tbuckley/cabot-search huggingface dataset:
Kidney-on-a-chip: untapped opportunities
Authors: Nureddin Ashammakhi, Katherine Wesseling-Perry, Anwarul Hasan, Elmahdi Elkhammas, Yu Shrike Zhang
Journal: Kidney International (2018)

The organs-on-a-chip technology has shown strong promise in mimicking the complexity of native tissues in vitro and ex vivo, and recently significant advances have been made in applying this technology to studies of the kidney and its diseases. Individual components of the nephron, including the glomerulus, proximal tubule, and distal tubule/medullary collecting duct, have been successfully mimicked using organs-on-a-chip technology and yielding strong promises in advancing the field of ex vivo drug toxicity testing and augmenting renal replacement therapies. Although these models show promise over 2-dimensional cell systems in recapitulating important nephron features in vitro, nephron functions, such as tubular secretion, intracellular metabolism, and renin and vitamin D production, as well as prostaglandin synthesis are still poorly recapitulated in on-chip models. Moreover, construction of multiple-renal-components-on-a-chip models, in which various structures and cells of the renal system interact with each other, has remained a challenge. Overall, on-chip models show promise in advancing models of normal and pathological renal physiology, in predicting nephrotoxicity, and in advancing treatment of chronic kidney diseases.
A phase III study of nivolumab (nivo) in previously treated advanced gastric or gastric esophageal junction (G/GEJ) cancer (ATTRACTION-2): Two-years update data
Authors: T. Satoh, L.-T. Chen, Y.-K. Kang, Y. Chao, K. Kato, H.C. Chung, J.-S. Chen, K. Muro, W.K. Kang, T. Yoshikawa, S.C. Oh, T. Tamura, K.-W. Lee, N. Boku
Journal: Annals of Oncology (2018)
IL-33 drives influenza-induced asthma exacerbations by halting innate and adaptive antiviral immunity
Authors: Lara Ravanetti, Annemiek Dijkhuis, Tamara Dekker, Yanaika S. Sabogal Pineros, Abilash Ravi, Barbara S. Dierdorp, Jonas S. Erjefält, Michiko Mori, Stelios Pavlidis, Ian M. Adcock, Navin L. Rao, René Lutter
Journal: Journal of Allergy and Clinical Immunology (2018)
Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer
Authors: P. Cottu, V. D'Hondt, S. Dureau, F. Lerebours, I. Desmoulins, P.-E. Heudel, F.P. Duhoux, C. Levy, M.-A. Mouret-Reynier, F. Dalenc, J.-S. Frenel, C. Jouannaud, L. Venat-Bouvet, S. Nguyen, J.-M. Ferrero, J.-L. Canon, J. Grenier, C. Callens, D. Gentien, J. Lemonnier, A. Vincent-Salomon, S. Delaloge
Journal: Annals of Oncology (2018)

BackgroundPalbociclib is a CDK4/6 inhibitor with demonstrated efficacy and safety in combination with endocrine therapy in advanced luminal breast cancer (LBC). We evaluated the respective efficacy and safety of chemotherapy and letrozole–palbociclib (LETPAL) combination as neoadjuvant treatment in patients with high-risk LBC.Patients and methodsNeoPAL (UCBG10/4, NCT02400567) is a randomised, parallel, non-comparative phase II study. Patients with ER-positive, HER2-negative, Prosigna®-defined luminal B, or luminal A and node-positive, stage II–III breast cancer, not candidate for breast-conserving surgery, were randomly assigned to either letrozole (2.5 mg daily) and palbociclib (125 mg daily, 3 weeks/4) during 19 weeks, or to FEC100 (5FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2)×3 21-day courses followed by docetaxel 100 mg/m2×3 21-day courses. Primary end point was residual cancer burden (RCB 0–I rate). Secondary end points included clinical response, proliferation-based markers, and safety.ResultsOverall, 106 patients were randomised [median Prosigna® ROR Score 71 (22–93)]. RCB 0–I was observed in four and eight patients in LETPAL [7.7% (95% CI 0.4–14.9)] and chemotherapy [15.7% (95% CI 5.7–25.7)] arms, respectively. Pathological complete response rates were 3.8% and 5.9%. Clinical response (75%) and breast-conserving surgery rates (69%) were similar in both arms. Preoperative Endocrine Prognostic Index 0 scores (breast cancer-specific survival) were observed in 17.6% and 8.0% of patients in LETPAL and chemotherapy arms, respectively. Safety profile was as expected, with 2 versus 17 serious adverse events (including 11 grade 4 serious AEs in the chemotherapy arm).ConclusionLETPAL combination was associated with poor pathological response but encouraging clinical and biomarker responses in Prosigna®-defined high-risk LBC. Contemporary chemotherapy regimen was associated with poor pathological and biomarker responses, with a much less favourable safety profile. LETPAL combination might represent an alternative to chemotherapy in early high-risk LBC.Clinical Trial NumberNCT02400567.
GW29-e1572 Ginsenoside Rb1 Ameliorates Autophagy of Hypoxia Cardiomyocytes from Neonatal Rats via AMP-Activated Protein Kinase Pathway
Authors: Shengnan Dai, Shumei Zhao, Xiaoming Chen, Huating Huang, Bohan Chen, Hongliang Kong, Aijie Hou
Journal: Journal of the American College of Cardiology (2018)
Abstract P224: The Association of Surgical versus Natural Menopause with Future Left Ventricular Structure and Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Duke Appiah, Pamela J Schreiner, Chike C Nwabuo, Melissa F Wellons, Cora E Lewis, Joao A Lima
Journal: Circulation (2016)

Introduction: The association of surgical and natural menopause (SM and NM, respectively) with CVD outcomes is controversial. We assessed the hypothesis that CVD risk factor levels antecedent to menopause explain differences in future left ventricular (LV) structure and function parameters rather than type of menopause. Methods: We studied 825 premenopausal women (49% black) from the CARDIA study in 1990-1991 (baseline, mean age: 32 years) who later reached menopause by 2010-2011 and had echocardiographs at these two time points. Results: During 20 years of follow up, 508 women reached NM while 317 underwent SM (34% with bilateral oophorectomy). At baseline, women who later underwent SM were more likely to be black, younger, have higher mean values of systolic blood pressure, body mass index as well as lower mean HDL cholesterol, physical activity, parity and years of education. With the exception of race, no statistically significant differences were found by ovarian status among women with SM. In 1990-1991, no differences in LV structure and function were found between women who later reach NM or SM. In 2010-2011, women with SM had significantly higher LV mass, LV mass/volume ratio, E/e’ ratio, and impaired longitudinal and circumferential strain than women with NM (Table 1). No significant differences in these measures were found among SM by ovarian status. Controlling for baseline echocardiographic parameters, demographics, BMI, physical activity, parity, smoking, systolic blood pressure and age at menarche in linear regression models attenuated these differences between groups (Table 1). Further adjustment for age at menopause and hormone therapy use did not change these results. Conclusion: In this study, presurgical CVD risk factors among women with SM attenuated the adverse postsurgical measures of LV structure and function found among such women. These data suggest that premenopausal CVD risk factors rather than gynecologic surgery predispose women with SM to elevated future CVD risk.
The Severe Paediatric Asthma Collaborative in Europe (SPACE) ERS Clinical Research Collaboration: enhancing participation of children with asthma in therapeutic trials of new biologics and receptor blockers
Authors: Franca Rusconi, Ricardo M. Fernandes, Mariëlle W.H. Pijnenburg, Jonathan Grigg
Journal: European Respiratory Journal (2018)

<b>The Severe Paediatric Asthma Collaborative in Europe (SPACE) ERS Clinical Research Collaboration is devoted to describing phenotypes of children with severe asthma and to enhancing their participation in therapeutic trials of new drugs</b>http://ow.ly/zxgB30m01zR
Abstract 19086: Reducing Infarct Size by Protection of Ischemic Myocardium With Targeted Growth Factors
Authors: Henry H Chang, Yan Zhang, Timothy R Stowe, Kristopher M Kuchenbecker, Bjorn L Millard, Andrea D Nickerson, Birgit M Schoeberl, Ulrik B Nielson
Journal: Circulation (2016)

Introduction/Hypothesis: After AMI, patients suffer irreversible loss of heart function due to cardiomyocyte (CM) death and tissue scarring that may lead to heart failure. Growth factors can reduce...
PTMC (Percutaneous Transvenous Mitral Commissurotomy,経皮経静脈的僧帽弁交連裂開術)の最近の術式 : 僧帽弁膜症の治療 : 第56回日本循環器学会学術集会
Authors: 哲郎 不藤, 俊一 田巻, 出 中江, 達雄 藤岡, 茂 久保, 寛治 井上
Journal: Circulation (1993)
Prolonged Prothrombotic Effects of Antecedent Hypoglycemia in Individuals With Type 2 Diabetes
Authors: Elaine Chow, Ahmed Iqbal, Emma Walkinshaw, Fladia Phoenix, Ian A. Macdonald, Robert F. Storey, Ramzi Ajjan, Simon R. Heller
Journal: Diabetes Care (2018)

OBJECTIVE Hypoglycemia has been linked to persistent increases in cardiovascular (CV) mortality in type 2 diabetes after the event. Our aim was to examine acute and downstream effects of hypoglycemia on markers of thrombosis risk and inflammation in type 2 diabetes. RESEARCH DESIGN AND METHODS Twelve individuals with type 2 diabetes with no history of CV disease and 11 age- and BMI-matched volunteers without diabetes underwent paired hyperinsulinemic-euglycemic (glucose 6 mmol/L for two 60-min periods) and hypoglycemic (glucose 2.5 mmol/L for two 60-min periods) clamps on separate occasions on day 0. Fibrin clot properties, platelet reactivity, and inflammatory markers were measured at baseline, end of and after recovery from the initial clamp, day 1, and day 7 using validated assays and electron microscopy. RESULTS Euglycemic hyperinsulinemia reduced platelet reactivity, decreased fibrin clot density, and improved fibrinolytic efficiency in both groups. Platelet reactivity and aggregation increased during acute hypoglycemia in both groups, resolving at recovery. In type 2 diabetes, clot lysis times and clot maximum absorbance increased up to day 7 (P = 0.002 and 0.001 vs. euglycemia, respectively), but clots from control subjects without diabetes showed limited changes. Fibrin network density increased Δ 1.15 ± 0.28 fibers/μm2 at day 7 after the hypoglycemic clamp (P &amp;lt; 0.01 for glycemic arm), whereas fibrinogen and complement C3 increased after hypoglycemia up to day 7 in type 2 diabetes only. CONCLUSIONS Antecedent hypoglycemia has acute and persistent prothrombotic effects, lasting at least 7 days, that were enhanced in individuals with type 2 diabetes. These findings identify mechanisms by which hypoglycemia might increase short- and medium-term risk of CV mortality.
Abstract 19827: The Stk25 Kinase Promotes Cell Survival and Metabolism in Cardiac Progenitor Cells
Authors: Barry Fine, Ying Shih, Paolo Colombo, Gordana Vunjak-Novakovic
Journal: Circulation (2016)

Rationale and Objective: c-Kit positive cardiac progenitor cells (CPC’s) have the capacity for expansion ex vivo and promote cardiac repair when applied therapeutically. They also provide a means f...
Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Kohei Shitara, Toshihiko Doi, Mikhail Dvorkin, Wasat Mansoor, Hendrik-Tobias Arkenau, Aliaksandr Prokharau, Maria Alsina, Michele Ghidini, Catia Faustino, Vera Gorbunova, Edvard Zhavrid, Kazuhiro Nishikawa, Ayumu Hosokawa, Şuayib Yalçın, Kazumasa Fujitani, Giordano D Beretta, Eric Van Cutsem, Robert E Winkler, Lukas Makris, David H Ilson, Josep Tabernero
Journal: The Lancet Oncology (2018)
Venous Thromboembolism
Authors: Tobias Tritschler, Noémie Kraaijpoel, Grégoire Le Gal, Philip S. Wells
Journal: JAMA (2018)

<h3>Importance</h3> Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially fatal disease. <h3>Objective</h3> To summarize the advances in diagnosis and treatment of VTE of the past 5 years. <h3>Evidence Review</h3> A systematic search was conducted in EMBASE Classic, EMBASE, Ovid MEDLINE, and other nonindexed citations using broad terms for diagnosis and treatment of VTE to find systematic reviews and meta-analyses, randomized trials, and prospective cohort studies published between January 1, 2013, and July 31, 2018. The 10th edition of the American College of Chest Physicians Antithrombotic Therapy Guidelines was screened to identify additional studies. Screening of titles, abstracts, and, subsequently, full-text articles was performed in duplicate, as well as data extraction and risk-of-bias assessment of the included articles. <h3>Findings</h3> Thirty-two articles were included in this review. The application of an age-adjusted D-dimer threshold in patients with suspected PE has increased the number of patients in whom imaging can be withheld. The Pulmonary Embolism Rule-Out Criteria safely exclude PE when the pretest probability is low. The introduction of direct oral anticoagulants has allowed for a simplified treatment of VTE with a lower risk of bleeding regardless of etiology or extent of the VTE (except for massive PE) and has made extended secondary prevention more acceptable. Thrombolysis is best reserved for patients with massive PE or those with DVT and threatened limb loss. Insertion of inferior vena cava filters should be avoided unless anticoagulation is absolutely contraindicated in patients with recent acute VTE. Graduated compression stockings are no longer recommended to treat DVT but may be used when acute or chronic symptoms are present. Anticoagulation may no longer be indicated for patients with isolated distal DVT at low risk of recurrence. <h3>Conclusions and Relevance</h3> Over the past 5 years, substantial progress has been made in VTE management, allowing for diagnostic and therapeutic strategies tailored to individual patient characteristics, preferences, and values.
Level of Reconciliation Payments by Safety-Net Hospital Status Under the First Year of the Comprehensive Care for Joint Replacement Program
Authors: Hyunjee Kim, Jenny I. Grunditz, Thomas H. A. Meath, Ana R. Quiñones, Said A. Ibrahim, K. John McConnell
Journal: JAMA Surgery (2018)

This study uses data from the Comprehensive Care for Joint Replacement program to assess the level of Medicare reconciliation payments and examine these levels by hospital size and teaching hospital status to understand hospital performance.
Submucosal tunneling and septum myotomy as an endoscopic treatment for symptomatic epiphrenic diverticulum
Authors: Felipe Pimentel, Jérôme Rivory, Alexandru Lupu, Sabine Roman, François Mion, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2018)

Epiphrenic diverticulum is a rare disorder, with an incidence of 1/500 000, and is more usually related to esophageal motility disorders including achalasia [1].
GW29-e0741 The clock gene, brain and muscle Arnt-like 1, regulates NLRP3 inflammasome in diabetic cardiomyocyte pyroptosis
Authors: Bingyan Guo, Dafang DU, Xiaoyue Qin, Suyun Liu, Xin Jin, Yongjun Li
Journal: Journal of the American College of Cardiology (2018)
Long-Term Benefit of Empagliflozin on Life Expectancy in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease
Authors: Brian Claggett, John M. Lachin, Stefan Hantel, David Fitchett, Silvio E. Inzucchi, Hans J. Woerle, Jyothis T. George, Bernard Zinman
Journal: Circulation (2018)
Tenosynovial and Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release
Authors: Brett W. Sperry, Bryan A. Reyes, Asad Ikram, Joseph P. Donnelly, Dermot Phelan, Wael A. Jaber, David Shapiro, Peter J. Evans, Steven Maschke, Scott E. Kilpatrick, Carmela D. Tan, E. Rene Rodriguez, Cecilia Monteiro, W.H. Wilson Tang, Jeffery W. Kelly, William H. Seitz, Mazen Hanna
Journal: Journal of the American College of Cardiology (2018)
Characteristics of Opioid Prescriptions to Veterans With Cirrhosis
Authors: Shari S. Rogal, Lauren A. Beste, Ada Youk, Michael J. Fine, Bryan Ketterer, Hongwei Zhang, Steven Leipertz, Maggie Chartier, Chester B. Good, Kevin L. Kraemer, Matthew Chinman, Timothy Morgan, Walid F. Gellad
Journal: Clinical Gastroenterology and Hepatology (2018)
Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of “A+” Subtypes of Ketosis-Prone Diabetes
Authors: Surya N. Mulukutla, Maria Acevedo-Calado, Christiane S. Hampe, Massimo Pietropaolo, Ashok Balasubramanyam
Journal: Diabetes Care (2018)

OBJECTIVE Autoantibodies directed against tyrosine phosphatase IA-2 antibody (IA-2 Ab) are diagnostic for autoimmune type 1 diabetes. Conventional assays target the intracellular domain of IA-2. Among patients with ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA), &amp;gt;60% of adults lack three classic islet autoantibodies—IA-2, GAD65, and ZnT8 Abs—associated with type 1 diabetes. We aimed to determine whether apparently autoantibody-negative (“A−”) KPD patients possess occult IA-2 Ab directed against full-length IA-2 (IA-2FL) or its extracellular domain (IA-2EC). RESEARCH DESIGN AND METHODS We developed an assay that targets IA-2FL and IA-2EC and used it to analyze 288 subjects with A− KPD. RESULTS Ten A− KPD patients were positive for IA-2EC Ab (3.5%), and three were also positive for IA-2FL Ab (1.0%), similar to frequencies in type 1 and type 2 diabetes. CONCLUSIONS Measurement of IA-2FL Ab and IA-2EC Ab improves the accuracy of the Aβ classification of KPD patients.
Distinguishing Variant Pathogenicity From Genetic Diagnosis
Authors: Leslie G. Biesecker, Robert L. Nussbaum, Heidi L. Rehm
Journal: JAMA (2018)

This Genomics and Precision Health article explains the use of genomic testing in clinical settings when a genetic basis for disease is suspected, but the evaluation has not provided enough specificity to guide selection of a single gene test or a gene panel test.
Abstract 15870: Selective Nuclear CaMKII Activation and HDAC4 Export in Atrial Fibrillation
Authors: Xiao-Yan Qi, JieNing Xiao, Feng Xiong, Jonathan Melka, Yoshihiro Sobue, Qiang Hua, Dobromir Dobrev, Stanley Nattel
Journal: Circulation (2017)

Introduction: We have shown that atrial fibrillation (AF) alters atrial cardiomyocyte nucleoplasmic Ca2+ handling to increase nuclear Ca2+ load. Here, we studied the consequences for CaMKII signali...
Antibody-based Delivery of TNF to the Tumor Neovasculature Potentiates the Therapeutic Activity of a Peptide Anticancer Vaccine
Authors: Philipp Probst, Marco Stringhini, Danilo Ritz, Tim Fugmann, Dario Neri
Journal: Clinical Cancer Research (2018)

Abstract Purpose: There is a growing interest in the use of tumor antigens for therapeutic vaccination strategies. Unfortunately, in most cases, the use of peptide vaccines in patients does not mediate shrinkage of solid tumor masses. Experimental Design: Here, we studied the opportunity to boost peptide vaccination with F8-TNF, an antibody fusion protein that selectively delivers TNF to the tumor extracellular matrix. AH1, a model antigen to investigate CD8+ T-cell immunity in BALB/c mice, was used as vaccine. Results: Peptide antigens alone exhibited only a modest tumor growth inhibition. However, anticancer activity could be substantially increased by combination with F8-TNF. Analysis of T cells in tumors and in draining lymph nodes revealed a dramatic expansion of AH1-specific CD8+ T cells, which were strongly positive for PD-1, LAG-3, and TIM-3. The synergistic anticancer activity, observed in the combined use of peptide vaccination and F8-TNF, was largely due to the ability of the fusion protein to induce a rapid hemorrhagic necrosis in the tumor mass, thus leaving few residual tumor cells. While the cell surface phenotype of tumor-infiltrating CD8+ T cells did not substantially change upon treatment, the proportion of AH1-specific T cells was strongly increased in the combination therapy group, reaching more than 50% of the CD8+ T cells within the tumor mass. Conclusions: Because both peptide vaccination strategies and tumor-homing TNF fusion proteins are currently being studied in clinical trials, our study provides a rationale for the combination of these 2 regimens for the treatment of patients with cancer.
THU0673 Disease activity during and after pregnancy in women with psoriatic arthritis
Authors: K. Ursin, S. Lydersen, J. Skomsvoll, M. Wallenius
Journal: Annals of the Rheumatic Diseases (2018)

impairment"). 2 The dimensions of RAND-36 have scores between 0-100 (where 100="best possible health"). 3 Results: BASFI-scores were highest in third trimester, significantly higher than six weeks postpartum (mean BASFI 3.6 vs. 2.6, p<0.001).In line with this result, scores of RAND-36 physical functioning was significantly lower in third trimester compared to six weeks postpartum (mean physical function 54.5 vs. 71.0,p<0.001).The women reported considerable pain throughout the study period, with worst reported pain in second trimester, when scores of RAND-36 bodily pain were significantly lower than six weeks after postpartum (mean bodily pain 44.3 vs. 49.6,p=0.01).Scores of RAND-36 mental health were high and stable throughout the study period, with best reported mental health six weeks after delivery, when mental health was significantly better than in all time points in pregnancy.Abstract THU0672figure 1. shows changes in functionality and mental health from preconception to one year after delivery, and disease activity and CRP in the same time period.Conclusions: Even though women with axSpA reported considerable pain and gradually worsening of physical function in pregnancy, they experienced good and stable mental health from preconception to one year after delivery.