tbuckley/cabot-search huggingface dataset:
Abstract 13002: Sociodemographic Disparities in Awareness of Heart Attack Symptoms in the United States
Authors: Shiwani Mahajan, Javier Valero Elizondo, Rohan Khera, Nihar R Desai, Ron Blankstein, Michael J Blaha, Salim S Virani, Bita A Kash, Harlan M Krumholz, Khurram Nasir
Journal: Circulation (2019)

Introduction: Prompt recognition of myocardial infarction symptoms is critical for timely access to lifesaving emergency cardiac care. To target public health education efforts, it is important to ...
Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder
Authors: Takashi Yamamura, Ingo Kleiter, Kazuo Fujihara, Jacqueline Palace, Benjamin Greenberg, Beata Zakrzewska-Pniewska, Francesco Patti, Ching-Piao Tsai, Albert Saiz, Hayato Yamazaki, Yuichi Kawata, Padraig Wright, Jerome De Seze
Journal: New England Journal of Medicine (2019)

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear.In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed.A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups.Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).
Differences in expression and function of LEF1 isoforms in normal versus leukemic hematopoiesis
Authors: Kristin Feder, Katrin Edmaier-Schröger, Vijay P. S. Rawat, Nicole Kirsten, Klaus Metzeler, Johann M. Kraus, Konstanze Döhner, Hartmut Döhner, Hans A. Kestler, Michaela Feuring-Buske, Christian Buske
Journal: Leukemia (2019)
The renaissance of the tumor infiltrating B lymphocytes. The proof of principle: Novel ganglioside antigen recognizing capacity of B cells in breast carcinomas
Authors: Feng Wang-Johanning, Pramod N. Nehete, Kiera Rycaj, Janice Treit, Gary L. Johanning, K. Jagannadha Sastry
Journal: Cancer Research (2005)

5128  Despite the great efforts and achievements in cancer diagnostics and therapy, the main problems are not solved. To obtain tumorspecific antibodies is one of the basic questions. Our hypothesis was, that the tumor tissue itself is a potential source for building tumorspecific antibody fragments by the advantages of antibody engineering. As an experimental system we used human medullary breast carcinoma, where the heavy B lymphocytic infiltration paralleled to a better prognosis. Furtherly other types of breast carcinomas were tested for tumor binder immunoglobulins from the B cells accumulated in the tumor tissue. Detailed immunoglobulin repertore DNA sequence analysis was performed on the rearranged variable region VH-JH, Vκ-Jκ and Vλ-Jλ genes, amplified by RT-PCR of the infiltrating B cells. Combinatorial single chain Fv (scFv) antibody fragment mini-libraries were constructed out of randomly selected VH and Vκ aswell as VH and Vλ clones and tested for binding activity by phage display. Our data analysis revealed among the overrrepresented clusters ganglioside D3 (GD3) binder VH-JH and ganglioside M3 (GM3) Vκ-Jκ region sequences. We selected ScFvK clones that bind ganglioside GD3 on invasive breast carcinoma and medullary breast carcinoma out of the mini-library. Tumor specific binding was tested against membrane fractions of breast tumor cells (TU1, TU2) and other cell lines (MDA-MB 231, SKBR-3, MCF-7, SK-Mel-28, PANC-1, LS174T, COS) in ELISA and immunofluorescence by FACS analysis and confocal laser microscopy. Thin layer chromatography and dot blot experiments with purified gangliosides and different cell membrane fractions served to characterize further the target ganglioside antigen. Tumor infiltrating B cells of other solid tumor tissue origin (neuroblastoma) were tested for ganglioside GD2 binder antibodies. We conlude, that our results serve as ,,proof of principle“ concerning B cells’ capacity to reveal key cancer related antigens, such as gangliosides. Analysis of tumor associated gangliosides may aid the characterization of tumor cells and their degree of malignant transformation. The GD3 / GD2 specific antibodies influence tumor cell progression and are candidates for new tumor diagnostic and therapeutic immunoconjugates. Acknowledgement: Supported by NATO CLG 978639, OTKA T030380 and Rajko Medenica Research Foundation
Therapeutic Potential of the miRNA–ATM Axis in the Management of Tumor Radioresistance
Authors: Abdol-Hossein Rezaeian, Hashem Khanbabaei, George A. Calin
Journal: Cancer Research (2019)

The ataxia-telangiectasia mutated (ATM) protein kinase is widely known for its function as a chief mobilizer of the DNA damage response (DDR) upon DNA double-strand breaks. ATM orchestrates the DDR by modulating the expression of various miRNAs through several mechanisms. On the other hand, a set of miRNAs contribute to tight regulation of ATM by directly targeting the 3'-untranslated region of ATM mRNA. This review addresses the therapeutic application and molecular mechanisms that underlie the intricate interactions between miRNAs and ATM. It also describes therapeutic delivery of miRNAs in different environments such as hypoxic tumor microenvironments.
Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host
Authors: Jun Seishima, Noriho Iida, Kazuya Kitamura, Masahiro Yutani, Ziyu Wang, Akihiro Seki, Taro Yamashita, Yoshio Sakai, Masao Honda, Tatsuya Yamashita, Takashi Kagaya, Yukihiro Shirota, Yukako Fujinaga, Eishiro Mizukoshi, Shuichi Kaneko
Journal: Genome biology (2019)

Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level.We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn's disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10-/- mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients.E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.
Exercise schemes lead to small health improvements but impact is still unclear, claims study
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Exercise referral schemes lead to small improvements in patient health, but the size of these changes are not “clinically meaningful,” a study has claimed.1

A team of researchers measured health outcomes in patients before and after they took part in an exercise scheme, and found that while most of the outcomes showed statistically significant improvements, their impact was “unclear.”

However, they recommended that rather than ending these schemes, they should be overhauled to “maximise their potential,” as the benefits of exercise on health are known and the schemes already have considerable …
Th1/2 Immune Response Signature Predicts Outcome after Dose-Dense Immunochemotherapy in Patients with High Risk Diffuse Large B-Cell Lymphoma - Results from Nordic Lymphoma Group Trials
Authors: Matias Autio, Suvi-Katri Leivonen, Judit Meszaros Jorgensen, Marja-Liisa Karjalainen-Lindsberg, Klaus Beiske, Harald Holte, Sirpa Leppä
Journal: Blood (2017)
High-Throughput, Contact-Free Detection of Atrial Fibrillation From Video With Deep Learning
Authors: Bryan P. Yan, William H. S. Lai, Christy K. Y. Chan, Alex C. K. Au, Ben Freedman, Yukkee C. Poh, Ming-Zher Poh
Journal: JAMA Cardiology (2019)

High-Throughput, Contact-Free Detection of Atrial Fibrillation From Video With Deep Learning Approaches for atrial fibrillation (AF) detection can screen only 1 patient at a time. 1 In 2018, 2 we demonstrated a novel method of AF detection by analyzing facial photoplethysmographic (FPPG) signals without physical contact using a smartphone camera. 2 In this proof-ofconcept study, we prospectively evaluated the feasibility of high-throughput AF detection by analyzing FPPG signals 3 from multiple patients concurrently using a single digital cam-era and a pretrained deep convolutional neural network (DCNN). 4Methods | After institutional approval from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee and individual written informed consent, 20 patients (mean [SD] age, 76.6 [7.6] years; 12 men [60%]) with permanent AF and 24 control individuals (mean [SD] age, 56.8 [20.2] years; 14 men [58.3%]) in sinus rhythm (SR) were recruited.A digital camera (50D; Canon) was used to film 5 patients sitting in a row 150 cm away (Figure).We recorded 64 videos (1-minute duration, 24 FPS), each capturing 5 patients simultaneously in 32 different heart-rhythm A, Example video recording of 5 patients arranged in 1 of the 32 different heart rhythm permutations with extracted facial photoplethysmographic (FPPG) signals and reference electrocardiogram (ECG) traces.B, The 5-participant binary (atrial fibrillation [AF]/sinus rhythm [SR]) matrix.
Reply to Wang et al.
Authors: Yosuke Kataoka, Yosuke Tsuji, Kingo Hirasawa, Kengo Takimoto, Tomonori Wada, Satoshi Mochizuki, Ken Ohata, Yoshiki Sakaguchi, Keiko Niimi, Satoshi Ono, Shinya Kodashima, Nobutake Yamamichi, Mitsuhiro Fujishiro, Kazuhiko Koike
Journal: Endoscopy (2019)

See also: Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: a prospective multicenter randomized controlled trialEndoscopy 2019; 51(07): 619-627DOI: 10.1055/a-0860-5280 See also: Disputes about the efficacy of polyglycolic acid shielding for prevention of bleeding after endoscopic submucosal dissectionEndoscopy 2019; 51(12): 1183-1183DOI: 10.1055/a-0999-5452
Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice
Authors: Pei Wang, Xueyan Shao, Yifan Bao, Junjie Zhu, Liming Chen, Lirong Zhang, Xiaochao Ma, Xiao-bo Zhong
Journal: Acta Pharmaceutica Sinica B (2019)

The prevalence of obesity-associated conditions raises new challenges in clinical medication. Although altered expression of drug-metabolizing enzymes (DMEs) has been shown in obesity, the impacts of obese levels (overweight, obesity, and severe obesity) on the expression of DMEs have not been elucidated. Especially, limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children. Here, a high-fat diet (HFD) and three feeding durations were used to mimic different obese levels in C57BL/6 mice. The hepatic expression of five nuclear receptors (NRs) and nine DMEs was examined. In general, a trend of induced expression of NRs and DMEs (except for
Deregulating MYC in a model of HER2+ breast cancer mimics human intertumoral heterogeneity
Authors: Tyler Risom, Xiaoyan Wang, Juan Liang, Xiaoli Zhang, Carl Pelz, Lydia G. Campbell, Jenny Eng, Koei Chin, Caroline Farrington, Goutham Narla, Ellen M. Langer, Xiao-Xin Sun, Yulong Su, Colin J. Daniel, Mu-Shui Dai, Christiane V. Löhr, Rosalie C. Sears
Journal: Journal of Clinical Investigation (2019)

The c-MYC (MYC) oncoprotein is often overexpressed in human breast cancer; however, its role in driving disease phenotypes is poorly understood. Here, we investigate the role of MYC in HER2+ disease, examining the relationship between HER2 expression and MYC phosphorylation in HER2+ patient tumors and characterizing the functional effects of deregulating MYC expression in the murine NeuNT model of amplified-HER2 breast cancer. Deregulated MYC alone was not tumorigenic, but coexpression with NeuNT resulted in increased MYC Ser62 phosphorylation and accelerated tumorigenesis. The resulting tumors were metastatic and associated with decreased survival compared with NeuNT alone. MYC;NeuNT tumors had increased intertumoral heterogeneity including a subtype of tumors not observed in NeuNT tumors, which showed distinct metaplastic histology and worse survival. The distinct subtypes of MYC;NeuNT tumors match existing subtypes of amplified-HER2, estrogen receptor–negative human tumors by molecular expression, identifying the preclinical utility of this murine model to interrogate subtype-specific differences in amplified-HER2 breast cancer. We show that these subtypes have differential sensitivity to clinical HER2/EGFR–targeted therapeutics, but small-molecule activators of PP2A, the phosphatase that regulates MYC Ser62 phosphorylation, circumvents these subtype-specific differences and ubiquitously suppresses tumor growth, demonstrating the therapeutic utility of this approach in targeting deregulated MYC breast cancers.
JAK2V617F-Mediated Endothelial Dysfunction Promotes Congestive Heart Failure in a Murine Model of Myeloproliferative Neoplasm
Authors: Melissa Castiglione, Christopher Mazzeo, Ya-Ping Jiang, Juei-Suei Chen, Wei Yin, Richard Lin, Huichun Zhan
Journal: Blood (2019)
Identification of Cognitive Dysfunction in Patients with T2DM Using Whole Brain Functional Connectivity
Authors: Zhenyu Liu, Jiangang Liu, Huijuan Yuan, Taiyuan Liu, Xingwei Cui, Zhenchao Tang, Yang Du, Meiyun Wang, Yusong Lin, Jie Tian
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Majority of type 2 diabetes mellitus (T2DM) patients are highly susceptible to several forms of cognitive impairments, particularly dementia. However, the underlying neural mechanism of these cognitive impairments remains unclear. We aimed to investigate the correlation between whole brain resting state functional connections (RSFCs) and the cognitive status in 95 patients with T2DM. We constructed an elastic net model to estimate the Montreal Cognitive Assessment (MoCA) scores, which served as an index of the cognitive status of the patients, and to select the RSFCs for further prediction. Subsequently, we utilized a machine learning technique to evaluate the discriminative ability of the connectivity pattern associated with the selected RSFCs. The estimated and chronological MoCA scores were significantly correlated with R = 0.81 and the mean absolute error (MAE) = 1.20. Additionally, cognitive impairments of patients with T2DM can be identified using the RSFC pattern with classification accuracy of 90.54% and the area under the receiver operating characteristic (ROC) curve (AUC) of 0.9737. This connectivity pattern not only included the connections between regions within the default mode network (DMN), but also the functional connectivity between the task-positive networks and the DMN, as well as those within the task-positive networks. The results suggest that an RSFC pattern could be regarded as a potential biomarker to identify the cognitive status of patients with T2DM.
Bone and Joint Health Markers in Persons with Hemophilia A (PwHA) Treated with Emicizumab in HAVEN 3
Authors: Anna Kiialainen, Markus Niggli, Christine L. Kempton, Giancarlo Castaman, Tiffany Y. Chang, Ido Paz-Priel, Joanne I Adamkewicz, Gallia G. Levy
Journal: Blood (2019)
Clinical Outcomes Before and After Complete Everolimus-Eluting Bioresorbable Scaffold Resorption
Authors: Dean J. Kereiakes, Stephen G. Ellis, D. Christopher Metzger, Ronald P. Caputo, David G. Rizik, Paul S. Teirstein, Marc R. Litt, Annapoorna Kini, Ameer Kabour, Steven O. Marx, Jeffrey J. Popma, Siok Hwee Tan, Divine E. Ediebah, Charles Simonton, Gregg W. Stone
Journal: Circulation (2019)

Background: The Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) provides early drug delivery and mechanical support similar to those of metallic drug-eluting stents, followed by complete resorption in ≈3 years with recovery of vascular structure and function. The ABSORB III trial demonstrated noninferior rates of target lesion failure (cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year with BVS compared with cobalt chromium everolimus-eluting stents. Between 1 and 3 years and cumulative to 3 years, adverse event rates (particularly target vessel myocardial infarction and scaffold thrombosis) were increased after BVS. We sought to assess clinical outcomes after BVS through 5 years, including beyond the 3-year time point of complete scaffold resorption. Methods: Clinical outcomes from ABSORB III were analyzed by randomized device (intention to treat) cumulative to 5 years and between 3 and 5 years. Results: Rates of target lesion failure, target vessel myocardial infarction, and scaffold thrombosis were increased through the 5-year follow-up with BVS compared with everolimus-eluting stents. However, between 3 and 5 years, reductions in the relative hazards of the BVS compared with everolimus-eluting stents were observed, particularly for target lesion failure (hazard ratio, 0.83 [95% CI, 0.55–1.24] versus 1.35 [95% CI, 1.02–1.78]; P int =0.052) and scaffold thrombosis (hazard ratio, 0.26 [95% CI, 0.02–2.87] versus 3.23 [95% CI, 1.25–8.30]; P int =0.056) compared with the 0- to 3-year time period. Conclusions: In the ABSORB III trial, cumulative 5-year adverse event rates were increased after BVS compared with everolimus-eluting stents. However, the period of excess risk for BVS ended at 3 years, coincident with complete scaffold resorption. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01751906.
Varying Estimations of Surgical Work Value Units
Authors: Francis C. Nichols, Stephen J. Lahey, James M. Levett
Journal: JAMA Surgery (2019)

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Does telephone-delivered exercise advice and support by physiotherapists improve pain and/or function in people with knee osteoarthritis? Telecare randomised controlled trial
Authors: Rana S Hinman, Penny K Campbell, Belinda J Lawford, Andrew M Briggs, Janette Gale, Caroline Bills, Jessica Kasza, Anthony Harris, Simon D French, Stephen J Bunker, Andrew Forbes, Kim L Bennell
Journal: British Journal of Sports Medicine (2019)

Objective Evaluate a physiotherapist-led telephone-delivered exercise advice and support intervention for people with knee osteoarthritis. Methods Participant-blinded, assessor-blinded randomised controlled trial. 175 people were randomly allocated to (1) existing telephone service (≥1 nurse consultation for self-management advice) or (2) exercise advice and support (5–10 consultations with a physiotherapist trained in behaviour change for a personalised strengthening and physical activity programme) plus the existing service. Primary outcomes were overall knee pain (Numerical Rating Scale, range 0–10) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, range 0–68) at 6 months. Secondary outcomes, cost-effectiveness and 12-month follow-up were included. Results 165 (94%) and 158 (90%) participants were retained at 6 and 12 months, respectively. At 6 months, exercise advice and support resulted in greater improvement in function (mean difference 4.7 (95% CI 1.0 to 8.4)), but not overall pain (0.7, 0.0 to 1.4). Eight of 14 secondary outcomes favoured exercise advice and support at 6 months, including pain on daily activities, walking pain, pain self-efficacy, global improvements across multiple domains (overall improvement, improved pain, improved function and improved physical activity) and satisfaction. By 12 months, most outcomes were similar between groups. Exercise advice and support cost $A514/participant and did not save other health service resources. Conclusion Telephone-delivered physiotherapist-led exercise advice and support modestly improved physical function but not the co-primary outcome of knee pain at 6 months. Functional benefits were not sustained at 12 months. The clinical significance of this effect is uncertain. Trial registration number Australian New Zealand Clinical Trials Registry (#12616000054415).