tbuckley/cabot-search huggingface dataset:
MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
Authors: Ying Zhang, Lu Guo, Yuhuan Li, Gui-Hai Feng, Fei Teng, Wei Li, Qi Zhou
Journal: Molecular Cancer (2018)

Aberrant activation of the Wnt/β-catenin signaling pathway is frequently observed in colorectal cancer (CRC). β-catenin is the major Wnt signaling pathway effector and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. It has been suggested that inactivation of APC plays an important role in activation of the Wnt/β-catenin pathway and in the progression of colorectal tumorigenesis. However, the mechanism through which APC mediates colorectal tumorigenesis is not understood. Increasing evidence suggests that the dysregulation of microRNAs (miRNAs) is involved in colorectal tumorigenesis. Although miR-494 has been reported as being an upregulated miRNA, the interplay between miR-494 and APC-mediated colorectal tumorigenesis progression remains unclear. The expression of miR-494 in tissues from patients diagnosed with CRC was analyzed using a microarray and real-time PCR. The effects of miR-494 on cell proliferation and tumorigenesis in CRC cells were analyzed by flow cytometry, colony formation assays, BrdU incorporation assays, and CCK8 assays. The correlation between miR-494 expression and APC expression, as well as the mechanisms by which miR-494 regulates APC in CRC were also addressed. miR-494 was significantly upregulated in CRC tissues, and this increase was negatively associated with APC expression. APC was confirmed to be a direct target of miR-494 in CRC. Furthermore, overexpression of miR-494 induced Wnt/β-catenin signaling by targeting APC, thus promoting CRC cell growth. This study provides novel insights into the role of miR-494 in controlling CRC cell proliferation and tumorigenesis, and identifies miR-494 as a potential prognostic marker and therapeutic target.
Abstract 16980: Walking Training Improves Local Inflammation and Blood Pressure in Patients With Intermittent Claudication: Preliminary Data
Authors: Aluísio Andrade Lima, Marcel Chehuen, Natan Silva, Luiz Costa, Nelson Wolosker, Cláudia Forjaz
Journal: Circulation (2016)

Introduction:  Patients with intermittent claudication (IC) present limited walking capacity and increased cardiovascular risk, which are associated with inflammatory markers and hemodynamic alterations. Walking training (WT) is recommended for these patients due to the improvements in the walking capacity, however, its effect on local inflammation and cardiovascular function need to be clarified. Thus, the aim of the present study was to evaluate, in individuals with IC, the effects of the WT on cardiovascular function and inflammation.   Methods:  Fifteen men with IC were randomly allocated in two groups: WT (2 sessions/week, 15 bouts of 2 min walking with 2 min of passive pause) and control group (CG - 2 sessions/week, 30 min of stretching). Before and after 12 weeks of the study, walking capacity (total walking distance), blood pressure - BP (auscultatory), heart rate - HR (ECG) and inflammatory markers (vascular cell adhesion molecule - VCAM and intercellular adhesion molecules - ICAM) were measured. Data were evaluated by 2-way ANOVA, with P    Results:  Walking capacity improved only in WT (pre: 567 ± 196 m vs post 904 ± 284 m; P 0.05). Diastolic BP and HR did not chance in either group (p>0.05). ICAM decreased in the WT and increased in CG, while VCAM increased only in CG. Thus, post-intervention values of ICAM and VCAM differered between the groups (p   Conclusion:  WT improves walking capacity and reduces local inflammation and systolic BP, which may reduce cardiovascular risk in patients with IC.
Erratum: Corrigendum: TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum
Authors: Erica E Davis, Qi Zhang, Qin Liu, Bill H Diplas, Lisa M Davey, Jane Hartley, Corinne Stoetzel, Katarzyna Szymanska, Gokul Ramaswami, Clare V Logan, Donna M Muzny, Alice C Young, David A Wheeler, Pedro Cruz, Margaret Morgan, Lora R Lewis, Praveen Cherukuri, Baishali Maskeri, Nancy F Hansen, James C Mullikin, Robert W Blakesley, Gerard G Bouffard, Gabor Gyapay, Susanne Rieger, Burkhard Tönshoff, Ilse Kern, Neveen A Soliman, Thomas J Neuhaus, Kathryn J Swoboda, Hulya Kayserili, Tomas E Gallagher, Richard A Lewis, Carsten Bergmann, Edgar A Otto, Sophie Saunier, Peter J Scambler, Philip L Beales, Joseph G Gleeson, Eamonn R Maher, Tania Attié-Bitach, Hélène Dollfus, Colin A Johnson, Eric D Green, Richard A Gibbs, Friedhelm Hildebrandt, Eric A Pierce, Nicholas Katsanis
Journal: Nature Genetics (2011)
Динаміка сироваткових пепсиногенів на тлі прийому подвійних стандартних доз омепразолу у хворих на гастроезофагеальну рефлюксну хворобу та функціональні шлункові диспепсії
Authors: S.G. Melashchenko, V.M. Chernobrovy, Ya.O. Bayol, N.M. Kizlova
Journal: GASTROENTEROLOGY (2013)

У літературі повідомлялося, що концентрації сироваткових пепсиногенів наростають під час прийому інгібіторів протонної помпи (ІПП). Однак величина цих змін остаточно не оцінена. Метою даного дослідження було вивчення змін рівнів пепсиногену I (ПГ-1) і пепсиногену II (ПГ-2) на тлі терапії омепразолом, що приймали перед сніданком у подвійній стандартній дозі (40 мг). Режим призначення ІПП повністю відповідає звичайному ІПП-тесту. Було дві групи хворих: 1-ша (гастроезофагеальна рефлюксна хвороба) — 10 жінок і 9 чоловіків, середній вік (52,37 ± 3,25) року; 2-га (функціональна диспепсія) — 11 жінок і 8 чоловіків, середній вік (48,37 ± 3,56) року. Було з’ясовано, що в 1-й групі рівень ПГ-1 збільшувався з (141,90 ± 7,99) мкг/л до (177,61 ± 7,81) мкг/л, у 2-й групі — із (115,02 ± 10,16) мкг/л до (152,37 ± 12,33) мкг/л (р &lt; 0,05). Рівень ПГ-2 змінювався аналогічно. У 1-й групі рівень ПГ-2 підвищувався з (21,65 ± 3,13) мкг/л до (32,64 ± 3,42) мкг/л, у 2-й групі — із (14,84 ± 1,64) мкг/л до (23,55 ± 2,37) мкг/л (р &lt; 0,05). У 6 випадках абсолютне збільшення ПГ-1 (ΔПГ-1) не сягало порогового значення 7,0 мкг/л, визначеного нами як рівень недостатньої ацидоінгібіції. Двоє з цих пацієнтів мали атрофічний гастрит (ПГ-1 &lt; 50 мкг/л, співвідношення ПГ-I/ПГ-II &lt; 3,0), у решти 4 пацієнтів не було атрофічного гастриту, але в половині випадків вони не реагували адекватно на прийом ІПП. Виявлена вірогідна кореляція між підвищенням рівня ПГ-1 і зникненням рефлюксних скарг, оцінених за динамікою RS-кластера опитувальника GSRS.
Differences in Morbidity and Mortality Rates in Black, White, and Hispanic Very Preterm Infants Among New York City Hospitals
Authors: Elizabeth A. Howell, Teresa Janevic, Paul L. Hebert, Natalia N. Egorova, Amy Balbierz, Jennifer Zeitlin
Journal: JAMA Pediatrics (2018)

Substantial quality improvements in neonatal care have occurred over the past decade yet racial and ethnic disparities in morbidity and mortality remain. It is uncertain whether disparate patterns of care by race and ethnicity contribute to disparities in neonatal outcomes.To examine differences in neonatal morbidity and mortality rates among non-Hispanic black (black), Hispanic, and non-Hispanic white (white) very preterm infants and to determine whether these differences are explained by site of delivery.Population-based retrospective cohort study of 7177 nonanomalous infants born between 24 and 31 completed gestational weeks in 39 New York City hospitals using linked 2010 to 2014 New York City discharge abstract and birth certificate data sets. Mixed-effects logistic regression with a random hospital-specific intercept was used to generate risk-adjusted neonatal morbidity and mortality rates for very preterm infants in each hospital. Hospitals were ranked using this measure, and differences in the distribution of black, Hispanic, and white very preterm births were assessed among these hospitals. The statistical analysis was performed in 2016-2017.Race/ethnicity.Composite of mortality (neonatal or in-hospital up to 1 year) or severe neonatal morbidity (bronchopulmonary dysplasia, severe necrotizing enterocolitis, retinopathy of prematurity stage 3 or greater, or intraventricular hemorrhage grade 3 or greater).Among 7177 very preterm births (VPTBs), morbidity and mortality occurred in 2011 (28%) and was higher among black (893 [32.2%]) and Hispanic (610 [28.1%]) than white (319 [22.5%]) VPTBs (2-tailed P < .001). The risk-standardized morbidity and mortality rate was twice as great for VPTB infants born in hospitals in the highest morbidity and mortality tertile (0.40; 95% CI, 0.38-0.41) as for those born in the lowest morbidity and mortality tertile (0.16; 95% CI, 0.14-0.18). Black (1204 of 2775 [43.4%]) and Hispanic (746 of 2168 [34.4%]) VPTB infants were more likely than white (325 of 1418 [22.9%]) VPTB infants to be born in hospitals in the highest morbidity and mortality tertile (2-tailed P < .001; black-white difference, 20%; 95% CI, 18%-23% and Hispanic-white difference, 11%; 95% CI, 9%-14%). The largest proportion of the explained disparities can be attributed to differences in infant health risks among black, Hispanic, and white VPTB infants. However, 40% (95% CI, 30%-50%) of the black-white disparity and 30% (95% CI, 10%-49%) of the Hispanic-white disparity was explained by birth hospital.Black and Hispanic VPTB infants are more likely to be born at hospitals with higher risk-adjusted neonatal morbidity and mortality rates, and these differences contribute to excess morbidity and mortality among black and Hispanic infants.
Abstract 20088: Ubiquitin-Specific Protease 20 Attenuates Atherosclerosis through Activity in Smooth Muscle Cells
Authors: Jiao-Hui Wu, Lisheng Zhang, Pierre-Yves Jean-Charles, A. Kyle Davidson, Leigh Brian, Rui Qi, Sudha K Shenoy, Neil J Freedman
Journal: Circulation (2016)

Integral to atherosclerosis (athero) is smooth muscle cell (SMC) NFκB-activating signaling, which involves reversible ubiquitination that enhances protein activity downstream of pro-atherogenic tum...
Analysis of Anti-CMV T-Cell Immunity and CMV Reactivation after Allogeneic Hematopoietic Cell Transplantation
Authors: George Chen, Yali Zhang, Joseph Dennis Tario, Amanda Herko Przespolewski, Dalin Pan, Patrick Mellors, Christine Ho, Sophia R. Balderman, Maureen Ross, Liselotte Brix, Paul K. Wallace, Philip L. McCarthy, Theresa Hahn
Journal: Blood (2017)
Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A
Authors: Jihye Kim, Dong-Yeop Chang, Hyun Woong Lee, Hoyoung Lee, Jong Hoon Kim, Pil Soo Sung, Kyung Hwan Kim, Seon-Hui Hong, Wonseok Kang, Jino Lee, So Youn Shin, Hee Tae Yu, Sooseong You, Yoon Seok Choi, Insoo Oh, Dong Ho Lee, Dong Hyeon Lee, Min Kyung Jung, Kyung-Suk Suh, Shin Hwang, Won Kim, Su-Hyung Park, Hyung Joon Kim, Eui-Cheol Shin
Journal: Immunity (2018)
Are randomised control trials best for evaluating the effect of complex physical therapy interventions?
Authors: Håvard Østerås, Fredrik Paulsberg, Karin Gravare Silbernagel
Journal: British Journal of Sports Medicine (2018)

Well-executed randomised controlled trials (RCTs) provide high levels of evidence for treatment efficacy. They enable the cause and effect of sports physical therapy treatments to be explored under ideal circumstances, with one treatment element often evaluated at a time. However, treatment elements are rarely delivered in isolation in contemporary practice and are inherently complex. Treatments are customised to address a patient’s impairments, with intervention dose, frequency and intensity adjusted for each individual. Treatment elements may also have interacting effects. If an RCT evaluates only one aspect of a treatment, there would be evidence for that individual component’s efficacy, but it would be inefficient and expensive to study all components in isolation and interactions between treatment elements would go unrecognised. Therefore, RCTs have potential limitations when considering the most efficient path forward for sports physiotherapy research.

It is not feasible to test every detail in best clinical practice. Thus, clinicians need to incorporate the best available evidence with their own experiences and their …
Recombination of ecologically and evolutionarily significant loci maintains genetic cohesion in the Pseudomonas syringae species complex
Authors: Marcus M. Dillon, Shalabh Thakur, Renan N. D. Almeida, Pauline W. Wang, Bevan S. Weir, David S. Guttman
Journal: Genome biology (2019)

Pseudomonas syringae is a highly diverse bacterial species complex capable of causing a wide range of serious diseases on numerous agronomically important crops. We examine the evolutionary relationships of 391 agricultural and environmental strains using whole-genome sequencing and evolutionary genomic analyses.We describe the phylogenetic distribution of all 77,728 orthologous gene families in the pan-genome, reconstruct the core genome phylogeny using the 2410 core genes, hierarchically cluster the accessory genome, identify the diversity and distribution of type III secretion systems and their effectors, predict ecologically and evolutionary relevant loci, and establish the molecular evolutionary processes operating on gene families. Phylogenetic and recombination analyses reveals that the species complex is subdivided into primary and secondary phylogroups, with the former primarily comprised of agricultural isolates, including all of the well-studied P. syringae strains. In contrast, the secondary phylogroups include numerous environmental isolates. These phylogroups also have levels of genetic diversity typically found among distinct species. An analysis of rates of recombination within and between phylogroups revealed a higher rate of recombination within primary phylogroups than between primary and secondary phylogroups. We also find that "ecologically significant" virulence-associated loci and "evolutionarily significant" loci under positive selection are over-represented among loci that undergo inter-phylogroup genetic exchange.While inter-phylogroup recombination occurs relatively rarely, it is an important force maintaining the genetic cohesion of the species complex, particularly among primary phylogroup strains. This level of genetic cohesion, and the shared plant-associated niche, argues for considering the primary phylogroups as a single biological species.
Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial
Authors: Jason Grebely, Olav Dalgard, Brian Conway, Evan B Cunningham, Philip Bruggmann, Behzad Hajarizadeh, Janaki Amin, Julie Bruneau, Margaret Hellard, Alain H Litwin, Philippa Marks, Sophie Quiene, Sharmila Siriragavan, Tanya L Applegate, Tracy Swan, Jude Byrne, Melanie Lacalamita, Adrian Dunlop, Gail V Matthews, Jeff Powis, David Shaw, Maria Christine Thurnheer, Martin Weltman, Ian Kronborg, Curtis Cooper, Jordan J Feld, Chris Fraser, John F Dillon, Phillip Read, Ed Gane, Gregory J Dore
Journal: The Lancet. Gastroenterology & hepatology (2018)
Abstract 19972: Use of Whole Exome Sequencing for the Identification of Ito Based Arrhythmia Mechanism and Therapy
Authors: Sara H Adelman, Amy C Sturm, Crystal F Kline, Patric Glynn, Benjamin L Johnson, Jerry Curran, Ahmet Kilic, Robert S Higgins, Philip F Binkley, Paul M Janssen, Raul Weiss, Subha V Raman, Steven J Fowler, Silvia G Priori, Thomas J Hund, Cynthia A Carnes, Peter J Mohler
Journal: Circulation (2015)

Background: Identified genetic variants are insufficient to explain all cases of inherited arrhythmia. We tested whether the integration of whole exome sequencing with well-established clinical, translational, and basic science platforms could provide rapid and novel insight into human arrhythmia pathophysiology and disease treatment. Methods and Results: We report a proband with recurrent ventricular fibrillation, resistant to standard therapeutic interventions. Using whole-exome sequencing, we identified a variant in a previously unidentified exon of the dipeptidyl aminopeptidase-like protein-6 (DPP6) gene. This variant is the first identified coding mutation in DPP6 and augments cardiac repolarizing current (Ito) causing pathological changes in Ito and action potential morphology. We designed a therapeutic regimen incorporating dalfampridine to target Ito. Dalfampridine, approved for multiple sclerosis, normalized the ECG and reduced arrhythmia burden in the proband by &gt; 90-fold. This was combined with cilostazol to accelerate the heart rate to minimize the reverse-rate dependence of augmented Ito. Conclusions: We describe a novel arrhythmia mechanism and therapeutic approach to ameliorate the disease. Specifically, we identify the first coding variant of DPP6 in human ventricular fibrillation. These findings illustrate the power of genetic approaches for the elucidation and treatment of disease when carefully integrated with clinical and basic/translational research teams.
Safety and Effectiveness of Ledipasvir and Sofosbuvir, With or Without Ribavirin, in Treatment-Experienced Patients With Genotype 1 Hepatitis C Virus Infection and Cirrhosis
Authors: Joseph K. Lim, Ann Marie Liapakis, Mitchell L. Shiffman, Anna S. Lok, Stefan Zeuzem, Norah A. Terrault, James S. Park, Charles S. Landis, Mohamed Hassan, Joel Gallant, Alexander Kuo, Paul J. Pockros, Monika Vainorius, Lucy Akushevich, Larry Michael, Michael W. Fried, David R. Nelson, Ziv Ben-Ari
Journal: Clinical Gastroenterology and Hepatology (2018)
An Oral Disease Severity Score validated for use in oral pemphigus vulgaris
Authors: M. Ormond, H. McParland, A.N.A. Donaldson, M. Andiappan, R.J. Cook, M. Escudier, E. Hullah, J. Higham, R. McMillan, J. Taylor, P.J. Shirlaw, S.J. Challacombe, J.F. Setterfield
Journal: British Journal of Dermatology (2018)

Pemphigus vulgaris (PV) is a rare autoimmune bullous disease, which can present with recalcitrant oral mucosal lesions. Optimal management of PV relies upon careful clinical assessment and documentation.The primary aim of this study was to validate the Oral Disease Severity Score (ODSS) for the assessment of oral involvement in PV. A secondary aim was to compare its inter- and intraobserver variability and ease of use with the Physician's Global Assessment (PGA) and the oral scoring methods used in the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and the Pemphigus Disease Area Index (PDAI).Fifteen patients with mild-to-moderately severe oral PV were scored for disease severity by 10 oral medicine clinicians using the ODSS, the PGA and the oral sections of ABSIS and PDAI. Two clinicians rescored all patients after a minimum 2-h interval.Interobserver reliability was assessed using an intraclass correlation coefficient (ICC). For the ODSS total score the ICC was 0·83, for PDAI (oral total activity) 0·79, ABSIS (oral total) 0·71 and PGA 0·7. Intraobserver agreement between initial scoring and rescoring of the same patient by two clinicians demonstrated an ICC for each of 0·97 and 0·96 for ODSS total score; 0·99 and 0·82 for PDAI oral activity; 0·86 and 0·45 for ABSIS total; and 0·99 and 0·64 for PGA. Convergent validity was good, with a correlation coefficient > 0·5 (P < 0·001). The mean ± SD times taken to complete each scoring method were ODSS 76 ± 37 s, PDAI 117 ± 16 s and ABSIS 75 ± 19 s.This study has validated the ODSS for the assessment of oral PV. It has shown superior inter- and intraobserver reliability to PDAI, ABSIS and PGA and is quick to perform.
Minor Allergens in Moderate-Severe Allergic Rhinitis: Group 4 Mite Amylasa (Blo t4) and Geographical Variations
Authors: Ruperto Gonzalez-Perez, Fernando Pineda, Paloma Poza-Guedes, Victor Matheu, Inmaculada Sanchez-Machin
Journal: Journal of Allergy and Clinical Immunology (2018)
Dupilumab in Moderate-to-Severe Atopic Dermatitis With or Without Comorbid Food Allergy: Pooled Analysis of 2 Randomized Phase 3 Trials (LIBERTY AD SOLO 1 &amp; 2)
Authors: Eric L. Simpson, Jean-Philippe Lacour, Jonathan I. Silverberg, Margitta Worm, Andreas Wollenberg, Neil M.H. Graham, Gianluca Pirozzi, Bolanle Akinlade, Laurent Eckert, Abhijit Gadkari, Marius Ardeleanu
Journal: Journal of Allergy and Clinical Immunology (2018)
Limitations of Observational Data in Interpreting SPRINT Results
Authors: Nicholas M. Pajewski, Mark A. Supiano, Jeff D. Williamson
Journal: JAMA Internal Medicine (2018)

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Association of Visual Impairment in Neuromyelitis Optica Spectrum Disorder With Visual Network Reorganization
Authors: Carsten Finke, Hanna Zimmermann, Florence Pache, Frederike C. Oertel, Velina Sevdalinova Chavarro, Yelyzaveta Kramarenko, Judith Bellmann-Strobl, Klemens Ruprecht, Alexander U. Brandt, Friedemann Paul
Journal: JAMA Neurology (2018)

Severe visual impairment is one of the major symptoms in neuromyelitis optica spectrum disorder (NMOSD), but functional network reorganization induced by the diminished sensory input has not been investigated thus far.To examine adaptive visual network connectivity changes in NMOSD.In this cross-sectional study, data were collected from May 1, 2013, through February 31, 2016, from 31 patients with aquaporin-4 antibody-positive NMOSD and 31 age- and sex-matched healthy control individuals at the Department of Neurology and NeuroCure Clinical Research Center at Charité-Universitätsmedizin Berlin, Berlin, Germany.Visual function (high-contrast visual acuity and contrast sensitivity), optical coherence tomography (peripapillary retinal nerve fiber layer and ganglion cell layer thickness), and resting-state functional magnetic resonance imaging (functional connectivity of large-scale brain networks).Thirty-one patients with NMOSD (mean [SD] age, 48.2 [13.9] years; 28 women and 3 men) and 31 healthy controls (mean [SD] age, 47.2 [15.3] years; 28 women and 3 men) participated in the study. Patients had a selective and pronounced increase of functional connectivity in the primary and secondary visual networks. Increased primary visual network connectivity correlated with reduced high-contrast visual acuity (r = -0.39, P = .006), reduced low-contrast sensitivity (r = -0.33, P = .03), and more severe retinal damage measured by optical coherence tomography (r = -0.4, P = .01). Furthermore, visual functional connectivity was significantly higher in patients with a history of optic neuritis compared with patients without optic neuritis (mean [SD] regression coefficients, 50.0 [4.3] vs 34.6 [5.6]; P = .04).Impaired visual function and retinal damage are associated with selective reorganization of the visual network in NMOSD. These findings advance the understanding of visual system dysfunction in NMOSD and, more generally, provide insight into pathophysiologic responses of the visual system to impaired visual input.