bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modifiable environmental exposure and risk of rheumatoid arthritis—current evidence from genetic studies
Authors: Jiang Xia , Alfredsson Lars 
Published: June 2020

AbstractRheumatoid arthritis (RA) is a multifactorial chronic autoimmune disease, which involves a complex interplay of environmental triggers and genetic components in its etiology. It has been shown that genetics only explain about half of the liability to develop RA, leaving a large room for non-genetic factors. Indeed, several environmental exposures including smoking, drinking, obesity, and dietary patterns (and more) have been identified to be associated with RA risk, yet the observational nature of conventional epidemiological investigation hampers causal inference, as the validity of results could be plagued by measurement error, confounding, and/or reverse causality. Mendelian randomization (MR) is a novel statistical approach that uses genetic variants as instrumental variables (IV) to make causal inferences from observational data. The current genetic discoveries in the many heritable and modifiable human complex traits have provided an exceptional opportunity to evaluate a putative causal relationship between exposure and outcome in the absence of high-quality experimental or intervention studies, through a MR design. In the current review, we detail the contribution of MR studies hitherto conducted for modifiable environmental exposures with the risk of RA to understand the role of these factors in RA pathogenesis. We start with a brief introduction of each study, follow by a summarization of shortcomings and conclude by highlighting future directions. The application of MR design in the field of rheumatology remains limited. Only a few MR studies have examined the causal roles of vitamin D, cigarette smoking, alcohol consumption, coffee consumption, and levels of education in RA, where, no consistent evidence for a causal relationship has been found. Most studies lacked sensitivity analyses to verify MR model assumptions and to guarantee the validity of results. Almost all studies are likely to bias the strength of association towards a null value, since they used IVs from earlier GWAS(s) of exposures with a small sample size (i.e., few genetic markers). As the magnitudes of GWAS expand rapidly, additional trait-associated loci have been discovered. Incorporating these loci would greatly improve the strength of genetic instruments, as well as both the accuracy and precision of MR estimates. To conclude, there is a need for an update and a huge space for improvement of future MR studies in RA.
Comprehensive evaluation of targeted multiplex bisulphite PCR sequencing for validation of DNA methylation biomarker panels
Authors: Lam Dilys , Luu Phuc-Loi , Song Jenny Z. , Qu Wenjia , Risbridger Gail P. , Lawrence Mitchell G. , Lu Jennifer , Trau Matt , Korbie Darren , Clark Susan J. , Pidsley Ruth , Stirzaker Clare 
Published: June 2020

Abstract
Background
DNA methylation is a well-studied epigenetic mark that is frequently altered in diseases such as cancer, where specific changes are known to reflect the type and severity of the disease. Therefore, there is a growing interest in assessing the clinical utility of DNA methylation as a biomarker for diagnosing disease and guiding treatment. The development of an accurate loci-specific methylation assay, suitable for use on low-input clinical material, is crucial for advancing DNA methylation biomarkers into a clinical setting. A targeted multiplex bisulphite PCR sequencing approach meets these needs by allowing multiple DNA methylated regions to be interrogated simultaneously in one experiment on limited clinical material.

Results
Here, we provide an updated protocol and recommendations for multiplex bisulphite PCR sequencing (MBPS) assays for target DNA methylation analysis. We describe additional steps to improve performance and reliability: (1) pre-sequencing PCR optimisation which includes assessing the optimal PCR cycling temperature and primer concentration and (2) post-sequencing PCR optimisation to achieve uniform coverage of each amplicon. We use a gradient of methylated controls to demonstrate how PCR bias can be assessed and corrected. Methylated controls also allow assessment of the sensitivity of methylation detection for each amplicon. Here, we show that the MBPS assay can amplify as little as 0.625 ng starting DNA and can detect methylation differences of 1% with a sequencing coverage of 1000 reads. Furthermore, the multiplex bisulphite PCR assay can comprehensively interrogate multiple regions on 1–5 ng of formalin-fixed paraffin-embedded DNA or circulating cell-free DNA.

Conclusions
The MBPS assay is a valuable approach for assessing methylated DNA regions in clinical samples with limited material. The optimisation and additional quality control steps described here improve the performance and reliability of this method, advancing it towards potential clinical applications in biomarker studies.
An update on long intergenic noncoding RNA p21: a regulatory molecule with various significant functions in cancer
Authors: Amirinejad Roya , Rezaei Mina , Shirvani-Farsani Zeinab 
Published: June 2020

AbstractLong intergenic noncoding RNA p21 was mapped on the human chromosome 6p21.2. Accordingly, it was firstly described by promoting the p53-dependent apoptosis in the mouse. Also, it is a new lncRNA playing some vital roles in the cell cycle, apoptosis, cell proliferation, tumorigenesis, invasion, metastasis, and angiogenesis. In this regard, it was shown that,lincRNA-p21regulates these biological processes involved in carcinogenesis through various signaling pathways including Notch signaling, JAK2/STAT3, and AKT/mTOR pathways. Another mechanism by thatlincRNA-p21can affect these processes is a cross-talk with different miRNAs. In vitro and in vivo studies revealed dysregulation oflincRNA-p21in various human cancers. In addition, emerging evidence demonstrated that,lincRNA-p21can be considered as a potential prognostic and therapeutic biomarker in cancers. Also,lincRNA-p21enhances the response to radiotherapy for colorectal cancer. However, the molecular mechanisms oflincRNA-p21in carcinogenesis have not been fully elucidated so far. So, this review summarizes the function oflincRNA-p21,as a tumor suppressor factor in different biological processes implicated in cancers.
Differences in alexithymia, emotional awareness, and facial emotion recognition under conditions of self-focused attention among women with high and low eating disorder symptoms: a 2 x 2 experimental study
Authors: Vander Wal Jillon S. , Kauffman Alicia A. , Soulliard Zachary A. 
Published: June 2020

Abstract
Background
Women with eating disorders generally perform more poorly on measures of alexithymia, defined as difficulty identifying and describing emotions, and theory of mind, or the ability to infer what others are thinking and feeling. The extent to which these abilities may be influenced by variables such as self-focused attention, or directing attention toward internally generated information, has yet to be investigated. Thus, the purpose of the present study was to examine differences between women high and low in disordered eating symptoms on measures of emotional awareness and facial affect recognition under conditions of high and low self-focused attention.

Methods
University women scoring high or low on a measure of disordered eating (n = 79) were randomly assigned to a condition of high or low self-focused attention. Outcomes included alexithymia (self-rated ability to identify and describe emotions), emotional awareness (ability to describe the emotions of oneself and others), and facial affect recognition. Scores on a measure of negative affect were statistically controlled.

Results
Women with high disordered eating symptom scores rated themselves as having more difficulties identifying, but not describing emotions after controlling for negative affect, but demonstrated greater difficulties describing their own and others’ emotions on a measure of emotional awareness. In the self-focused attention condition, women scored lower on self emotional awareness and were quicker to identify expressions of negative facial affect regardless of eating disorder symptom status than women in the non-self-focused attention condition. There were no significant interactions between eating disorder status and self-focused attention.

Conclusions
Further examination of different types of emotion recognition and description in oneself and others as well as processes that may influence these abilities is warranted.
Designing and integrating a quality management program for patients undergoing head and neck resection with free-flap reconstruction
Authors: Dort Joseph C. , Sauro Khara M. , Schrag Christiaan , Chandarana Shamir , Matthews Jennifer , Nakoneshny Steven , Manoloto Vida , Miller Tanya , McKenzie C. David , Hart Robert D. , Matthews T. Wayne 
Published: June 2020

Background Care pathways (CPs) offer a proven method of systematically improving patient care. CPs are particularly helpful in complex clinical conditions where variation in care is a problem such as patients undergoing major head and neck resection with free flap reconstruction. Although CPs have been used to manage this patient group, most CPs are implemented as part of relatively short-term quality improvement projects. This paper outlines a detailed methodology for designing and delivering a quality management program sustained for 9 years. Methods We describe a change management approach informed by Kotter's “8 Step Process” that provided a useful framework to guide program development and implementation. We then provide a detailed, step by step description of how such a program can be implemented as well as a detailed summary of time and costs for design, implementation and sustainability phases. An approach to design and delivery of a measurement, audit and feedback system is also provided. Results We present a summary of resources needed to design and implement a head and neck surgery quality management program. The primary result of this study is a design for a sustainable quality management program that can be used to guide and improve care for patients undergoing major head and neck resection with free flap reconstruction. Conclusions A change management approach to design and delivery of a head and neck quality management program is practical and feasible.
Telephone consultations with otolaryngology – head and neck surgery reduced emergency visits and specialty consultations in northern Alberta
Authors: Tian Peter George Jaminal , Eurich Dean , Seikaly Hadi , Boisvert Douglas , Montpetit John , Harris Jeffrey 
Published: June 2020

Background RAAPID (Referral, Access, Advice, Placement, Information, and Destination) is a 24-h call center in Alberta, Canada, facilitating urgent telephone consultations between physicians and specialists. We evaluated the extent to which RAAPID calls to Otolaryngology-Head and Neck Surgery (OHNS) reduced visits to the emergency department and specialty clinics. Methods This was a cross-sectional study evaluating all telephone consultations to OHNS from physicians in northern Alberta between 2013 and 2014 (T1) (where consultations by residents occurred) and 2015 to 2017 (T2) (where consultations were done by consultants during office hours and residents during after hours). Outcomes of the calls included medical advice, specialty clinic referrals, and emergency department (ED) referrals. Differences in the reduction of ED visits and costs, overall as well as in T1 and T2, were assessed using multivariate logistic regression. Results Overall, 62.3% (1064/1709) of telephone consultations reduced ED visits consisting of advice being provided ( n = 884; 83.1%) and referral to specialty clinics ( n = 180; 16.9%). The adjusted odds ratio of calls reducing emergency visits in T2 as compared to T1 was 2.47 (95% CI 1.99 to 3.08). The adjusted odds ratio of reducing ED visits during office hours compared to after-hours 2.54 (95% CI 1.77–3.64). The estimated direct costs avoided from ED visits in T1 and T2 were $42,224.22 and $114,393.86, respectively. Conclusion RAAPID telephone consultations to OHNS were effective in reducing ED visits and healthcare costs. This model should be considered in other areas to improve efficiencies within the health system.
Tau Ser208 phosphorylation promotes aggregation and reveals neuropathologic diversity in Alzheimer’s disease and other tauopathies
Authors: Xia Yuxing , Prokop Stefan , Gorion Kimberly-Marie M. , Kim Justin D. , Sorrentino Zachary A. , Bell Brach M. , Manaois Alyssa N. , Chakrabarty Paramita , Davies Peter , Giasson Benoit I. 
Published: June 2020

AbstractTau protein abnormally aggregates in tauopathies, a diverse group of neurologic diseases that includes Alzheimer’s disease (AD). In early stages of disease, tau becomes hyperphosphorylated and mislocalized, which can contribute to its aggregation and toxicity. We demonstrate that tau phosphorylation at Ser208 (pSer208) promotes microtubule dysfunction and tau aggregation in cultured cells. Comparative assessment of the epitopes recognized by antibodies AT8, CP13, and 7F2 demonstrates that CP13 and 7F2 are specific for tau phosphorylation at Ser202 and Thr205, respectively, independently of the phosphorylation state of adjacent phosphorylation sites. Supporting the involvement of pSer208 in tau pathology, a novel monoclonal antibody 3G12 specific for tau phosphorylation at Ser208 revealed strong reactivity of tau inclusions in the brains of PS19 and rTg4510 transgenic mouse models of tauopathy. 3G12 also labelled neurofibrillary tangles in brains of patients with AD but revealed differential staining compared to CP13 and 7F2 for other types of tau pathologies such as in neuropil threads and neuritic plaques in AD, tufted astrocytes in progressive supranuclear palsy and astrocytic plaques in corticobasal degeneration. These results support the hypothesis that tau phosphorylation at Ser208 strongly contributes to unique types of tau aggregation and may be a reliable marker for the presence of mature neurofibrillary tangles.
Association between low pH and unfavorable neurological outcome among out-of-hospital cardiac arrest patients treated by extracorporeal CPR: do not dismiss confounders!
Authors: Jouffroy Romain , Vivien Benoît 
Published: June 2020

AbstractRecently, Okada et al. reported an association between low pH value before the implementation of extracorporeal cardiopulmonary resuscitation (ECPR) and 1-month unfavorable neurological outcome among out-of-hospital cardiac arrest (OHCA) patients treated with ECPR.Nevertheless, we believe that some methodological flaws deserve their conclusions.The time duration between OHCA occurrence and blood gas analysis (BGA), a major confounder for misinterpretation, was not taken into account. It is not reported whether the result of BGA analysis was considered and/or treated, and if ECPR implementation decision had been influenced by the results analysis. Furthermore, the no-flow duration and the in-hospital phase confounders for neurological outcome are not included as covariates in the logistic regression. Therefore, we believe that causes and consequences should not be confused: the longer is the no-flow duration, the greater are the metabolic consequences.
Orange peel as low-cost adsorbent in the elimination of Cd(II) ion: kinetics, isotherm, thermodynamic and optimization evaluations
Authors: Akinhanmi Temilade Fola , Ofudje Edwin Andrew , Adeogun Abideen Idowu , Aina Peter , Joseph Ilo Mayowa 
Published: June 2020

AbstractThe presence of heavy metals in polluted water is known not only to cause severe harm to marine organisms, but also to terrestrial plants and animals including human beings. This research applied low-cost and environmentally benign adsorbent primed from waste orange peel (OP) for the removal of Cd(II) ions from aqueous solution via batch adsorption process. The surface properties of the orange peel powder were studied using scanning electron microscopy (SEM), X-ray spectroscopy (XRD) and Fourier transform infrared spectroscopy (FT-IR). Operational conditions like temperature, contact time, sorbent dosage, solution pH and initial adsorbate concentration were investigated. The utmost uptake of Cd(II) ion was obtained at a contact time of 120 min, initial metal concentration of 240 mg/L, adsorbent dosage of 0.04 g/L, temperature of 45 °C and solution pH of 5.5. Equilibrium results showed that the orange peel adsorbent has an adsorption capacity of 128.23 mg/g as obtained from the Langmuir isotherm. The adsorption kinetics data followed a pseudo-first-order kinetic model with correlation coefficient (R2) > 0.9 and low standard % error values. The adsorption process was found to be endothermic in nature with enthalpy of 0.0046 kJ mol−1 and entropy of-636.865 Jmol−1K−1. Results from the optimization study indicated that higher adsorbent dosage and lower Cd(II) ion concentration increased the percentage of Cd(II) ion removal. Thus, orange peel could be used in the removal of Cd(II) ion from aqueous solutions.
Proposal for a layer-based IoT construction method and its implementation and evaluation on a rolling stand-up walker
Authors: Ogawa Katsushi , Uegami Kenji , Chiba Itaru , Uno Kyono , Aoyama Hiroki , Yonenobu Kazuo , Jeong Seonghee 
Published: June 2020

AbstractIt is a problem that the poor gait function of many elderly people affects their activities of daily living (ADL), and deteriorates their quality of life (QoL). To enhance rehabilitation of the gait function, it is desirable to increase the amount of training received. In this research, we develop a measurement system for a gait training device that enables effective rehabilitation using the internet of things (IoT) and measurement technology proactively, which aims to realize gconstant rehabilitation h by considering ADL (except training time) as rehabilitation. We propose an IoT measurement system model that classifies each function of the IoT system in a hierarchical structure to promote systematic development more efficiently. Based on this model, we (1) modularize a device for measuring the upper limb load, acceleration, and gait distance, (2) develop a device for presenting the target value of rehabilitation visually to the user using the internet, and (3) implement the model on a commercial rolling stand-up walker and gait training device. We confirm that we can obtain excellent measurements using each mounted module.
Parathyroid carcinoma in a 13-year-old girl with a long-term survival
Authors: Omi Yoko , Yamamoto Tomoko , Nagashima Yoji , Abe Koichiro , Karasawa Kumiko , Tanaka Yukichi , Okamoto Takahiro 
Published: June 2020

AbstractBackgroundParathyroid carcinoma as a cause of primary hyperparathyroidism in children is extremely rare. We report a case of parathyroid carcinoma which occurred in a 13-year-old girl who survived for more than 45 years after the first operation.Case presentationA woman was admitted to our hospital for the treatment of recurrent parathyroid carcinoma in the neck. She had been diagnosed with primary hyperparathyroidism from a fibula fracture and underwent parathyroidectomy at 13 years old. She had no family history of multiple endocrine neoplasia or jaw tumor syndrome. Genetic testing was not performed, and the histopathological diagnosis of the tumor had been parathyroid adenoma at the time. At 22 years old, she showed hypercalcemia after a femur fracture. Pulmonary metastases of parathyroid carcinoma in the bilateral lungs were found and surgically removed. Regarding the clinical course, her diagnosis was corrected from parathyroid adenoma to parathyroid carcinoma. At 33 years old, re-resection of the lung metastases was performed. For 10 years, her serum calcium level stayed within the normal range. However, her serum calcium level and intact parathyroid hormone eventually began to increase. Two masses suspected of being parathyroid carcinoma recurrence were found in the neck when she was 57 years old. En bloc resection was performed. Pathologically, the tumors were diagnosed as parathyroid adenoma. The serum calcium level and intact parathyroid hormone did not decrease after the operation. A99mTc-methoxy-isobutyl-isonitrile- and18F-fluorodeoxyglucose-negative,11C-methionine-positive tumor was detected at the right side of the trachea in the neck. The tumor was removed, along with the thyroid, muscle, and trachea that were involved. The pathological diagnosis was parathyroid carcinoma recurrence. The serum calcium level and intact parathyroid hormone decreased temporarily but had increased again 8 months later. Methionine-positive tumors were found at the right side of the trachea and suspected of being a recurrence. Denosumab reduced her serum calcium level, and radiation successfully suppressed the growth of the recurrent tumors.ConclusionWe have reported a rare case of parathyroid carcinoma in a child who has survived for over 40 years. Positron emission tomography of11C-methionine was useful for detecting local recurrence. This patient’s long-term survival has been attributed to multimodality treatment including repeated surgery, medication, and radiation.
Premarital sex and pregnancy in Greater Jakarta
Authors: O’Donnell James , Utomo Iwu Dwisetyani , McDonald Peter 
Published: June 2020

AbstractSocial taboos and stigmas around sexuality and non-marital sex in Indonesia have led to substantial underreporting of the prevalence of premarital sex. In this study, we explore underreporting amongst young adults in Greater Jakarta. We use the 2010 Greater Jakarta Transition to Adulthood Survey (GJTAS), a survey of more than 3000 people aged 20–34 years, to derive estimates of underreporting based on discrepancies reported in the timing of marriage, first child birth and first sexual intercourse and sexual activities. Survival and life table analyses are utilised to identify individual and societal predictors of premarital sex and its reporting and to estimate cumulative incidence across young adulthood. The results reveal substantial evidence of underreporting, particularly amongst women, arising from premarital pregnancies. We estimate that the proportion of the female cohort who will engage in premarital sex by the age of 35 years increases from 4.4 to 22% after taking into account evidence of underreporting. Premarital pregnancies and unreported premarital sex is found to be particularly common amongst lower educated people. This raises important questions for policy and research in terms of the provision of information and support for young couples and the methodological implications of substantial underreporting.