tbuckley/cabot-search huggingface dataset:
Financial Burden of Lymphedema Hospitalizations in the United States
Authors: Mya L. Roberson, Paula D. Strassle, Luther-King Okunade Fasehun, Daniel O. Erim, E. Gene Deune, Adeyemi A. Ogunleye
Journal: JAMA Oncology (2021)

This cohort study uses data from the Healthcare Cost and Utilization Project Inpatient Sample to identify factors associated with high costs incurred during lymphedema-related hospitalizations in adults.
Characterization of rare germline variants in familial multiple myeloma
Authors: Calogerina Catalano, Nagarajan Paramasivam, Joanna Blocka, Sara Giangiobbe, Stefanie Huhn, Matthias Schlesner, Niels Weinhold, Rolf Sijmons, Mirjam de Jong, Christian Langer, Klaus-Dieter Preuss, Björn Nilsson, Brian Durie, Hartmut Goldschmidt, Obul Reddy Bandapalli, Kari Hemminki, Asta Försti
Journal: Blood Cancer Journal (2021)
Abstract 2813: Endothelin-1 Increases L-type Ca Current of Rat Ventricular Myocytes via an Activation of Protein Kinase C and Ca/calmodulin Dependent Protein Kinase II
Authors: Kimiaki Komukai, Jin O-Uchi, Kenichi Hongo, Makoto Kawai, Satoshi Morimoto, Michihiro Yoshimura, Satoshi Kurihara
Journal: Circulation (2009)

[Introduction] Endothelin-1 (ET-1) shows a positive inotropic effect but the effect of ET-1 on L-type Ca current (ICa) is controversial. The effect appears to depend on patch clamp configuration. W...
Guiding Left Ventricular Lead Positioning and Refining Ability to Predict Response and Nonresponse to Cardiac Resynchronization Therapy Using dP/dtmax: Killing 3 Birds With 1 High-Fidelity Wire?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Biykem Bozkurt, Kumudha Ramasubbu
Journal: Journal of the American College of Cardiology (2011)
Doctors faced with impossible rationing decisions must seek legal advice
Authors: Christine Tomkins
Journal: BMJ (2021)

At the Medical Defence Union, we help thousands of members each year with complaints and claims around patients’ clinical care. Unfortunately, we do not share the optimistic view of the barrister quoted in The BMJ about the potential for pandemic related complaints.1

Many people have been understanding about the constraints and compromises forced on practitioners by the health crisis. But patients and their representatives have …
Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer
Authors: Ila J. Datar, Sacha C. Hauc, Shruti Desai, Nicole Gianino, Brian Henick, Yuting Liu, Kostas Syrigos, David L. Rimm, Paula Kavathas, Soldano Ferrone, Kurt A. Schalper
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non–small cell lung cancer (NSCLC). Experimental Design: Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell–specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II β chain in &amp;gt;700 immunotherapy-naïve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts. Results: Cancer cell–specific downregulation of HLA markers was identified in 30.4% of cases. β2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of β2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in &amp;lt;5% of lung malignancies. Tumors with cancer cell–specific β2M downregulation displayed reduced T cells and increased natural killer (NK)–cell infiltration. Samples with cancer cell HLA-A downregulation displayed modest increase in CD8+ T cells and NK-cell infiltration. Samples with cancer cell–selective HLA-B,-C or HLA class-II downregulation displayed reduced T cells and NK-cell infiltration. There was limited association of the markers with clinicopathologic variables and KRAS/EGFR mutations. Cancer cell–selective downregulation of the HLA subunits was associated with shorter overall survival. Conclusions: Our results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naïve NSCLCs associated with distinct tumor microenvironment composition and patient survival.
Abstract PS5-41: Machine learning model of gut microbiota predicts neratinib induced diarrhea in patients with breast cancer
Authors: Chi Wah Wong, Susan E. Yost, Jin Sun Lee, John D. Gillece, Megan Folkerts, Lauren Reining, Sarah K. Highlander, Zahra Eftekhari, Joanne Mortimer, Yuan Yuan
Journal: Cancer Research (2021)

Abstract Background: Neratinib is a potent small molecule tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptors (HER1,2,4). One of the major side effects of neratinib is diarrhea. The human gut contains a dense microbiome ecosystem that is essential in maintaining a healthy host physiology, and its disruption may lead to increased risk of toxicities from cancer therapy. In this study, we aimed to develop a machine learning model based on analysis of gut microbiota data to predict neratinib-induced diarrhea. Methods: Patients were enrolled in a phase II trial evaluating safety and tolerability of neratinib in older adults with HER2+ breast cancer (NCT02673398). Neratinib was administered as single agent, 240 mg oral daily in a 28-day cycle. Stool samples were collected at baseline and during treatment for 16S rRNA gene sequencing. Using microbial relative abundance data, we developed gradient-boosted tree models with two nested loops of cross validations to classify whether diarrhea would occur or not after treatment onset. For the inner validation loop, we used ten-fold cross validation to determine the optimal model from hyper-parameters including regularization. For the outer validation loop, we utilized a leave-one-patient-out cross validation to test this model on the hold-out patient’s baseline data and the predictions were used for model assessment. Results: A total of 11 patients and 50 longitudinal stool samples were collected. The median age was 66 years. 73% developed grade ≥ 1 diarrhea attributed to neratinib. Shannon diversity index of gut microbiome was not associated with diarrhea. For predictive modeling, the outer validation loop Area Under the Receiver Operating Characteristic Curve (AUROC) and Area Under the Precision Recall Curve (AUPRC) were 0.92 and 0.97, respectively. The two most important taxa predictive of protection from diarrhea were Ruminiclostridium 9, and Bacteroides sp. HPS0048. We found that patients with a larger relative abundance of Ruminiclostridium 9 and Bacteroides sp. HPS0048 have reduced risk of neratinib-related diarrhea. Conclusions: The machine learning model can identify breast cancer patients at risk of diarrhea prior to neratinib use. Future studies are required to validate this finding. Citation Format: Chi Wah Wong, Susan E. Yost, Jin Sun Lee, John D. Gillece, Megan Folkerts, Lauren Reining, Sarah K. Highlander, Zahra Eftekhari, Joanne Mortimer, Yuan Yuan. Machine learning model of gut microbiota predicts neratinib induced diarrhea in patients with breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-41.
Abstract PS3-20: Rapid beside diagnosis of breast core needle biopsies using stimulated raman histology
Authors: Daniel Avram Orringer, Thomas Chen, Steve Pastore, Farbod Darvishian, Hildegard Toth, Freya Schnabel
Journal: Cancer Research (2021)

Abstract Image-guided core needle biopsy plays a central role in the diagnosis and management of a wide range of breast lesions. After collection, tissue cylinders are transported from a biopsy suite to a pathology laboratory for analysis. The existing workflow for microscopic diagnosis of tissue specimens precludes the option of using histologic data to inform clinical decision-making at the time of biopsy. Here, we introduce stimulated Raman histology (SRH), a rapid label-free optical imaging method that enables microscopic imaging of unprocessed breast biopsy specimens in the biopsy suite within minutes of sample collection. SRH has been thoroughly validated for use in the detection and diagnosis of brain tumors but its use has not been validated in breast lesions. In our study, we collected core needle biopsy specimens and allocated a 2mm portion of the tissue sample for SRH imaging. Each specimen was imaged with SRH and subsequently fixed in formalin, embedded, stained and sectioned in a conventional manner. A board-certified breast pathologist first analyzed the diagnostic features of the imaged specimens with SRH and then with conventional H&amp;E-stained sections. In a pilot series of six patients, we found that SRH could differentiate between lesions that can mimic cancer such as a radial scar from neoplastic ones like invasive ductal carcinoma. SRH also demonstrated histologic differences between a benign tumor like a fibroadenoma and a malignant tumor like an invasive ductal carcinoma. We also observed diagnostic differences amongst benign processes such as radial scar and pseudoangiomatous stromal hyperplasia. Importantly, we showed that SRH is non-consumptive and the imaged tissue can be used for downstream histologic and immunohistochemical analysis. Our data provide proof of concept that SRH can reveal the diagnostic features of tissue collected in breast core needle biopsies, supporting further validation of this technology. Ultimately, we envision the use of SRH to create new, efficient workflows for managing patients with breast lesions, especially those in which fine needle aspiration is of limited value, and where rapid diagnosis of tissue biopsies could streamline care and increase patient satisfaction. Citation Format: Daniel Avram Orringer, Thomas Chen, Steve Pastore, Farbod Darvishian, Hildegard Toth, Freya Schnabel. Rapid beside diagnosis of breast core needle biopsies using stimulated raman histology [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-20.
KDM6B-mediated histone demethylation of LDHA promotes lung metastasis of osteosarcoma
Authors: Yuhang Jiang, Fengfeng Li, Bowen Gao, Mengjun Ma, Meng Chen, Yanfeng Wu, Weidong Zhang, Yangbai Sun, Sanhong Liu, Huiyong Shen
Journal: Theranostics (2021)

Rationale: Osteosarcoma (OS), the most common type of bone tumor, which seriously affects the patients' limb function and life quality. OS has a strong tendency of lung metastasis, and the five-year survival rate of patients with metastatic osteosarcoma is less than 20%. Thus, new treatment targets and strategies are urgently needed. Methods: The expression of the histone demethylase KDM6B and H3K27me3 levels in OS specimens were analyzed using quantitative PCR and immunohistochemical assays. The biological functions of KDM6B were determined using in vitro transwell, wound healing assays, and an in vivo orthotopic injection-induced lung metastasis model. Subsequently, chromatin immunoprecipitation sequencing (ChIP-seq) combined with transcriptomic RNA sequencing (RNA-seq), and subsequent ChIP-qPCR, western blot, and aerobic glycolysis assays were used to explore the mechanism of KDM6B function and validate the candidate target gene of KDM6B. Results: KDM6B expression was significantly upregulated in OS patients, and high KDM6B expression was associated with poorer prognosis in OS patients. Targeting KDM6B significantly inhibited OS cell migration in vitro and lung metastasis in vivo. RNA-seq and ChIP-seq analysis revealed that KDM6B increases lactate dehydrogenase LDHA expression in OS cells by directly mediating H3K27me3 demethylation. The phenotypes of inhibited cell metastasis in KDM6B-knockdown OS cells was reversed upon overexpression of LDHA. Finally, a small molecule inhibitor targeting KDM6B significantly inhibited OS cell migration in vitro and lung metastasis in vivo. Conclusions: Collectively, we elucidated that upregulated KDM6B facilitates tumor metastasis in OS via modulating LDHA expression. Our findings deepen the recognition of OS metastasis mechanism and suggest that KDM6B might be a new potential therapeutic target for the treatment of OS (especially highly metastatic OS).
Pre-Diabetes Increases Stroke Risk in Patients With Nonvalvular Atrial Fibrillation
Authors: Louise Kezerle, Meytal Avgil Tsadok, Amichay Akriv, Adi Berliner Senderey, Asaf Bachrach, Maya Leventer-Roberts, Moti Haim
Journal: Journal of the American College of Cardiology (2021)
Abstract 9799: Pulse Pressure is Associated With High Cardiovascular Mortality After Adjustment for Systolic Blood Pressure and Risk Factors
Authors: William J Kostis, Javier Cabrera, Chun Pang Lin, John B Kostis
Journal: Circulation (2019)

Introduction: In the Systolic Blood Pressure Intervention Trial (SPRINT), the primary composite outcome and all cause mortality at 3.26 years of follow up were lower in the intensive treatment grou...
Establishment of injury models in studies of biological effects induced by microwave radiation
Authors: Yun-Fei Lai, Hao-Yu Wang, Rui-Yun Peng
Journal: Military Medical Research (2021)

Abstract Microwave radiation has been widely used in various fields, such as communication, industry, medical treatment, and military applications. Microwave radiation may cause injuries to both the structures and functions of various organs, such as the brain, heart, reproductive organs, and endocrine organs, which endanger human health. Therefore, it is both theoretically and clinically important to conduct studies on the biological effects induced by microwave radiation. The successful establishment of injury models is of great importance to the reliability and reproducibility of these studies. In this article, we review the microwave exposure conditions, subjects used to establish injury models, the methods used for the assessment of the injuries, and the indicators implemented to evaluate the success of injury model establishment in studies on biological effects induced by microwave radiation.
Honing in on the effectors of oxidative stress in the asthmatic lung: oxidised phosphatidylcholines
Authors: Raymond B. Penn
Journal: European Respiratory Journal (2021)

<b>Pascoe <i>et al</i>. examine BAL samples from asthmatic patients challenged with diluent or allergen, and from patients with/without AHR, to establish the specific oxidised PCs that associate with AHR and are induced by allergic lung challenge.</b>https://bit.ly/2TeSzH6
Molecular typing of group B Neisseria meningitidis’subcapsular antigens directly on biological samples demonstrates epidemiological congruence between culture-positive and -negative cases: A surveillance study of invasive disease over a 13-year period
Authors: Lorenzo Lodi, Maria Moriondo, Francesco Nieddu, Silvia Ricci, Sara Guiducci, Francesca Lippi, Clementina Canessa, Elisa Calistri, Francesco Citera, Mattia Giovannini, Giuseppe Indolfi, Massimo Resti, Chiara Azzari
Journal: Journal of Infection (2021)
Re: Lucia Nappi, Marisa Thi, Nabil Adra, et al. Integrated Expression of Circulating miR375 and miR371 to Identify Teratoma and Active Germ Cell Malignancy Components in Malignant Germ Cell Tumors. Eur Urol 2021;79:16–9
Authors: John T. Lafin, Aditya Bagrodia
Journal: European Urology (2020)
Abstract PS13-05: A phase 2 study of oral paclitaxel and encequidar (oPac+E) in the treatment of cutnaeous angiosarcoma: The breast angiosarcoma subgroup
Authors: Vinod Ravi, Michael Wagner, Tom Wei-Wu Chen, Herbert H Loong, Robert Mennel, Cheuh-Chuan Yen, Glen Clack, David Cutler, Rudolf Kwan, Wing=Kai CHan
Journal: Cancer Research (2021)

Abstract Background Cutaneous angiosarcomas are highly aggressive malignant tumors with poor prognosis. Currently there is no FDA-approved treatment. oPac+E is a combination of oral paclitaxel and a novel oral P-glycoprotein inhibitor, Encequidar. Materials and Methods: This is a phase-2 study evaluating the activity, safety and tolerability of oPac 205mg/m2 + E 12.9 mg once daily for 3 consecutive days weekly for patients with unresectable cutaneous angiosarcoma. Tumour response was evaluated every 6 weeks using RECIST and photography. Results: From Aug-2018 to May-2020, 7 of 26 enrolled patients (pts) had breast cutaneous angiosarcoma. All had previous breast cancer, mastectomy and radiotherapy and/or adjuvant chemotherapy, no prior taxane for angiosacoma and no metastatic disease. Median age was 66 yrs (range 49-76). Best objective response rates were: complete response (CR) 43% (3/7 pts), partial response (PR) 14% (1/7 pts), stable disease (SD) 43% (3/7 pts), progressive disease (PD) 0%. Furthermore, 3 pts (43%) who had inoperable lesions were deemed operable after Oraxol treatment and received curative intent surgical resection. Median progression free survival (PFS) was 17 weeks. oPac+E was generally well tolerated. Grade-3 treatment related adverse events (AEs) occurred in 5 pts: diarrhea=1, fatigue=2, neutropenia =1, dyspnea=1, dehydration=1, pneumonitis=1. Grade-4 AE were neutropenia in 2 pts. Grade-2 paraesthesia=1. All pts fully recovered. Dose reductions were needed in 3 subjects. No patients discontinued treatment due to AEs. To date no patients died. Conclusions: oPac+E may provide an effective oral treatment for radiation-associated breast angiosarcoma, with a high clinical benefit rate (CR + PR+ SD=100%), durable response and enabled resection of unresectable tumors. It is generally well tolerated even in elderly patients; with low incidence of neuropathy. It may allow patients to avoid hospital IV chemotherapy visits and the option of home treatment. Citation Format: Vinod Ravi, Michael Wagner, Tom Wei-Wu Chen, Herbert H Loong, Robert Mennel, Cheuh-Chuan Yen, Glen Clack, David Cutler, Rudolf Kwan, Wing=Kai CHan. A phase 2 study of oral paclitaxel and encequidar (oPac+E) in the treatment of cutnaeous angiosarcoma: The breast angiosarcoma subgroup [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-05.
Abstract 1484: Role of T- and B-Lymphocytes in Hypercholesterolemia-Induced Vasomotor Dysfunction
Authors: Ryan M Wolfort, Karen Y Stokes, D N Granger
Journal: Circulation (2006)

Hypercholesterolemia, a major risk factor for atherogenesis, is associated with inflammation and endothelial damage in large arteries. While immune cells have been implicated in the early endotheli...
Abstract 20311: Rapid Response Teams and BedsidePEWS: Planned Subgroup Analysis of a Cluster Randomized Trial
Authors: Christopher S Parshuram, Karen Dryden-Palmer, Catherine Farrell, Ronald Gottesman, Martin Gray, James S Hutchison, Mark Helfaer, Elizabeth A Hunt, Ari Joffe, Jacques Lacroix, Michael-Alice Moga, Vinay Nadkarni, Nelly Ninis, Patricia Parkin, David Wensley, Andrew R Willan
Journal: Circulation (2017)

Background: Ideally, rapid response systems identify at-risk inpatients and standardize ICU consultation. Scores and rapid response teams (RRT) are increasingly used to achieve these goals. Knowled...
An Unusual Case of Chest Pain With Wide Complex Arrhythmia—No Stents Needed
Authors: Usman A. Hasnie, Haren Patel, Harish Doppalapudi
Journal: JAMA Internal Medicine (2021)

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Race, Racism, and Structural Injustice: Equitable Allocation and Distribution of Vaccines for the COVID-19
Authors: Helene D. Gayle, James F. Childress
Journal: The American Journal of Bioethics (2021)

Inequity has been a hallmark of the COVID-19 pandemic in the United States, especially in the sharply disproportionate impacts among people of color (CDC 2020). Recent studies have confirmed that t...
Gender Differences in Treatment and Outcomes of Patients With COVID-19 Respiratory Failure
Authors: R. A. Feroze, T. Azam, H. Shadid, M. Pan, H. Berlin, C. Meloche, J. Leya, P. O'Hayer, E. Anderson, R. Kaakati, A. Bitar, K. Padalia, D. Perry, P. Blakely, P. Y. Zhao, L. L. Zhao, S. Hayek
Journal: Circulation (2020)
David Oliver: We can support primary care without blaming hospital doctors
Authors: David Oliver
Journal: BMJ (2021)

At the end of 2020, delegates at the local medical committee (LMC) conference of GPs backed a motion demanding “financial sanctions” against hospitals that failed to limit the “unfunded transfer of work to primary care.” They warned that the covid-19 pandemic had led to a major surge in tasks “dumped on GPs by hospitals.”1

As a hospital doctor working in acute care, I have great sympathy for GPs’ concerns. Primary care (GPs and other practice staff—notably nurses) does around 90% of NHS patient contacts for about 10% of the budget and an annual budget of around £155 (€179; $217) per patient on the practice list.2 A 2019 …
Abstract 14672: Comparison of QT Interval Measurements Between a Smartphone Electrocardiogram and a 12-Lead Electrocardiogram in Patients Undergoing Maintenance Methadone Therapy in a Narcotic Treatment Center
Authors: Erika Titus-Lay, Heather Jaynes, Elena Tomaselli-Muensterman, Todd Walroth, Carol A Ott, Gabriela Williams, Paul Moe, James E Tisdale
Journal: Circulation (2019)

Introduction: Methadone is associated with QT interval prolongation and torsades de pointes, a catastrophic event that can result in sudden cardiac death. Expert panel recommendations advocate obta...
Sex Differences in Myocardial Injury and Outcomes of Covid-19 Infection
Authors: N. Talmor, A. Mukhopadhyay, Y. H. Xia, S. Adhikari, C. Pulgarin, E. Iturrate, L. I. Horwitz, J. S. Hochman, J. S. Berger, G. I. Fishman, A. B. Troxel, H. Reynolds
Journal: Circulation (2020)