outlined inclusion criteria. The average age of patient presentation was 55.6 years, ranging from 23-77 years. Average time from primary cancer diagnosis to identification of cardiac metastasis was 2.2 years, varying from 0.2-11.0 years. Shortness of breath (29.0%) and chest pain (29.0%) were the most common presenting symptoms, while effusion (21.2%) and right ventricular outflow obstruction (18.2%) were the predominant echocardiogram findings. Right sided metastases (76.7%) were identified more commonly than left sided metastases (53.3%) and septal metastases (36.7%). Cardiac metastases most commonly presented within the right ventricle (56.7%), followed by the left ventricle (43.3%) (Figure 1). Surgical resection (80.6%) and radiotherapy (74.2%) were the most frequently utilized interventions. No patients obtained remission with treatment and all patients expired within one year of metastatic diagnosis. Conclusions: Cardiac metastases of LSCC demonstrate ventricular predominance and suggest a poor prognosis. Patients may benefit from palliative measures, rather than invasive intervention.
薬物溶出ステント(DES)とベア金属ステント(BMS)の不完全ステント付着(ISA)と血栓形成の関連
Authors: Okumura Masanori, Ozaki Yukio, Hattori Kosuke, Ishikawa Makoto, Kan Shino, Kawai Tomoko, Ohta Masaya, Naruse Hiroyuki, Matsui Shigeru, Hashimoto Tousei, Harigaya Hiroto, Sarai Masayoshi, Ishii Junichi
Journal: Circulation (2011)
NOGEA: A Network-Oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning
Authors: Zihu Guo, Yingxue Fu, Chao Huang, Chunli Zheng, Ziyin Wu, Xuetong Chen, Shuo Gao, Yaohua Ma, Mohamed Shahen, Yan Li, Pengfei Tu, Jingbo Zhu, Zhenzhong Wang, Wei Xiao, Yonghua Wang
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.
Abstract 20724: The Absence of the Chromatin Reader Brd2 Decreases Heart Function and Increases Mortality After Pressure Overload
Authors: Dawid Lbik, Sara Khadjeh, Belal A Mohamed, Andre Fischer, Gerd Hasenfuß, Karl Toischer
Journal: Circulation (2017)

Introduction: Mechanical stress is a known risk factor that triggers pathologic changes of the heart. Such stress response can be implemented by epigenetic mechanisms like histone modifications. Th...
PERI-OPERATIVE STATIN THERAPY DOES NOT ALTER THE INCIDENCE OF ACUTE KIDNEY INJURY AFTER CARDIOPULMONARY BYPASS: CREAT, THE CARDIOPULMONARY BYPASS, RENAL INJURY AND ATORVASTATIN TRIAL. CLINICALTRIALS.GOV NCT00910221
Authors: JR Prowle, E Licari, P Calzavacca, EV Ligabo, JE Echeverri, M Hasse, SM Bagshaw, R Bellomo
Journal: Intensive Care Medicine (2010)
Neutrophil and Nanoparticles Delivery to Tumor: Is It Going to Carry That Weight?
Authors: Daniil A. Vishnevskiy, Anastasiia S. Garanina, Anastasia A. Chernysheva, Vladimir P. Chekhonin, Victor A. Naumenko
Journal: Advanced Healthcare Materials (2021)

Abstract The application of cell carriers for transporting nanodrugs to the tumor draws much attention as the alternative to the passive drug delivery. In this concept, the neutrophil (NΦ) is of special interest as this cell is able to uptake nanoparticles (NPs) and cross the vascular barrier in response to tumor signaling. There is a growing body of literature describing NP–NΦ interactions in vitro and in vivo that demonstrates the opportunity of using these cells to improve the efficacy of cancer therapy. However, a number of conceptual and technical issues need to be resolved for translating the technology into clinics. The current review summarizes the recent advances and challenges associated with NP–NΦ interactions, with the special focus on the complex interplay between the NP internalization pathways and the modulation of NΦ activity, and its potential consequences for nanodrug delivery.
Of hits, players, and goalkeepers: the case of arrhythmias in diabetes
Authors: Raffaele Coppini, Elisabetta Cerbai
Journal: Cardiovascular Research (2021)

Corrected proof Of hits, players, and goalkeepers: the case of arrhythmias in diabetes Raffaele Coppini, Raffaele Coppini Department of Neurosciences, Psychology, Drugs and Child Health, University of Florence, Florence, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Elisabetta Cerbai Elisabetta Cerbai Department of Neurosciences, Psychology, Drugs and Child Health, University of Florence, Florence, Italy Corresponding author. Tel: +39 055 2758207, E-mail: elisabetta.cerbai@unifi.it https://orcid.org/0000-0001-7839-1361 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, cvab101, https://doi.org/10.1093/cvr/cvab101 Published: 08 April 2021
Abstract 11577: Higher Mortality Risk in Octogenarians Undergoing Mechanicalthrombectomyfor Ischemic Stroke: A Single Center Experience
Authors: Eric M Deshaies, Jake Durden, Brian Delpino
Journal: Circulation (2018)

Introduction: Questions remain about the risks of mechanical thrombectomy (MT) in octogenarians. We hypothesized the odds of mortality at discharge and ninety days are significantly greater for pat...
Reopening businesses and risk of COVID-19 transmission
Authors: Ashley O’Donoghue, Tenzin Dechen, Whitney Pavlova, Michael Boals, Garba Moussa, Manvi Madan, Aalok Thakkar, Frank J. DeFalco, Jennifer P. Stevens
Journal: npj Digital Medicine (2021)

Abstract The true risk of a COVID-19 resurgence as states reopen businesses is unknown. In this paper, we used anonymized cell-phone data to quantify the potential risk of COVID-19 transmission in business establishments by building a Business Risk Index that measures transmission risk over time. The index was built using two metrics, visits per square foot and the average duration of visits, to account for both density of visits and length of time visitors linger in the business. We analyzed trends in traffic patterns to 1,272,260 businesses across eight states from January 2020 to June 2020. We found that potentially risky traffic behaviors at businesses decreased by 30% by April. Since the end of April, the risk index has been increasing as states reopen. There are some notable differences in trends across states and industries. Finally, we showed that the time series of the average Business Risk Index is useful for forecasting future COVID-19 cases at the county-level ( P &lt; 0.001). We found that an increase in a county’s average Business Risk Index is associated with an increase in positive COVID-19 cases in 1 week (IRR: 1.16, 95% CI: (1.1–1.26)). Our risk index provides a way for policymakers and hospital decision-makers to monitor the potential risk of COVID-19 transmission from businesses based on the frequency and density of visits to businesses. This can serve as an important metric as states monitor and evaluate their reopening strategies.