tbuckley/cabot-search huggingface dataset:
Causal association of gut microbiome on the risk of rheumatoid arthritis: a Mendelian randomisation study
Authors: Young Ho Lee
Journal: Annals of the Rheumatic Diseases (2020)

Causal association of gut microbiome on the risk of rheumatoid arthritis: a Mendelian randomisation study I read with interest the articles by Inamo 1 and Alpizar-Rodriguez et al 2 regarding the effects of the gut microbiome on the risk of rheumatoid arthritis (RA).The Mendelian randomisation (MR) study suggested that dysbiosis may be a secondary phenomenon, rather than a trigger, in the pathogenesis of RA, 1 while the cohort study by Alpizar-Rodriguez et al suggested a role for intestinal dysbiosis in the development of RA. 2 However, some methodological issues in the MR study must be discussed.First, I applied a two-sample MR analysis in the MR base platform to the same data analysed with the MR by Inamo. 1 From this analysis, I could obtain 32 single nucleotide polymorphisms as instrumental variables.The MR estimates determined using inverse variance weighted (IVW) and MR-Egger regression analyses support a causal association between gut microbiome and the occurrence of RA (IVW: beta=-0.024,SE=0.007, p=0.0006;MR-Egger: beta=-0.027,SE=0.009, p=0.005), while the weighted median approach yielded no evidence of a causal association between gut microbiome and RA (beta=-0.005,SE=0.003, p=0.144).Unlike the MR results by Inamo, 1 a 'leave-one-out' analysis demonstrated that the IVW method without rs1230666 remained significant (p=0.034) and no single single nucleotide polymorphism (SNP) was driving the IVW point estimate.Second, MR studies are susceptible to bias from pleiotropy.Therefore, sensitivity analysis is required to verify the validity of conclusions drawn from the MR study. 3Two methods are commonly used for sensitivity testing: a weighted median estimator, which provides valid estimates even if 50% of the SNPs are not valid instruments 4 and MR-Egger regression, which tests for unbalanced pleiotropy and estimates the causal effect of an exposure on an outcome. 5Here, I found that the results of the MR analysis are supported by significant findings of the MR-Egger analysis (also similar to the IVW estimates), thus providing additional confidence in these findings.Considering that the weighted median estimator allowing 50% of the instruments to be invalid may be a conservative method and no method can provide an infallible test of causation, 3 the MR data may provide support for previous observational studies that have shown an association between microbiome and RA. 2 Thus, I believe that the findings of this MR study should be interpreted by taking the aforementioned methodological concerns into consideration.In conclusion, the MR analysis results may support epidemiological evidence for a relationship between gut microbiome and RA, 2 suggesting further investigation on how much gut microbiome affects the development of RA.
Diagnosis, prevention and treatment of common lower extremity muscle injuries in sport – grading the evidence: a statement paper commissioned by the Danish Society of Sports Physical Therapy (DSSF)
Authors: Lasse Ishøi, Kasper Krommes, Rasmus Skov Husted, Carsten B Juhl, Kristian Thorborg
Journal: British Journal of Sports Medicine (2020)

This statement summarises and appraises the evidence on diagnosis, prevention and treatment of the most common lower extremity muscle injuries in sport. We systematically searched electronic databases, and included studies based on the highest available evidence. Subsequently, we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework, grading the quality of evidence from high to very low. Most clinical tests showed very low to low diagnostic effectiveness. For hamstring injury prevention, programmes that included the Nordic hamstring exercise resulted in a hamstring injury risk reduction when compared with usual care (medium to large effect size; moderate to high quality of evidence). For prevention of groin injuries, both the FIFA 11+programme and the Copenhagen adductor strengthening programme resulted in a groin injury risk reduction compared with usual care (medium effect size; low to moderate quality of evidence). For the treatment of hamstring injuries, lengthening hamstring exercises showed the fastest return to play with a lower reinjury rate compared with conventional hamstring exercises (large effect size; very low to low quality of evidence). Platelet-rich plasma had no effect on time to return-to-play and reinjury risk (trivial effect size; moderate quality of evidence) after a hamstring injury compared with placebo or rehabilitation. At this point, most outcomes for diagnosis, prevention and treatment were graded as very low to moderate quality of evidence, indicating that further high-quality research is likely to have an important impact on the confidence in the effect estimates.
Prevalence of steatosis and fibrosis in young adults in the UK: a population-based study
Authors: Kushala W M Abeysekera, Gwen S Fernandes, Gemma Hammerton, Andrew J Portal, Fiona H Gordon, Jon Heron, Matthew Hickman
Journal: The Lancet. Gastroenterology & hepatology (2020)

The estimated worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) in adults is 25%; however, prevalence in young adults remains unclear. We aimed to identify the prevalence of steatosis and fibrosis in young adults in a sample of participants recruited through the Avon Longitudinal Study of Parents and Children (ALSPAC), based on transient elastography and controlled attenuation parameter (CAP) score.
Quality of Life Incriminating Symptoms in Cancer Patients and Their Weight in the Doctor-Patient-Talk: a Survey of the “Quality Of Life” Working Group of the “Arbeitsgemeinschaft Internistische Onkologie” (AIO): a Preliminary Analysis
Authors: F.K. Tauchert, R. Hofheinz, J. Quidde, N. Marschner, M. Hipp, M. Weber, H. Hoeffkes, E. Jaeger, S. Al-Batran
Journal: Annals of Oncology (2012)
Association of Physician Education and Feedback on Hypertension Management With Patient Blood Pressure and Hypertension Control
Authors: Mattias Brunström, Nawi Ng, John Dahlström, Lars H. Lindholm, Göran Lönnberg, Margareta Norberg, Lennarth Nyström, Lars Weinehall, Bo Carlberg
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Elevated systolic blood pressure (SBP) is the most important risk factor for premature death worldwide. However, hypertension detection and control rates continue to be suboptimal. <h3>Objective</h3> To assess the association of education and feedback to primary care physicians with population-level SBP and hypertension control rates. <h3>Design, Setting, and Participants</h3> This pooled series of 108 population-based cohort studies involving 283 079 patients used data from primary care centers in 2 counties (Västerbotten and Södermanland) in Sweden from 2001 to 2009. Participants were individuals aged 18 years or older who had their blood pressure (BP) measured and recorded in either county during the intervention period. All analyses were performed in February 2019. <h3>Exposures</h3> An intervention comprising education and feedback for primary care physicians in Västerbotten County (intervention group) compared with usual care in Södermanland County (control group). <h3>Main Outcomes and Measures</h3> Difference in mean SBP levels between counties and likelihood of hypertension control in the intervention county compared with the control county during 24 months of follow-up. <h3>Results</h3> A total of 136 541 unique individuals (mean [SD] age at inclusion, 64.6 [16.1] years; 57.0% female; mean inclusion BP, 142/82 mm Hg) in the intervention county were compared with 146 538 individuals (mean [SD] age at inclusion, 65.7 [15.9] years; 58.3% female; mean inclusion BP, 144/80 mm Hg) in the control county. Mean SBP difference between counties during follow-up, adjusted for inclusion BP and other covariates, was 1.1 mm Hg (95% CI, 1.0-1.1 mm Hg). Hypertension control improved by 8.4 percentage points, and control was achieved in 37.8% of participants in the intervention county compared with 29.4% in the control county (adjusted odds ratio, 1.30; 95% CI, 1.29-1.31). Differences between counties increased during the intervention period and were more pronounced in participants with higher SBP at inclusion. Results were consistent across all subgroups. <h3>Conclusions and Relevance</h3> This study suggests that SBP levels and hypertension control rates in a county population may be improved by educational approaches directed at physicians and other health care workers. Similar strategies may be adopted to reinforce the implementation of clinical practice guidelines for hypertension management.
Laparoscopic Lymph Node Resection of Post-Chemotherapy (POST-CHT) Residual Retroperitoneal (RP) Tumor Masses in Patients with Non-Seminomatous Testicular Germ-Cell Tumors (NSTGCT)
Authors: I.G. Sullivan, G. Anguera, C. Arqueros, D. Condori, J. Palou, J.A. Peña, H. Villavicencio, P. Maroto
Journal: Annals of Oncology (2012)
Axitinib vs Sorafenib for Advanced Renal Cell Carcinoma: Phase III Overall Survival Results and Analysis of Prognostic Factors
Authors: R.J. Motzer, B. Escudier, P. Tomczak, S. Negrier, M.E. Gore, J. Tarazi, S. Hariharan, B. Rosbrook, S. Kim, B.I. Rini
Journal: Annals of Oncology (2012)
Impact of Lymph Node Level Assessment for Survival on Time to Relapse in Biliary Tract Cancers
Authors: J. Martinez-Galan, P. Ballesteros, B. Gonzalez-Astorga, J.A. Ortega, A. González-Vicente, J. Soberino García, C. González-Rivas, J. Ruíz Vozmediano, T. Villegas, J.R. Delgado
Journal: Annals of Oncology (2012)
Envisioning a Better U.S. Health Care System for All: Reducing Barriers to Care and Addressing Social Determinants of Health
Authors: Renee Butkus, Katherine Rapp, Thomas G. Cooney, Lee S. Engel
Journal: Annals of Internal Medicine (2020)

The American College of Physicians (ACP) has long advocated for universal access to high-quality health care in the United States. Yet, it is essential that the U.S. health system goes beyond ensuring coverage, efficient delivery systems, and affordability. Reductions in nonfinancial barriers to care and improvements in social determinants of health are also necessary. This ACP position paper calls for ending discrimination based on personal characteristics; correcting workforce shortages, including the undersupply of primary care physicians; and understanding and ameliorating social determinants of health. The ACP calls for increased efforts to address urgent public health threats, including injuries and deaths from firearms; environmental hazards; climate change; maternal mortality; substance use disorders; and the health risks associated with nicotine, tobacco use, and electronic nicotine delivery systems in order to achieve ACP's vision for a better U.S. health care system.
Phase I Study of Trifluridine/Tipiracil Plus Irinotecan and Bevacizumab in Advanced Gastrointestinal Tumors
Authors: Anna M. Varghese, Dana B. Cardin, Jonathan Hersch, Al B. Benson, Howard S. Hochster, Lukas Makris, Kensuke Hamada, Jordan D. Berlin, Leonard B. Saltz
Journal: Clinical Cancer Research (2020)

This two-part phase Ib trial determined the maximum tolerated dose (MTD) of the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with advanced gastrointestinal tumors, and evaluated the safety, pharmacokinetics, and antitumor activity of the FTD/TPI, irinotecan, and bevacizumab triplet combination in previously treated metastatic colorectal cancer (mCRC).Dose escalation (3+3 design) in advanced gastrointestinal tumors was followed by expansion in mCRC. During dose escalation, patients received FTD/TPI (20-35 mg/m2 twice daily; days 1-5 of a 14-day cycle) and irinotecan (120-180 mg/m2; day 1). During expansion, the MTD of FTD/TPI and irinotecan plus bevacizumab (5 mg/kg; day 1) was administered.Fifty patients (26 across six dose-escalation cohorts and 24 in the expansion phase) were enrolled. Two dose-limiting toxicities (fatigue and neutropenia) were observed in the dose-escalation phase, and MTD was defined as FTD/TPI 25 mg/m2 twice daily plus irinotecan 180 mg/m2. In the expansion phase, 83% (20/24) experienced any-cause grade ≥3 adverse events (AEs) with the triplet combination, most frequently neutropenia (42%), leukopenia (25%), and diarrhea (12%). AEs of any-cause led to dosing interruptions, modifications, and discontinuations in 29%, 17%, and 4% of patients, respectively. No treatment-related deaths occurred. Three patients (12%) experienced partial responses and 16 (67%) patients had stable disease lasting >4 months. The median progression-free survival was 7.9 months (95% confidence interval, 5.1-13.4 months).Tolerability and activity observed in this phase I trial support further investigation of the FTD/TPI-irinotecan-bevacizumab combination in previously treated mCRC.
Phase II Study of Amrubicin (AMR) Combined with Carboplatin (CBDCA) for Refractory Relapsed Small Cell Lung Cancer (SCLC): North Japan Lung Cancer Group 0802
Authors: S. Oizumi, A. Inoue, T. Sakakibara, H. Asahina, S. Sugawara, M. Maemondo, K. Okudera, T. Suzuki, K. Usui, M. Harada, N. Morikawa, Y. Hasegawa, O. Ishimoto, T. Nukiwa
Journal: Annals of Oncology (2012)
PD-0004 Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer; A Multicenter, Single Arm Phase I/II Trial: Asso Lm1
Authors: Thomas Gruenberger, Friedrich Längle, Josef Thaler, Wolfgang Eisterer, Alfred Lenauer, Stefan Stremitzer, Judith Stift, Birgit Gruenberger
Journal: Annals of Oncology (2012)
O-0006 Dose Escalation to Rash for Erlotinib Plus Gemcitabine in Patients with Metastatic Pancreatic Cancer: The Phase II RACHEL (BO21128) Study
Authors: Eric Van Cutsem, Elzbieta Nowara, Tudor Ciuleanu, Giuseppe Aprile, Malcolm Moore, Irena Federowicz, Jean Luc Van Laethem, Chiun Hsu, Sajid Ali, Zsuzsanna Csutor, Xianhua Meng, Chung-Pin Li
Journal: Annals of Oncology (2012)
IL-32γ suppressed atopic dermatitis through inhibition of miR-205 expression via inactivation of nuclear factor-kappa B
Authors: Yong Sun Lee, Sang-Bae Han, Hyeon Joo Ham, Ju Ho Park, Jong Sung Lee, Dae Yeon Hwang, Young Suk Jung, Do Young Yoon, Jin Tae Hong
Journal: Journal of Allergy and Clinical Immunology (2020)

IL-32 is a novel cytokine involved in many inflammatory diseases. However, the role of IL-32γ, an isotype of IL-32, in atopic dermatitis (AD) has not been reported.We investigated the effects of IL-32γ on development of AD and its action mechanisms.We used phthalic anhydride (PA) and an MC903-induced AD model using wild-type and IL-32γ transgenic mice. We conducted the therapy experiments by using recombinant IL-32γ protein in a reconstructed human skin model and PA-induced model. We conducted a receiver operating characteristic analysis of IL-32γ with new AD biomarkers, IL-31 and IL-33, in serum from patients with AD.Dermatitis severity and epidermal thickness were significantly reduced in PA- and MC903-induced IL-32γ transgenic mice compared with in wild-type mice. The concentration of AD-related cytokines was reduced in PA- and MC903-induced IL-32γ transgenic mice compared with in wild-type mice. Subsequent analysis showed that IL-32γ inhibits miR-205 expression in PA- and MC903-induced skin tissue samples and TNF-α/IFN-γ-treated HaCaT cells. IL-32γ reduced NF-κB activity in skin tissue samples from PA- and MC903-induced mice and TNF-α/IFN-γ-treated HaCaT cells. NF-κB inhibitor treatment with IL-32γ expression further suppressed expression of inflammatory mediators as well as miR-205 in TNF-α/IFN-γ-treated HaCaT cells. Furthermore, recombinant IL-32γ protein alleviated AD-like inflammation in in vivo and reconstructed human skin models. Spearman correlation analysis showed that serum levels of IL-32γ and miR-205 were significantly concordant in patients with AD.Our results indicate that IL-32γ reduces AD through the inhibition of miR-205 expression via inactivation of NF-κB.
Adverse Cardiovascular Effects of Traffic Noise with a Focus on Nighttime Noise and the New WHO Noise Guidelines
Authors: Thomas Münzel, Swenja Kröller-Schön, Matthias Oelze, Tommaso Gori, Frank P. Schmidt, Sebastian Steven, Omar Hahad, Martin Röösli, Jean-Marc Wunderli, Andreas Daiber, Mette Sørensen
Journal: Annual Review of Public Health (2020)

Exposure to traffic noise is associated with stress and sleep disturbances. The World Health Organization (WHO) recently concluded that road traffic noise increases the risk for ischemic heart disease and potentially other cardiometabolic diseases, including stroke, obesity, and diabetes. The WHO report focused on whole-day noise exposure, but new epidemiological and translational field noise studies indicate that nighttime noise, in particular,is an important risk factor for cardiovascular disease (CVD) through increased levels of stress hormones and vascular oxidative stress, leading to endothelial dysfunction and subsequent development of various CVDs. Novel experimental studies found noise to be associated with oxidative stress–induced vascular and brain damage, mediated by activation of the NADPH oxidase, uncoupling of endothelial and neuronal nitric oxide synthase, and vascular/brain infiltration with inflammatory cells. Noise-induced pathophysiology was more pronounced in response to nighttime as compared with daytime noise. This review focuses on the consequences of nighttime noise.
Efficacy and Safety of Gemcitabine Plus Cisplatin Chemotherapy for Advanced Biliary Tract Cancer: A Retrospective Study
Authors: G. Hirano, Y. Takii, T. Kamihira, K. Fujisawa, Y. Ichiki, T. Suzuki, T. Matsuo, S. Uraoka, K.-i. Aoki, K.-i. Sakai, R. Ogawa, M. Higuchi
Journal: Annals of Oncology (2012)
Extracellular Myocardial Volume in Patients With Aortic Stenosis
Authors: Russell J. Everett, Thomas A. Treibel, Miho Fukui, Heesun Lee, Marzia Rigolli, Anvesha Singh, Petra Bijsterveld, Lionel Tastet, Tarique Al Musa, Laura Dobson, Calvin Chin, Gabriella Captur, Sang Yong Om, Stephanie Wiesemann, Vanessa M. Ferreira, Stefan K. Piechnik, Jeanette Schulz-Menger, Erik B. Schelbert, Marie-Annick Clavel, David E. Newby, Saul G. Myerson, Phillipe Pibarot, Sahmin Lee, João L. Cavalcante, Seung-Pyo Lee, Gerry P. McCann, John P. Greenwood, James C. Moon, Marc R. Dweck
Journal: Journal of the American College of Cardiology (2020)

Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.
Multisite validation of a 92-gene molecular classifier: Diagnostic accuracy and clinical utility in metastatic cancer.
Authors: Catherine A. Schnabel, Sarah E Kerr, Peggy S Sullivan, Yi Zhang, Veena Singh, Brittany Carey, Mark G. Erlander, W Edward Highsmith, Sarah M Dry, Elena F Brachtel
Journal: Journal of Clinical Oncology (2012)

10588 Background: Accurate tumor classification is increasingly critical to individualized care as patient outcomes improve with use of targeted cancer therapies and predictive biomarkers. In metastatic cancers of uncertain or unknown origin, identification of a primary site remains equivocal in a significant number of cases. Gene expression signatures may improve accuracy and specificity of tumor classification, however, large-scale, blinded validation studies that demonstrate stable performance in metastatic and poorly differentiated cases are currently lacking. Methods: Seven hundred and ninety cases (51% female, 44% metastatic, 63% grade 2 and 3, 14% limited tissue specimens) representing 28 tumor types and 50 subtypes were processed and adjudicated between Mayo Clinic, UCLA and Massachusetts General Hospital. Blinded FFPE tumor sections were submitted and tested using a 92-gene RT-PCR assay (CancerTYPE ID, bioTheranostics Inc.). Molecular predictions were evaluated for concordance with the reference diagnosis; diagnostic accuracy between clinical subsets was compared. Results: The 92-gene assay demonstrated overall sensitivities of 87% for tumor classification and 82% for subtyping. Forty-seven (5.9%) cases were considered unclassifiable. Comparative analysis of performance between metastatic (n=329) and primary (n=414) tumors showed no statistically significant difference in accuracy (85% vs 88%, p=0.16). Similarly, no significant decreases in performance were observed across histological grades (p=0.58) and when comparing limited tissue to excisional biopsy specimens (p=0.16). Strong precision was demonstrated for accurate identification of a primary tumor in tissues biopsied from common metastatic sites, reported as positive predictive values of 100% for lung, brain and peritoneum, 92% for ovary and 80% for liver. Conclusions: Results from this multisite, blinded study validate the diagnostic accuracy of the 92-gene assay for classifying a diverse set of tumors, and support its clinical utility in the diagnosis of metastatic tumors to determine tissue of origin, and in the differential diagnosis of metastatic vs new primary disease.
Electrochemotherapy (ECT) with Bleomycin as a Palliative Treatment of Regional Relapse in Head and Neck Cancer (H&amp;NC) Patients (PTS). a Pilot Study
Authors: J.J. Grau, M. Caballero, A. Vilalta, I. Victoria, O. Reig, P. Gascon, C. Carrera, J. Malvehy
Journal: Annals of Oncology (2012)