bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of programmed cell death protein 1 and T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule‐3 on peripheral blood CD4+CD8+ double positive T cells in patients with chronic hepatitis C virus infection and in subjects who spontaneously cleared the virus
Authors: Caraballo Cortés Kamila , Osuch Sylwia , Perlejewski Karol , Pawełczyk Agnieszka , Kaźmierczak Justyna , Janiak Maciej , Jabłońska Joanna , Nazzal Khalil , Stelmaszczyk‐Emmel Anna , Berak Hanna , Bukowska‐Ośko Iwona , Paciorek Marcin , Laskus Tomasz , Radkowski Marek 
Published: April 2019

AbstractChronic hepatitis C virus (HCV) infection is characterized by increased proportion of CD4+CD8+ double positive (DP) T cells, but their role in this infection is unclear. In chronic hepatitis C, immune responses to HCV become functionally exhausted, which manifests itself by increased expression of programmed cell death protein 1 (PD‐1) and T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule‐3 (Tim‐3) on T cells. The aim of our study was to determine PD‐1 and Tim‐3 phenotype of DP T cells in subjects with naturally resolved and chronic HCV infection. Peripheral blood mononuclear cells from 16 patients with chronic infection and 14 subjects who cleared HCV in the past were stained with anti‐CD3, anti‐CD4, anti‐CD8, anti‐PD‐1 and anti‐Tim‐3 antibodies and, in 12 HLA‐A*02‐positive subjects, MHC class I pentamer with HCV NS31406 epitope. In chronic and past HCV infection, proportions of total DP T cells and PD‐1+ DP T cells were similar but significantly higher than in healthy controls. DP T cells were more likely to be PD‐1+ than either CD4+ or CD8+ single positive (SP) T cells. HCV‐specific cells were present in higher proportions among DP T cells than among CD8+ SP T cells in both patient groups. Furthermore, while the majority of HCV‐specific DP T cells were PD‐1+, the proportion of HCV‐specific CD8+ T cells which were PD‐1+ was 4.9 and 1.9 times lower (chronic and past infection, respectively). PD‐1 and Tim‐3 were predominantly expressed on CD4highCD8low and CD4lowCD8high cells, respectively, and co‐expression of both markers was uncommon.
Functional and mechanistic characterization of an atypical flavin reductase encoded by the pden_5119 gene in Paracoccus denitrificans
Authors: Sedláček Vojtěch , Kučera Igor 
Published: April 2019

SummaryPden_5119, annotated as an NADPH‐dependent FMN reductase, shows homology to proteins assisting in utilization of alkanesulfonates in other bacteria. Here, we report that inactivation of the pden_5119 gene increased susceptibility to oxidative stress, decreased growth rate and increased growth yield; growth on lower alkanesulfonates as sulfur sources was not specifically influenced. Pden_5119 transcript rose in response to oxidative stressors, respiratory chain inhibitors and terminal oxidase downregulation. Kinetic analysis of a fusion protein suggested a sequential mechanism in which FMN binds first, followed by NADH. The affinity of flavin toward the protein decreased only slightly upon reduction. The observed strong viscosity dependence of kcat demonstrated that reduced FMN formed tends to remain bound to the enzyme where it can be re‐oxidized by oxygen or, less efficiently, by various artificial electron acceptors. Stopped flow data were consistent with the enzyme‐FMN complex being a functional oxidase that conducts the reduction of oxygen by NADH. Hydrogen peroxide was identified as the main product. As shown by isotope effects, hydride transfer occurs from the pro‐S C4 position of the nicotinamide ring and partially limits the overall turnover rate. Collectively, our results point to a role for the Pden_5119 protein in maintaining the cellular redox state.
Conflict Style Associations with Cooperativeness, Directness, and Relational Satisfaction: A Case for a Six‐Style Typology
Authors: Guerrero Laura K. 
Published: April 2019

AbstractPast research has been inconsistent in identifying the number and type of conflict styles individuals perceive themselves to use. Many typologies of conflict styles are built on the premise that level of cooperation versus competition, as well as directness versus indirectness, underlie various conflict styles. Grounded in a communication perspective, the present study uses dyadic data from 256 romantic couples to examine how self‐reported tendencies to use each of six conflict styles—collaborating, compromising, competitive fighting, yielding, avoiding, and indirect fighting—associate with how (un)cooperative and (in)direct partners generally perceive actors to be during conflict, as well as how relationally satisfied both members of the dyad are. The associations that emerged suggest each of the six styles has a unique profile, that a comprehensive typology of conflict styles should include indirect fighting as well as a more neutral avoiding style, and that compromising is a weak form of collaborating that is lower in cooperativeness and directness.
Efficient genetic transformation and CRISPR/Cas9‐mediated genome editing in Lemna aequinoctialis
Authors: Liu Yu , Wang Yu , Xu Shuqing , Tang Xianfeng , Zhao Jinshan , Yu Changjiang , He Guo , Xu Hua , Wang Shumin , Tang Yali , Fu Chunxiang , Ma Yubin , Zhou Gongke 
Published: April 2019

SummaryThe fast growth, ease of metabolic labelling and potential for feedstock and biofuels production make duckweeds not only an attractive model system for understanding plant biology, but also a potential future crop. However, current duckweed research is constrained by the lack of efficient genetic manipulation tools. Here, we report a case study on genome editing in a duckweed species, Lemna aequinoctialis, using a fast and efficient transformation and CRISPR/Cas9 tool. By optimizing currently available transformation protocols, we reduced the duration time of Agrobacterium‐mediated transformation to 5–6 weeks with a success rate of over 94%. Based on the optimized transformation protocol, we generated 15 (14.3% success rate) biallelic LaPDS mutants that showed albino phenotype using a CRISPR/Cas9 system. Investigations on CRISPR/Cas9‐mediated mutation spectrum among mutated L. aequinoctialis showed that most of mutations were short insertions and deletions. This study presents the first example of CRISPR/Cas9‐mediated genome editing in duckweeds, which will open new research avenues in using duckweeds for both basic and applied research.
Bisphenol A attenuates thyroxine‐induced apoptosis in ovarian granulosa cells of pigs
Authors: Song Dan , Wu Guoyun , Wei Quanwei , Shi Fangxiong 
Published: April 2019

ContentsBisphenol A (BPA) is a chemical of high production volume that is used widely in many industries and is known as a xenooestrogen and anti‐thyroid hormone endocrine disrupter. There is little information regarding the effects of BPA in the presence of thyroid hormone on porcine granulosa cell development. Thus, the primary granulosa cells were treated with thyroxine (T4, 10 nM), BPA (10 µM) or T4 plus BPA; we subsequently evaluated the effects of T4 or BPA on 17β‐estradiol synthesis, cellular proliferation and apoptosis. Our data showed that BPA significantly increased the accumulation of 17β‐estradiol and promoted granulosa cell proliferation, whereas T4 significantly decreased 17β‐estradiol and had no effect on cellular proliferation. In addition, it was noteworthy that T4 treatment induced apoptosis in porcine granulosa cells and BPA co‐incubation attenuated T4‐induced apoptosis as shown from flow cytometric assay analysis. We hypothesized that BPA attenuates T4‐induced apoptosis by regulating 17β‐estradiol accumulation and oestrogen receptor‐mediated signalling pathways. In conclusion, our results demonstrated that T4 affected 17β‐estradiol accumulation and induced cellular apoptosis, but did not affect granulosa cell proliferation. Exposure to BPA increased 17β‐estradiol accumulation, promoted granulosa cell proliferation and attenuated T4‐induced apoptosis in porcine granulosa cells in vitro.
Emergency medical services and cardiac arrest from drug overdose: a protocol for a systematic review of incidence and survival outcomes
Authors: Alqahtani Saeed , Nehme Ziad , Williams Brett , Smith Karen 
Published: April 2019

Review question:
The primary review question is: what is the global incidence rate of emergency medical services (EMS)-attended and EMS-treated out-of-hospital cardiac arrest (OHCA) precipitated by drug overdose in adults?
The secondary review questions are: what proportion of adults with EMS-treated overdose OHCA: i) survived to hospital discharge or 30 days, ii) survived with intact neurological function at hospital discharge (i.e. Cerebral Performance Category or modified Rankin Scale ≤ 2), iii) achieved prehospital return of spontaneous circulation, iv) survived to hospital, and v) survived to 12 months?
Effectiveness of interventions to reduce occupational stress among emergency department staff: a systematic review protocol
Authors: Xu Hui (Grace) , Kynoch Kathryn , Tuckett Anthony , Eley Robert , Newcombe Peter 
Published: April 2019

Review question:
The aim of the review is to synthesize the best available evidence on interventions targeting occupational stress and burnout among emergency department (ED) staff. The specific review questions are:
Because space matters: conceptual framework to help distinguish slum from non-slum urban areas
Authors: Lilford Richard , Kyobutungi Catherine , Ndugwa Robert , Sartori Jo , Watson Samuel I , Sliuzas Richard , Kuffer Monika , Hofer Timothy , Porto de Albuquerque Joao , Ezeh Alex 
Published: April 2019

Despite an estimated one billion people around the world living in slums, most surveys of health and well-being do not distinguish between slum and non-slum urban residents. Identifying people who live in slums is important for research purposes and also to enable policymakers, programme managers, donors and non-governmental organisations to better target investments and services to areas of greatest deprivation. However, there is no consensus on what a slum is let alone how slums can be distinguished from non-slum urban precincts. Nor has attention been given to a more fine-grained classification of urban spaces that might go beyond a simple slum/non-slum dichotomy. The purpose of this paper is to provide a conceptual framework to help tackle the related issues of slum definition and classification of the urban landscape. We discuss:The concept of space as an epidemiological variable that results in ‘neighbourhood effects’.The problems of slum area definition when there is no ‘gold standard’.A long-list of variables from which a selection must be made in defining or classifying urban slum spaces.Methods to combine any set of identified variables in an operational slum area definition.Two basic approaches to spatial slum area definitions—top-down (starting with a predefined area which is then classified according to features present in that area) and bottom-up (defining the areal unit based on its features).Different requirements of a slum area definition according to its intended use.Implications for research and future development.
Youth lost to homicides: disparities in survival in Latin America and the Caribbean
Authors: Canudas-Romo Vladimir , Aburto José Manuel 
Published: April 2019

IntroductionThe homicide rates among young men in Latin America and the Caribbean (LAC) are the highest in the world. It is not clear how this has impacted the life expectancy in these countries. This research has two purposes: (1) to quantify the impact of homicides on the mortality gap between LAC and high-income countries over recent years and (2) to assess the changes in homicide impact in overall survival over time.MethodsCauses of death data were extracted for 23 countries in the LAC and 15 European countries (average European union-15 [EU-15]), using UN, UNODC, WHO, HMD and IHME databases for the period 2005–2014. The contribution by homicide deaths to the change in life expectancy, over time and as a difference between two populations, was quantified using decomposition methods.ResultsThe contribution by homicide mortality to changes in life expectancy levels differed widely across the examined LAC countries. In Honduras, homicide mortality accounted for 1.75 (95% CI 1.64 to 1.86) and 6.30 (95% CI 6.07 to 6.53) years lower life expectancy than in the EU-15 countries for women and men, respectively. Contrary to this, homicide was just accountable for less than a couple of months of life expectancy differences between Chile and EU-15. Jamaica had the largest reduction in homicides and its impact increased life expectancy over time by almost half a year for men. However, Mexican men and Honduran women have experienced increases in mortality by homicide, which decreased their life expectancy by more than a quarter of a year between 2005 and 2014.ConclusionsExcess mortality related to homicides in young people accounted for major changes in life expectancy in the LAC region. Furthermore, reducing excess mortality due to homicides is a crucial goal to further increase longevity towards levels of low-mortality countries. These reductions might prevent homicides spreading to other parts of Latin America. Decision and policy-makers in LAC need to address this immediately, and investing in the young population needs to be given a high priority.
Tracking global trends in the effectiveness of antibiotic therapy using the Drug Resistance Index
Authors: Klein Eili Y , Tseng Katie K , Pant Suraj , Laxminarayan Ramanan 
Published: April 2019

BackgroundEvaluating trends in antibiotic resistance and communicating the results to a broad audience are important for dealing with this global threat. The Drug Resistance Index (DRI), which combines use and resistance into a single measure, was developed as an easy-to-understand measure of the effectiveness of antibiotic therapy. We demonstrate its utility in communicating differences in the effectiveness of antibiotic therapy across countries.MethodsWe calculated the DRI for countries with data on antibiotic use and resistance for the disease-causing organisms considered by the WHO as priority pathogens:Acinetobacter baumannii,Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa,Staphylococcus aureus,Enterococcus faeciumandEnterococcus faecalis. Additionally, we estimated pooled worldwide resistance rates for these pathogens.Results41 countries had the requisite data and were included in the study. Resistance and use rates were highly variable across countries, butA. baumanniiresistance rates were uniformly higher, on average, than other organisms. High-income countries, particularly Sweden, Canada, Norway, Finland and Denmark, had the lowest DRIs; the countries with the highest DRIs, and therefore the lowest effectiveness of antibiotic therapy, were all low-income and middle-income countries.ConclusionsThe DRI is a useful indicator of the problem of resistance. By combining data on antibiotic use with resistance, it captures a snapshot of how the antibiotics a country typically uses match their resistance profiles. This single measure of the effectiveness of antibiotic therapy provides a means of benchmarking against other countries and can, over time, indicate changes in drug effectiveness that can be easily communicated.
Personal Wellbeing Score (PWS)—a short version of ONS4: development and validation in social prescribing
Authors: Benson Tim , Sladen Joe , Liles Andrew , Potts Henry W W 
Published: April 2019

AimsOur aim was to develop a short generic measure of subjective well-being for routine use in patient-centred care and healthcare quality improvement alongside other patient-reported outcome and experience measures.MethodsThe Personal Wellbeing Score (PWS) is based on the Office of National Statistics (ONS) four subjective well-being questions (ONS4) and thresholds. PWS is short, easy to use and has the same look and feel as other measures in the same family of measures. Word length and reading age were compared with eight other measures.Anonymous data sets from five social prescribing projects were analysed. Internal structure was examined using distributions, intra-item correlations, Cronbach’s α and exploratory factor analysis. Construct validity was assessed based on hypothesised associations with health status, health confidence, patient experience, age, gender and number of medications taken. Scores on referral and after referral were used to assess responsiveness.ResultsDifferences between PWS and ONS4 include brevity (42 vs 114 words), reading age (9 vs 12 years), response options (4 vs 11), positive wording throughout and a summary score. 1299 responses (60% female, average age 81 years) from people referred to social prescribing services were analysed; missing values were less than 2%. PWS showed good internal reliability (Cronbach’s α=0.90). Exploratory factor analysis suggested that all PWS items relate to a single dimension. PWS summary scores correlate positively with health confidence (r=0.60), health status (r=0.58), patient experience (r=0.30) and age group (r=0.24). PWS is responsive to social prescribing intervention.ConclusionsThe PWS is a short variant of ONS4. It is easy to use with good psychometric properties, suitable for routine use in quality improvement and health services research.
Combining a robust PCA of logratio transformed data and geostatistical sequential Gaussian simulation approach for geochemical characterization of orogenic gold deposits: a case study from the Alut area, NW of Iran
Authors: Sharifi Fereydoun , Arab-Amiri Ali Reza , Kamkar-Rouhani Abolghasem , Alipour-Asll Masood 
Published: April 2019

Robust principal component analysis (PCA) has been proved to be an efficient multivariate statistical method for extraction of a multivariate structure of geochemical data containing outlier values. Furthermore, because of the compositional characteristics of geochemical data, logratio transformation approaches also have to be implemented to transform the data from the simplex space into real space. In order to model the extracted principal component of transformed data, we used sequential Gaussian simulation (SGS) to overcome the drawbacks associated with the traditional kriging method, e.g. bias conditionally relevant to underestimation and overestimation, the smoothing effect and so on.
The results of implementing robust PCA on both untransformed and logratio transformed data, which have been acquired from an orogenic gold deposit, indicate that robust PCA analysis of untransformed data is not capable of certifying element association of gold occurrences. However, in robust PCA analysis of transformed data, both varieties of gold mineralization, associated with pyrite mineral and quartz veins, have been revealed. The first variety of gold occurrence is detected in an integrated PC obtained from PC1, PC2 and PC3, which are associated with Pb, As, Hg, Mo, S and Sb elements in quartz–sulphide veins. The second one, PC4, could be correlated with quartz veins. Furthermore, the results of the geostatistical SGS approach are compatible with the detected anomaly in the Alut gold deposit.
Oxygen dependence of glucose sensing: role in glucose homeostasis and related pathology
Authors: Wilson David F. , Matschinsky Franz M. 
Published: April 2019

In glucose homeostasis, glucose concentration is sensed by its metabolism through glucokinase (GCK) and oxidative phosphorylation. Because oxidative phosphorylation is an integral part of the sensory system, glucose sensing is necessarily dependent on oxygen pressure. Much of the dependence on oxygen is suppressed by location of glucose sensing cells in tissues with well-regulated blood flow. In healthy individuals the oxygen dependence is primarily observed in response to transient global hypoxia events such as during birth or transition to high altitude. The GCK sensing system is, however, used to control release of both insulin and glucagon, the preeminant hormonal regulators of blood glucose, as well as glucose sensitive neuronal activity. Suppression of oxygen delivery to glucose-sensing cells or interference with regulation of tissue blood flow by either local or systemic causes, stresses the glucose regulatory system. This is true whether the stress is imposed locally, such as by altered oxygen delivery to the pancreas, or globally, as in pulmonary insufficiency or exposure to high altitude. It may be expected that chronic application of this stress predisposes individuals to developing diabetes. Type 2 diabetes is a broad class of diseases characterized by disturbance of glucose homeostasis, i.e., having either hyperglycemia and/or decreased sensitivity to insulin. Given the role of oxidative phosphorylation in glucose sensing, tissue oxygen deprivation may predispose individuals to developing diabetes as well as contributing to the disease itself. This is particularly true in age-related diabetes because the incidence of vascular insufficiency increases markedly with increasing age.NEW & NOTEWORTHY Glucose sensing requires glucose metabolism through glycolysis and oxidative phosphorylation. Dependence of the latter on oxygen concentration imposes an oxygen dependence on glucose sensing. We have used a validated computational model to quantify that dependence. Evidence is presented that tissue oxygenation plays an important role in predisposition of individuals to developing type 2 diabetes and in progression of the disease.
The alcohol breath test in practice: effects of exhaled volume
Authors: Anderson Joseph C. , Hlastala Michael P. 
Published: April 2019

Alcohol breath test (ABT) measurements are sensitive to the volume of the exhaled breath. Although a minimum breath volume is required for a legally acceptable sample, any additional increase in the volume of exhaled air increases the measurement of breath alcohol concentration (BrAC). Using a sample of 115 ABTs collected by police agencies for evidentiary purposes, we studied the influence of exhaled air volume on the measurement of BrAC. The 115 ABTs were performed on 30 different Alcotest 9510s. Each of the tests included paired, time series measurements of exhaled breath flow rates and breath alcohol content. The exhalation flow rates and exhalation times were used to create exhalation volume-BrAC plots. On average, exhaled air volumes were ~50% of the subjects’ age-, height-, race-, and sex-predicted vital capacities (VC). More than 80% of the samples had exhaled air volumes ranging between 30 and 70% of the subject’s predicted VC. Breath volumes for duplicate breath samples were similar. For all breath samples, BrAC increased with exhalation volume, an expected behavior for any very high blood solubility compound such as alcohol. Beyond the legally accepted minimum expiratory volume, BrAC increased, on average, at a rate of 9.2 ± 2.8%/liter air exhaled. As a result, a person who exhales just beyond the minimum volume will have a lower BrAC compared with a person who exhales a full VC. Exhaled volume materially impacts the measurement of an ABT. NEW & NOTEWORTHY Subjects who provide breath samples for evidentiary alcohol breath tests exhale, on average, about half of their predicted vital capacity. Because breath alcohol concentration increases with greater exhaled air volume, subjects who exhale more than average volume will have a greater breath alcohol concentration, whereas subjects who exhale less than average volume will have a lesser breath alcohol concentration. A quantification of air volume impact on breath alcohol concentration is provided.