tbuckley/cabot-search huggingface dataset:
Clinical and Cognitive Significance of Auditory Sensory Processing Deficits in Schizophrenia
Authors: Holly K. Hamilton, Terrance J. Williams, Joseph Ventura, Leland J. Jasperse, Emily M. Owens, Gregory A. Miller, Kenneth L. Subotnik, Keith H. Nuechterlein, Cindy M. Yee
Journal: American Journal of Psychiatry (2017)

Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap.P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to clinical symptom and cognitive performance measures.Schizophrenia patients demonstrated a deficit in P50 suppression when compared with healthy subjects, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed.Impaired suppression of auditory stimuli was associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.
Contemporary Hormonal Contraception and the Risk of Breast Cancer
Authors: Lina S. Mørch, Charlotte W. Skovlund, Philip C. Hannaford, Lisa Iversen, Shona Fielding, Øjvind Lidegaard
Journal: New England Journal of Medicine (2017)

Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer.We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders.Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year.The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).
Dynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel Tissue Engineering Materials
Authors: Kiara F. Bruggeman, Richard J. Williams, David R. Nisbet
Journal: Advanced Healthcare Materials (2017)

Abstract Tissue engineering scaffolds are designed to mimic physical, chemical, and biological features of the extracellular matrix, thereby providing a constant support that is crucial to improved regenerative medicine outcomes. Beyond mechanical and structural support, the next generation of these materials must also consider the more dynamic presentation and delivery of drugs or growth factors to guide new and regenerating tissue development. These two aspects are explored expansively separately, but they must interact synergistically to achieve optimal regeneration. This review explores common tissue engineering materials types, electrospun polymers and hydrogels, and strategies used for incorporating drug delivery systems into these scaffolds.
Biological and therapeutic implications of multisector sequencing in newly diagnosed glioblastoma
Authors: Tatenda Mahlokozera, Ananth K Vellimana, Tiandao Li, Diane D Mao, Zohny S Zohny, David H Kim, David D Tran, Daniel S Marcus, Sarah J Fouke, Jian L Campian, Gavin P Dunn, Christopher A Miller, Albert H Kim
Journal: Neuro-Oncology (2017)

Diagnostic workflows for glioblastoma (GBM) patients increasingly include DNA sequencing–based analysis of a single tumor site following biopsy or resection. We hypothesized that sequencing of multiple sectors within a given tumor would provide a more comprehensive representation of the molecular landscape and potentially inform therapeutic strategies. Ten newly diagnosed, isocitrate dehydrogenase 1 (IDH1) wildtype GBM tumor samples were obtained from 2 (n = 9) or 4 (n = 1) spatially distinct tumor regions. Tumor and matched blood DNA samples underwent whole-exome sequencing. Across all 10 tumors, 51% of mutations were clonal and 3% were subclonal and shared in different sectors, whereas 46% of mutations were subclonal and private. Two of the 10 tumors exhibited a regional hypermutator state despite being treatment naïve, and remarkably, the high mutational load was predominantly limited to one sector in each tumor. Among the canonical cancer-associated genes, only telomerase reverse transcriptase (TERT) promoter mutations were observed in the founding clone in all tumors. Reconstruction of the clonal architecture in different sectors revealed regionally divergent evolution, and integration of data from 2 sectors increased the resolution of inferred clonal architecture in a given tumor. Predicted therapeutic mutations differed in presence and frequency between tumor regions. Similarly, different sectors exhibited significant divergence in the predicted neoantigen landscape. The substantial spatial heterogeneity observed in different GBM tumor sectors, especially in spatially restricted hypermutator cases, raises important caveats to our current dependence on single-sector molecular information to guide either targeted or immune-based treatments.
Long-Term Coarse Particulate Matter Exposure Is Associated with Asthma among Children in Medicaid
Authors: Corinne A. Keet, Joshua P. Keller, Roger D. Peng
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Short- and long-term fine particulate matter (particulate matter ≤2.5 μm in aerodynamic diameter [PM2.5]) pollution is associated with asthma development and morbidity, but there are few data on the effects of long-term exposure to coarse PM (PM10–2.5) on respiratory health.Objectives: To understand the relationship between long-term fine and coarse PM exposure and asthma prevalence and morbidity among children.Methods: A semiparametric regression model that incorporated PM2.5 and PM10 monitor data and geographic characteristics was developed to predict 2-year average PM2.5 and PM10–2.5 exposure during the period 2009 to 2010 at the zip-code tabulation area level. Data from 7,810,025 children aged 5 to 20 years enrolled in Medicaid from 2009 to 2010 were used in a log-linear regression model with predicted PM levels to estimate the association between PM exposure and asthma prevalence and morbidity, adjusting for race/ethnicity, sex, age, area-level urbanicity, poverty, education, and unmeasured spatial confounding.Measurements and Main Results: Exposure to coarse PM was associated with increased asthma diagnosis prevalence (rate ratio [RR] for 1-μg/m3 increase in coarse PM level, 1.006; 95% confidence interval [CI], 1.001–1.011), hospitalizations (RR, 1.023; 95% CI, 1.003–1.042), and emergency department visits (RR, 1.017; 95% CI, 1.001–1.033) when adjusting for fine PM. Fine PM exposure was more strongly associated with increased asthma prevalence and morbidity than coarse PM. The estimates remained elevated across different levels of spatial confounding adjustment.Conclusions: Among children enrolled in Medicaid, exposure to higher average coarse PM levels is associated with increased asthma prevalence and morbidity. These results suggest the need for direct monitoring of coarse PM and reconsideration of limits on long-term average coarse PM pollution levels.
Abstract 13110: Pediatric Heart Transplantation in Pre-Sensitized Recipients: A Current Perspective
Authors: Bibhuti Das, Elizabeth Pruitt, Kimberly Molina, William Ravekes, Scott Auerbach, Andrew Savage, Leah Knox, James Kirklin, David Naftel, Daphne Hsu
Journal: Circulation (2016)

Introduction: Anti-HLA antibodies (Ab) are increasingly prevalent in pediatric patients (pts) awaiting heart transplant (HT) and may result in a significant delay in time to HT because of the need to wait for a negative prospective donor HLA crossmatch (XM). Methods: Data from pts in the Pediatric HT Study transplanted between 2010-2014 were analyzed to determine the association of pre-HT percent reactive anti-HLA Ab (PRA) detected by flow cytometry with retrospective donor XM results and outcomes after HT. Sensitization was defined as a PRA &gt;20%. Results: HT was performed in 1,596 pts, 1,459 had a PRA calculated and 1,419 had XM results available. Sensitization was present in 32% of pts; 25% were sensitized against Class I and 20% were sensitized against Class II Ab (p&lt;0.01). Sensitization was more common in pts with congenital heart disease (CHD) compared to cardiomyopathy (CM), 28% vs. 15%, respectively, p&lt;0.01). Sensitization was similar between pts with and without ventricular assist device support, 20% vs. 25%, respectively, p=0.07. The level of sensitization was significantly associated with a +XM (p&lt;0.01, Table). Sensitized pts who had a +XM were at higher risk for rejection than those who had a - XM and those who were not sensitized (p&lt;0.01, Figure). There was no difference in post-HT survival between sensitized and nonsensitized pts, p=0.11, or those with and without a +XM, p=0.06. Conclusions: In the current era, 32% of pediatric HT pts are sensitized, with a higher incidence seen in pts with CHD compared to those with CM. Although, increasing PRA levels were associated with a higher likelihood of a positive retrospective XM, 68% of pts with a pre-HT PRA &gt;50% had a negative XM. XM was positive in 9% of pts with a PRA between 1-20%. Sensitized pts with a positive XM had a higher incidence of rejection than all other pts. Better methods of identifying pts at risk for a positive XM are needed to refine the indications for a prospective XM in pediatric pts listed for HT.
Humane Language for People in the Criminal Justice System
Authors: Lorie S. Goshin
Journal: JAMA (2017)

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Coercion and HIV self-testing in Chinese men who have sex with men: implementation data from a cross-sectional survey
Authors: Jason J Ong, Haochu Li, Wu Dan, Hongyun Fu, Ewen Liu, Wei Ma, Demin Kang, Meizhen Liao, Gifty Marley, Chongyi Wei, Weiming Tang, Stephen Pan, Chuncheng Liu, Bin Yang, Ligang Yang, Shujie Huang, Joseph D Tucker
Journal: The Lancet (2017)
Transformation of health systems: contribution of population health intervention research
Authors: François Alla, Linda Cambon
Journal: The Lancet Public Health (2017)

The growing prevalence of chronic diseases is a major challenge in the sustainability of health systems. There is a need to transform health systems by increasing prevention and by implementating innovative organisations in management of these diseases. This transformation will require development and analysis of research-based and field-based interventions and organisations. Health system transformation also requires the transfer of innovative models into public decisions and practices, and requires these actions to occur across health systems.
Comparison of Laboratory-Developed Tests and FDA-Approved Assays for <i>BRAF, EGFR,</i> and <i>KRAS</i> Testing
Authors: Annette S. Kim, Angela N. Bartley, Julia A. Bridge, Suzanne Kamel-Reid, Alexander J. Lazar, Neal I. Lindeman, Thomas A. Long, Jason D. Merker, Alex J. Rai, David L. Rimm, Paul G. Rothberg, Patricia Vasalos, Joel T. Moncur
Journal: JAMA Oncology (2017)

The debate about the role of the Food and Drug Administration (FDA) in the regulation of laboratory-developed tests (LDTs) has focused attention on the analytical performance of all clinical laboratory testing. This study provides data comparing the performance of LDTs and FDA-approved companion diagnostics (FDA-CDs) in proficiency testing (PT) provided by the College of American Pathologists Molecular Oncology Committee.To compare the analytical performance of LDTs and FDA-CDs on well-characterized PT samples and to compare the practice characteristics of laboratories using these assays.This comparison of PT responses examines the performance of laboratories participating in the College of American Pathologists PT for 3 oncology analytes for which both FDA-CDs and LDTs are used: BRAF, EGFR, and KRAS. A total of 6897 PT responses were included: BRAF (n = 2524; 14 PT samples), EGFR (n = 2216; 11 PT samples), and KRAS (n = 2157, 10 PT samples). US Food and Drug Administration companion diagnostics and LDTs are compared for both accuracy and preanalytic practices of the laboratories.As per the College of American Pathologists PT standards, results were scored and the percentages of acceptable responses for each analyte were compared. These were also broken down by the specific variants tested, by kit manufacturer for laboratories using commercial reagents, and by preanalytic practices.From analysis of 6897 PT responses, this study demonstrates that both LDTs and FDA-CDs have excellent performance overall, with both test types exceeding 97% accuracy for all 3 genes (BRAF, EGFR, and KRAS) combined. Rare variant-specific differences did not consistently favor LDTs or FDA-CDs. Additionally, more than 60% of participants using an FDA-CD reported adapting their assay from the approved procedure to allow for a greater breadth of sample types, minimum tumor content, and instrumentation, changing the classification of their assay from FDA-CD to LDT.This study demonstrates the high degree of accuracy and comparable performance of both LDTs and FDA-CDs for 3 oncology analytes. More significantly, the majority of laboratories using FDA-CDs have modified the scope of their assay to allow for more clinical practice variety, rendering them LDTs. These findings support both the excellent and equivalent performance of both LDTs and FDA-CDs in clinical diagnostic testing.
How many melanomas might be prevented if more people applied sunscreen regularly?
Authors: C.M. Olsen, L.F. Wilson, A.C. Green, N. Biswas, J. Loyalka, D.C. Whiteman
Journal: British Journal of Dermatology (2017)

Ultraviolet radiation causes cutaneous melanoma. Sunscreen prevents sunburn and protects skin cells against mutations. High‐quality epidemiological studies suggest regular sunscreen use prevents melanoma. To calculate the potential impact fraction (PIF) for melanoma in the U.S.A. and Australia assuming a range of different intervention scenarios intended to increase sunscreen use. We calculated the PIF, the proportional difference between the observed number of melanomas arising under prevailing levels of sunscreen use compared with the number expected under counterfactual scenarios. We used published melanoma incidence projections for Australia and the white population in the U.S.A. from 2012 through to 2031 as the baseline condition, with estimates for protective effects of 'regular sunscreen use' from the literature. Sunscreen prevalence was sourced from national or state surveys. Under a plausible public health intervention scenario comprising incremental increases in sunscreen prevalence over a 10‐year implementation programme, we estimated that cumulatively to 2031, 231 053 fewer melanomas would arise in the U.S. white population (PIF 11%) and 28 071 fewer melanomas would arise in Australia (PIF 10%). Under the theoretical maximum model of sunscreen use, almost 797 000 (PIF 38%) and approximately 96 000 (PIF 34%) melanomas would be prevented in the U.S.A. and Australia, respectively between 2012 and 2031. A sensitivity analysis using weaker effect estimates resulted in more conservative PIF estimates. Overall, interventions to increase use of sunscreen would result in moderate reductions in melanoma incidence, assuming no compensatory overexposure to the sun. Countries with a high incidence of melanoma should monitor levels of sunscreen use in the community.
Abstract 19257: Mesenchymal Stem Cells Require CD73 Activity to Reduce Leukocyte Associated Inflammation Following Myocardial Ischemia-Reperfusion Injury
Authors: Eric Shin, Lanfang Wang, Andres Garcia, Rabin Tirouvanziam, Rebecca Levit
Journal: Circulation (2016)

Introduction: Cell death following myocardial ischemia-reperfusion (MI/R) injury releases toxic metabolites in the interstitium, eliciting a potent immune response. Therapeutic use of MSCs represen...
Prevalence of chronic obstructive pulmonary disease in the global population with HIV: a systematic review and meta-analysis
Authors: Jean Joel Bigna, Angeladine Malaha Kenne, Serra Lem Asangbeh, Aurelie T Sibetcheu
Journal: The Lancet Global Health (2017)

In recent years, the concept has been raised that people with HIV are at risk of developing chronic obstructive pulmonary disease (COPD) because of HIV infection. However, much remains to be understood about the relationship between COPD and HIV infection. We aimed to investigate this association by assessing studies that reported the prevalence of COPD in the global population with HIV.In this systematic review and meta-analysis, we assessed observational studies of COPD in people with HIV. We searched PubMed, Embase, Web of Science, and Global Index Medicus, with no language restriction, to identify articles published until June 21, 2017, and we searched the reference lists of the retrieved articles. Eligible studies reported the prevalence of COPD or had enough data to compute these estimates. We excluded studies in subgroups of participants selected on the basis of the presence of COPD; studies that were limited to other specific groups or populations, such as people with other chronic respiratory diseases; and case series, letters, reviews, commentaries, editorials, and studies without primary data or an explicit description of methods. The main outcome assessed was prevalence of COPD. Each study was independently reviewed for methodological quality. We used a random-effects model to pool individual studies and assessed heterogeneity (I2) using the χ2 test on Cochrane's Q statistic. This study is registered with PROSPERO, number CRD42016052639.Of 4036 studies identified, we included 30 studies (151 686 participants) from all WHO regions in the meta-analysis of COPD prevalence. 23 studies (77%) had low risk of bias, six (20%) had moderate risk of bias, and one (3%) had high risk of bias in their methodological quality. The overall prevalence of COPD was 10·5% (95% CI 6·2-15·7; I2=97·2%; six studies) according to the lower limit of normal definition of COPD, and 10·6% (6·9-15·0; 94·7%; 16 studies) according to the fixed-ratio definition. COPD prevalence was higher in Europe and among current and ever smokers, and increased with level of income and proportion of participants with detectable HIV viral load. Prevalence of COPD was significantly higher in patients with HIV than in HIV-negative controls (pooled odds ratio 1·14, 95% CI 1·05-1·25, I2=63·5%; 11 studies), even after adjustment for tobacco consumption (2·58, 1·05-6·35, 74·9%; four studies).Our findings suggest a high prevalence of COPD in the global population with HIV, and an association with HIV. As such, COPD deserves more attention from HIV health-care providers, researchers, policy makers, and stakeholders for improved detection, overall proper management, and efficient control of COPD in people with HIV. Efforts to address this burden should focus on promoting the decrease of tobacco consumption and adherence to highly active antiretroviral therapy to reduce viral load.None.
Genomic Aberrations that Activate D-type Cyclins Are Associated with Enhanced Sensitivity to the CDK4 and CDK6 Inhibitor Abemaciclib
Authors: Xueqian Gong, Lacey M. Litchfield, Yue Webster, Li-Chun Chio, Swee Seong Wong, Trent R. Stewart, Michele Dowless, Jack Dempsey, Yi Zeng, Raquel Torres, Karsten Boehnke, Cecilia Mur, Carlos Marugán, Carmen Baquero, Chunping Yu, Steven M. Bray, Isabella H. Wulur, Chen Bi, Shaoyou Chu, Hui-Rong Qian, Philip W. Iversen, Farhana F. Merzoug, Xiang S. Ye, Christoph Reinhard, Alfonso De Dios, Jian Du, Charles W. Caldwell, María José Lallena, Richard P. Beckmann, Sean G. Buchanan
Journal: Cancer Cell (2017)
Transmission network structure and newly diagnosed HIV infections: a molecular epidemiology study
Authors: Tsz Ho Kwan, Ngai Sze Wong, Kenny Chi Wai Chan, Owen Tak Yin Tsang, Man Po Lee, Grace Chung Yan Lui, Denise Pui Chung Chan, Wing Cheong Yam, Shui Shan Lee
Journal: The Lancet (2017)
Nanoparticle targeting to the endothelium during normothermic machine perfusion of human kidneys
Authors: Gregory T. Tietjen, Sarah A. Hosgood, Jenna DiRito, Jiajia Cui, Deeksha Deep, Eric Song, Jan R. Kraehling, Alexandra S. Piotrowski-Daspit, Nancy C. Kirkiles-Smith, Rafia Al-Lamki, Sathia Thiru, J. Andrew Bradley, Kourosh Saeb-Parsy, John R. Bradley, Michael L. Nicholson, W. Mark Saltzman, Jordan S. Pober
Journal: Science Translational Medicine (2017)

Anti-CD31 antibody conjugation can enhance nanoparticle accumulation in the vascular endothelium of human kidneys during ex vivo normothermic machine perfusion.