tbuckley/cabot-search huggingface dataset:
Diabetes mellitus and latent tuberculosis infection: baseline analysis of a large UK cohort
Authors: Charlotte Jackson, Jo Southern, Ajit Lalvani, Francis Drobniewski, Chris J Griffiths, Marc Lipman, Graham H Bothamley, Jonathan J Deeks, Ambreen Imran, Onn Min Kon, Sithembinkosi Mpofu, Vladyslav Nikolayevskyy, Melanie Rees-Roberts, Alice Sitch, Saranya Sridhar, Chuen-Yan Tsou, Hilary Whitworth, Ibrahim Abubakar
Journal: Thorax (2018)

We conducted a cross-sectional analysis of baseline data from a UK cohort study which enrolled participants at risk of latent tuberculosis infection (LTBI, defined as a positive result for either of the two interferon gamma release assays). Binomial regression with a log link was used to estimate crude and adjusted prevalence ratios (PRs) and 95% CIs for the relationship between diabetes mellitus (DM) and LTBI. Adjusted for age, sex, ethnicity, body mass index and the presence of other immunocompromising conditions, DM was associated with a 15% higher prevalence of LTBI (adjusted PR=1.15, 95% CI 1.02 to 1.30, p=0.025). TRIAL REGISTRATION NUMBER: PREDICT is registered on clinicaltrials.gov (NCT01162265).
Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza
Authors: Jake Dunning, Simon Blankley, Long T. Hoang, Mike Cox, Christine M. Graham, Philip L. James, Chloe I. Bloom, Damien Chaussabel, Jacques Banchereau, Stephen J. Brett, Miriam F. Moffatt, Anne O’Garra, Peter J. M. Openshaw
Journal: Nature Immunology (2018)
Maria Theresa Goretti Thaddeus Campbell
Authors: P Cronin, E Whitfield, K Hurren
Journal: BMJ (2018)

Maria Theresa Goretti Thaddeus Campbell attributed her remarkable list of names to her maternal grandmother, who, she said, was a McGregor and thought the daughter of a Campbell would need to have a claim on as many saints as possible.

After hospital and GP training posts, Maria worked for four years in Zambia, where …
Abstract IA14: Lessons from modeling neural tumors in mice
Authors: Xuan-Hua Xie, Sheila Alcantara, Dan Laks, Yufeng Shi, Luis F. Parada
Journal: Cancer Research (2018)

Abstract We have used genetically engineered mouse models to study GBM. In particular, through mutation of glioma relevant genes (P53; Pten; Nf1) we have examined the scope of the cell of origin for these tumors. We find that as cells in the adult neural stem cell lineage progress, their capacity to undergo glioma formation is largely compromised though cellular phenotypes arise as a consequence of mutation. We find that in the subventricular zone, only quiescent stem cells and early progenitors can readily form GBM following mutation. Our search for additional cells of origin has further identified additional source cells for these tumors. GBM can arise from the OPC lineage following the same mutations, and these tumors have a distinct signature that can be identified among the TCGA GBM data sets. Thus the cell of origin is constrained to stem-like cells and tumor characteristics include signatures revealing the lineage of origin. We have further examined the properties of tumor growth and transplantation and find that these tumors grow in hierarchical fashion with a relatively small and quiescent cell population at the apex. These “cancer stem cells” can be identified and isolated. New single-cell sequencing technology promises to reveal many previous secrets from these cells. Understanding how a stem cell transforms into a cancer stem cell may provide novel approaches for therapeutic targeting. Citation Format: Xuan-Hua Xie, Sheila Alcantara, Dan Laks, Yufeng Shi, Luis F. Parada. Lessons from modeling neural tumors in mice [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA14.
Ultrahigh-resolution optical coherence microscopy accurately classifies precancerous and cancerous human cervix free of labeling
Authors: Xianxu Zeng, Xiaoan Zhang, Canyu Li, Xiaofang Wang, Jason Jerwick, Tao Xu, Yuan Ning, Yihong Wang, Linlin Zhang, Zhan Zhang, Yutao Ma, Chao Zhou
Journal: Theranostics (2018)

Cervical cancer remains the fourth most common cause of cancer worldwide and the third leading cause of cancer deaths for women in developing countries.Traditional screening tools, such as human papillomavirus and Pap tests, cannot provide results in real-time and cannot localize suspicious regions.Colposcopy-directed biopsies are invasive in nature and only a few sites of the cervix may be chosen for investigation.A non-invasive, label-free and real-time imaging method with a resolution approaching that of histopathology is desirable for early detection of the disease.Methods: Ultrahigh-resolution optical coherence microscopy (OCM) is an emerging imaging technique used to obtain 3-dimensional (3-D) "optical biopsies" of biological samples with cellular resolution.In this study, 497 3-D OCM datasets from 159 specimens were collected from 92 patients.Results: Distinctive patterns for normal cervix, squamocolumnar junction, ectropion, low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL) and invasive cervical lesions were clearly observed from OCM images, which matched well with corresponding histological slides.OCM images demonstrated a sensitivity of 80% (95% confidence interval, CI, 72%-86%) and a specificity of 89% (95% CI, 84%-93%) for detecting high-risk lesions (HSIL and invasive lesions) when blindly tested by three investigators.A substantial inter-observer agreement was observed (κ=0.627), which showed high diagnostic consistency among three investigators. Conclusion:These results laid the foundation for future non-invasive optical evaluation of cervical tissue in vivo, which could lead to a less invasive and more effective screening and "see-and-treat" strategy for the management of cervical cancer.
National Rates of Initiation and Intensification of Antidiabetic Therapy Among Patients With Commercial Insurance
Authors: Lauren G. Gilstrap, Ateev Mehrotra, Barbara Bai, Sherri Rose, Rachel A. Blair, Michael E. Chernew
Journal: Diabetes Care (2018)

OBJECTIVE Prompt initiation and intensification of antidiabetic therapy can delay or prevent complications from diabetes. We sought to understand the rates of and factors associated with the initiation and intensification of antidiabetic therapy among commercially insured patients in the U.S. RESEARCH DESIGN AND METHODS Using 2008–2015 commercial claims linked with laboratory and pharmacy data, we created an initiation cohort with no prior antidiabetic drug use and an HbA1c ≥8% (64 mmol/mol) and an intensification cohort of patients with an HbA1c ≥8% (64 mmol/mol) who were on a stable dose of one noninsulin diabetes drug. Using multivariable logistic regression, we determined the rates of and factors associated with initiation and intensification. In addition, we determined the percent of variation in treatment patterns explained by measurable patient factors. RESULTS In the initiation cohort (n = 9,799), 63% of patients received an antidiabetic drug within 6 months of the elevated HbA1c test. In the intensification cohort (n = 10,941), 82% had their existing antidiabetic therapy intensified within 6 months of the elevated HbA1c test. Higher HbA1c levels, lower generic drug copayments, and more frequent office visits were associated with higher rates of both initiation and intensification. Better patient adherence prior to the elevated HbA1c level, existing therapy with a second-generation antidiabetic drug, and lower doses of existing therapy were also associated with intensification. Patient factors explained 7.96% of the variation in initiation and 7.35% of the variation in intensification. CONCLUSIONS Approximately two-thirds of patients were newly initiated on antidiabetic therapy, and four-fifths of those already receiving antidiabetic therapy had it intensified within 6 months of an elevated HbA1c in a commercially insured population. Patient factors explain 7–8% of the variation in diabetes treatment patterns.
Effect of Acupuncture vs Sham Acupuncture on Live Births Among Women Undergoing In Vitro Fertilization
Authors: Caroline A. Smith, Sheryl de Lacey, Michael Chapman, Julie Ratcliffe, Robert J. Norman, Neil P. Johnson, Clare Boothroyd, Paul Fahey
Journal: JAMA (2018)

Acupuncture is widely used by women undergoing in vitro fertilization (IVF), although the evidence for efficacy is conflicting.To determine the efficacy of acupuncture compared with a sham acupuncture control performed during IVF on live births.A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016.Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points.The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks' gestation or birth weight of at least 400 g.Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean [SD] age, 35.4 [4.3] years); 371 [45.0%] had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% [95% CI, -4.9% to 5.8%]; relative risk, 1.02 [95% CI, 0.76 to 1.38]).Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF.anzctr.org.au Identifier: ACTRN12611000226909.
Genomic Epidemiology Reconstructs the Introduction and Spread of Zika Virus in Central America and Mexico
Authors: Julien Thézé, Tony Li, Louis du Plessis, Jerome Bouquet, Moritz U.G. Kraemer, Sneha Somasekar, Guixia Yu, Mariateresa de Cesare, Angel Balmaseda, Guillermina Kuan, Eva Harris, Chieh-hsi Wu, M. Azim Ansari, Rory Bowden, Nuno R. Faria, Shigeo Yagi, Sharon Messenger, Trevor Brooks, Mars Stone, Evan M. Bloch, Michael Busch, José E. Muñoz-Medina, Cesar R. González-Bonilla, Steven Wolinsky, Susana López, Carlos F. Arias, David Bonsall, Charles Y. Chiu, Oliver G. Pybus
Journal: Cell Host & Microbe (2018)

The Zika virus (ZIKV) epidemic in the Americas established ZIKV as a major public health threat and uncovered its association with severe diseases, including microcephaly. However, genetic epidemiology in some at-risk regions, particularly Central America and Mexico, remains limited. We report 61 ZIKV genomes from this region, generated using metagenomic sequencing with ZIKV-specific enrichment, and combine phylogenetic, epidemiological, and environmental data to reconstruct ZIKV transmission. These analyses revealed multiple independent ZIKV introductions to Central America and Mexico. One introduction, likely from Brazil via Honduras, led to most infections and the undetected spread of ZIKV through the region from late 2014. Multiple lines of evidence indicate biannual peaks of ZIKV transmission in the region, likely driven by varying local environmental conditions for mosquito vectors and herd immunity. The spatial and temporal heterogeneity of ZIKV transmission in Central America and Mexico challenges arbovirus surveillance and disease control measures.
びまん性石灰化冠動脈責任病変(DCCL)の糖尿病患者におけるエベロリムス溶出ステント(EES)留置の有効性:2年間臨床フォローアップの転帰
Authors: Ishikawa Mayuko, Yano Hideki, Horinaka Shigeo, Ishimitsu Toshihiko
Journal: Circulation (2013)
Evolution of pancreatectomy with en bloc venous resection for pancreatic cancer in Italy. Retrospective cohort study on 425 cases in 10 pancreatic referral units
Authors: Giuseppe Nigri, Niccolò Petrucciani, Antonio Daniele Pinna, Matteo Ravaioli, Elio Jovine, Francesco Minni, Gian Luca Grazi, Piero Chirletti, Gianpaolo Balzano, Fabio Ferla, Luciano De Carlis, Giuseppe Tisone, Niccolò Napoli, Ugo Boggi, Giovanni Ramacciato
Journal: International Journal of Surgery (2018)
The Evolution of Gene Expression Underlying Vision Loss in Cave Animals
Authors: David B Stern, Keith A Crandall
Journal: Molecular Biology and Evolution (2018)

Dissecting the evolutionary genetic processes underlying eye reduction and vision loss in obligate cave-dwelling organisms has been a long-standing challenge in evolutionary biology. Independent vision loss events in related subterranean organisms can provide critical insight into these processes as well as into the nature of convergent loss of complex traits. Advances in evolutionary developmental biology have illuminated the significant role of heritable gene expression variation in the evolution of new forms. Here, we analyze gene expression variation in adult eye tissue across the freshwater crayfish, representing four independent vision-loss events in caves. Species and individual expression patterns cluster by eye function rather than phylogeny, suggesting convergence in transcriptome evolution in independently blind animals. However, this clustering is not greater than what is observed in surface species with conserved eye function after accounting for phylogenetic expectations. Modeling expression evolution suggests that there is a common increase in evolutionary rates in the blind lineages, consistent with a relaxation of selective constraint maintaining optimal expression levels. This is evidence for a repeated loss of expression constraint in the transcriptomes of blind animals and that convergence occurs via a similar trajectory through genetic drift.
IL‐3–producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model
Authors: R. Rignault‐Bricard, F. Machavoine, S. Mecheri, O. Hermine, E. Schneider, M. Dy, M. Leite‐de‐Moraes
Journal: Allergy (2018)

Basophils are commonly associated with allergic responses because of their ability to produce large amounts of pro-Th2 cytokines and histamine. However, the mechanisms through which bone marrow-resident basophils (BMRB) become fully competent cytokine and histamine producers in response to IgE crosslinking are poorly understood. Here, we sought to determine the role of IL-3 in promoting pro-Th2 basophils.BMRB and basophils exposed to IL-3 in vitro and in vivo were evaluated for their production of Th2 cytokines and histamine in response to FcεRI crosslinking on both protein and gene expression levels. In vivo relevance of our findings was assessed in a model of ovalbumin-induced allergic asthma using IL-3-deficient and wild-type mice in a protocol of adoptive basophil transfer.We show that BMRB and basophils previously exposed to IL-3 differ in their ability to generate cytokines (IL-4, IL-6, IL-13, and GM-CSF) and histamine in response to FcεRI crosslinking, reflecting two stages of maturation. Exposure to IL-3 initiated an autocrine loop of endogenous IL-3 production that enhanced histamine and cytokine production upon FcεRI crosslinking. This increased responsiveness required calcium flux and was dependent on calcineurin and store-operated calcium channels. Our findings are of pathophysiological relevance, as assessed by the failure of IL-3-deficient mice to develop airway hyperreactivity, which could be restored by adoptive transfer of IL-3-derived basophils recovered from wild-type mice.IL-3-dependent basophils promote Th2 allergic AHR, which designates the IL-3/basophil axis as a promising therapeutic target for the treatment of basophil-dependent asthma.
Biomarkers for Homologous Recombination Deficiency in Cancer
Authors: Michal M Hoppe, Raghav Sundar, David S P Tan, Anand D Jeyasekharan
Journal: JNCI Journal of the National Cancer Institute (2018)

Defective DNA repair is a common hallmark of cancer. Homologous recombination is a DNA repair pathway of clinical interest due to the sensitivity of homologous recombination-deficient cells to poly-ADP ribose polymerase (PARP) inhibitors. The measurement of homologous recombination deficiency (HRD) in cancer is therefore vital to the appropriate design of clinical trials incorporating PARP inhibitors. However, methods to identify HRD in tumors are varied and controversial. Understanding existing and new methods to measure HRD is important to their appropriate use in clinical trials and practice. The aim of this review is to summarize the biology and clinical validation of current methods to measure HRD, to aid decision-making for patient stratification and translational research in PARP inhibitor trials. We discuss the current clinical development of PARP inhibitors, along with established indicators for HRD such as germline BRCA1/2 mutation status and clinical response to platinum-based therapy. We then examine newer assays undergoing clinical validation, including 1) somatic mutations in homologous recombination genes, 2) "genomic scar" assays using array-based comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) analysis or mutational signatures derived from next-generation sequencing, 3) transcriptional profiles of HRD, and 4) phenotypic or functional assays of protein expression and localization. We highlight the strengths and weaknesses of each of these assays, for consideration during the design of studies involving PARP inhibitors.
Risk of Psychosis in Recurrent Episodes of Psychotic and Nonpsychotic Major Depressive Disorder: A Systematic Review and Meta-Analysis
Authors: J. Craig Nelson, David Bickford, Kevin Delucchi, Jess G. Fiedorowicz, William H. Coryell
Journal: American Journal of Psychiatry (2018)

The authors conducted a systematic review and meta-analysis to determine whether the risk of psychosis is higher in past or future episodes in patients with major depression with psychotic features than in patients with nonpsychotic depression.PubMed, Embase, and PsycINFO were searched, and studies were selected that 1) identified patients with unipolar major depression, 2) made diagnoses of psychosis based on the presence of delusions or hallucinations, 3) characterized past or subsequent episodes as psychotic or nonpsychotic, and 4) were published in English. Two meta-analyses were then conducted using data from patients having index depressive episodes with or without psychosis at study entry to determine the risk of any prior or subsequent psychotic episode and the risk of psychosis in all episodes.Twelve studies met the inclusion criteria, and altogether they included 546 psychotic and 1,583 nonpsychotic patients with unipolar depression. In seven of the studies, the risk ratio for a prior or subsequent psychotic episode in patients whose index depressive episode was psychotic compared with those whose index episode was nonpsychotic was 9.98 (95% CI=4.75, 20.94). In eight studies, the risk ratio for psychosis among all episodes of depression in the subgroups with psychotic and nonpsychotic index episodes was 7.24 (95% CI=5.03, 10.43). Differences in risk of psychosis between these subgroups remained robust when potential sources of heterogeneity were explored.The findings support the hypothesis that psychotic depression runs true to form, and they support the distinction between psychotic and nonpsychotic depression. Because patients with psychotic depression are at high risk for psychosis in future episodes, determination of effective preventive treatments is imperative.
Antibodies Against <i>Chlamydia trachomatis</i> and Ovarian Cancer Risk in Two Independent Populations
Authors: Britton Trabert, Tim Waterboer, Annika Idahl, Nicole Brenner, Louise A Brinton, Julia Butt, Sally B Coburn, Patricia Hartge, Katrin Hufnagel, Federica Inturrisi, Jolanta Lissowska, Alexander Mentzer, Beata Peplonska, Mark E Sherman, Gillian S Wills, Sarah C Woodhall, Michael Pawlita, Nicolas Wentzensen
Journal: JNCI Journal of the National Cancer Institute (2018)

Pelvic inflammatory disease (PID) has been associated with ovarian cancer risk. To clarify the role of Chlamydia trachomatis and other infectious agents in the development of ovarian cancer, we evaluated the association of serologic markers with incident ovarian cancer using a staged approach in two independent populations. Studies included: 1) a case–control study in Poland (244 ovarian cancers/556 control subjects) and 2) a prospective nested case–control study in the PLCO Cancer Screening Trial (160 ovarian cancers/159 control subjects). Associations of serologic marker levels with ovarian cancer risk at diagnostic as well as higher thresholds, identified in Poland and independently evaluated in PLCO, were estimated using multivariable adjusted logistic regression. In the Polish study, antibodies (based on laboratory cut-point) against the chlamydia plasmid-encoded Pgp3 protein (serological gold standard) were associated with increased ovarian cancer risk (adjusted odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.20 to 2.22); when a positive result was redefined at higher levels, ovarian cancer risk was increased (cut-point 2: OR = 2.00, 95% CI = 1.38 to 2.89; cut-point 3 [max OR]: OR = 2.19, 95% CI = 1.29 to 3.73). In the prospective PLCO study, Pgp3 antibodies were associated with elevated risk at the laboratory cut-point (OR = 1.43, 95% CI = 0.78 to 2.63) and more stringent cut-points (cut-point 2: OR = 2.25, 95% CI = 1.07 to 4.71); cut-point 3: OR = 2.53, 95% CI = 0.63 to 10.08). In both studies, antibodies against other infectious agents measured were not associated with risk. In two independent populations, antibodies against prior/current C. trachomatis (Pgp3) were associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. These findings lend support for an association between PID and ovarian cancer.