bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allergic disease and risk of stress in pregnant women: a PreventADALL study
Authors: Olsson Mägi Caroline-Aleksi , Bjerg Bäcklund Anders , Lødrup Carlsen Karin , Almqvist Catarina , Carlsen Kai-Håkon , Granum Berit , Haugen Guttorm , Hilde Katarina , Lødrup Carlsen Oda C. , Jonassen Christine Monceyron , Rehbinder Eva Maria , Sjøborg Katrine D. , Skjerven Håvard , Staff Anne Cathrine , Vettukattil Riyas , Söderhäll Cilla , Nordlund Björn 
Published: October 2020

BackgroundMaternal stress during pregnancy may negatively affect the health of mother and child. We therefore aimed to identify the proportion of women reporting high maternal stress in mid and late pregnancy and explore whether symptoms of maternal allergic disease are associated with perceived maternal stress in late pregnancy.MethodThe population-based Preventing Atopic Dermatitis and Allergy in Children (PreventADALL) study enrolled 2697 pregnant women at their 18-week routine ultrasound examination in Norway and Sweden. Information about sociodemographic factors, symptoms and doctor-diagnosed asthma, allergic rhinitis, atopic dermatitis, food allergy, and anaphylaxis and stress using the 14-item perceived stress scale (PSS) was collected at 18 weeks (mid) and 34 weeks (late) pregnancy. High stress was defined as a PSS score ≥29. Scores were analysed using multivariate logistic and linear regression.ResultsAmong the 2164 women with complete PSS data, 17% reported asthma, 20% atopic dermatitis, 23% allergic rhinitis, 12% food allergy and 2% anaphylaxis. The proportion of women reporting high stress decreased from 15% at mid to 13% at late pregnancy (p<0.01). The adjusted odds ratio for high stress in late pregnancy was 2.25 (95% CI 1.41–3.58) for self-reported symptoms of asthma, 1.46 (95% CI 1.02–2.10) for allergic rhinitis and 2.25 (95% CI 1.32–3.82) for food allergy. A multivariate linear regression model confirmed that symptoms of asthma (β coefficient 2.11; 0.71–3.51), atopic dermatitis (β coefficient 1.76; 0.62–2.89) and food allergy (β coefficient 2.24; 0.63–3.84) were independently associated with increased PSS score.ConclusionAllergic disease symptoms in pregnancy were associated with increased stress, highlighting the importance of optimal disease control in pregnancy.
The IAB Job Vacancy Survey: design and research potential
Authors: Bossler Mario , Gürtzgen Nicole , Kubis Alexander , Küfner Benjamin , Lochner Benjamin 
Published: October 2020

AbstractThis article provides an overview of the IAB Job Vacancy Survey and its research potential. The IAB Job Vacancy Survey is a quarterly establishment survey covering the (un-)satisfied labor demand in Germany. This survey identifies the entire number of vacancies on the German labor market, including those vacancies that are not reported to the Federal Employment Agency. The main questionnaire obtains information about the number and structure of vacancies, future labor demand, the current economic situation and the expected development of participating establishments. In addition, the questionnaire collects information about the last new hiring and the last case of a failed recruitment process. Finally, the questionnaire enquires about employer attitudes and firms’ use of current labor market instruments. The Research Data Centre of the German Federal Employment Agency offers access to the data starting from the survey waves 2000 onwards.
Protein–protein and protein-nucleic acid binding residues important for common and rare sequence variants in human
Authors: Qiu Jiajun , Nechaev Dmitrii , Rost Burkhard 
Published: October 2020

Abstract
Background
Any two unrelated people differ by about 20,000 missense mutations (also referred to as SAVs: Single Amino acid Variants or missense SNV). Many SAVs have been predicted to strongly affect molecular protein function. Common SAVs (> 5% of population) were predicted to have, on average, more effect on molecular protein function than rare SAVs (< 1% of population). We hypothesized that the prevalence of effect in common over rare SAVs might partially be caused by common SAVs more often occurring at interfaces of proteins with other proteins, DNA, or RNA, thereby creating subgroup-specific phenotypes. We analyzed SAVs from 60,706 people through the lens of two prediction methods, one (SNAP2) predicting the effects of SAVs on molecular protein function, the other (ProNA2020) predicting residues in DNA-, RNA- and protein-binding interfaces.

Results
Three results stood out. Firstly, SAVs predicted to occur at binding interfaces were predicted to more likely affect molecular function than those predicted as not binding (p value < 2.2 × 10–16). Secondly, for SAVs predicted to occur at binding interfaces, common SAVs were predicted more strongly with effect on protein function than rare SAVs (p value < 2.2 × 10–16). Restriction to SAVs with experimental annotations confirmed all results, although the resulting subsets were too small to establish statistical significance for any result. Thirdly, the fraction of SAVs predicted at binding interfaces differed significantly between tissues, e.g. urinary bladder tissue was found abundant in SAVs predicted at protein-binding interfaces, and reproductive tissues (ovary, testis, vagina, seminal vesicle and endometrium) in SAVs predicted at DNA-binding interfaces.

Conclusions
Overall, the results suggested that residues at protein-, DNA-, and RNA-binding interfaces contributed toward predicting that common SAVs more likely affect molecular function than rare SAVs.
Combined primary carnitine deficiency with neonatal intrahepatic cholestasis caused by citrin deficiency in a Chinese newborn
Authors: Lin Yiming , Lin Weihua , Chen Yanru , Lin Chunmei , Zheng Zhenzhu , Zhuang Jianlong , Fu Qingliu 
Published: October 2020

Abstract
Background
Primary carnitine deficiency (PCD) is an autosomal recessive disorder affecting the carnitine cycle and resulting in defective fatty acid oxidation. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder and one of the main causes of inherited neonatal cholestasis. Both PCD and NICCD are included in the current expanded newborn screening (NBS) targets.

Case presentation
Targeted exome sequencing was performed on a Chinese proband, and Sanger sequencing was utilised to validate the detected mutations. The patient who was initially suspected to have PCD based on the NBS results presented with neonatal intrahepatic cholestasis and ventricular septal defect. Further investigations not only confirmed PCD but also revealed the presence of NICCD. Four distinct mutations were detected, including c.51C > G (p.F17L) and c.760C > T (p.R254X) in SLC22A5 as well as c.615 + 5G > A and IVS16ins3kb in SLC25A13.

Conclusions
This is the first reported case of PCD and NICCD occurring in the same patient. The dual disorders in a newborn broaden our understanding of inherited metabolic diseases. Thus, this study highlighted the importance of further genetic testing in patients presenting with unusual metabolic screening findings.
Designing and evaluating an interprofessional education conference approach to antimicrobial education
Authors: Guilding Clare , Hardisty Jessica , Randles Elsa , Statham Louise , Green Alan , Bhudia Roshni , Thandi Charan Singh , Teodorczuk Andrew , Scott Lesley , Matthan Joanna 
Published: October 2020

Abstract
Background
Arguably, Medical School curricula are deficient in learning opportunities related to the safe and effective use of medicines, in particular antimicrobials. Infection management is complex and multidisciplinary, and learning opportunities should reflect these principles. Aligned to the complexity of the subject matter, simulation and interprofessional based teaching are methods that can foster the collaborative skills required of future healthcare professionals. There have been calls to develop these methods in the teaching of safe prescribing and the management of infections; however, reports of such studies are limited.

Methods
We developed an interprofessional education (IPE) conference for second year undergraduate medical and pharmacy students based in the North East of England. We considered contact theory in the design of three small group interprofessional workshops, on the broad themes of antimicrobial stewardship, infection management and patient safety. A mixed methods approach assessed students’ attitudes towards IPE, barriers and facilitators of learning, and perceived learning gains. Qualitative data from workshop evaluation forms were analysed thematically, while quantitative data were analysed descriptively and differences between medical and pharmacy cohorts analysed using unpaired two-tailed t-tests.

Results
226/352 students returned the workshop evaluation forms (66% of pharmacy students, 62% of medical students). 281/352 students responded to a series of Likert scale questions on the value of interprofessional education (88% of pharmacy students, 70% of medical students). Students reported acquisition of knowledge and skills, including concepts and procedures related to infection management and antimicrobial prescribing, and the development of problem-solving and critical evaluation skills. Students reflected on their attitude towards interprofessional collaboration. They reported a greater understanding of the roles of other healthcare professionals, reflected on the importance of effective communication in ensuring patient safety, and were more confident to work in interprofessional teams after the conference.

Conclusions
A robust IPE event, theoretically underpinned by contact theory and developed collaboratively, achieved interprofessional learning at scale and helped develop healthcare professionals willing to collaborate across disciplines. The resources, and evaluation insights based on the 3P (presage, process, and product) model of learning and teaching, will be of value to other educators who seek to develop theoretically-sound IPE interventions.
Importance of scientific collaboration in contemporary drug discovery and development: a detailed network analysis
Authors: Cheng Feixiong , Ma Yifang , Uzzi Brian , Loscalzo Joseph 
Published: October 2020

Abstract
Background
Growing evidence shows that scientific collaboration plays a crucial role in transformative innovation in the life sciences. For example, contemporary drug discovery and development reflects the work of teams of individuals from academic centers, the pharmaceutical industry, the regulatory science community, health care providers, and patients. However, public understanding of how collaborations between academia and industry catalyze novel target identification and first-in-class drug discovery is limited.

Results
We perform a comprehensive network analysis on a large scientific corpus of collaboration and citations (97,688 papers with 1,862,500 citations from 170 million scientific records) to quantify the success trajectory of innovative drug development. By focusing on four types of cardiovascular drugs, we demonstrate how knowledge flows between institutions to highlight the underlying contributions of many different institutions in the development of a new drug. We highlight how such network analysis could help to increase industrial and governmental support, and improve the efficiency or accelerate decision-making in drug discovery and development.

Conclusion
We demonstrate that network analysis of large public databases can identify and quantify investigator and institutional relationships in drug discovery and development. If broadly applied, this type of network analysis may help to enhance public understanding of and support for biomedical research, and could identify factors that facilitate decision-making in first-in-class drug discovery among academia, the pharmaceutical industry, and healthcare systems.
SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
Authors: Wechsler Michael E. , Colice Gene , Griffiths Janet M. , Almqvist Gun , Skärby Tor , Piechowiak Teresa , Kaur Primal , Bowen Karin , Hellqvist Åsa , Mo May , Garcia Gil Esther 
Published: October 2020

Abstract
Background
Many patients with severe asthma continue to experience asthma symptoms and exacerbations despite standard-of-care treatment. A substantial proportion of these patients require long-term treatment with oral corticosteroids (OCS), often at high doses, which are associated with considerable multiorgan adverse effects, including metabolic disorders, osteoporosis and adrenal insufficiency. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma. Several ongoing phase 3 trials (SOURCE, NCT03406078; NAVIGATOR, NCT03347279; DESTINATION, NCT03706079) are assessing the efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma. Here, we describe the design and objectives of SOURCE, a phase 3 OCS-sparing study.

Methods
SOURCE is an ongoing phase 3, multicentre, randomized, double-blind, placebo-controlled study to evaluate the effect of tezepelumab 210 mg administered subcutaneously every 4 weeks on OCS dose reduction in adults with OCS-dependent asthma. The study comprises a 2-week screening and enrolment period, followed by an OCS optimization phase of up to 8 weeks and a 48-week treatment period, which consists of a 4-week induction phase, followed by a 36-week OCS reduction phase and an 8-week maintenance phase. The primary objective is to assess the effect of tezepelumab compared with placebo in reducing the prescribed OCS maintenance dose. The key secondary objective is to assess the effect of tezepelumab on asthma exacerbation rates. Other secondary objectives include the proportion of patients with a reduction in OCS dose (100% or 50% reduction or those receiving < 5 mg) and the effect of tezepelumab on lung function and patient-reported outcomes.

Conclusions
SOURCE is evaluating the OCS-sparing potential of tezepelumab in patients with OCS-dependent asthma. SOURCE also aims to demonstrate that treatment with tezepelumab in patients with severe asthma is associated with reductions in exacerbation rates and improvements in lung function, asthma control and health-related quality of life, while reducing OCS dose.

Trial registration
NCT03406078 (ClinicalTrials.gov). Registered 23 January 2018. https://clinicaltrials.gov/ct2/show/NCT03406078
Health of refugees and migrants from former Soviet Union countries in the Russian Federation: a narrative review
Authors: Bakunina Nataliia , Gil Artyom , Polushkin Vitaly , Sergeev Boris , Flores Margarita , Toskin Igor , Madyanova Viktoriya , Khalfin Ruslan 
Published: October 2020

AbstractThis narrative review was conducted to synthesize and summarize available up-to-date evidence on current health status, including both non-communicable diseases and infectious diseases, of migrants and refugees from the former Soviet Union countries in the Russian Federation. Epidemiological and sociological studies with one or more determinants of the health, as well as relevant qualitative studies characterizing risk factors, well-being indicators, and lifestyles of migrants and refugees from the former Soviet Union countries in Russia published from 2004 to 2019 in Russian and English languages were included in the review. Despite significant limitations of the available research literature in the field, some patterns in migrants’ health in Russia and issues that need to be addressed were identified. In particular, the syndemic epidemics of communicable and non-communicable diseases, additively increasing negative health consequences, including cardiovascular diseases and chronic digestive system diseases, high rates of sexually transmitted infections and HIV, respiratory diseases and a growing percentage of new tuberculosis cases among migrants from the former Soviet Union countries are all of great concern. Possibly, the burden of these co-occurring morbidities is linked to commonly reported issues among this population group, such as poor nutrition and living conditions, high prevalence of unskilled manual labour, non-compliance with sanitary norms, lack of basic vaccinations, lack of basic knowledge about safe sexual practices and risky sexual behaviour, low healthcare seeking behaviour and limited access to health care. Importantly, these findings may urge the government to increase efforts and promote international collaboration in combating the threat of infectious diseases. Additionally, it was found that migrants had higher levels of anxiety and post-traumatic stress disorder, and those who stayed in the receiving country 5 years or more had a higher level of somatic pathology than those whose stay was less than 5 years. In order to ensure an adequate health system response and fulfil the main Universal Health Coverage principle of “leaving no one behind”, a robust monitoring system of the health status of refugees and migrants and an integrated legal framework for the standardized and more inclusive routine care for this population in Russia is urgently needed.
Review of psychological stress on oocyte and early embryonic development in female mice
Authors: Zhai Qiu-Yue , Wang Jun-Jie , Tian Yu , Liu Xiaofang , Song Zhenhua 
Published: October 2020

AbstractPsychological stress can cause adverse health effects in animals and humans. Accumulating evidence suggests that psychological stress in female mice is associated with ovarian developmental abnormalities accompanied by follicle and oocyte defects. Oocyte and early embryonic development are impaired in mice facing psychological stress, likely resulting from hormone signalling disorders, reactive oxygen species (ROS) accumulation and alterations in epigenetic modifications, which are primarily mediated by the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-ovarian (HPO) axes. The present evidence suggests that psychological stress is increasingly becoming the most common causative factor for female subfertility. Here, we review recent progress on the impact of psychological stress on female reproduction, particularly for oocyte and early embryonic development in female mice. This review highlights the connection between psychological stress and reproductive health and provides novel insight on human subfertility.
Acute toxicity of normofractionated intensity modulated radiotherapy with simultaneous integrated boost compared to three-dimensional conformal radiotherapy with sequential boost in the adjuvant treatment of breast cancer
Authors: Krug David , Köder Christine , Häfner Matthias F. , Arians Nathalie , Harrabi Semi B. , Koerber Stefan A. , Forster Tobias , Schlampp Ingmar , Sohn Christof , Heil Joerg , Hof Holger , Hörner-Rieber Juliane , Debus Jürgen 
Published: October 2020

Abstract
Background
Intensity-modulated radiotherapy (IMRT) improves dose homogeneity and late toxicity compared to simple tangential techniques in adjuvant whole-breast radiotherapy for patients with breast cancer. Simultaneous-integrated boost (SIB) radiotherapy shortens the overall treatment time and improves dose homogeneity. However, prospective randomized trials regarding IMRT with SIB for adjuvant radiotherapy in breast cancer are lacking.

Methods
The IMRT-MC2 (MINT) trial is a phase III prospective randomized controlled trial comparing IMRT with SIB (Arm A: whole breast 28 × 1.8 Gy, Boost 28 × 2.3 Gy) to 3D-conformal radiotherapy with a sequential boost (Arm B: whole breast 28 × 1.8 Gy, boost 8 × 2 Gy) in patients with breast cancer after BCS. Indication for boost radiotherapy was defined as age < 70 years or age > 70 years with presence of additional risk factors. This is a retrospective analysis of acute toxicity at one of two trial sites.

Results
Five hundred two patients were randomized, of which 446 patients were eligible for this analysis. There was no statistically significant difference in terms of any grade radiation dermatitis between the two treatment arms at the end of treatment (p = 0.26). However, radiation dermatitis grade 2/3 (29.1% vs. 20.1 and 3.5% vs. 2.3%) occurred significantly more often in Arm A (p = 0.02). Breast/chest wall pain at the first follow-up visit was significantly more common in patients treated on Arm B (p = 0.02).

Conclusions
Treatment on both arms was well tolerated, however there were some differences regarding radiodermatitis and breast pain. Further analyses are ongoing.

Trial registration
clinicaltrials.gov, NCT01322854, registered 24th March 2011.
Clinicopathologic significance of protein lysine methyltransferases in cancer
Authors: Vougiouklakis Theodore , Bernard Benjamin J. , Nigam Nupur , Burkitt Kyunghee , Nakamura Yusuke , Saloura Vassiliki 
Published: October 2020

AbstractProtein lysine methyltransferases (PKMTs) constitute a large family of approximately 50 chromatin modifiers that mono-, di- and/or tri-methylate lysine residues on histone and non-histone substrates. With the advent of The Cancer Genome Atlas, it became apparent that this family of chromatin modifiers harbors frequent genetic and expression alterations in multiple types of cancer. In this regard, past and ongoing preclinical studies have provided insight into the mechanisms of action of some of these enzymes, laying the ground for the ongoing development of PKMT inhibitors as novel anticancer therapeutics. The purpose of this review is to summarize existing data obtained by different research groups through immunohistochemical analysis of the protein expression levels of PKMTs, and their respective clinicopathologic associations. We focused on studies that used immunohistochemistry to associate protein expression levels of specific PKMTs, as well as several established histone methylation marks, with clinicopathologic features and survival outcomes in various cancer types. We also review ongoing clinical trials of PKMT inhibitors in cancer treatment. This review underscores the clinical relevance and potential of targeting the family of PKMT enzymes as the next generation of cancer therapy.