tbuckley/cabot-search huggingface dataset:
Association of Type 2 Diabetes With Cancer: A Meta-analysis With Bias Analysis for Unmeasured Confounding in 151 Cohorts Comprising 32 Million People
Authors: Suping Ling, Karen Brown, Joanne K. Miksza, Lynne Howells, Amy Morrison, Eyad Issa, Thomas Yates, Kamlesh Khunti, Melanie J. Davies, Francesco Zaccardi
Journal: Diabetes Care (2020)

Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial. The goal of this work is to assess the robustness of the observational associations between T2D and cancer to unmeasured confounding.PubMed, Web of Science, and the Cochrane library were systematically searched on 10 January 2019 for observational studies investigating associations between T2D and cancer incidence or mortality.Cohort-level relative risk (RR) was extracted. RRs were combined in random-effects meta-analyses and pooled estimates used in bias analyses. A total of 151 cohorts (over 32 million people, 1.1 million cancer cases, and 150,000 cancer deaths) were included. In meta-analyses, T2D was associated with incidence of several cancers, from prostate (RR 0.83; 95% CI 0.79, 0.88) to liver (2.23; 1.99, 2.49), and with mortality from pancreatic cancer (1.67; 1.30, 2.14). In bias analyses, assuming an unmeasured confounding associated with both T2D and cancer with a RR of 1.5, the proportion of studies with a true effect size larger than a RR of 1.1 (i.e., 10% increased risk in individuals with T2D) was nearly 100% for liver, pancreatic, and endometrial, 86% for gallbladder, 67% for kidney, 64% for colon, 62% for colorectal, and <50% for other cancer incidences, and 92% for pancreatic cancer mortality.Biases other than unmeasured confounding were not analytically assessed.Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancer mortality. Conversely, associations with other cancers were less robust to unmeasured confounding.
Minimally Invasive Surgery and Risk of Capsule Rupture for Women With Early-Stage Ovarian Cancer
Authors: Koji Matsuo, Yongmei Huang, Shinya Matsuzaki, Maximilian Klar, Lynda D. Roman, Anil K. Sood, Jason D. Wright
Journal: JAMA Oncology (2020)

Roni Nitecki, MD; Pedro T. Ramirez, MD; Michael Frumovitz, MD, MPH; Kate J. Krause, MLIS; Ana I. Tergas, MD, MPH; Jason D. Wright, MD; J. Alejandro Rauh-Hain, MD, MPH; Alexander Melamed, MD, MPH
Oral epithelial IL-22/STAT3 signaling licenses IL-17–mediated immunity to oral mucosal candidiasis
Authors: Felix E. Y. Aggor, Timothy J. Break, Giraldina Trevejo-Nuñez, Natasha Whibley, Bianca M. Coleman, Rachel D. Bailey, Daniel H. Kaplan, Julian R. Naglik, Wei Shan, Amol C. Shetty, Carrie McCracken, Scott K. Durum, Partha S. Biswas, Vincent M. Bruno, Jay K. Kolls, Michail S. Lionakis, Sarah L. Gaffen
Journal: Science Immunology (2020)

IL-22 signaling limits oral candidiasis via proliferation of basal epithelial cells and replenishment of an IL-17–responsive layer.
GRK5 Controls SAP97-Dependent Cardiotoxic β <sub>1</sub> Adrenergic Receptor-CaMKII Signaling in Heart Failure
Authors: Bing Xu, Minghui Li, Ying Wang, Meimi Zhao, Stefano Morotti, Qian Shi, Qingtong Wang, Federica Barbagallo, Jian-Peng Teoh, Gopireddy R. Reddy, Elizabeth F. Bayne, Yongming Liu, Ao Shen, Jose L. Puglisi, Ying Ge, Ji Li, Eleonora Grandi, Madeline Nieves-Cintron, Yang K. Xiang
Journal: Circulation Research (2020)

Cardiotoxic β1 adrenergic receptor (β1AR)-CaMKII (calmodulin-dependent kinase II) signaling is a major and critical feature associated with development of heart failure. SAP97 (synapse-associated protein 97) is a multifunctional scaffold protein that binds directly to the C-terminus of β1AR and organizes a receptor signalosome.We aim to elucidate the dynamics of β1AR-SAP97 signalosome and its potential role in chronic cardiotoxic β1AR-CaMKII signaling that contributes to development of heart failure.The integrity of cardiac β1AR-SAP97 complex was examined in heart failure. Cardiac-specific deletion of SAP97 was developed to examine β1AR signaling in aging mice, after chronic adrenergic stimulation, and in pressure overload hypertrophic heart failure. We show that the β1AR-SAP97 signaling complex is reduced in heart failure. Cardiac-specific deletion of SAP97 yields an aging-dependent cardiomyopathy and exacerbates cardiac dysfunction induced by chronic adrenergic stimulation and pressure overload, which are associated with elevated CaMKII activity. Loss of SAP97 promotes PKA (protein kinase A)-dependent association of β1AR with arrestin2 and CaMKII and turns on an Epac (exchange protein directly activated by cAMP)-dependent activation of CaMKII, which drives detrimental functional and structural remodeling in myocardium. Moreover, we have identified that GRK5 (G-protein receptor kinase-5) is necessary to promote agonist-induced dissociation of SAP97 from β1AR. Cardiac deletion of GRK5 prevents adrenergic-induced dissociation of β1AR-SAP97 complex and increases in CaMKII activity in hearts.These data reveal a critical role of SAP97 in maintaining the integrity of cardiac β1AR signaling and a detrimental cardiac GRK5-CaMKII axis that can be potentially targeted in heart failure therapy. Graphical Abstract: A graphical abstract is available for this article.
Evaluation of Tumor Burden for Predicting Survival in Patients with Follicular Lymphoma Receiving First-Line R-CHOP Treatment: Comparison of Different Definition of GELF Criteria
Authors: Harumi Kato, Naoyuki Tange, Chisako Iriyama, Yuki Kojima, Hirofumi Taji, Tomohiro Kinoshita, Yasushi Yatabe, Shigeo Nakamura, Kazuhito Yamamoto
Journal: Blood (2017)
Autism-associated SHANK3 mutations impair maturation of neuromuscular junctions and striated muscles
Authors: Anne-Kathrin Lutz, Stefanie Pfaender, Berra Incearap, Valentin Ioannidis, Ilaria Ottonelli, Karl J. Föhr, Judith Cammerer, Marvin Zoller, Julia Higelin, Federica Giona, Maximilian Stetter, Nicole Stoecker, Najwa Ouali Alami, Michael Schön, Michael Orth, Stefan Liebau, Gotthold Barbi, Andreas M. Grabrucker, Richard Delorme, Michael Fauler, Benjamin Mayer, Sarah Jesse, Francesco Roselli, Albert C. Ludolph, Thomas Bourgeron, Chiara Verpelli, Maria Demestre, Tobias M. Boeckers
Journal: Science Translational Medicine (2020)

The autism-associated protein SHANK3 is essential for the maturation of neuromuscular junctions and striated muscles.
The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice
Authors: Samantha M. Solon-Biet, Aisling C. McMahon, J. William O. Ballard, Kari Ruohonen, Lindsay E. Wu, Victoria C. Cogger, Alessandra Warren, Xin Huang, Nicolas Pichaud, Richard G. Melvin, Rahul Gokarn, Mamdouh Khalil, Nigel Turner, Gregory J. Cooney, David A. Sinclair, David Raubenheimer, David G. Le Couteur, Stephen J. Simpson
Journal: Cell Metabolism (2020)
SAT0096 DISCORDANCE BETWEEN SUBJECTIVE AND OBJECTIVE INDEX OF THE DISEASE ACTIVITY SCORE MAY REDUCE THE CORRELATION BETWEEN CLINICAL AND ULTRASOUND ASSESSMENT IN RHEUMATOID ARTHRITIS
Authors: A. Xie, L. Ji, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: There was discordance between subjective and objective index of the disease activity score, or between clinical parameters and ultrasound findings in some RA patients. Therefore, we set out to determine whether the discordance between subjective and objective index of the composite score could reduce the correlation between clinical and ultrasound parameters in RA. Objectives: To investigate whether the discordance between tender and swollen joint count (TJC and SJC) as well as patient’s and evaluator’s global assessment (PGA and EGA) influences the correlation between clinical and US parameters in RA. Methods: RA patients with available ultrasonography of 28 joints from Jan 2014 to Jan 2018 were enrolled in the study. Gray-scale (GS) synovial hypertrophy and Power Doppler (PD) synovitis were measured and semi-quantitatively graded. The total GS/PD score was the sum score of 28 joints. SJC and TJC based on 28 joints, PGA and EGA of all the patients were evaluated by one rheumatologist. The numeric difference between TJC and SJC (ΔTSJ) and that between PGA and EGA (ΔPEG) were calculated. The correlation between clinical and ultrasound parameters in different ΔTSJ and ΔPEG subgroups was explored. Results: Totally 163 patients were enrolled in the study. Clinical composite disease activity scores and all the components were significantly correlated with the total GS and PD scores (p&lt;0.01 for all). But the relevance between the clinical disease parameters and total PD score became weak, with the increase of ΔTSJ. For the patients with ΔTSJ &gt; 5, the total PD score was only correlated with CRP, EGA and PGA, while the total GS score was only correlated with CRP. Similarly, no correlation between total PD score and clinical parameters, except for SJC, was observed in patients with ΔPEG &lt; 0 (p &lt; 0.05). Conclusion: Total PD/GS score was correlated well with the clinical parameters of disease activity, including both the subjective and objective indexes. But for patients with ΔTSJ &gt; 5,there was no correlation between total GS/PD scores and clinical composite disease activity scores, except that only the objective index (CRP, SJC and EGA) were more likely to correlate with total GS/PD scores. Disclosure of Interests: None declared
BACH2 drives quiescence and maintenance of resting Treg cells to promote homeostasis and cancer immunosuppression
Authors: Francis M. Grant, Jie Yang, Rabab Nasrallah, James Clarke, Firas Sadiyah, Sarah K. Whiteside, Charlotte J. Imianowski, Paula Kuo, Panagiota Vardaka, Tihomir Todorov, Nordin Zandhuis, Ilinca Patrascan, David F. Tough, Kohei Kometani, Robert Eil, Tomohiro Kurosaki, Klaus Okkenhaug, Rahul Roychoudhuri
Journal: The Journal of Experimental Medicine (2020)

Regulatory T (Treg) cell populations are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification, but its function following lineage commitment is unresolved. Here, we show that BACH2 is repurposed following Treg lineage commitment and promotes the quiescence and long-term maintenance of rTreg cells. Bach2 is highly expressed in rTreg cells but is down-regulated in aTreg cells and during inflammation. In rTreg cells, BACH2 binds to enhancers of genes involved in aTreg differentiation and represses their TCR-driven induction by competing with AP-1 factors for DNA binding. This function promotes rTreg cell quiescence and long-term maintenance and is required for immune homeostasis and durable immunosuppression in cancer. Thus, BACH2 supports a "division of labor" between quiescent rTreg cells and their activated progeny in Treg maintenance and function, respectively.
Managing ICU surge during the COVID-19 crisis: rapid guidelines
Authors: Shadman Aziz, Yaseen M. Arabi, Waleed Alhazzani, Laura Evans, Giuseppe Citerio, Katherine Fischkoff, Jorge Salluh, Geert Meyfroidt, Fayez Alshamsi, Simon Oczkowski, Elie Azoulay, Amy Price, Lisa Burry, Amy Dzierba, Andrew Benintende, Jill Morgan, Giacomo Grasselli, Andrew Rhodes, Morten H. Møller, Larry Chu, Shelly Schwedhelm, John J. Lowe, Du Bin, Michael D. Christian
Journal: Intensive Care Medicine (2020)

Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff.
Recurrent vulvovaginal candidiasis
Authors: Annabel Lines, Inna Vardi-Flynn, Clare Searle
Journal: BMJ (2020)

### What you need to know A 22 year old woman asks your advice for treating recurrent thrush. She has self managed with over-the-counter treatments eight times in the past six months. She is frustrated and wants to know why it keeps coming back. Recurrent vulvovaginal candidiasis (RVVC) is a common problem, with an estimated prevalence of 9% in women aged 25-34 years.1 In this article we offer an approach to a safe and effective assessment of a woman presenting in primary care with symptoms of RVVC. We highlight key points from the recently updated British Association of Sexual Health and HIV (BASHH) guideline2 combined with tips from our clinical experience as general practitioners with a special interest in women's health. ### What are the symptoms of recurrent vulvovaginal candidiasis? Typical symptoms of RVVC are vulval itching and a non-offensive vaginal discharge. Other common symptoms include soreness, superficial dyspareunia, and a cyclical pattern of symptoms.2 Although a curd-like discharge is typical, discharge can be thin or absent altogether. A green or yellow discharge, or one with an offensive odour, may indicate other causes of infection. ### What else should you cover in the history? Ask if the patient has a history of skin problems such as psoriasis or eczema. Does she have poorly controlled diabetes or symptoms of undiagnosed diabetes? Does she have any medical conditions or take any medications that might cause immunosuppression? Patients are often keen to explore any underlying causes or contributing factors, to help avoid further recurrences. These are listed in box 1. Box 1 ### Causes and triggers for recurrent vulvovaginal candidiasis (RVVC)RETURN TO TEXT
Complications following symptom-limited thoracentesis using suction
Authors: Ala Eddin S. Sagar, Maria F. Landaeta, Andres M. Adrianza, Grecia L. Aldana, Leonardo Pozo, Aristides Armas-Villalba, Christian C. Toquica, Andrew J. Larson, Macarena R. Vial, Horiana B. Grosu, David E. Ost, George A. Eapen, Ajay Sheshadri, Rodolfo C. Morice, Vickie R. Shannon, Lara Bashoura, Diwakar D. Balachandran, Francisco A. Almeida, Mateen H. Uzbeck, Roberto F. Casal, Saadia A. Faiz, Carlos A. Jimenez
Journal: European Respiratory Journal (2020)

Background Thoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO. Methods A retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included. Results Pleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04–0.54%; 95% CI 0.13–2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p&lt;0.01). Conclusions Symptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.
Association of Low-Value Testing With Subsequent Health Care Use and Clinical Outcomes Among Low-risk Primary Care Outpatients Undergoing an Annual Health Examination
Authors: Zachary Bouck, Andrew J. Calzavara, Noah M. Ivers, Eve A. Kerr, Cherry Chu, Jacob Ferguson, Danielle Martin, Joshua Tepper, Peter C. Austin, Peter Cram, Wendy Levinson, R. Sacha Bhatia
Journal: JAMA Internal Medicine (2020)

The association of low-value testing with downstream care and clinical outcomes among primary care outpatients is unknown to date.To assess the association of low-value testing with subsequent care among low-risk primary care outpatients undergoing an annual health examination (AHE).This population-based retrospective cohort study used administrative health care claims from Ontario, Canada, for primary care outpatients undergoing an AHE between April 1, 2012, and March 31, 2016, to identify individuals who could be placed into one (or more) of the following 3 cohorts: adult patients (18 years or older) at low risk for cardiovascular and pulmonary disease, adult patients at low risk for cardiovascular disease, and female patients (aged 13-20 years or older than 69 years) at low risk for cervical cancer. The dates of analysis were June 3 to September 12, 2019.Low-value screening tests were defined per cohort as (1) a chest radiograph within 7 days, (2) an electrocardiogram (ECG) within 30 days, or (3) a Papanicolaou test within 7 days after an AHE.Subsequent specialist visits, diagnostic tests, and procedures within 90 days after a low-value test (if the patient had a chest radiograph, ECG, or Papanicolaou test) or end of the exposure observation window (if not tested).Included in the chest radiograph, ECG, and Papanicolaou test cohorts of propensity score-matched pairs were 43 532 patients (mean [SD] age, 47.5 [14.4] years; 38.5% female), 245 686 patients (mean [SD] age, 49.9 [13.7] years; 51.1% female), and 29 194 patients (mean [SD] age, 45.5 [27.1] years; 100% female), respectively. At 90 days, chest radiographs in low-risk patients were associated with an additional 0.87 (95% CI, 0.69-1.05) and 1.96 (95% CI, 1.71-2.22) patients having an outpatient pulmonology visit or an abdominal or thoracic computed tomography scan per 100 patients, respectively, and ECGs in low-risk patients were associated with an additional 1.92 (95% CI, 1.82-2.02), 5.49 (95% CI, 5.33-5.65), and 4.46 (95% CI, 4.31-4.61) patients having an outpatient cardiologist visit, a transthoracic echocardiogram, or a cardiac stress test per 100 patients, respectively. At 180 days, Papanicolaou testing in low-risk patients was associated with an additional 1.31 (95% CI, 0.84-1.78), 52.8 (95% CI, 51.9-53.6), and 0.84 (95% CI, 0.66-1.01) patients having an outpatient gynecology visit, a follow-up Papanicolaou test, or colposcopy per 100 patients, respectively.Observed associations in this population-based cohort study suggest that testing in low-risk patients as part of an AHE increases the likelihood of subsequent specialist visits, diagnostic tests, and procedures.
SARS-CoV-2 Infections and Serologic Responses from a Sample of U.S. Navy Service Members — USS Theodore Roosevelt, April 2020
Authors: Daniel C. Payne, Sarah E. Smith-Jeffcoat, Gosia Nowak, Uzo Chukwuma, Jesse R. Geibe, Robert J. Hawkins, Jeffrey A. Johnson, Natalie J. Thornburg, Jarad Schiffer, Zachary Weiner, Bettina Bankamp, Michael D. Bowen, Adam MacNeil, Monita R. Patel, Eric Deussing, Bruce L. Gillingham, Rebekah Tiller, Rene Galloway, Shannon Rogers, Brett Whitaker, Ashley Kondas, Peyton Smith, Christopher Lee, James Graziano
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Compared with the volume of data on coronavirus disease 2019 (COVID-19) outbreaks among older adults, relatively few data are available concerning COVID-19 in younger, healthy persons in the United States (1,2). In late March 2020, the aircraft carrier USS Theodore Roosevelt arrived at port in Guam after numerous U.S. service members onboard developed COVID-19. In April, the U.S. Navy and CDC investigated this outbreak, and the demographic, epidemiologic, and laboratory findings among a convenience sample of 382 service members serving aboard the aircraft carrier are reported in this study. The outbreak was characterized by widespread transmission with relatively mild symptoms and asymptomatic infection among this sample of mostly young, healthy adults with close, congregate exposures. Service members who reported taking preventive measures had a lower infection rate than did those who did not report taking these measures (e.g., wearing a face covering, 55.8% versus 80.8%; avoiding common areas, 53.8% versus 67.5%; and observing social distancing, 54.7% versus 70.0%, respectively). The presence of neutralizing antibodies, which represent antibodies that inhibit SARS-CoV-2, among the majority (59.2%) of those with antibody responses is a promising indicator of at least short-term immunity. This report improves the understanding of COVID-19 in the U.S. military and among young adults in congregate settings and reinforces the importance of preventive measures to lower risk for infection in similar environments.
THU0146 DAS28-REMISSION IS ASSOCIATED WITH AN INCREASE OF FINGER JOINT SPACE WIDTH IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Pfeil, A. Nussbaum, D. Renz, A. Malich, J. Böttcher, P. Oelzner, G. Wolf
Journal: Annals of the Rheumatic Diseases (2020)

Background: The reduction of finger joint space width in patients with rheumatoid arthritis (RA) is associated with joint destruction. Anti-TNF treatment with certolizumab pegol is an effective therapy in RA-patients. The computer-assisted joint space analysis is a new computer based technique to measure joint space width on hand radiographs. Objectives: The aim of this post-hoc analysis of the data set used in the RAPID 1 trial was to quantify finger joint space width of RA patients treated with Certolizumab pegol in Association to DAS28-remission. Methods: The post-hoc analysis includes 297 patients. These patients were treated with certolizumab pegol 200 mg (every two weeks) plus methotrexate and certolizumab pegol 400 mg (every two weeks) plus methotrexate. All patients underwent x-rays of the hand at baseline and week 52 as well as the quantification of finger joint space width of the metacarpal-phalangeal articulations (MCP) using the computer-assisted joint space analysis (Version 1.3.6; Sectra; Sweden). The joint space distance is expressed as mean joint space width of the MCP joints I to V (JSD-MCP total). Remission was defined with a Disease Activity Score 28 &lt; 2.6. Results: The group with DAS28-remission (DAS28 &lt; 2.6) presented a significant joint space increase with 3.3 % for JSD-MCP total from 0.152 ± 0.033 cm (baseline) to 0.157 ± 0.033 cm (week 52) treated with certolizumab pegol 200 mg as well as with 3.9 % for JSD-MCP total from 0.152 ± 0.031 cm (baseline) to 0.158 ± 0.032 cm (week 52). For the patients without DAS28-remission (DAS28 &gt; 2.6) under the treatment with certolizumab pegol 400 mg a non-significant change of JSD-MCP total from 0.145 ± 0.034 cm (baseline) to 0.144 ± 0.036 cm (week 52) was observed. A similar result was evaluated for the certolizumab pegol 200 mg group (JSD-MCP total: 0.146 ± 0.037 cm [baseline] to 0.143 ± 0.037 cm [week 52]). Conclusion: The study highlights that patients treated with certolizumab pegol plus methotrexat and a DAS-Remission showed an increase of joint space width of the metacarpal-phalangeal articulations which is potentially associated with reparative effects of the cartilage under the anti-TNF treatment with certolizumab pegol. References: N/A Disclosure of Interests: Alexander Pfeil Grant/research support from: This study Investigator Initiated Study “Automatic assessment of joint space narrowing in rheumatoid arthritis based on the Post-hoc analysis” (number: IIS-2016-110818) is a part of the of the Investigator Initiated Study “The quantification of inflammatory related periarticular bone loss in certolizumab pegol treated patients with rheumatoid arthritis” (number: IIS-2014-101458) which is supported by UCB Pharma GmbH, Monheim, Germany., Anica Nussbaum: None declared, Diane Renz: None declared, Ansgar Malich: None declared, Joachim Böttcher: None declared, Peter Oelzner: None declared, Gunter Wolf: None declared