bluuebunny/crossref_metadata_2025_split huggingface dataset:
Violence experience by perpetrator and associations with HIV/STI risk and infection: a cross-sectional study among female sex workers in Karnataka, south India
Authors: Beksinska Alicja , Prakash Ravi , Isac Shajy , Mohan H L , Platt Lucy , Blanchard James , Moses Stephen , Beattie Tara S 
Published: September 2018

ObjectivesFemale sex workers (FSWs) experience violence from a range of perpetrators, but little is known about how violence experience across multiple settings (workplace, community, domestic) impacts on HIV/sexually transmitted infection (STI) risk. We examined whether HIV/STI risk differs by the perpetrator of violence.MethodsAn Integrated Biological and Behavioural Assessment survey was conducted among random samples of FSWs in two districts (Bangalore and Shimoga) in Karnataka state, south India, in 2011. Physical and sexual violence in the past six months, by workplace (client, police, coworker, pimp) or community (stranger, rowdy, neighbour, auto-driver) perpetrators was assessed, as was physical and sexual intimate partner violence in the past 12 months. Weighted, bivariate and multivariate analyses were used to examine associations between violence by perpetrator and HIV/STI risk.Results1111 FSWs were included (Bangalore=718, Shimoga=393). Overall, 34.9% reported recent physical and/or sexual violence. Violence was experienced from domestic (27.1%), workplace (11.1%) and community (4.2%) perpetrators, with 6.2% of participants reporting recent violence from both domestic and non-domestic (workplace/community) perpetrators. Adjusted analysis suggests that experience of violence by workplace/community perpetrators is more important in increasing HIV/STI risk during sex work (lower condom use with clients; client or FSW under the influence of alcohol at last sex) than domestic violence. However, women who reported recent violence by domestic and workplace/community perpetrators had the highest odds of high-titre syphilis infection, recent STI symptoms and condom breakage at last sex, and the lowest odds of condom use at last sex with regular clients compared with women who reported violence by domestic or workplace/community perpetrators only.ConclusionHIV/STI risk differs by the perpetrator of violence and is highest among FSWs experiencing violence in the workplace/community and at home. Effective HIV/STI prevention programmes with FSWs need to include violence interventions that address violence across both their personal and working lives.
Are noise and air pollution related to the incidence of dementia? A cohort study in London, England
Authors: Carey Iain M , Anderson H Ross , Atkinson Richard W , Beevers Sean D , Cook Derek G , Strachan David P , Dajnak David , Gulliver John , Kelly Frank J 
Published: September 2018

ObjectiveTo investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.DesignRetrospective cohort study using primary care data.Setting75 Greater London practices.Participants130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.Primary and secondary outcome measuresA first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer’s disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.Results2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5specifically from primary traffic sources only and Lnight, but only NO2and PM2.5remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.ConclusionsWe have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.
Prevalence of respiratory bacterial infections in people with lower respiratory tract infections in Africa: the BARIAFRICA systematic review and meta-analysis protocol
Authors: Tchatchouang Serges , Bigna Jean Joel , Nzouankeu Ariane , Fonkoua Marie-Christine , Nansseu Jobert Richie , Ndangang Marie S , Kenmoe Sebastien , Penlap Véronique B , Njouom Richard 
Published: September 2018

IntroductionThe burden of lower respiratory tract infections (LRTIs) is a substantial public health concern. However, the epidemiology of LRTI and its bacterial aetiologies are poorly characterised, particularly in the African continent. Providing accurate data can help design cost-effective interventions to curb the burden of respiratory infections in Africa. Therefore, the aim of this systematic review and meta-analysis will be to determine the prevalence of respiratory Bacterial Aetiologies in people with low Respiratory tract Infections in Africa (BARIAFRICA) and associated factors.Methods and analysisWe will search PubMed, EMBASE, Web of Science, African Journals Online, Cumulative Index to Nursing and Allied Health Literature, and Global Index Medicus to identify studies that reported the prevalence (of enough data to compute this estimate) of respiratory bacterial infections in people with LRTIs in Africa from 1 January 2000 to 31 March 2018, without any linguistic restrictions. Study selection, data extraction and risk of bias assessment will be conducted independently by two investigators. Heterogeneity will be evaluated using the χ² test on Cochran’s Q statistic and quantified with H and I² statistics. Prevalence will be pooled using a random-effect meta-analysis model. Subgroup and meta-regression analyses will be used to identify sources of heterogeneity of prevalence estimates. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Ethics and disseminationSince this study will be based on published data, it does not require ethical approval. This systematic review and meta-analysis is intended to serve as a basis for determining the burden of LRTIs, for identifying data gaps and for guiding future investigations in Africa. The final report will be published in peer-reviewed journals, presented in conferences and submitted to relevant health policy makers.PROSPERO registration numberCRD42018092359.
Vascular endothelial function is impaired by aerosol from a single IQOS HeatStick to the same extent as by cigarette smoke
Authors: Nabavizadeh Pooneh , Liu Jiangtao , Havel Christopher M , Ibrahim Sharina , Derakhshandeh Ronak , Jacob III Peyton , Springer Matthew L 
Published: September 2018

BackgroundHeated tobacco products (also called ‘heat-not-burn’ products) heat tobacco at temperatures below that of combustion, causing nicotine and other compounds to aerosolise. One such product, IQOS from Philip Morris International, is being marketed internationally with claims of harm reduction. We sought to determine whether exposure to IQOS aerosol impairs arterial flow-mediated dilation (FMD), a measure of vascular endothelial function that is impaired by tobacco smoke.MethodsWe exposed anaesthetised rats (n=8/group) via nose cone to IQOS aerosol from single HeatSticks, mainstream smoke from single Marlboro Red cigarettes or clean air for a series of consecutive 30 s cycles over 1.5–5 min. Each cycle consisted of 15 or 5 s of exposure followed by removal from the nose cone. We measured pre-exposure and postexposure FMD, and postexposure serum nicotine and cotinine.ResultsFMD was impaired comparably by ten 15 s exposures and ten 5 s exposures to IQOS aerosol and to cigarette smoke, but not by clean air. Serum nicotine levels were similar to plasma levels after humans have smoked one cigarette, confirming that exposure conditions had real-world relevance. Postexposure nicotine levels were ~4.5-fold higher in rats exposed to IQOS than to cigarettes, despite nicotine being measured in the IQOS aerosol at ~63% the amount measured in smoke. When IQOS exposure was briefer, leading to comparable serum nicotine levels to the cigarette group, FMD was still comparably impaired.ConclusionsAcute exposures to IQOS aerosol impairs FMD in rats. IQOS use does not necessarily avoid the adverse cardiovascular effects of smoking cigarettes.
Control of glyphosate-resistant waterhemp with preemergence herbicides in glyphosate- and dicamba-resistant soybean
Authors: Hedges Brittany K. , Soltani Nader , Hooker David C. , Robinson Darren E. , Sikkema Peter H. 
Published: September 2018

Glyphosate-resistant (GR) waterhemp was first discovered in Ontario, Canada, in 2014. In Ontario, GR waterhemp interference in previous studies reduced soybean yield up to 73%. Tank-mixes of herbicides with multiple modes-of-action are important for delaying the evolution of herbicide resistance. The objective of this study was to evaluate the efficacy of pyroxasulfone (150 g a.i. ha−1), S-metolachlor/metribuzin (1943 g a.i. ha−1), pyroxasulfone/sulfentrazone (300 g a.i. ha−1), and pyroxasulfone/flumioxazin (240 g a.i. ha−1) applied preemergence (PRE) with and without the addition of glyphosate/dicamba (1800 g a.e. ha−1) for the control of GR waterhemp in soybean. At 8 wk after treatment application (WAA), glyphosate/dicamba applied PRE controlled GR waterhemp 45%. Pyroxasulfone, S-metolachlor/metribuzin, pyroxasulfone/sulfentrazone, and pyroxasulfone/flumioxazin applied PRE controlled GR waterhemp 79%, 87%, 91%, and 95%, respectively. At 2, 4, 8, and 12 WAA, the addition of glyphosate/dicamba to the aforementioned PRE herbicides did not improve GR waterhemp control. There was no increase in GR waterhemp control with the addition glyphosate/dicamba; however, multiple herbicide modes-of-action should be utilized to reduce the selection intensity for herbicide-resistant weeds.
Diverse Functions of Macrophages in Different Tumor Microenvironments
Authors: Yang Ming , McKay Daniel , Pollard Jeffrey W. , Lewis Claire E. 
Published: September 2018

AbstractTumor-associated macrophages are a major constituent of malignant tumors and are known to stimulate key steps in tumor progression. In our review in this journal in 2006, we postulated that functionally distinct subsets of these cells exist in different areas within solid tumors. Here, we review the many experimental and clinical studies conducted since then to investigate the function(s), regulation, and clinical significance of macrophages in these sites. The latter include three sites of cancer cell invasion, tumor nests, the tumor stroma, and areas close to, or distant from, the tumor vasculature. A more complete understanding of macrophage diversity in tumors could lead to the development of more selective therapies to restore the formidable, anticancer functions of these cells. Cancer Res; 78(19); 5492–503. ©2018 AACR.
Methodological Challenges and Updated Findings from a Meta-analysis of the Association between Mammographic Density and Breast Cancer
Authors: Bond-Smith Daniela , Stone Jennifer 
Published: September 2018

Abstract
Mammographic density (MD) is an established predictor of breast cancer risk. However, there is limited information on the robustness of the risk associations for different study designs and the associated methodologic challenges. Our analysis includes 165 samples from studies published since 2006. We use a weakly informative Bayesian approach to avoid unduly optimistic estimates of uncertainty, as found in the previous literature. We find that the existing consensus from previous review studies has underestimated the strength and precision of MD as a risk marker. Moreover, although much of the published literature is based on categorical measurement of MD, there are tangible advantages in using continuous data in terms of estimate precision and relevance for different patient populations. Estimates based on the percentage of MD are more precise for lower density women, whereas absolute MD has advantages for higher density. We show that older results might not be a good proxy for current and future findings, and it would be pertinent to adjust clinical interpretations based on the older data. Using an appropriate estimation method cognizant of the importance of heterogeneity is critical to obtaining reliable and robust clinical findings that are relevant for broad patient populations.
Temporal Variability and Stability of the Fecal Microbiome: The Multiethnic Cohort Study
Authors: Fu Benjamin C. , Randolph Timothy W. , Lim Unhee , Monroe Kristine R. , Cheng Iona , Wilkens Lynne R. , Le Marchand Loïc , Lampe Johanna W. , Hullar Meredith A.J. 
Published: September 2018

AbstractBackground:Measurement reliability and biological stability need to be considered when developing sampling protocols for population-based fecal microbiome studies.Methods:Stool samples were collected biannually over a 2-year period and sequenced for the V1–V3 region of the 16S rRNA gene in 50 participants from the Multiethnic Cohort Study. We evaluated the temporal stability of the fecal microbiome on a community level with permutational multivariate analysis of variance (PERMANOVA), as well as on taxa and diversity measures with intraclass correlation coefficients.Results:Interindividual differences were the predominant source of fecal microbiome variation, and variation within individual was driven more by changing abundances than by the complete loss or introduction of taxa. Phyla and diversity measures were reliable over the 2 years. Most genera were stable over time, although those with low abundances tended to be more dynamic. Reliability was lower among participants who used antibiotics, with the greatest difference seen in samples taken within 1 month of reported use.Conclusions:The fecal microbiome as a whole is stable over a 2-year period, although certain taxa may exhibit more temporal variability.Impact:When designing large epidemiologic studies, a single sample is sufficient to capture the majority of the variation in the fecal microbiome from 16S rRNA gene sequencing, while multiple samples may be needed for rare or less-abundant taxa.
Combining Vascular Normalization with an Oncolytic Virus Enhances Immunotherapy in a Preclinical Model of Advanced-Stage Ovarian Cancer
Authors: Matuszewska Kathy , Santry Lisa A. , van Vloten Jacob P. , AuYeung Amanda W.K. , Major Pierre P. , Lawler Jack , Wootton Sarah K. , Bridle Byram W. , Petrik Jim 
Published: September 2018

Abstract

Purpose:
Intravenous delivery of oncolytic viruses often leads to tumor vascular shutdown, resulting in decreased tumor perfusion and elevated tumor hypoxia. We hypothesized that using 3TSR to normalize tumor vasculature prior to administration of an oncolytic Newcastle disease virus (NDV) would enhance virus delivery and trafficking of immunologic cell subsets to the tumor core, resulting in systemically enhanced immunotherapy and regression of advanced-stage epithelial ovarian cancer (EOC).

Experimental Design:
Using an orthotopic, syngeneic mouse model of advanced-stage EOC, we pretreated mice with 3TSR (4 mg/kg per day) alone or followed by combination with fusogenic NDV(F3aa) (1.0 × 108 plaque-forming units).

Results:
Treatment with 3TSR normalized tumor vasculature, enhanced blood perfusion of primary EOC tumors, and induced disease regression. Animals treated with combination therapy had the greatest reduction in primary tumor mass, ascites accumulation, and secondary lesions (50% of mice were completely devoid of peritoneal metastases). Combining 3TSR + NDV(F3aa) led to enhanced trafficking of immunologic cells into the primary tumor core.

Conclusions:
We have shown, for the first time, that NDV, like other oncolytic viruses, is a potent mediator of acute vascular shutdown and that preventing this through vascular normalization can promote regression in a preclinical model of advanced-stage ovarian cancer. This challenges the current focus on induction of intravascular thrombosis as a requisite for successful oncolytic virotherapy.
See related commentary by Bykov and Zamarin, p. 1446
Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients
Authors: Taylor Olga A. , Brown Austin L. , Brackett Julienne , Dreyer ZoAnn E. , Moore Ida Ki , Mitby Pauline , Hooke Mary C. , Hockenberry Marilyn J. , Lupo Philip J. , Scheurer Michael E. 
Published: September 2018

Abstract
Purpose: Methotrexate chemotherapy can be associated with neurologic complications during therapy and long-term neurologic deficits. This study evaluated demographic and clinical factors associated with incidence of methotrexate neurotoxicity and described the impact of neurotoxicity on acute lymphoblastic leukemia (ALL) therapy in pediatric patients.
Experimental Design: Patients were enrolled between 2012 and 2017 from three pediatric cancer treatment centers in the United States. Medical records for suspected cases of methotrexate neurotoxicity, defined as an acute neurologic event following methotrexate therapy, were reviewed. Cox proportional hazards models were used to estimate the association between race/ethnicity and methotrexate neurotoxicity. Multivariable linear regression models compared treatment outcomes between patients with and without methotrexate neurotoxicity.
Results: Of the 280 newly diagnosed patients enrolled, 39 patients (13.9%) experienced methotrexate neurotoxicity. Compared with non-Hispanic whites, Hispanic patients experienced the greatest risk of methotrexate neurotoxicity (adjusted HR, 2.43; 95% CI, 1.06–5.58) after accounting for sex, age at diagnosis, BMI Z-score at diagnosis, and ALL risk stratification. Patients who experienced a neurotoxic event received an average of 2.25 fewer doses of intrathecal methotrexate. Six of the 39 cases of neurotoxicity (15.4%) experienced relapse during the study period, compared with 13 of the 241 (2.1%) patients without neurotoxicity (P = 0.0038).
Conclusions: Hispanic ethnicity was associated with increased risk of methotrexate neurotoxicity, which was associated with treatment modifications and relapse. Understanding the mechanism and predictors of methotrexate neurotoxicity is important to improving treatment outcomes in pediatric ALL. Clin Cancer Res; 24(20); 5012–7. ©2018 AACR.
Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade
Authors: Lo Russo Giuseppe , Moro Massimo , Sommariva Michele , Cancila Valeria , Boeri Mattia , Centonze Giovanni , Ferro Simona , Ganzinelli Monica , Gasparini Patrizia , Huber Veronica , Milione Massimo , Porcu Luca , Proto Claudia , Pruneri Giancarlo , Signorelli Diego , Sangaletti Sabina , Sfondrini Lucia , Storti Chiara , Tassi Elena , Bardelli Alberto , Marsoni Silvia , Torri Valter , Tripodo Claudio , Colombo Mario Paolo , Anichini Andrea , Rivoltini Licia , Balsari Andrea , Sozzi Gabriella , Garassino Marina Chiara 
Published: September 2018

Abstract

Purpose:
Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified.

Experimental Design:
Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutational subsets, were assessed for tumor growth after treatment with antibodies against mouse and human programmed death receptor-1 (PD-1). The immune microenvironment was evaluated by flow cytometry and IHC.

Results:
Among 187 patients, 152 were evaluable for clinical response. We identified four categories: 32 cases were defined as responders (21%), 42 patients with stable disease (27.7%), 39 cases were defined as progressors (25.7%), and 39 patients with HP (25.7%). Pretreatment tissue samples from all patients with HP showed tumor infiltration by M2-like CD163+CD33+PD-L1+ clustered epithelioid macrophages. Enrichment by tumor-associated macrophages (TAM) was observed, even in tumor nodules from immunodeficient mice injected with human lung cancer cells and with PDXs. In these models, tumor growth was enhanced by treatment with anti–PD-1 but not anti–PD-1 F(ab)2 fragments.

Conclusions:
These results suggest a crucial role of TAM reprogramming, upon Fc receptor engagement by ICI, eventually inducing HP and provide clues on a distinctive immunophenotype potentially able to predict HP.
See related commentary by Knorr and Ravetch, p. 904
Dual PAK4-NAMPT Inhibition Impacts Growth and Survival, and Increases Sensitivity to DNA-Damaging Agents in Waldenström Macroglobulinemia
Authors: Li Na , Lopez Michael A. , Linares Maria , Kumar Subodh , Oliva Stefania , Martinez-Lopez Joaquin , Xu Lian , Xu Yan , Perini Tommaso , Senapedis William , Baloglu Erkan , Shammas Masood A. , Hunter Zachary , Anderson Kenneth C. , Treon Steven P. , Munshi Nikhil C. , Fulciniti Mariateresa 
Published: September 2018

Abstract

Purpose:
p21-activated kinase 4 (PAK4) plays a significant biological and functional role in a number of malignancies, including multiple myeloma (MM). On the basis of our promising findings in MM, we here characterize PAK4 expression and role in WM cells, as well effect of dual PAK4-NAMPT inhibitor (KPT-9274) against WM cell growth and viability.

Experimental Design:
We have analyzed mRNA and protein expression levels of PAK4 in WM cells, and used loss-of-function approach to investigate its contribution to WM cell viability. We have further tested the in vitro and in vivo effect of KPT-9274 against WM cell growth and viability.

Results:
We report here high-level expression and functional role of PAK4 in WM, as demonstrated by shRNA-mediated knockdown; and significant impact of KPT-9274 on WM cell growth and viability. The growth inhibitory effect of KPT-9274 was associated with decreased PAK4 expression and NAMPT activity, as well as induction of apoptosis. Interestingly, in WM cell lines treated with KPT-9274, we detected a significant impact on DNA damage and repair genes. Moreover, we observed that apart from inducing DNA damage, KPT-9274 specifically decreased RAD51 and the double-strand break repair by the homologous recombination pathway. As a result, when combined with a DNA alkylating agents bendamustine and melphalan, KPT-9274 provided a synergistic inhibition of cell viability in WM cell lines and primary patient WM cells in vitro and in vivo.

Conclusions:
These results support the clinical investigation of KPT-9274 in combination with DNA-damaging agent for treatment of WM.