tbuckley/cabot-search huggingface dataset:
Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: a systematic review and meta-analysis
Authors: G.S. Tansarli, K.C. Chapin
Journal: Clinical Microbiology and Infection (2019)

BackgroundThe FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.ObjectivesThe aim was to evaluate the ME panel in a diagnostic test accuracy review.Data sourcesThe PubMed and EMBASE databases were systematically searched through May 2019.Study eligibility criteriaEligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately.ParticipantsPatients with suspected ME for whom a panel was ordered were included.MethodsThe ME panel was compared to reference standard methods for diagnosing community-acquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel.ResultsThirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86–93%) and 97% (95% CI 94–99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease.ConclusionsThe currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.
Microrna-31 Regulates T-Cell Metabolism Via HIF1α and Promotes Effector Function
Authors: Yongxia Wu, Mengmeng Zhang, David Bastian, Mohammed Hanief Sofi, Steven Douglas Schutt, Hee-Jin Choi, Corey Mealer, Hung D Nguyen, Linlu Tian, Xue-Zhong Yu
Journal: Blood (2019)
Erratum: Corrigendum: PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin
Authors: Khalid Bajou, Stephanie Herkenne, Victor L Thijssen, Salvino D'Amico, Ngoc-Quynh-Nhu Nguyen, Ann Bouché, Sébastien Tabruyn, Mohammed Srahna, Jean-Yves Carabin, Olivier Nivelles, Cécile Paques, Ivo Cornelissen, Michelle Lion, Agnès Noel, Ann Gils, Stefan Vinckier, Paul J Declerck, Arjan W Griffioen, Mieke Dewerchin, Joseph A Martial, Peter Carmeliet, Ingrid Struman
Journal: Nature Medicine (2014)
CANOPY-1: A phase III, placebo-controlled study of pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) with/without canakinumab in untreated patients (pts) with stage IIIB/IIIC-IV NSCLC
Authors: D.S.W. Tan, T.M. Kim, B.J. Solomon, W.L. Tan, C.-J. Yu, S. Geater, G. De Castro, A. Greystoke, E. Felip, B.E. Johnson, S. Deudon, A.-L. Louveau, V.Q. Passos, B.C. Cho
Journal: Annals of Oncology (2019)
Functional Characterization of E3 Ligases and Their Regulators: Therapeutic Implications for Development of New Proteolysis-Targeting Chimeric Degraders of Oncoproteins
Authors: Ryosuke Shirasaki, Sara Gandolfi, Ricardo De Matos Simoes, Geoffrey M Matthews, Dennis Buckley, Joseline Raja, Quinlan L Sievers, Olga Dashevsky, Haley Poarch, Huihui Tang, Megan Bariteau, Michal Sheffer, Sondra L. Downey-Kopyscinski, Paul Hengeveld, Brian Glassner, Eugen Dhimolea, Christopher J. Ott, Tinghu Zhang, Nicholas P Kwiatkowski, Jacob P. Laubach, Robert L. Schlossman, Paul G. Richardson, Aedin Culhane, Richard W.J. Groen, Eric Fischer, Benjamin L. Ebert, Francisca Vazquez, Aviad Tsherniak, William C. Hahn, Joan Levy, Daniel Auclair, Jonathan D. Licht, Jonathan J Keats, Lawrence H. Boise, James Bradner, Nathanael Gray, Constantine S. Mitsiades
Journal: Blood (2019)
RNA-binding protein IGF2BP1 maintains leukemia stem cell properties by regulating HOXB4, MYB, and ALDH1A1
Authors: Irina A. Elcheva, Tyler Wood, Kathryn Chiarolanzio, Bryan Chim, Madeline Wong, Vikash Singh, Chethana P. Gowda, Qingli Lu, Markus Hafner, Sinisa Dovat, Zhenqiu Liu, Stefan A. Muljo, Vladimir S. Spiegelman
Journal: Leukemia (2019)
Patient perspectives on participation in phase 1 clinical trials.
Authors: Thomas J. Smith, Anna Cathy Williams, Betty R. Ferrell, Tami R. Borneman, Vincent Chung, Marianna Koczywas
Journal: Journal of Clinical Oncology (2019)

48 Background: Patients with solid tumors in Phase 1 clinical trials are at an important phase in the cancer trajectory. Understanding patients’ experiences can guide healthcare providers to provide optimum care. The main objectives of this study were to describe patient perspectives on participating in a Phase 1 trial, understand their disease status and treatment options and, to describe the impact of the disease and clinical trial participation on quality of life (QOL). Methods: Phase 1 patients (n = 30) who were participating in a larger randomized NCI-funded intervention trial (n = 470), were interviewed and tape recorded. The interviews were transcribed and content analysis methods were used to identify common themes. Results: Patients reported participating in the Phase 1 clinical trial because their doctors informed and encouraged them, they had no other treatment options if they wanted to live longer, or they wanted to help future cancer patients. Most patients believed that participation would improve or stabilize their illness and improve quality of life. They believed that when the clinical trial ended, there would be new treatments available. Participants reported that the physicians, nursing staff, social worker, and their families had been supportive. They reported that the treatment had been difficult on their families. Patients reported that compassion, cultural awareness, spiritual support, and the need for individual attention was important. There was little mention of end-of-life care or advance care planning. Conclusions: Patients participating in Phase 1 trials remain optimistic about treatment options while aware of their mortality. They have important needs for support to address quality of life concerns as well as better understanding their disease status, treatment options, and advance care planning for end of life care. Clinical trial information: NCT01828775.
DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells
Authors: Fangfang Zhang, Xuelei Ruan, Jun Ma, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Shuyuan Shen, Lianqi Shao, Di Wang, Chunqing Yang, Heng Cai, Zhen Li, Ziyi Feng, Yixue Xue
Journal: Molecular Therapy (2019)

Studies have found that RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are dysregulated and play an important regulatory role in the development of tumors. Based on The Cancer Genome Atlas (TCGA) database, our findings from experiments, and the evidence of previous studies, we screened DiGeorge syndrome critical region gene 8 (DGCR8), ZFAT antisense RNA 1 (ZFAT-AS1), and caudal type homeobox 2 (CDX2) as research candidates. In the present study, DGCR8 and CDX2 were highly expressed and ZFAT-AS1 was markedly downregulated in glioma tissues and cells. DGCR8 or CDX2 knockdown or ZFAT-AS1 overexpression suppressed glioma cell proliferation, migration, and invasion and facilitated apoptosis. DGCR8 might decrease ZFAT-AS1 expression by attenuating its stability in a manner of inducing its cleavage. Importantly, ZFAT-AS1 could inhibit CDX2 transcription by mediating the methylation of histone H3 on lysine 27 (H3K27me3) modification induced by PRC2 in the CDX2 promoter region. In addition, CDX2 transcriptionally activated DGCR8 expression by binding to its promoter regions, forming a positive feedback loop of DGCR8/ZFAT-AS1/CDX2. In conclusion, DGCR8/ZFAT-AS1 promotes CDX2 transcription in a PRC2 complex-dependent manner to facilitate the malignant biological behavior of glioma cells.
Regulatory T cell frequencies in patients with rheumatoid arthritis are increased by conventional and biological DMARDs but not by JAK inhibitors
Authors: Anja Meyer, Paula S Wittekind, Konstantin Kotschenreuther, Joanna Schiller, Julia von Tresckow, Thomas H Haak, David M Kofler
Journal: Annals of the Rheumatic Diseases (2019)

Regulatory T (Treg) cells play an important role in controlling immune responses. Their frequency is decreased in many autoimmune diseases, including rheumatoid arthritis (RA). We read with great interest the article by Rosenzwajg et al which presents the results of a clinical trial with low-dose interleukin-2 (ld-IL-2).1 The authors report that Treg cell frequencies were significantly increased following ld-IL-2 administration in 46 patients with autoimmune diseases. Among them, four patients had RA and received a background therapy with low-dose prednisolone (PRED) or methotrexate (MTX). The study demonstrates that ld-IL-2 administration is a successful strategy to overcome Treg cell deficiency and to increase the ratio between Treg cells and effector T cells in patients with RA and other autoimmune diseases.

Here we want to draw attention to the fact that Treg cell frequencies in patients with RA can be increased by some, but not by all, antirheumatic drugs and that the background treatment can therefore affect the results of clinical trials with IL-2. Using flow cytometry, we analysed the ex vivo frequency of CD25highCD127lowFoxP3high CD4+ Treg cells in …
Short term exposure to fine particulate matter and hospital admission risks and costs in the Medicare population: time stratified, case crossover study
Authors: Yaguang Wei, Yan Wang, Qian Di, Christine Choirat, Yun Wang, Petros Koutrakis, Antonella Zanobetti, Francesca Dominici, Joel D Schwartz
Journal: BMJ (2019)

To assess risks and costs of hospital admission associated with short term exposure to fine particulate matter with diameter less than 2.5 µm (PM
Prognostic impact of the C-reactive protein/albumin ratio in advanced pancreatic cancer treated with GEM plus nab-PTX or FOLFIRINOX: Based on the results of a multicenter retrospective study (the NAPOLEON study)
Authors: A. Makiyama, J. Nakazawa, T. Otsuka, M. Shimokawa, F. Koga, Y. Ueda, A. Komori, S. Arima, M. Fukahori, T. Honda, T. Shibuki, T. Shirakawa, K. Nio, Y. Ide, N. Ureshino, K. Mitsugi
Journal: Annals of Oncology (2019)
Abstract P210: Systolic Blood Pressure Trajectories From Childhood to Adulthood and Depression in Middle Age: The Bogalusa Heart Study
Authors: Patrick Stuchlik, Emily Harville, Wei Chen, Lydia Bazzano
Journal: Circulation (2016)

Introduction: Few studies have examined the long term patterns of blood pressure change in relation to depression in middle age. Methods: We examined data from the Bogalusa Heart Study, a long-term community-based observational study of a biracial cohort, with first measurements in childhood in 1973. Men and women (n=909) who completed the Center for Epidemiologic Studies Depression Scale (CES-D) in 2010 with at least two childhood and two adult SBP measurements were included. CES-D scores were categorized using established cut points (&lt;8, 8-15, &gt;15). Discrete mixture modeling was employed to identify trajectory groupings of (SBP), adjusted for race (time-independent) and body mass index (time-varying). The association between SBP trajectory and CES-D scores were determined using multivariable logistic regression adjusted for antihypertensive use, education, and physical activity in 2010. Results: Mean (±SD) age was 43.1±4.5 years, 57.9% were female, and 31.7% were Black. 27.7% of participants were current smokers in 2010. Mean (SD) BMI was 31.0 (7.7). We identified four SBP patterns: always low but slightly increasing (46.8%), low and modestly increasing (22.6%), healthy and stable (21.8%), and profoundly increasing (8.9%). Relative to the largest group, the multivariable adjusted odds ratio (OR) of higher CES-D categorization, i.e. more depressed, for the modestly increasing was 1.47 (95% CI, 1.01-2.15), for the stable, 0.96 (95% CI, 0.66-1.39), and for the profoundly increasing, 1.93 (95% CI, 0.66-1.39). Each additional year of education was associated with 33% decreased odds of higher CES-D categorization (OR=0.67, 95% CI 0.59-0.77). Conclusions: Trajectories of SBP from childhood through adulthood are associated with depression in middle age. Individuals with increasing SBP may benefit from depression screening in early adulthood.
Clinical and virological findings in patients with Usutu virus infection, northern Italy, 2018
Authors: Monia Pacenti, Alessandro Sinigaglia, Thomas Martello, Maria Elena De Rui, Elisa Franchin, Silvana Pagni, Elektra Peta, Silvia Riccetti, Adelaide Milani, Fabrizio Montarsi, Gioia Capelli, Carlo Giovanni Doroldi, Francesco Bigolin, Luca Santelli, Lucia Nardetto, Marco Zoccarato, Luisa Barzon
Journal: Eurosurveillance (2019)

BackgroundUsutu virus (USUV) is a mosquito-borne flavivirus, which shares its transmission cycle with the phylogenetically related West Nile virus (WNV). USUV circulates in several European countries and its activity has increased over the last 5 years.AimTo describe human cases of USUV infection identified by surveillance for WNV and USUV infection in the Veneto Region of northern Italy in 2018.MethodsFrom 1 June to 30 November 2018, all cases of suspected autochthonous arbovirus infection and blood donors who had a reactive WNV nucleic acid test were investigated for both WNV and USUV infection by in-house molecular methods. Anti-WNV and anti-USUV IgM and IgG antibodies were detected by ELISA and in-house immunofluorescence assay, respectively; positive serum samples were further tested by WNV and USUV neutralisation assays run in parallel.ResultsEight cases of USUV infection (one with neuroinvasive disease, six with fever and one viraemic blood donor who developed arthralgia and myalgia) and 427 cases of WNV infection were identified. A remarkable finding of this study was the persistence of USUV RNA in the blood and urine of three patients during follow-up. USUV genome sequences from two patients shared over 99% nt identity with USUV sequences detected in mosquito pools from the same area and clustered within lineage Europe 2.ConclusionsClinical presentation and laboratory findings in patients with USUV infection were similar to those found in patients with WNV infection. Cross-reactivity of serology and molecular tests challenged the differential diagnosis.
A consensus-based transparency checklist
Authors: Balazs Aczel, Barnabas Szaszi, Alexandra Sarafoglou, Zoltan Kekecs, Šimon Kucharský, Daniel Benjamin, Christopher D. Chambers, Agneta Fisher, Andrew Gelman, Morton A. Gernsbacher, John P. Ioannidis, Eric Johnson, Kai Jonas, Stavroula Kousta, Scott O. Lilienfeld, D. Stephen Lindsay, Candice C. Morey, Marcus Munafò, Benjamin R. Newell, Harold Pashler, David R. Shanks, Daniel J. Simons, Jelte M. Wicherts, Dolores Albarracin, Nicole D. Anderson, John Antonakis, Hal R. Arkes, Mitja D. Back, George C. Banks, Christopher Beevers, Andrew A. Bennett, Wiebke Bleidorn, Ty W. Boyer, Cristina Cacciari, Alice S. Carter, Joseph Cesario, Charles Clifton, Ronán M. Conroy, Mike Cortese, Fiammetta Cosci, Nelson Cowan, Jarret Crawford, Eveline A. Crone, John Curtin, Randall Engle, Simon Farrell, Pasco Fearon, Mark Fichman, Willem Frankenhuis, Alexandra M. Freund, M. Gareth Gaskell, Roger Giner-Sorolla, Don P. Green, Robert L. Greene, Lisa L. Harlow, Fernando Hoces de la Guardia, Derek Isaacowitz, Janet Kolodner, Debra Lieberman, Gordon D. Logan, Wendy B. Mendes, Lea Moersdorf, Brendan Nyhan, Jeffrey Pollack, Christopher Sullivan, Simine Vazire, Eric-Jan Wagenmakers
Journal: Nature Human Behaviour (2019)

We present a consensus-based checklist to improve and document the transparency of research reports in social and behavioural research. An accompanying online application allows users to complete the form and generate a report that they can submit with their manuscript or post to a public repository.
Results of a pilot randomized controlled trial: A couple-based meditation intervention for patients with metastatic lung cancer and their partners.
Authors: Kathrin Milbury, Yisheng Li, Sania Durrani, Zhongxing X. Liao, Claire Chunyi Yang, Anne S. Tsao, Lorenzo Cohen, Eduardo Bruera
Journal: Journal of Clinical Oncology (2019)

135 Background: Although mindfulness-based interventions have been widely examined in patients with early stage cancer, the feasibility and efficacy of these types of programs are largely unknown in the palliative care setting. We developed a couple-based intervention integrating meditation training with emotional disclosure exercises to target psychological distress in patients with metastatic lung cancer and their partners. Methods: Dyads completed baseline self-report measures and were then randomized to a couple-based meditation (CBM), a supportive-expressive (SE), or a waitlist control (WLC) group. Couples in the CBM and ES groups attended 4 weekly, 60 min. therapist-led sessions that were delivered via FaceTime. All groups were reassessed 1 month and 3 months later. Results: Seventy-five patients (51% female; mean age = 64 years) and their partners’ (52% female; mean age = 64 years) were randomized (63% consent rate) of which 79% completed the first and 65% completed the second follow-up assessments. Attrition was mainly due to patients’ death (44%). Although attendance was high in both groups (means: CBM = 3.12; SE = 3.08), dyads in the CBM group indicated greater benefit (P &lt; .003) and usefulness (P &lt; .05) of the sessions compared to those in the SE group. Compared with the WLC group, patients in the CBM group reported significantly lower depressive symptoms (P = .02; d = .49; CES-D means: CBM = 7.87; SE = 11.51; WLC = 12.76) and cancer specific distress (P = .05; d = .44; IES means: CBM = 12.40; SE = 16.34; WLC = 18.22). Similarly, compared with the WLC group, partners in the CBM group reported significantly lower depressive symptoms (P = .02; d = .58; means: CBM = 7.18; AC = 8.91; WLC = 11.62). For both patients and partners, there were no effects between SE and WLC groups. While small effects (d = .22-.42) in favor of the CBM group relative to the SE group were revealed, these differences were not significant. Conclusions: It seems to be feasible, acceptable and possibly efficacious to deliver dyadic interventions via FaceTime to couples coping with metastatic lung cancer. Mindfulness-based interventions may be of value to manage symptom burden in the palliative care setting. Clinical trial information: NCT02596490.
Major Vault Protein Promotes Hepatocellular Carcinoma Through Targeting Interferon Regulatory Factor 2 and Decreasing p53 Activity
Authors: Haisheng Yu, Mengqi Li, Rui He, Peining Fang, Qiming Wang, Yu Yi, Fubing Wang, Li Zhou, Yi Zhang, Aidong Chen, Nanfang Peng, Dan Liu, Mirko Trilling, Ruth Broering, Erik A.C. Wiemer, Mengji Lu, Ying Zhu, Shi Liu
Journal: Hepatology (2019)

Background and Aims Major vault protein (MVP) is up‐regulated during infections with hepatitis B virus (HBV) and hepatitis C virus (HCV). Here, we found that MVP deficiency inhibited hepatocellular carcinoma (HCC) development induced by diethylnitrosamine, hepatitis B X protein, and HCV core. Approach and Results Forced MVP expression was sufficient to induce HCC in mice. Mechanistic studies demonstrate that the ubiquitin ligase human double minute 2 (HDM2) forms mutual exclusive complexes either with interferon regulatory factor 2 (IRF2) or with p53. In the presence of MVP, HDM2 is liberated from IRF2, leading to the ubiquitination of the tumor suppressor p53. Mouse xenograft models showed that HBV and HCV promote carcinogenesis through MVP induction, resulting in a loss of p53 mediated by HDM2. Analyses of clinical samples from chronic hepatitis B, liver cirrhosis, and HCC revealed that MVP up‐regulation correlates with several hallmarks of malignancy and associates with poor overall survival. Conclusions Taken together, through the sequestration of IRF2, MVP promotes an HDM2‐dependent loss of p53 that promotes HCC development.
One-year outcomes in a multicentre cohort study of incident rare diffuse parenchymal lung disease in children (ChILD)
Authors: Steve Cunningham, Catriona Graham, Morag MacLean, Paul Aurora, Michael Ashworth, Angelo Barbato, Alistair Calder, Julia Carlens, Annick Clement, Meike Hengst, Birgit Kammer, Nural Kiper, Katarzyna Krenke, Kai Kronfeld, Joanna Lange, Julia Ley-Zaporozhan, Andrew G Nicholson, Simone Reu, Traudl Wesselak, Martin Wetzke, Andrew Bush, Nicolaus Schwerk, Matthias Griese
Journal: Thorax (2019)

We performed a prospective, observational, cohort study of children newly diagnosed with children’s interstitial lung disease (ChILD), with structured follow-up at 4, 8, 12 weeks and 6 and 12 months. 127 children, median age 0.9 (IQR 0.3–7.9) years had dyspnoea (68%, 69/102), tachypnoea (75%, 77/103) and low oxygen saturation (SpO 2 ) median 92% (IQR 88–96). Death (n=20, 16%) was the most common in those &lt;6 months of age with SpO 2 &lt;94% and developmental/surfactant disorders. We report for the first time that ChILD survivors improved multiple clinical parameters within 8–12 weeks of diagnosis. These data can inform family discussions and support clinical trial measurements.
Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study
Authors: Diane Apostolopoulos, Rangi Kandane-Rathnayake, Worawit Louthrenoo, Shue Fen Luo, Yeong-Jian Wu, Aisha Lateef, Vera Golder, Sargunan Sockalingam, Sandra Navarra, Leonid Zamora, Laniyati Hamijoyo, Yasuhiro Katsumata, Masayoshi Harigai, Madelynn Chan, Sean O'Neill, Fiona Goldblatt, Chak Sing Lau, Zhan Guo Li, Alberta Hoi, Mandy Nikpour, Eric Morand
Journal: The Lancet Rheumatology (2019)
Abstract 10703: PBI-4050 Reduces Angio-proliferative Pulmonary Arterial Hypertension: Decreased Human Pulmonary Artery Smooth Muscle Cell Proliferation and Microvascular Endothelial Cell Endoplasmic Reticulum Stress
Authors: Mohamed Jalloul Nsaibia, Quang Nguyen, Lyne Gagnon, Brigitte Grouix, Jocelyn Dupuis
Journal: Circulation (2019)

Introduction: Pulmonary arterial hypertension (PAH) is an angio-proliferative disorder leading to vascular obliteration and loss of perfusion. PBI-4050 is a dual GPR40 agonist/GPR84 antagonist with...
Anti-Ku antibodies: important points to consider
Authors: Michael Mahler, Minoru Satoh, Marvin J Fritzler
Journal: Annals of the Rheumatic Diseases (2019)

Figure 1Potential reactivity of anti-dsDNA antibodies in anti-Ku antibody assays.The Ku70/80 heterodimer exhibits dsDNA binding capacities.Consequently, if the antigen used in the Ku assay contains dsDNA, anti-dsDNA antibodies can also bind directly to the Ku70/80-dsDNA complex on the solid phase.In addition, anti-dsDNA/dsDNA complexes that might be present in the sera of patients with autoimmune diseases can generate a positive test result.In addition, other DNA-binding proteins can bind to DNA or the Ku70/80-DNA complex and also serve as autoantigenic targets (not shown for simplicity).on July 21,