bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences, perspectives and expectations of adolescents with juvenile idiopathic arthritis regarding future work participation; a qualitative study
Authors: van Gulik E. Charlotte , Verkuil Floris , Barendregt Anouk M. , Schonenberg-Meinema Dieneke , Nassar-Sheikh Rashid Amara , Kuijpers Taco W. , van den Berg J. Merlijn , Hoving Jan L. 
Published: April 2020

Abstract
Background
Having Juvenile idiopathic Arthritis (JIA) has widespread implications for a person’s life. Patients have to deal with recurring arthritis, characterized by pain often accompanied by a loss of energy. Since JIA often persists into adulthood, patients with JIA are likely to encounter difficulties in their working life. We expect that the experiences in school life may be comparable to the barriers and opportunities which patients affected by JIA encounter in adult working life. Therefore, the aim of this study was to elicit the experiences during school life and the perspectives and expectations regarding future work participation of adolescents with JIA.

Methods
This study used individual, semi-structured interviews and followed a predefined interview guide. Participants between 14 and 18 years of age (n = 22) were purposively selected to achieve a broad range of participant characteristics. Open coding was performed, followed by axial coding and selective coding.

Results
Great differences were seen in the support and understanding that adolescents received in dealing with JIA at school, leisure activities and work. Varying approaches were mentioned on how to pursue a desired vocation. Perspectives regarding disclosure varied. Participants wished to be approached like any other healthy adolescent. Expectations regarding work participation were positively expressed.

Conclusion
This study showed that participants often disregarded having JIA when making plans for their future career. Facilitating an open discussion about the possible limitations accompanying JIA with educators and employers might prevent overburden and increase the chance of starting a career which would accommodate the patient with JIA in the near and distant future.
Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring
Authors: Wijenayake Sanoji , Rahman Mouly F. , Lum Christine M. W. , De Vega Wilfred C. , Sasaki Aya , McGowan Patrick O. 
Published: April 2020

AbstractBackgroundMaternal obesity as a result of high levels of saturated fat (HFD) consumption leads to significant negative health outcomes in both mother and exposed offspring. Offspring exposed to maternal HFD show sex-specific alterations in metabolic, behavioral, and endocrine function, as well as increased levels of basal neuroinflammation that persists into adulthood. There is evidence that psychosocial stress or exogenous administration of corticosterone (CORT) potentiate inflammatory gene expression; however, the response to acute CORT or immune challenge in adult offspring exposed to maternal HFD during perinatal life is unknown. We hypothesize that adult rat offspring exposed to maternal HFD would show enhanced pro-inflammatory gene expression in response to acute administration of CORT and lipopolysaccharide (LPS) compared to control animals, as a result of elevated basal pro-inflammatory gene expression. To test this, we examined the effects of acute CORT and/or LPS exposure on pro and anti-inflammatory neural gene expression in adult offspring (male and female) with perinatal exposure to a HFD or a control house-chow diet (CHD).MethodsRat dams consumed HFD or CHD for four weeks prior to mating, during gestation, and throughout lactation. All male and female offspring were weaned on to CHD. In adulthood, offspring were ‘challenged’ with administration of exogenous CORT and/or LPS, and quantitative PCR was used to measure transcript abundance of glucocorticoid receptors and downstream inflammatory markers in the amygdala, hippocampus, and prefrontal cortex.ResultsIn response to CORT alone, male HFD offspring showed increased levels of anti-inflammatory transcripts, whereas in response to LPS alone, female HFD offspring showed increased levels of pro-inflammatory transcripts. In addition, male HFD offspring showed greater pro-inflammatory gene expression and female HFD offspring exhibited increased anti-inflammatory gene expression in response to simultaneous CORT and LPS administration.ConclusionsThese findings suggest that exposure to maternal HFD leads to sex-specific changes that may alter inflammatory responses in the brain, possibly as an adaptive response to basal neuroinflammation.
Tumor sequencing is useful to refine the analysis of germline variants in unexplained high-risk breast cancer families
Authors: Van Marcke Cédric , Helaers Raphaël , De Leener Anne , Merhi Ahmad , Schoonjans Céline A. , Ambroise Jérôme , Galant Christine , Delrée Paul , Rothé Françoise , Bar Isabelle , Khoury Elsa , Brouillard Pascal , Canon Jean-Luc , Vuylsteke Peter , Machiels Jean-Pascal , Berlière Martine , Limaye Nisha , Vikkula Miikka , Duhoux François P. 
Published: April 2020

Abstract
Background
Multigene panels are routinely used to assess for predisposing germline mutations in families at high breast cancer risk. The number of variants of unknown significance thereby identified increases with the number of sequenced genes. We aimed to determine whether tumor sequencing can help refine the analysis of germline variants based on second somatic genetic events in the same gene.

Methods
Whole-exome sequencing (WES) was performed on whole blood DNA from 70 unrelated breast cancer patients referred for genetic testing and without a BRCA1, BRCA2, TP53, or CHEK2 mutation. Rare variants were retained in a list of 735 genes. WES was performed on matched tumor DNA to identify somatic second hits (copy number alterations (CNAs) or mutations) in the same genes. Distinct methods (among which immunohistochemistry, mutational signatures, homologous recombination deficiency, and tumor mutation burden analyses) were used to further study the role of the variants in tumor development, as appropriate.

Results
Sixty-eight patients (97%) carried at least one germline variant (4.7 ± 2.0 variants per patient). Of the 329 variants, 55 (17%) presented a second hit in paired tumor tissue. Of these, 53 were CNAs, resulting in tumor enrichment (28 variants) or depletion (25 variants) of the germline variant. Eleven patients received variant disclosure, with clinical measures for five of them. Seven variants in breast cancer-predisposing genes were considered not implicated in oncogenesis. One patient presented significant tumor enrichment of a germline variant in the oncogene ERBB2, in vitro expression of which caused downstream signaling pathway activation.

Conclusion
Tumor sequencing is a powerful approach to refine variant interpretation in cancer-predisposing genes in high-risk breast cancer patients. In this series, the strategy provided clinically relevant information for 11 out of 70 patients (16%), adapted to the considered gene and the familial clinical phenotype.
Ethical issues in cluster randomized trials conducted in low- and middle-income countries: an analysis of two case studies
Authors: Choko Augustine T. , Roshandel Gholamreza , Conserve Donaldson F. , Corbett Elizabeth L. , Fielding Katherine , Hemming Karla , Malekzadeh Reza , Weijer Charles 
Published: April 2020

Abstract
Background
Cluster randomized trials are common in health research in low- and middle-income countries raising issues that challenge interpretation of standard ethical guidelines. While the Ottawa Statement on the ethical design and conduct of cluster randomized trials provides guidance for researchers and research ethics committees, it does not explicitly focus on low- and middle-income settings.

Main body
In this paper, we use the lens of the Ottawa Statement to analyze two cluster randomized trials conducted in low- and middle-income settings in order to identify gaps or ethical issues requiring further analysis and guidance. The PolyIran trial was a parallel-arm, cluster trial examining the effectiveness of a polypill for prevention of cardiovascular disease in Golestan province, Iran. The PASTAL trial was an adaptive, multistage, parallel-arm, cluster trial evaluating the effect of incentives for human immunodeficiency virus self-testing and follow-up on male partners of pregnant women in Malawi. Through an in-depth case analysis of these two studies we highlight several issues in need of further exploration. First, standards for verbal consent and waivers of consent require methods for operationalization if they are to be employed consistently. Second, the appropriate choice of a control arm remains contentious. Particularly in the case of implementation interventions, locally available care is required as the comparator to address questions of comparative effectiveness. However, locally available care might be lower than standards set out in national guidelines. Third, while the need for access to effective interventions post-trial is widely recognized, it is often not possible to guarantee this upfront. Clarity on what is required of researchers and sponsors is needed. Fourth, there is a pressing need for ethics education and capacity building regarding cluster randomized trials in these settings.

Conclusion
We identify four issues in cluster randomized trials conducted in low- and middle-income countries for which further ethical analysis and guidance is required.
Disease features associated with a low disease impact in patients with psoriatic arthritis: results of a cross-sectional multicenter study
Authors:   on behalf of the MAAPS study group, Queiro Ruben , Cañete Juan D. , Montoro María , Gómez Susana , Cábez Ana 
Published: April 2020

Abstract
Background
Patient-reported outcomes measures, such as those provided by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, have been found to be a reliable indicator of change during treatment, predictive of long-term outcomes, and the impact of psoriatic arthritis (PsA) on patients’ lives. The objective of the study was to describe the demographic and clinical characteristics of PsA patients with a low disease impact and to analyze predictive factors for that state.

Methods
Post hoc analysis of a cross-sectional multicenter study that included 223 consecutive patients. PsAID questionnaire was used to estimate disease impact. Patients with a PsAID < 4 were considered in low disease impact. Minimal disease activity (MDA) response and the Health Assessment Questionnaire (HAQ) were also assessed. The degree of agreement between the different outcomes was addressed by Cohen’s kappa index.

Results
One hundred and twenty-two (54.7%) patients reached a PsAID < 4. Among them, 52.0% and 68.0% presented articular or skin remission, respectively. Almost 75% of patients were in MDA state and 85.2% presented a low disability state according to the HAQ. A moderate concordance between HAQ ≤ 0.5 and PsAID < 4 (k = 0.53), fair between MDA and PsAID < 4 (k = 0.36), and moderate between DAPSA remission and PsAID < 4 (k = 0.46) was observed. Multivariate logistic regression analysis showed that patients with distal interphalangeal joint (DIP) disease (OR 0.40, 95%CI, 0.20–0.79, p = 0.009), family history of PsA (OR 0.25, 95%CI, 0.09–0.72, p = 0.010), and higher C-reactive protein (OR 0.92, 95%CI, 0.85–0.99, p = 0.036) were significantly less likely to reach a PsAID < 4.

Conclusions
There is certain discrepancy between disease activity measures and a low impact of disease in PsA. Clinical features (DIP joint involvement), biologic activity, and genetic factors (familial history) seem to be associated with lower odds of reaching a low disease impact.
Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis
Authors: Zhong Wen , Zeng Jiaoe , Xue Junli , Du Aimin , Xu Yancheng 
Published: April 2020

Abstract
Background
Diabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2. Long non-coding RNAs (lncRNAs) are being found to be involved in the DN pathogenesis. In this study, we aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis.

Methods
The expression levels of PVT1, miR-23b-3p, and Wilms tumor protein 1 (WT1) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was performed to determine protein expression. Cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS) assay. The targeted correlation between miR-23b-3p and PVT1 or WT1 was verified by dual-luciferase reporter assay.

Results
PVT1 and WT1 were highly expressed in the serum of DN patients and high glucose (HG)-induced mesangial cells (MCs). The knockdown of PVT1 or WT1 ameliorated HG-induced proliferation and fibrosis in MCs. Mechanistically, PVT1 modulated WT1 expression through acting as a molecular sponge of miR-23b-3p. The miR-23b-3p/WT1 axis mediated the protective effect of PVT1 knockdown on HG-induced proliferation and fibrosis in MCs. The NF-κB pathway was involved in the regulatory network of the PVT1/miR-23b-3p/WT1 axis in HG-induced MCs.

Conclusion
Our study suggested that PVT1 knockdown ameliorated HG-induced proliferation and fibrosis in MCs at least partially by regulating the miR-23b-3p/WT1/NF-κB pathway. Targeting PVT1 might be a potential therapeutic strategy for DN treatment.
Effect of circulating exosomes derived from normal-weight and obese women on gluconeogenesis, glycogenesis, lipogenesis and secretion of FGF21 and fetuin A in HepG2 cells
Authors: Afrisham Reza , Sadegh-Nejadi Sahar , Meshkani Reza , Emamgholipour Solaleh , Paknejad Maliheh 
Published: April 2020

Abstract
Background
It is generally accepted that obesity can lead to metabolic disorders such as NAFLD and insulin resistance. However, the underlying mechanism has been poorly understood. Moreover, there is evidence to support the possible role of exosomes in the metabolic homeostasis regulation. Accordingly, we aimed to determine the effect of plasma circulating exosomes derived from obese and normal-weight women on insulin signaling and the secretion of hepatokines in human liver cells.

Methods
Plasma exosomes isolated from four obese (O-Exo) women and four normal-weight (N-Exo) female candidates were characterized for size, zeta potential, and CD63 protein expression and were used for stimulation of HepG2 cells. Then, cell viability, as well as levels of glycogen and triglyceride (TG), were evaluated. Levels of fetuin-A and FGF21 were measured using the ELISA kit. Expression of glucose 6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) genes were determined using qRT-PCR. Western blot analysis was carried out to evaluating the phosphorylation of GSK3β.

Results
The TG levels increased significantly in the cells treated with O-Exo than the control (vehicle) group (P = 0.005) and normal-weight group (P = 0.018). Levels of p-GSK3β and glycogen were significantly reduced by O-Exo in comparison with control (P = 0.002, P = 0.018, respectively). The mRNA expression of G6pase and PEPCK enzymes increased in the cells treated with O-Exo in comparison with the vehicle group (P = 0.017, P = 0.010, respectively). The levels of FGF21 in the supernatant of cells treated with O-Exo and N-Exo were significantly lower than the control group (P = 0.007).

Conclusion
It appears that obesity-related circulating exosomes can impair insulin signaling pathways and associated components, increase intracellular TG content, and decrease FGF21 secretion in the hepatocytes.
Epinephrine auto-injector needle length
Authors: Dreborg Sten , Tsai Gina , Kim Harold 
Published: April 2020

Abstract
Background
Epinephrine auto-injectors are expected to deliver the drug intramuscularly.

Objective
To study whether injection through clothing influences the frequency of subcutaneous and intraosseous/periosteal deposition of epinephrine.

Methods
Skin to muscle and skin to bone distances were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, with high or low pressure on the ultrasound probe. The risk/percentage of subcutaneous and intraosseous/periosteal injections was calculated using the lower and upper limits for the authority-approved length of EAI needles as provided by two high pressure EAI manufacturers and one low pressure EAI manufacturer. The addition winter clothing on the delivery of epinephrine was illustrated by comparing drug delivery fissue depth with no clothes. Furthermore, the riof non-intramuscular delivery for the shortest and longest approved needle length was calculated.

Results
When using EpipenJr® in children < 15 kg the risk of intraosseous/periostal injection was reduced from 1% and 59% for the shortest and longest approved needle length to 0 and 15% with winter clothes. The Auvi-Q® 0.1 mg had no risk of intraosseous/periosteal injection. However, the subcutaneous deposition risk increased from 94% and 28% to 100% and 99% with winter clothes. The risk of subcutaneous injection using EpipenJr® in the youngest children increased from 13% and 0% to 81% and 1% with winter clothes, and with Epipen® in adults from 45% and 17% to 60% and 38%. Emerade®, had a risk of subcutaneous injection in adults increasing from 14% and 10% to 28% and 21% adding winter clothes.

Conclusion
The risk of intraosseous/periosteal injections decreases and the risk of subcutaneous injection increases when injecting through winter clothes for all EAIs.
Sex differences in cancer mechanisms
Authors: Rubin Joshua B. , Lagas Joseph S. , Broestl Lauren , Sponagel Jasmin , Rockwell Nathan , Rhee Gina , Rosen Sarah F. , Chen Si , Klein Robyn S. , Imoukhuede Princess , Luo Jingqin 
Published: April 2020

AbstractWe now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab- and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.
Sex differences in vascular aging in response to testosterone
Authors: Moreau Kerrie L. , Babcock Matthew C. , Hildreth Kerry L. 
Published: April 2020

AbstractLarge elastic arterial stiffening and endothelial dysfunction are phenotypic characteristics of vascular aging, a major risk factor for age-associated cardiovascular diseases. Compared to men, vascular aging in women appears to be slowed until menopause, whereafter vascular aging accelerates to match that seen in men. These sex differences in vascular aging have been attributed to changes in sex hormones that occur with aging. Although the role of estradiol in vascular aging in women has been highlighted in recent aging research, little is known about the impact of declining testosterone concentrations in both sexes. Importantly, while androgen concentrations generally decline with age in men, there are data that indicate reductions in androgen concentrations in women as well. Evidence suggests that low testosterone is associated with impaired endothelial function and increased arterial stiffness in men, although the effect of androgens on vascular aging in women remains unclear. Testosterone may modulate vascular aging by mitigating the effects of oxidative stress and inflammation, although there is sex specificity to this effect. The purpose of this review is to present and summarize the research regarding sex differences in vascular aging in response to androgens, specifically testosterone. Because exercise is a potent lifestyle factor for slowing and reversing vascular aging, we briefly summarize the available literature regarding the regulatory function of testosterone on vascular adaptations to exercise training.
Heterologous expression of genes for bioconversion of xylose to xylonic acid in Corynebacterium glutamicum and optimization of the bioprocess
Authors: Sundar M. S. Lekshmi , Susmitha Aliyath , Rajan Devi , Hannibal Silvin , Sasikumar Keerthi , Wendisch Volker F. , Nampoothiri K. Madhavan 
Published: April 2020

AbstractIn bacterial system, direct conversion of xylose to xylonic acid is mediated through NAD-dependent xylose dehydrogenase (xylB) and xylonolactonase (xylC) genes. Heterologous expression of these genes from Caulobacter crescentus into recombinant Corynebacterium glutamicum ATCC 13032 and C. glutamicum ATCC 31831 (with an innate pentose transporter, araE) resulted in an efficient bioconversion process to produce xylonic acid from xylose. Process parameters including the design of production medium was optimized using a statistical tool, Response Surface Methodology (RSM). Maximum xylonic acid of 56.32 g/L from 60 g/L xylose, i.e. about 76.67% of the maximum theoretical yield was obtained after 120 h fermentation from pure xylose with recombinant C. glutamicum ATCC 31831 containing the plasmid pVWEx1 xylB. Under the same condition, the production with recombinant C. glutamicum ATCC 13032 (with pVWEx1 xylB) was 50.66 g/L, i.e. 69% of the theoretical yield. There was no significant improvement in production with the simultaneous expression of xylB and xylC genes together indicating xylose dehydrogenase activity as one of the rate limiting factor in the bioconversion. Finally, proof of concept experiment in utilizing biomass derived pentose sugar, xylose, for xylonic acid production was also carried out and obtained 42.94 g/L xylonic acid from 60 g/L xylose. These results promise a significant value addition for the future bio refinery programs.