tbuckley/cabot-search huggingface dataset:
Nedaplatin Plus Docetaxel Versus Cisplatin Plus Docetaxel as First-Line Chemotherapy for Advanced Squamous Cell Carcinoma of the Lung — A Multicenter, Open-label, Randomized, Phase III Trial
Authors: Shun Lu, Zhiwei Chen, Chengping Hu, Jian Zhang, Yuan Chen, Yong Song, Qiong Zhao, Yun Fan, Gang Wu, Zhiyong Ma, Jian Fang, Qitao Yu, Zhe Liu
Journal: Journal of Thoracic Oncology (2018)
Meta-Analysis of Cell Therapy Studies in Heart Failure and Acute Myocardial Infarction
Authors: Mariann Gyöngyösi, Paul M. Haller, Derek J. Blake, Enca Martin Rendon
Journal: Circulation Research (2018)

Heart failure (HF) is one of the leading causes of death worldwide and has reached epidemic proportions in most industrialized nations. Despite major improvements in the treatment and management of the disease, the prognosis for patients with HF remains poor with approximately only half of patients surviving for 5 years or longer after diagnosis. The poor prognosis of HF patients is in part because of irreparable damage to cardiac tissue and concomitant maladaptive changes associated with the disease. Cell-based therapies may have the potential to transform the treatment and prognosis of HF through regeneration or repair of damaged cardiac tissue. Accordingly, numerous phase I and II randomized clinical trials have tested the clinical benefits of cell transplant, mostly autologous bone marrow–derived mononuclear cells, in patients with HF, ischemic heart disease, and acute myocardial infarction. Although many of these trials were relatively small, meta-analyses of cell-based therapies have attempted to apply rigorous statistical methodology to assess the potential clinical benefits of the intervention. As a prelude to larger phase III trials, meta-analyses, therefore, remain the obvious means of evaluating the available clinical evidence. Here, we review the different meta-analyses of randomized clinical trials that evaluate the safety and potential beneficial effect of cell therapies in HF and acute myocardial infarction spanning nearly 2 decades since the first pioneering trials were conducted.
The S100A4 Protein Signals through the ErbB4 Receptor to Promote Neuronal Survival
Authors: Stanislava Pankratova, Jorg Klingelhofer, Oksana Dmytriyeva, Sylwia Owczarek, Alexander Renziehausen, Nelofer Syed, Alexandra E. Porter, David T. Dexter, Darya Kiryushko
Journal: Theranostics (2018)

Understanding the mechanisms of neurodegeneration is crucial for development of therapies to treat neurological disorders.S100 proteins are extensively expressed in the injured brain but S100's role and signalling in neural cells remain elusive.We recently demonstrated that the S100A4 protein protects neurons in brain injury and designed S100A4-derived peptides mimicking its beneficial effects.Here we show that neuroprotection by S100A4 involves the growth factor family receptor ErbB4 and its ligand Neuregulin 1 (NRG), key regulators of neuronal plasticity and implicated in multiple brain pathologies.The neuroprotective effect of S100A4 depends on ErbB4 expression and the ErbB4 signalling partners ErbB2/Akt, and is reduced by functional blockade of NRG/ErbB4 in cell models of neurodegeneration.We also detect binding of S100A4 with ErbB1 (EGFR) and ErbB3.S100A4-derived peptides interact with, and signal through ErbB, are neuroprotective in primary and immortalized dopaminergic neurons, and do not affect cell proliferation/motility -features which make them promising as potential neuroprotectants.Our data suggest that the S100-ErbB axis may be an important mechanism regulating neuronal survival and plasticity.
Abstract 16476: Usefulness of Our New Patient Screening System by Using Functional Capacity Based on the Aha Guideline, for Non-cardiac Surgery Candidates
Authors: Seiichi Taniai, Mayumi Y Finger, Toru Satoh, Hideaki Yoshino
Journal: Circulation (2016)

Introduction: We developed a new cardiovascular screening system “Cardiac Preparative Screening (CPS)” which is used to evaluate the needs of cardiac consultant for the patients who are planned for...
Re: Angela Huttner, Arina Kowalczyk, Adi Turjeman, et al. Effect of 5-Day Nitrofurantoin vs Single-dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial. JAMA 2018;319:1781–9
Authors: Maxime Vallée, Franck Bruyère
Journal: European Urology (2018)
αv Integrins regulate germinal center B cell responses through noncanonical autophagy
Authors: Fiona Raso, Sara Sagadiev, Samuel Du, Emily Gage, Tanvi Arkatkar, Genita Metzler, Lynda M. Stuart, Mark T. Orr, David J. Rawlings, Shaun W. Jackson, Adam Lacy-Hulbert, Mridu Acharya
Journal: Journal of Clinical Investigation (2018)

Germinal centers (GCs) are major sites of clonal B cell expansion and generation of long-lived, high-affinity antibody responses to pathogens. Signaling through TLRs on B cells promotes many aspects of GC B cell responses, including affinity maturation, class switching, and differentiation into long-lived memory and plasma cells. A major challenge for effective vaccination is identifying strategies to specifically promote GC B cell responses. Here, we have identified a mechanism of regulation of GC B cell TLR signaling, mediated by αv integrins and noncanonical autophagy. Using B cell-specific αv-KO mice, we show that loss of αv-mediated TLR regulation increased GC B cell expansion, somatic hypermutation, class switching, and generation of long-lived plasma cells after immunization with virus-like particles (VLPs) or antigens associated with TLR ligand adjuvants. Furthermore, targeting αv-mediated regulation increased the magnitude and breadth of antibody responses to influenza virus vaccination. These data therefore identify a mechanism of regulation of GC B cells that can be targeted to enhance antibody responses to vaccination.
Abstract 16282: Telemedicine Application in the Care of Acute Myocardial Infarction Patients: Systematic Review and Meta-Analysis
Authors: Milena S Marcolino, Luciana M Maia, João A Oliveira, Diomildo F Andrade-Junior, Bruno L Pereira, Antonio L Ribeiro
Journal: Circulation (2016)

Introduction:  Telemedicine strategies have the potential to increase healthcare professionals’ adherence to the therapeutic measures established for acute myocardial infarction (MI), to improve MI care. However, the real impact of this intervention in clinical outcomes is still unknown or poorly documented. Our aim is to conduct a systematic review and meta-analysis of studies assessing the impact of telemedicine interventions combined with usual care compared to usual care alone on AMI mortality.   Methods:  Electronic databases MEDLINE, Cochrane Central Register of Controlled Trials, LILACS, BDENF, IBECs, Web of Science, Scopus and Google Scholar were searched to identify relevant studies published from Jan/2004 to May/2015. The search was supplemented by references from the selected articles. Study search and selection were performed by independent reviewers. Random effects model was applied to estimate the pooled results. Methodological quality of non-randomized studies was assessed by Newcastle Ottawa scale (NOS).   Results:  Of the 5.407 articles retrieved, 16 studies (8,945 patients) were included: 8 in Europe, 5 in North America, 2 in South America and 1 in Asia. No randomized controlled trial was identified; 13 studies were nonrandomized controlled, 3 historically controlled, and 1 quasi-experimental. Fourteen studies were in ST elevation MI patients, and in 14 studies the intervention involved prehospital ECG and transmission to the emergency physician or cardiologist of a percutaneous coronary intervention center. The studies were classified as moderate quality by NOS. Telemedicine was associated with a statistically significant reduction in in-hospital mortality (12 studies [n=6033], risk ratio [RR] 0.54 [CI 95% 0.46-0.64], I 2   2  23%, no evidence of publication bias) and one-year mortality (3 studies[n=1549], RR 0.47 [IC 95% 0.33-0.68], I 2     Conclusions:  Telemedicine strategies combined with the usual care for MI patients are associated with improved in-hospital, 30-day and one-year mortality.
Oropharyngeal Tularemia from Freshly Pressed Grape Must
Authors: Florian Burckhardt, Dietmar Hoffmann, Klaus Jahn, Klaus Heuner, Daniela Jacob, Manfred Vogt, Stefan Bent, Roland Grunow, Philipp Zanger
Journal: New England Journal of Medicine (2018)

Tularemia and Wine Must A cluster of tularemia cases emerged at a vineyard in Germany. A curious source was identified.
NEW DESIGN DOUBLE BARE OR DOUBLE COVERED STENTS FOR MALIGNANT COLORECTAL OBSTRUCTION: COMPARATIVE, PROSPECTIVE, PANDOMIZED, SINGLE CENTRE TRIAL
Authors: A Vodoleev, V Duvanskiy, D Kryazhev
Journal: Endoscopy (2018)

Endoscopic stenting for malignant colonic obstruction has advantages and disadvantages. One of the actual problems associated with colorectal stenting is the recurrence of symptoms of obstruction. The most common cause is migration of covered stents and ingrown of uncovered stents. The aim of our study was to compare the results of the use of stents of a new design.
CD28-ζ CAR T Cells Resist TGF-β Repression through IL-2 Signaling, Which Can Be Mimicked by an Engineered IL-7 Autocrine Loop
Authors: Viktória Golumba-Nagy, Johannes Kuehle, Andreas A. Hombach, Hinrich Abken
Journal: Molecular Therapy (2018)

Adoptive cell therapy with chimeric antigen receptor (CAR)-redirected T cells induced spectacular regressions of leukemia and lymphoma, however, failed so far in the treatment of solid tumors. A cause is thought to be T cell repression through TGF-β, which is massively accumulating in the tumor tissue. Here, we show that T cells with a CD28-ζ CAR, but not with a 4-1BB-ζ CAR, resist TGF-β-mediated repression. Mechanistically, LCK activation and consequently IL-2 release and autocrine IL-2 receptor signaling mediated TGF-β resistance; deleting the LCK-binding motif in the CD28 CAR abolished both IL-2 secretion and TGF-β resistance, while IL-2 add-back restored TGF-β resistance. Other γ-cytokines like IL-7 and IL-15 could replace IL-2 in this context. This is demonstrated by engineering IL-2 deficient CD28ΔLCK-ζ CAR T cells with a hybrid IL-7 receptor to provide IL-2R β chain signaling upon IL-7 binding. Such modified T cells showed improved CAR T cell activity against TGF-β+ tumors. Data draw the concept that an autocrine loop resulting in IL-2R signaling can make CAR T cells more potent in staying active against TGF-β+ solid tumors. Adoptive cell therapy with chimeric antigen receptor (CAR)-redirected T cells induced spectacular regressions of leukemia and lymphoma, however, failed so far in the treatment of solid tumors. A cause is thought to be T cell repression through TGF-β, which is massively accumulating in the tumor tissue. Here, we show that T cells with a CD28-ζ CAR, but not with a 4-1BB-ζ CAR, resist TGF-β-mediated repression. Mechanistically, LCK activation and consequently IL-2 release and autocrine IL-2 receptor signaling mediated TGF-β resistance; deleting the LCK-binding motif in the CD28 CAR abolished both IL-2 secretion and TGF-β resistance, while IL-2 add-back restored TGF-β resistance. Other γ-cytokines like IL-7 and IL-15 could replace IL-2 in this context. This is demonstrated by engineering IL-2 deficient CD28ΔLCK-ζ CAR T cells with a hybrid IL-7 receptor to provide IL-2R β chain signaling upon IL-7 binding. Such modified T cells showed improved CAR T cell activity against TGF-β+ tumors. Data draw the concept that an autocrine loop resulting in IL-2R signaling can make CAR T cells more potent in staying active against TGF-β+ solid tumors.
INDICATORS FOR COLONOSCOPY IN PATIENTS WITH RECURRENT DIVERTICULAR DISEASE OF THE COLON
Authors: S Skridlevskiy, V Veselov
Journal: Endoscopy (2018)

The aim of the study was to clarify the significant indicators for colonoscopy in patients with recurrent diverticular disease of the colon. The study was due to the postulate that complete examination of the colon is a fundamental objective of colonoscopy and recommendations for a colonoscopy in patients with diverticular disease after resolution of an episode of complicated diverticulitis.
Preparación de limpieza colónica alcanzada en pacientes ingresado a los que se realiza gastroscopia y colonoscopia vs. sólo colonoscopia
Authors: A Guardiola Arévalo, A Granja Navacerrada, J García Alonso, P Bernal Checa, D Garza Jimenez, JM Jimenez Fernandez, I Guerra Marina, EM Andrés Esteban, A Albaga García, F Bermejo
Journal: Endoscopy (2017)

La preparación para colonoscopia se debe finalizar entre 3 y 5 horas. En pacientes que precisan gastroscopia y colonoscopia se realizan en una misma sesión, sin poder cumplir dicho periodo temporal.
COMPARATIVE EFFICACY OF VARIOUS ANTI-ULCER MEDICATIONS FOR ULCER HEALING AFTER GASTRIC SUBMUCOSAL DISSECTION: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: CH Park, EH Kim, SW Park
Journal: Endoscopy (2018)

Although proton pump inhibitors (PPIs) are usually used for iatrogenic ulcer healing after gastric submucosal dissection (ESD), comprehensive efficacy among various anti-ulcer drug regimens have not yet been fully evaluated. In addition to traditional drugs including PPI, vonoprazan, a novel potassium-competitive acid blocker, has been used in the treatment of ulcer after gastric ESD.
ENDOSCOPIC TREATMENT OF CYSTIC DUODENAL DUPLICATION
Authors: M Medhioub, M Lamine Hamzaoui, A Khsiba, M Mahmoudi, M Moussadek Azzouz
Journal: Endoscopy (2018)

A 61-year–old woman was admitted to our department because of a several years history of intermittent non radiating upper abdominal pain. She reported a recent exacerbation of the symptoms, associated with nausea and vomiting.
Genetic Lineage Tracing of Sca-1 <sup>+</sup> Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart
Authors: Ronald J. Vagnozzi, Michelle A. Sargent, Suh-Chin J. Lin, Nathan J. Palpant, Charles E. Murry, Jeffery D. Molkentin
Journal: Circulation (2018)

The adult mammalian heart displays a cardiomyocyte turnover rate of ≈1%/y throughout postnatal life and after injuries such as myocardial infarction (MI), but the question of which cell types drive this low level of new cardiomyocyte formation remains contentious. Cardiac-resident stem cells marked by stem cell antigen-1 (Sca-1, gene name Ly6a) have been proposed as an important source of cardiomyocyte renewal. However, the in vivo contribution of endogenous Sca-1+ cells to the heart at baseline or after MI has not been investigated.Here we generated Ly6a gene-targeted mice containing either a constitutive or an inducible Cre recombinase to perform genetic lineage tracing of Sca-1+ cells in vivo.We observed that the contribution of endogenous Sca-1+ cells to the cardiomyocyte population in the heart was <0.005% throughout all of cardiac development, with aging, or after MI. In contrast, Sca-1+ cells abundantly contributed to the cardiac vasculature in mice during physiological growth and in the post-MI heart during cardiac remodeling. Specifically, Sca-1 lineage-traced endothelial cells expanded postnatally in the mouse heart after birth and into adulthood. Moreover, pulse labeling of Sca-1+ cells with an inducible Ly6a-MerCreMer allele also revealed a preferential expansion of Sca-1 lineage-traced endothelial cells after MI injury in the mouse.Cardiac-resident Sca-1+ cells are not significant contributors to cardiomyocyte renewal in vivo. However, cardiac Sca-1+ cells represent a subset of vascular endothelial cells that expand postnatally with enhanced responsiveness to pathological stress in vivo.
Abstract P364: Preliminary Study of the Effects of Coffee Mannooligosaccharides Supplementation on Lipid Profile.
Authors: Stacy Tsai, Arindam RoyChoudhury, Majella O'Keeffe, Marie-Pierre St-Onge
Journal: Circulation (2012)

Introduction: Coffee-derived mannooligosaccharides (MOS) have been shown to have prebiotic activity and improve body composition in overweight individuals. However, the effects of MOS consumption on metabolic risk factors have not been studied. The overall goal of this study was to determine the effects of MOS consumption on body composition and metabolic risk factors. Hypothesis: We hypothesized that the intake of MOS would result in improvements in lipid profile after controlling for changes in body weight. Design: Two separate randomized, placebo-controlled studies, weight maintenance or weight loss, were conducted to assess the role of MOS for weight management. For each study, participants consumed MOS (4 g/d) or Placebo coffee beverages for 12 wk. Fasting blood samples were taken at baseline and endpoint of both studies. Complete datasets were available for 31 participants who consumed MOS (13 in weight loss study) and 32 (17 in weight loss study) who consumed the Placebo beverage. Regression analysis wasperformed including body weight, age, sex, time and time x beverage interaction as covariates to determine the effects of MOS supplementation on serum lipid levels. The regression analysis was additionally performed on a sub-sample with mildly elevated low-density lipoprotein cholesterol (LDL-C &amp;#8805; 130 mg/dL). Results: Participants had a mean age (SEM) and body mass index of 45.0 ± 11.3 y and 30.2 ± 2.6 kg/m2. In the whole sample analysis, there was no time x beverage interaction for any of the lipid parameters (all P&gt; 0.05). Total cholesterol (TC) changed by -2.5 ± 15.8% in the MOS group and by -1.0 ± 11.3% in the Placebo group. LDL-C changed by -2.0 ± 30.1% in the MOS group and by -2.2 ± 21.4% in the Placebo group. In the sub-sample analysis (MOS n = 12, Placebo n = 18), there was no time x beverage interaction on TC (MOS-17.1 ± 9.1% vs Placebo -5.6±10.1%, P = 0.197). Similar results were observed for LDL-C (MOS -25.6 ± 14.4% vs Placebo -8.4 ± 17.3%, P = 0.164) and triglycerides (MOS -8.5 ± 100.2% vs Placebo -3.4± 25.9%, P = 0.358). Conclusions: Our data provide preliminary information on the effects of MOS supplementation on cardiovascular risk profile. Although not significant, our results suggest that MOS consumption may be useful to improve lipid profile in individuals with elevated LDL-C but our sample size was inadequate to affirm this with confidence. Future studies should be specifically designed to determine the effects of MOS supplementation on lipid profiles of at risk individuals.
DIGITAL VS FIBEROPTIC CHOLANGIOSCOPY
Authors: I Dimas, E Vardas, M Fragaki, A Mpitouli, M Velegraki, E Voudoukis, A Theodoropoulou, G Paspatis
Journal: Endoscopy (2018)

Digital cholangioscopes provide higher-resolution imaging of the pancreatobiliary tract compared with the fiberoptic instruments. The aim of the study was primarily to assess the frequency of digital cholangioscopy (DC) to alter diagnosis and clinical management of bile duct disease compared with fiberoptic cholangioscopy (FC), and secondly to correlate the results of technical success according to the difficulty of the procedure.
Lessons from Gosport
Authors: Fiona Godlee
Journal: BMJ (2018)

The report of the inquiry into deaths at Gosport War Memorial Hospital is hard but essential reading (gosportpanel.independent.gov.uk).In cool clear prose it records the personal tragedies of patients, admitted for respite care and not in pain, for whom "keep patient comfortable" proved a death sentence.It describes the courage and persistence of the families, and the devastating roll call of professional and institutional failings.
Selecting patients with stage II/III colorectal cancer for 5-fluorouracil-based adjuvant chemotherapy using proteomic analysis.
Authors: Dongyao Yan, Ji Hyung Hong, Hee Yeon Lee, Jae Ho Byun, Fabiola Cecchi, Yuan Tian, Sarit Schwartz, Eunkyung An, Todd A. Hembrough
Journal: Journal of Clinical Oncology (2018)

708 Background: 5-fluorouracil (5-FU) is a common adjuvant treatment for stage III and high-risk stage II colorectal cancer (CRC). However, about 20% of patients relapse within 48 months of treatment with 5-FU, even when combined with oxaliplatin. To improve patient selection, tumor biomarkers that predict sensitivity to 5-FU have been proposed. These include proteins involved in 5-FU activation or metabolism such as uridine-cytidine kinase 2 (UCK2) and thymidylate synthase (TYMS). We used multiplexed mass spectrometry to evaluate the utility these biomarkers in the archived tumor samples of patients with stage II/III CRC. Methods: Tumor samples were from 143 patients with stage II/III CRC who received adjuvant 5-FU, folinic acid, and oxaliplatin during 2000-2014; 83% of patients received 12 cycles and the others received ≤ 11 cycles. Tumor cells were microdissected and solubilized, and 67 candidate biomarkers were quantitated using mass spectrometry. Overall survival (OS) and relapse-free survival (RFS) were assessed using the Kaplan-Meier method and log-rank test. Protein expression by tumor stage, lymph node (LN) status, tumor sidedness was compared using the Student’s t-test. Results: Of 143 patients, 45 had recurrence and 98 patients did not. UCK2 was detected in all samples, ranging from 187 to 1606 attomoles per microgram of total protein (amol/µg). Patients with UCK2 expression above 335 amol/μg (n = 109) had significantly longer OS than patients with lower expression (n = 34; HR: 0.42; p= 0.009). There was no significant difference in RFS (HR: 0.6; p= 0.088). UCK2 expression did not differ by disease stage, LN metastasis status, or tumor sidedness. TYMS expression was not associated with survival in this cohort. Analysis of other biomarkers associated with response to 5-FU and platinum is in progress. Conclusions: In stage II/III CRC, UCK2 expression above 335 amol/μg identifies a subgroup of 5-FU-treated CRC patients with longer survival, suggesting that quantitated UCK2 has potential for use in selecting patients for treatment. These findings warrant validation in larger cohorts.
Rhinovirus is the most common virus and rhinovirus-C is the most common species in paediatric intensive care respiratory admissions
Authors: Desmond W. Cox, Siew-Kim Khoo, Guicheng Zhang, Katie Lindsay, Anthony D. Keil, Geoff Knight, James E. Gern, Ingrid A. Laing, Joelene Bizzintino, Peter N. Le Souëf
Journal: European Respiratory Journal (2018)

<b>This is first report to examine the role of different RV species in ARIs in children admitted to paediatric ICU. Our study found that RV-C is the most common RV species in paediatric intensive care respiratory admissions.</b>http://ow.ly/P6EN30k9UnX