bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Structure of Mycobacterium bovis in Germany: a Long-Term Study Using Whole-Genome Sequencing Combined with Conventional Molecular Typing Methods
Authors: Kohl Thomas A. , Kranzer Katharina , Andres Sönke , Wirth Thierry , Niemann Stefan , Moser Irmgard 
Published: August 2020

Mycobacterium bovis
is the primary cause of bovine tuberculosis (bTB) and infects a wide range of domestic animal and wildlife species and humans. In Germany, bTB still emerges sporadically in cattle herds, free-ranging wildlife, diverse captive animal species, and humans. In order to understand the underlying population structure and estimate the population size fluctuation through time, we analyzed 131
M. bovis
strains from animals (
n
= 38) and humans (
n
= 93) in Germany from 1999 to 2017 by whole-genome sequencing (WGS), mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing, and spoligotyping.
Lower estimated bone strength and impaired bone microarchitecture in children with type 1 diabetes
Authors: Fuusager Gitte , Milandt Nikolaj , Shanbhogue Vikram Vinod , Hermann Anne Pernille , Schou Anders Jørgen , Christesen Henrik Thybo 
Published: August 2020

IntroductionPatients with type 1 diabetes has an increased risk of fracture. We wished to evaluate estimated bone strength in children and adolescents with type 1 diabetes and assess peripheral bone geometry, volumetric bone mineral density (vBMD) and microarchitecture.Research design and methodsIn a cross-sectional study, high-resolution peripheral quantitative CT (HR-pQCT) was performed of the radius and tibia in 84 children with type 1 diabetes and 55 healthy sibling controls. Estimated bone strength was assessed using a microfinite element analysis solver. Multivariate regression analyses were performed adjusting for age, sex, height and body mass index.ResultsThe median age was 13.0 years in the diabetes group vs 11.5 years in healthy sibling controls. The median (range) diabetes duration was 4.2 (0.4−15.9) years; median (range) latest year Hb1Ac was 7.8 (5.9−11.8) % (61.8 (41−106) mmol/mol). In adjusted analyses, patients with type 1 diabetes had reduced estimated bone strength in both radius, β −390.6 (−621.2 to −159.9) N, p=0.001, and tibia, β −891.9 (−1321 to −462.9) N, p<0.001. In the radius and tibia, children with type 1 diabetes had reduced cortical area, trabecular vBMD, trabecular number and trabecular bone volume fraction and increased trabecular inhomogeneity, adjusted p<0.05 for all. Latest year HbA1c was negatively correlated with bone microarchitecture (radius and tibia), trabecular vBMD and estimated bone strength (tibia).ConclusionChildren with type 1 diabetes had reduced estimated bone strength. This reduced bone strength could partly be explained by reduced trabecular bone mineral density, adverse microarchitecture and reduced cortical area. We also found increasing latest year HbA1c to be associated with several adverse changes in bone parameters. HR-pQCT holds potential to identify early adverse bone changes and to explain the increased fracture risk in young patients with type 1 diabetes.
Remodeling tumor immune microenvironment (TIME) for glioma therapy using multi-targeting liposomal codelivery
Authors: Zheng Zening , Zhang Jiaxin , Jiang Jizong , He Yang , Zhang Wenyuan , Mo Xiaopeng , Kang Xuejia , Xu Qin , Wang Bing , Huang Yongzhuo 
Published: August 2020

BackgroundGlioblastoma (GBM) treatment is undermined by the suppressive tumor immune microenvironment (TIME). Seek for effective methods for brain TIME modulation is a pressing need. However, there are two major challenges against achieving the goal: first, to screen the effective drugs with TIME-remodeling functions and, second, to develop a brain targeting system for delivering the drugs.MethodsIn this study, an α7 nicotinic acetylcholine receptors (nAChRs)-binding peptideDCDX was used to modify the codelivery liposomes to achieve a ‘three-birds-one-stone’ delivery strategy, that is, multi-targeting the glioma vessel endothelium, glioma cells, and tumor-associated macrophages that all overexpressed α7 nAChRs. A brain-targeted liposomal honokiol and disulfiram/copper codelivery system (CDX-LIPO) was developed for combination therapy via regulating mTOR (mammalian target of rapamycin) pathway for remodeling tumor metabolism and TIME. Honokiol can yield a synergistic effect with disulfiram/copper for anti-GBM.ResultsIt was demonstrated that CDX-LIPO remarkably triggered tumor cell autophagy and induced immunogenic cell death, and meanwhile, activated the tumor-infiltrating macrophage and dendritic cells, and primed T and NK (natural killer) cells, resulting in antitumor immunity and tumor regression. Moreover, CDX-LIPO promoted M1-macrophage polarization and facilitated mTOR-mediated reprogramming of glucose metabolism in glioma.ConclusionThis study developed a potential combinatory therapeutic strategy by regulation of TIME and a ‘three-birds-one-stone’-like glioma-targeting drug delivery system.
Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles
Authors: Orme Jacob J , Enninga Elizabeth Ann L , Lucien-Matteoni Fabrice , Dale Heather , Burgstaler Edwin , Harrington Susan M , Ball Matthew K , Mansfield Aaron S , Park Sean S , Block Mathew S , Markovic Svetomir N , Yan Yiyi , Dong Haidong , Dronca Roxana S , Winters Jeffrey L 
Published: August 2020

BackgroundTrans-acting programmed death-ligand 1 (PD-L1) derives from malignant cells in three known forms. High levels of secreted splice variant PD-L1 (sPD-L1), ADAM10/ADAM17-shed sPD-L1, and PD-L1-positive extracellular vesicles (evPD-L1) each predict poor prognosis and limited response to PD-(L)1 checkpoint inhibitors in cancer. To our knowledge, no clinical intervention has reduced any of these circulating forms of extracellular PD-L1. Here, we explore therapeutic plasma exchange (TPE) as a treatment to reduce circulating extracellular PD-L1.ResultsIn patients with melanoma, sPD-L1 levels above 0.277 ng/mL predicted inferior overall survival. In patients undergoing TPE for non-malignant indications, each TPE session removed a mean 70.8% sPD-L1 and 73.1% evPD-L1 detectable in plasma. TPE also reduced total and ADAM10-positive extracellular vesicles.ConclusionHere, we report the first known clinical intervention to remove either sPD-L1 or evPD-L1 from plasma in vivo. TPE reduces plasma sPD-L1 and evPD-L1 in vivo and may have a role in treatment with immunotherapy. TPE may also prove useful in patients with other extracellular vesicle-related conditions.
Atrial fibrillation in patients with an atrial septal defect in a single centre cohort during a long clinical follow-up: its association with closure and outcome of therapy
Authors: Evertz Reinder , Reinders Manon , Houck Charlotte , ten Cate Tim , Duijnhouwer Anthonie L. , Beukema Rypko , Westra Sjoerd , Vernooy Kevin , de Groot Natasja M S 
Published: August 2020

ObjectiveCurrently, consensus is lacking on the relation between closure of atrial septal defect (ASD) and the incidence of atrial fibrillation (AF), which is a known complication in ASD patients. More importantly, studies reporting on the treatment applied for AF in ASD patients are scarce. The aims of this study were (1) to assess the incidence of AF in ASD patients, (2) to study the relation between closure and AF and (3) to evaluate applied treatment strategies.MethodsA single-centre retrospective study in 173 patients with an ASD was performed. We analysed the incidence of AF, the relation of AF with closure, method of closure and the treatment success of therapies applied.ResultsAlmost 20% of patients with an ASD developed AF, with a mean age of 59 (±14) years at first presentation of AF during a median clinical follow-up of 43 (29–59) years. Older age (OR 1.072; p<0.001) and a dilated left atrium (OR 3.727; p=0.009) were independently associated with new-onset AF. Closure itself was not independently associated with AF. First applied treatment strategy was rhythm control in 77%. Of the 18 patients treated with antiarrhythmic drugs 50% had at least 1 recurrence of AF.ConclusionNo clear relation between closure of the ASD and AF could be assessed. This is the first study describing applied therapy for AF in ASD patients of which medical rhythm control was the most applied strategy with a disappointing efficacy.
Implementing smokeless tobacco control policy in Pakistan: a qualitative study among Naswar supply chain actors
Authors: Ahmad Fayaz , Boeckmann Melanie , Khan Zohaib , Zeeb Hajo , Khan Muhammad Naseem , Ullah Safat , Dreger Steffen , Haq Zia Ul , Forberger Sarah 
Published: August 2020

ObjectiveTo obtain insights into the perceptions of barriers and facilitators to implementation of the WHO Framework Convention on Tobacco Control (FCTC) among smokeless tobacco (SLT) supply chain actors in the Khyber Pakhtunkhwa province of Pakistan.MethodsWe conducted a qualitative study to investigate the perceptions about SLT control policy formulation and implementation among exclusive Naswar sellers and point of sale vendors. We conducted five focus group discussions in three districts of Khyber Pakhtunkhwa using combined deductive-inductive thematic analyses.ResultsWe identified three central themes that potentially impact policy formulation, its implementation and application. The first theme examines the role of children in the Naswar business: as potential customers, and as potential heirs to a Naswar-selling business. A second theme targets the ‘business of Naswar’, which includes a specific identity of Naswar sellers, its potential to generate profits and the special case of Naswar regulation as a socially accepted and culturally rooted product. The third theme addresses the unusual ingredients of Naswar and its production process, making Naswar a health risk for consumers and producers. We also report conflicting views regarding SLT control among the supply chain actors.ConclusionsThis study provides insights into the perceptions of important SLT supply-side stakeholders regarding various SLT control policy options based on the FCTC. While there is some opposition to policy approaches like taxation and switching of business, implementing a ban on selling SLT to minors may be a viable option for policymakers in the short term.
Prediction of coupled hydromechanical behavior of unsaturated soils based on seasonal variations in hydrologic conditions
Authors: Mahmoodabadi Majid , Bryson L. Sebastian 
Published: August 2020

Seasonal variations in hydrologic conditions greatly influence the hydromechanical properties of unsaturated soils. There are several models available to estimate shear strength of unsaturated soil under various hydrologic conditions. However, many of these existing models provide little to no data regarding the deformations associated with wetting and drying of unsaturated soils. The incremental hydromechanical behavior for an unsaturated soil is generally described by a constitutive framework. In this study, a modified Sheng, Fredlund, and Gens (SFG) soil constitutive model was utilized with in situ hydrologic data to simulate fully coupled mechanical behavior for an unsaturated slope over different hydrologic events. This paper also presents a hydrological prediction approach to estimate hydrologic characteristics of unsaturated soils over several wetting and drying events using only the soil-water characteristics parameters of the main drying curve. The proposed approach provides a possibility of describing long-term hydrologic behavior of unsaturated soils by means of a limited amount of in situ hydrologic data. The outcome of this study provides geotechnical engineers with the capability of estimating deformational behavior of unsaturated soils under various real-time rainfall–evapotranspiration conditions and implementing more effective emergency planning.
Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma
Authors: Martini Jean-François , Plimack Elizabeth R. , Choueiri Toni K. , McDermott David F. , Puzanov Igor , Fishman Mayer N. , Cho Daniel C. , Vaishampayan Ulka , Rosbrook Bradley , Fernandez Kathrine C. , Tarazi Jamal C. , George Saby , Atkins Michael B. 
Published: August 2020

AbstractPurpose:Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment.Patients and Methods:Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS).Results:Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS.Conclusions:With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.
Race-Dependent Differences in Risk, Genomics, and Epstein–Barr Virus Exposure in Monoclonal Gammopathies: Results of SWOG S0120
Authors: Dhodapkar Madhav V. , Sexton Rachael , Hoering Antje , Van Rhee Frits , Barlogie Bart , Orlowski Robert 
Published: August 2020

Abstract

Purpose:
Risk of multiple myeloma is increased in African American (AA) populations compared with European American (EA) cohorts. Current estimates of risk of progression of monoclonal gammopathy of undetermined significance (MGUS) are based largely on studies in EA cohorts. Prospective analyses of this risk in AA cohorts are lacking.

Patients and Methods:
Between 2003 and 2011, 331 eligible patients with IgG/A monoclonal gammopathy were enrolled in a prospective observational trial (SWOG S0120).

Results:
Of 331 eligible patients, 57 (17%) were of AA descent. The risk of transformation to clinical malignancy in AA patients was significantly lower than in non-AA cohort (2-year risk 5% vs. 15%; 5-year risk 13% vs. 24%; log-rank P = 0.047). Differences in risk were evident for both MGUS and asymptomatic multiple myeloma. Gene expression profile (GEP) of CD138-purified plasma cells revealed that all molecular multiple myeloma subsets can be identified in both cohorts. However, the proportion of patients with high-risk GEP risk score (GEP-70 gene risk &gt; −0.26) was lower in the AA cohort (0% vs. 33%, P = 0.01). AA cohorts also have higher levels of antibodies against Epstein–Barr nuclear antigen-1 (EBNA-1; P &lt; 0.001).

Conclusions:
These data provide the first prospective evidence that multiple myeloma precursor states in AA patients may have lower risk of disease compared with non-AA counterparts with lower incidence of high-risk GEP and increased EBV seropositivity. Race-dependent differences in biology and clinical risk of gammopathy may impact optimal management of these patients.
O imaginário como estrutura semiótica dos sintomas positivos da psicose paranoica: uma interface entre semiótica cognitiva e psicanálise
Authors: Lepesqueur Marcus 
Published: August 2020

A partir de uma análise dos sintomas positivos da psicose paranoica, este artigo propõe uma interlocução entre a semiótica cognitiva e a psicanálise. Pretende-se mostrar que a iconicidade pode constituir um sistema epistemológico que serve de pano de fundo para a semiose delirante. A adesão ao imaginário, característica da psicose lacaniana, torna-se, aqui, equiparável à predominância de um esquema icônico que modula a interação entre o sujeito psicótico e o outro. Por fim, apresenta-se um modelo preliminar da semiose delirante, capaz de oferecer uma inteligibilidade, em termos cognitivos, para o processo empático sobre o qual se desenrola os sintomas positivos da psicose.
Talking without words
Authors: Grenier Michelle , Lieberman Lauren 
Published: August 2020

This case study explored the inclusion of students with severe disabilities in a general elementary physical education program. Qualitative methods were used to capture the communication protocols and instructional practices used by the physical education (PE) teacher and Individual Education Plan (IEP) team members in one fourth grade and second grade physical education classroom. Data from three primary sources including field notes, interviews and a journal were analyzed to address questions of interest. Findings revealed four primary themes. The first “Collaboration-Needing to Know What I Don’t Know” described the process the PE teacher used in gaining information on her students with disabilities. The second, “Community in the Classroom,” revealed the value system shared by the IEP team members. The third theme, “The Role of Modeling” articulated the value of appropriated practices between teachers and students. The final theme, “Talking Without Words” highlighted the communicative processes and shared language between the students with and without disabilities.
Environmental impact on physical activity and health in transgender youth
Authors: Ferrey Alexandria 
Published: August 2020

Background: Physical Activity Guidelines for Americans suggest that youth should participate in at least one hour of age appropriate PA per day. Yet, fewer than 30% of high school students participate in at least 60 minutes of PA every day; ethnic minority youth report even less. Within the transgender community, students were less likely to be physically active, due to safety concerns which is mostly related to a sedentary adult. Purpose: To investigate the barriers and facilitators transgender adults faced when they were adolescents and experiencing PA environments (e.g. physical education, sport teams). Methods: Quantitative study using a questionnaire with 27 closed-ended questions. A sample of convenience was used to recruit participants. Data was coded, cleaned, and analyzed using Microsoft Excel 2018 and SPSS Statistics 24. Results: Quantitative results indicate that there is transphobic behavior present in a physical activity environment, furthermore, facilities prevented participants from participating in physical activity. Implications: The results of this study may possibly be used to inform programming in educational institutions, coaches, and support policy makers in developing what interventions are needed to increase safety for transgender youth.
4HNE Impairs Myocardial Bioenergetics in Congenital Heart Disease-Induced Right Ventricular Failure
Authors: Hwang HyunTae V. , Sandeep Nefthi , Paige Sharon L. , Ranjbarvaziri Sara , Hu Dong-Qing , Zhao Mingming , Lan Ingrid S. , Coronado Michael , Kooiker Kristina B. , Wu Sean M. , Fajardo Giovanni , Bernstein Daniel , Reddy Sushma 
Published: August 2020

Background:
In patients with complex congenital heart disease, such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload stress, leading to RV hypertrophy and eventually RV failure. The role of lipid peroxidation, a potent form of oxidative stress, in mediating RV hypertrophy and failure in congenital heart disease is unknown.

Methods:
Lipid peroxidation and mitochondrial function and structure were assessed in right ventricle (RV) myocardium collected from patients with RV hypertrophy with normal RV systolic function (RV fractional area change, 47.3±3.8%) and in patients with RV failure showing decreased RV systolic function (RV fractional area change, 26.6±3.1%). The mechanism of the effect of lipid peroxidation, mediated by 4-hydroxynonenal ([4HNE] a byproduct of lipid peroxidation) on mitochondrial function and structure was assessed in HL1 murine cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes.

Results:

RV failure was characterized by an increase in 4HNE adduction of metabolic and mitochondrial proteins (16 of 27 identified proteins), in particular electron transport chain proteins. Sarcomeric (myosin) and cytoskeletal proteins (desmin, tubulin) also underwent 4HNE adduction. RV failure showed lower oxidative phosphorylation (moderate RV hypertrophy, 287.6±19.75 versus RV failure, 137.8±11.57 pmol/[sec×mL];
P
=0.0004), and mitochondrial structural damage. Using a cell model, we show that 4HNE decreases cell number and oxidative phosphorylation (control, 388.1±23.54 versus 4HNE, 143.7±11.64 pmol/[sec×mL];
P
<0.0001). Carvedilol, a known antioxidant did not decrease 4HNE adduction of metabolic and mitochondrial proteins and did not improve oxidative phosphorylation.

Conclusions:
Metabolic, mitochondrial, sarcomeric, and cytoskeletal proteins are susceptible to 4HNE-adduction in patients with RV failure. 4HNE decreases mitochondrial oxygen consumption by inhibiting electron transport chain complexes. Carvedilol did not improve the 4HNE-mediated decrease in oxygen consumption. Strategies to decrease lipid peroxidation could improve mitochondrial energy generation and cardiomyocyte survival and improve RV failure in patients with congenital heart disease.
Microvolt QRS Alternans Without Microvolt T‐Wave Alternans in Human Cardiomyopathy: A Novel Risk Marker of Late Ventricular Arrhythmias
Authors: Suszko Adrian , Nayyar Sachin , Labos Christopher , Nanthakumar Kumaraswamy , Pinter Arnold , Crystal Eugene , Chauhan Vijay S. 
Published: August 2020

Background
Action potential alternans can induce ventricular tachyarrhythmias and manifest on the surface ECG as T‐wave alternans (TWA) and QRS alternans (QRSA). We sought to evaluate microvolt QRSA in cardiomyopathy patients in relation to TWA and ventricular tachyarrhythmia outcomes.

Methods and Results

Prospectively enrolled cardiomyopathy patients (n=100) with prophylactic defibrillators had 12‐lead ECGs recorded during ventricular pacing from 100 to 120 beats/min. QRSA and TWA were quantified in moving 128‐beat segments using the spectral method. Segments were categorized as QRSA positive (QRSA+) and/or TWA positive (TWA+) based on ≥2 precordial leads having alternans magnitude >0 and signal:noise >3. Patients were similarly categorized based on having ≥3 consecutive segments with alternans. TWA+ and QRSA+ occurred together in 31% of patients and alone in 18% and 14% of patients, respectively. Although TWA magnitude (1.4±0.4 versus 4.7±1.0 µV,
P
<0.01) and proportion of TWA+ studies (16% versus 46%,
P
<0.01) increased with rate, QRSA did not change. QRS duration was longer in QRSA+ than QRSA‐negative patients (138±23 versus 113±26 ms,
P
<0.01). At 3.5 years follow‐up, appropriate defibrillator therapy or sustained ventricular tachyarrhythmia was greater in QRSA+ than QRSA‐negative patients (30% versus 8%,
P
=0.02) but similar in TWA+ and TWA‐negative patients. Among QRSA+ patients, the event rate was greater in those without TWA (62% versus 21%,
P
=0.02). Multivariable Cox analysis revealed QRSA+ (hazard ratio [HR], 4.6; 95% CI, 1.5–14;
P
=0.009) and QRS duration >120 ms (HR, 4.1; 95% CI, 1.3–12;
P
=0.014) to predict events.

Conclusions
Microvolt QRSA is novel phenomenon in cardiomyopathy patients that can exist without TWA and is associated with QRS prolongation. QRSA increases the risk of ventricular tachyarrhythmia 4‐fold, which merits further study as a risk stratifier.