tbuckley/cabot-search huggingface dataset:
Abstract 2392: Effects of Combination Therapy with ACE and ARB in patients with Acute Decompensated Heart Failure or MI: A Meta-analysis
Authors: Nishant Jalandhara, Rohit Arora, Sandeep Khosla, Sashikanth Adigopula, Rohitkumar Bhuriya, Saravanan Balamuthusamy
Journal: Circulation (2008)

Angiotensin converting enzyme (ACE) therapy reduces mortality and morbidity from cardiovascular causes in patients with vascular diseases or high risk diabetes without heart failure. The role of combination therapy with ACE and angiotensin II receptor blockers (ARB) is not precisely known. We have assessed the effect of combination therapy with ACE and ARB in patients with heart failure or myocardial infarction. Large randomized control trials that included heart failure or myocardial infarction patients in which ACE and ARB were used in combination and compared with ACE therapy alone were included for the meta-analysis. Systematic review of literature was performed in MEDLINE and OVID search engines. Chi-square test was used to assess inter-study heterogeneity. The effect of combination therapy was assessed by calculating Odds ratio using Revmans software. Results were computed using 95% CI and were considered significant with double sided alpha error &lt; 0.05. Four trials (N = 29,732) fulfilled the inclusion criteria for the study. There was a significant benefit towards use of combination therapy using ACE and ARB in reducing the need for hospitalization for heart failure 0.89 [0.83, 0.95] (P = 0.0004). Although combination therapy had no benefit over ACE use for death due to cardiovascular cause and heart failure 0.96 [0.91, 1.01] (P = 0.15). Combination therapy is not inferior for mortality secondary to cardiovascular cause and heart failure. Although the combination therapy is shown to reduce hospitalization secondary to heart failure. There are more side effects with the use of combination therapy and should be used with caution.
肺静脈周囲隔離:本アブレーション法は,AF患者の洞調律維持に十分か?
Authors: Fuke Etsuko, Naitoh Shigeto, Kumagai Koji, Tsukada Naofumi, Nishiuchi Suguru, Matsuhashi Noritaka, Hayashi Tatsuya, Satoh Chizuru, Miki Yuko, Goto Koji, Sakamoto Tamotsu, Kaseno Kenichi, Nakamura Keijiro, Fukazawa Rie, Ohshima Shigeru, Taniguchi Koichi
Journal: Circulation (2011)
Investigating hierarchical and ensemble classification approaches to mitigate the negative effect of varying stress state on EEG-based detection of mental workload level - and vice versa
Authors: Mahsa Bagheri, Sarah D. Power
Journal: Brain-Computer Interfaces (2021)

Studies on EEG-based mental workload detection generally consider workload exclusively in terms of task demands, as manipulated through the variation of task difficulty. However, mental workload cannot be estimated precisely with the properties of the task alone because different aspects of the user's state could affect the mental effort needed to perform the task. We argue that affective states, specifically stress/anxiety, is of particular relevance. Thus, the overall objective of this work is to develop a passive brain–computer interface that detects mental workload and affective state simultaneously. Recently, we found that variation in affective state negatively affects EEG-based classification of mental workload, and vice versa. Thus, such variation should be explicitly considered when developing detection algorithms for use in real-world applications. Here, we investigated five classification approaches for detecting mental workload and affective state which explicitly consider variation in the other state. Significant improvements in classification accuracy were achieved.
Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination
Authors: Mark M. Painter, Divij Mathew, Rishi R. Goel, Sokratis A. Apostolidis, Ajinkya Pattekar, Oliva Kuthuru, Amy E. Baxter, Ramin S. Herati, Derek A. Oldridge, Sigrid Gouma, Philip Hicks, Sarah Dysinger, Kendall A. Lundgreen, Leticia Kuri-Cervantes, Sharon Adamski, Amanda Hicks, Scott Korte, Josephine R. Giles, Madison E. Weirick, Christopher M. McAllister, Jeanette Dougherty, Sherea Long, Kurt D’Andrea, Jacob T. Hamilton, Michael R. Betts, Paul Bates, Scott E. Hensley, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Allison R. Greenplate, E. John Wherry
Journal: Immunity (2021)
The Pediatric Precision Oncology INFORM Registry: Clinical Outcome and Benefit for Patients with Very High-Evidence Targets
Authors: Cornelis M. van Tilburg, Elke Pfaff, Kristian W. Pajtler, Karin P.S. Langenberg, Petra Fiesel, Barbara C. Jones, Gnana Prakash Balasubramanian, Sebastian Stark, Pascal D. Johann, Mirjam Blattner-Johnson, Kathrin Schramm, Nicola Dikow, Steffen Hirsch, Christian Sutter, Kerstin Grund, Arend von Stackelberg, Andreas E. Kulozik, Andrej Lissat, Arndt Borkhardt, Roland Meisel, Dirk Reinhardt, Jan-Henning Klusmann, Gudrun Fleischhack, Stephan Tippelt, Dietrich von Schweinitz, Irene Schmid, Christof M. Kramm, André O. von Bueren, Gabriele Calaminus, Peter Vorwerk, Norbert Graf, Frank Westermann, Matthias Fischer, Angelika Eggert, Birgit Burkhardt, Wilhelm Wößmann, Michaela Nathrath, Stefanie Hecker-Nolting, Michael C. Frühwald, Dominik T. Schneider, Ines B. Brecht, Petra Ketteler, Simone Fulda, Ewa Koscielniak, Michael T. Meister, Monika Scheer, Simone Hettmer, Matthias Schwab, Roman Tremmel, Ingrid Øra, Caroline Hutter, Nicolas U. Gerber, Olli Lohi, Bernarda Kazanowska, Antonis Kattamis, Maria Filippidou, Bianca Goemans, C. Michel Zwaan, Till Milde, Natalie Jäger, Stephan Wolf, David Reuss, Felix Sahm, Andreas von Deimling, Uta Dirksen, Angelika Freitag, Ruth Witt, Peter Lichter, Annette Kopp-Schneider, David T.W. Jones, Jan J. Molenaar, David Capper, Stefan M. Pfister, Olaf Witt
Journal: Cancer Discovery (2021)

Abstract INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days [95% confidence interval (CI), 99–not applicable], compared with 117 days (95% CI, 106–143; P = 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases. Significance: The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes. See related commentary by Eggermont et al., p. 2677 . This article is highlighted in the In This Issue feature, p. 2659
Biochemical and Pharmacological Differentiation of APC and Recombinant Thrombomodulin with Reference to the Effect on the Hemostatic and Fibrinolytic Processes
Authors: Jawed Fareed, Debra Hoppensteadt, Walter Jeske, Omer Iqbal, Schuharazad Abro, Destini Clarizio, Sanchayana Raghuvir, Rachael Wasmund, Kosuke Tanaka, Kazuhisa Tsuruta
Journal: Blood (2017)
P-210 Capecitabine and temozolomide for metastatic neuroendocrine neoplasms: A single-center “real-word” data analysis
Authors: A. Caetano, J. Monteiro, A. Elvas, C. Costa, F. Salgueiro, M. Pires, J. Couto, R. Martins, F. Rodrigues, J. Ribeiro
Journal: Annals of Oncology (2021)
Psyllium reduces inulin-induced colonic gas production in IBS: MRI and<i>in vitro</i>fermentation studies
Authors: David Gunn, Zainab Abbas, Hannah C Harris, Giles Major, Caroline Hoad, Penny Gowland, Luca Marciani, Samantha K Gill, Fred J Warren, Megan Rossi, Jose Maria Remes-Troche, Kevin Whelan, Robin C Spiller
Journal: Gut (2021)

Objective Health-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production. Design A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. Results Colonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC (0–360 min) 3145 (848–6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62–2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC (0–360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC (0–360 min) from 7230 (3255–17910) ppm·hour to 1035 (360–4320) ppm·hour, p=0.007. Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. Conclusions Psyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study. Trial registration number NCT03265002 .
The polycomb group protein EZH2 impairs DNA repair in breast epithelial cells
Authors: Michael G. Zeidler, Sooryanayana Varambally, Qi Cao, Arul M. Chinnaiyan, David O. Ferguson, Sofia D. Merajver, Celina G. Kleer
Journal: Cancer Research (2006)

1064  The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive and metastatic breast cancer. Here we report that EZH2 decreases the expression of five RAD51 paralog proteins involved in homologous recombination repair (HR) of DNA double strand breaks (DSB): RAD51B/RAD51L1, RAD51C/RAD51L2, RAD51D/RAD51L3, XRCC2 and XRCC3, but did not affect the levels of DMC1 a gene which only functions in meiosis. EZH2 overexpression impaired the formation of RAD51 repair foci at sites of DNA breaks. Overexpression of EZH2 resulted in decreased cell survival and clonogenic capacity following DNA damage induced independently by etoposide and ionizing radiation. We suggest that EZH2 may contribute to breast tumorigenesis by specific down-regulation of RAD51-like proteins and impairment of HR repair. We provide mechanistic insights into the function of EZH2 in mammalian cells and uncover a link between EZH2, a regulator of homeotic gene expression, and HR DNA repair. Our study paves the way to explore blockade of EZH2 overexpression as a novel approach for prevention and treatment of breast cancer.
Autophagy in healthy aging and disease
Authors: Yahyah Aman, Tomas Schmauck-Medina, Malene Hansen, Richard I. Morimoto, Anna Katharina Simon, Ivana Bjedov, Konstantinos Palikaras, Anne Simonsen, Terje Johansen, Nektarios Tavernarakis, David C. Rubinsztein, Linda Partridge, Guido Kroemer, John Labbadia, Evandro F. Fang
Journal: Nature Aging (2021)
The Complementarity of Public Health and Medicine — Achieving “the Highest Attainable Standard of Health”
Authors: David J Hunter
Journal: New England Journal of Medicine (2021)

Interview with Dr. David Hunter on the complementary approaches and achievements of public health and clinical medicine. (09:21)Download The approaches and achievements of public health and clinical medicine are often framed as dichotomies — “prevention versus cure” or “individual versus population health.” But the two fields are complementary, as their practitioners are increasingly recognizing.
27482 Efficacy of ruxolitinib cream among patients with atopic dermatitis based on previous medication history: Pooled results from two phase 3 studies
Authors: Andrew Blauvelt, Lawrence F. Eichenfield, Michael E. Kuligowski, May E. Venturanza, Kang Sun, Jonathan I. Silverberg
Journal: Journal of the American Academy of Dermatology (2021)
Harnessing electronic health records to study emerging environmental disasters: a proof of concept with perfluoroalkyl substances (PFAS)
Authors: Mary Regina Boland, Lena M. Davidson, Silvia P. Canelón, Jessica Meeker, Trevor Penning, John H. Holmes, Jason H. Moore
Journal: npj Digital Medicine (2021)

Environmental disasters are anthropogenic catastrophic events that affect health. Famous disasters include the Seveso disaster and the Fukushima-Daiichi nuclear meltdown, which had disastrous health consequences. Traditional methods for studying environmental disasters are costly and time-intensive. We propose the use of electronic health records (EHR) and informatics methods to study the health effects of emergent environmental disasters in a cost-effective manner. An emergent environmental disaster is exposure to perfluoroalkyl substances (PFAS) in the Philadelphia area. Penn Medicine (PennMed) comprises multiple hospitals and facilities within the Philadelphia Metropolitan area, including over three thousand PFAS-exposed women living in one of the highest PFAS exposure areas nationwide. We developed a high-throughput method that utilizes only EHR data to evaluate the disease risk in this heavily exposed population. We replicated all five disease/conditions implicated by PFAS exposure, including hypercholesterolemia, thyroid disease, proteinuria, kidney disease and colitis, either directly or via closely related diagnoses. Using EHRs coupled with informatics enables the health impacts of environmental disasters to be more easily studied in large cohorts versus traditional methods that rely on interviews and expensive serum-based testing. By reducing cost and increasing the diversity of individuals included in studies, we can overcome many of the hurdles faced by previous studies, including a lack of racial and ethnic diversity. This proof-of-concept study confirms that EHRs can be used to study human health and disease impacts of environmental disasters and produces equivalent disease-exposure knowledge to prospective epidemiology studies while remaining cost-effective.
Immune checkpoint blockade sensitivity and progression-free survival associates with baseline CD8 <sup>+</sup> T cell clone size and cytotoxicity
Authors: Robert A. Watson, Orion Tong, Rosalin Cooper, Chelsea A. Taylor, Piyush K. Sharma, Alba Verge de los Aires, Elise A. Mahé, Hélène Ruffieux, Isar Nassiri, Mark R. Middleton, Benjamin P. Fairfax
Journal: Science Immunology (2021)

The antitumor action of immune checkpoint blockade (ICB) is primarily mediated by CD8+ T cells. How sensitivity to ICB varies across CD8+ T cell subsets and clonotypes and the relationship of these with clinical outcome is unclear. To explore this, we used single-cell V(D)J and RNA-sequencing to track gene expression changes elicited by ICB across individual peripheral CD8+ T cell clones, identify baseline markers of CD8+ T cell clonal sensitivity, and chart how CD8+ T cell transcriptional changes vary according to phenotypic subset and clonal size. We identified seven subsets of CD8+ T cells with divergent reactivity to ICB and found that the cytotoxic effector subset showed the greatest number of differentially expressed genes while remaining stable in clonal size after ICB. At the level of CD8+ T cell clonotypes, we found a relationship between transcriptional changes and clone size, with large clones showing a greater number of differentially regulated genes enriched for pathways including T cell receptor (TCR) signaling. Cytotoxic CD8+ effector clones were more likely to persist following ICB and were more likely to correspond with public tumor-infiltrating lymphocyte clonotypes. Last, we demonstrated that individuals whose CD8+ T cell pretreatment showed low cytotoxicity and had fewer expanded clones typically had worse outcomes after ICB treatment. This work further advances understanding of the molecular determinants of ICB response, assisting in the search for peripheral prognostic biomarkers and highlighting the importance of the baseline CD8+ immune landscape in determining ICB response in metastatic melanoma.
Retrospective Concomitant Nonrandomized Comparison of “Touch” Cautery Versus Athermal Dissection of the Prostatic Vascular Pedicles and Neurovascular Bundles During Robot-assisted Radical Prostatectomy
Authors: Martin Hofmann, Erica Huang, Linda My Huynh, Kamaljot Kaler, Simone Vernez, Adam Gordon, Blanca Morales, Douglas Skarecky, Thomas E. Ahlering
Journal: European Urology (2021)
Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis
Authors: Zewen Jiang, Meng Zhao, Laetitia Voilquin, Yunshin Jung, Mari A. Aikio, Tanushi Sahai, Florence Y. Dou, Alexander M. Roche, Ivan Carcamo-Orive, Joshua W. Knowles, Martin Wabitsch, Eric A. Appel, Caitlin L. Maikawa, Joao Paulo Camporez, Gerald I. Shulman, Linus Tsai, Evan D. Rosen, Christopher D. Gardner, Bruce M. Spiegelman, Katrin J. Svensson
Journal: Cell Metabolism (2021)
X-Waiver Exemption in the Treatment of Opioid Use Disorder—Reply
Authors: Melissa B. Weimer, Sarah E. Wakeman, Richard Saitz
Journal: JAMA (2021)

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A 5-year retrospective review of skin adnexal tumours received at a tertiary dermatopathology service: implications for linked genetic diagnoses
Authors: S. Cook, D. Bajwa, L. Hollestein, A. Husain, N. Rajan
Journal: British Journal of Dermatology (2021)

Summary Background Skin adnexal tumours (SATs) comprise a diverse range of neoplasms, which are difficult to diagnose clinically. They present in paediatric and adult populations, and may be indicative of an underlying genetic syndrome. There is a lack of recent data on the presentation of these tumours in clinical practice in European populations. Objectives To characterize the clinical and pathological features of SATs received at a single tertiary centre over a 5-year period. Methods A retrospective health record audit of SATs received at the Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, during the period November 2012 to October 2017 was performed. Results In total, 107 144 skin cases were received during the audit period. A total of 1615 cases of SATs from 1359 patients were included; 1570 (97·2%) were benign and 45 (2·8%) were malignant. Overall, the average age at presentation was 55 years (range 11 months to 97 years) and the male to female ratio was 0·77 : 1. Sweat gland and hair follicle SATs were most frequently excised; in adults, the most frequent tumour was hidrocystoma, and in children, pilomatrixoma occurred most often. Prebiopsy diagnosis was correct in 28% of cases. Benign SATs are often markers of an associated genetic condition, which warrants improved discrimination of sporadic from genetically related SATs. Conclusions SATs are difficult to diagnose clinically, and clinicopathological correlation may help enhance discrimination of genetically related SATs from sporadic cases. These data have implications for clinical and dermatopathological training provision, the development of reporting standards, and genetic assessment of selected patients.
BMA is to survey trainees over industrial action for exclusion from pay award
Authors: Abi Rimmer
Journal: BMJ (2021)

Junior doctors in England will be surveyed on whether they wish to consider any form of action over the government’s decision to exclude them from a 3% pay rise for NHS staff, the BMA has said.

In 2019 the BMA agreed improvements to the 2016 junior doctor contract in England, …
Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma
Authors: Areeg Elmusrati, Justin Wang, Cun-Yu Wang
Journal: International Journal of Oral Science (2021)

Abstract Head and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.