bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis
Authors: Yang Da-Wei , Wang Tong-Min , Zhang Jiang-Bo , Li Xi-Zhao , He Yong-Qiao , Xiao Ruowen , Xue Wen-Qiong , Zheng Xiao-Hui , Zhang Pei-Fen , Zhang Shao-Dan , Hu Ye-Zhu , Shen Guo-Ping , Chen Mingyuan , Sun Ying , Jia Wei-Hua 
Published: June 2020

Abstract
Background
Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy.

Methods
A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes.

Results
We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10–6.57; P = 6.33 × 10−6). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10−7).

Conclusions
These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications.
Prevalence of co-existing autoimmune disease in juvenile idiopathic arthritis: a cross-sectional study
Authors: Simon Teresa A. , Harikrishnan Gowri Priya , Kawabata Hugh , Singhal Sanket , Brunner Hermine I. , Lovell Daniel J. 
Published: June 2020

Abstract
Background
Many autoimmune diseases share common pathogenic mechanisms, cytokine pathways and systemic inflammatory cascades; however, large studies quantifying the co-existence of autoimmune diseases in patients with juvenile idiopathic arthritis (JIA) have not been conducted.

Methods
We performed a cross-sectional study using two United States administrative healthcare claims databases (Truven Health MarketScan® Commercial Database and IMS PharMetrics database) to screen for the prevalence of multiple autoimmune diseases in patients with JIA and in a control group with attention deficit hyperactivity disorder (ADHD). Patients with a diagnosis code for JIA or ADHD between January 1, 2006 and September 30, 2017 were separated into two age cohorts (< 18 and ≥ 18 years) and matched (maximum 1:5) based on age, sex, number of medical encounters, and calendar year of diagnosis. The prevalence rates of 30 pre-specified autoimmune diseases during the 12-month periods before and after diagnosis were compared.

Results
Overall, 29,215 patients with JIA and 134,625 matched control patients with ADHD were evaluated. Among patients in the MarketScan database, 28/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 years and 29/30 were more prevalent in patients aged ≥ 18 years when compared with a matched cohort of patients with ADHD. In the PharMetrics database, 29/30 and 30/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 and ≥ 18 years, respectively, compared with a matched cohort of patients with ADHD. Among patients with JIA aged < 18 years, the greatest odds ratios (ORs) were seen for Sjögren’s syndrome/sicca syndrome and uveitis. Among patients aged ≥ 18 years in the MarketScan database, the greatest ORs were recorded for uveitis. Data from the PharMetrics database indicated that the greatest ORs were for uveitis and chronic glomerulonephritis.

Conclusions
Patients with JIA are more likely to have concurrent autoimmune diseases than matched patients with ADHD. Having an awareness of the co-existence of autoimmune diseases among patients with JIA may play an important role in patient management, treatment decisions, and outcomes.

Trial registration
Not applicable.
Testing a home-based model of care using misoprostol for prevention and treatment of postpartum hemorrhage: results from a randomized placebo-controlled trial conducted in Badakhshan province, Afghanistan
Authors: Abbas Dina F. , Mirzazada Shafiq , Durocher Jill , Pamiri Shahfaqir , Byrne Meagan E. , Winikoff Beverly 
Published: June 2020

Abstract
Background
Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide. In Afghanistan, where most births take place at home without the assistance of a skilled birth attendant, there is a need for options to manage PPH in community-based settings. Misoprostol, a uterotonic that has been used as prophylaxis at the household level and has also been proven to be effective in treating PPH in hospital settings, is one possible option.

Methods
A double-blind, randomized placebo-controlled trial was conducted in six districts in Badakhshan Province, Afghanistan to test the effectiveness and safety of administering 800mcg sublingual misoprostol to women after a home birth for treatment of excessive blood loss. Consenting women were enrolled prior to delivery and given 600mcg misoprostol to self-administer orally as prophylaxis. Community health workers (CHW) were trained to observe for signs of PPH after delivery and if PPH was diagnosed, administer the study medication (misoprostol or placebo) and immediately refer the woman. A hemoglobin (Hb) decline of 2 g/dL or greater, measured pre- and post-delivery, served as the primary outcome; side effects, additional interventions, and transfer rates were also analyzed.

Results
Among the 1884 women who delivered at home, nearly all (98.7%) reported self-use of misoprostol for PPH prevention. A small fraction was diagnosed with PPH (4.4%, 82/1884) and was administered treatment. Hb outcomes, including the proportion of women with a Hb drop of 2 g/dL or greater, were similar between the study groups (misoprostol: 56.4% (22/39), placebo: 60.6% (20/33), p = 0.45). Significantly more women randomized to receive misoprostol experienced shivering (82.5% vs. placebo: 61.5%, p = 0.03). Other side effects were similar between study groups and none required treatment, including among the subset of 39 women, who received misoprostol for both of its PPH indications.

Conclusions
While the study did not document a clinical benefit associated with misoprostol for treatment of PPH, study findings suggest that use of misoprostol for both prevention and treatment in the same birth as well as its use by lay level providers in home births does not result in any safety concerns.

Trial registration
This trial was registered with ClinicalTrials.gov, number NCT01508429 Registered on December 1, 2011.
Caloric restriction attenuates C57BL/6 J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure
Authors: Li Daochuan , Chen Shen , Li Qiong , Chen Liping , Zhang Haiyan , Li Huiyao , Yu Dianke , Zhang Rong , Niu Yujie , Lu Shaoyou , Ye Lizhu , Zeng Xiaowen , Dong Guanghui , Chen Rui , Aschner Michael , Zheng Yuxin , Chen Wen 
Published: June 2020

Abstract
Background
Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.

Results
Male C57BL/6 J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m3) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.

Conclusion
These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.
Revisiting the public health implications of the United States–Mexico– Canada agreement
Authors: Adekola Tolulope Anthony 
Published: June 2020

AbstractThis commentary re-examines a recent article by Labonté et al on the recent changes to two relevant provisions relating to patent rights in the final version of the United-States-Mexico-Canada Agreement (USMCA). Although the USMCA’s final revised version does not add more pharmaceutical patent protection than those that already exist in the three trading partners, the agreement has done little to enhance access to generic medicines and biosimilars.
Prevalence of drug use, alcohol consumption, cigarette smoking and measure of socioeconomic-related inequalities of drug use among Iranian people: findings from a national survey
Authors: Moradinazar Mehdi , Najafi Farid , Jalilian Farzad , Pasdar Yahya , Hamzeh Behrooz , Shakiba Ebraim , Hajizadeh Mohammad , Haghdoost Ali Akbar , Malekzadeh Reza , Poustchi Hossein , Nasiri Marzeyeh , Okati-Aliabad Hassan , Saeedi Majid , Mansour-Ghanaei Fariborz , Farhang Sara , Safarpour Ali Reza , Maharlouei Najmeh , Farjam Mojtaba , Amini Saeed , Amini Mahin , Mohammadi Ali , Mirzaei-Alavijeh Mehdi 
Published: June 2020

Abstract
Background
Drug use can lead to several psychological, medical and social complications. The current study aimed to measure and decomposes socioeconomic-related inequalities in drug use among adults in Iran.

Methods
This was a cross-sectional study The PERSIAN Cohort is the largest and most important cohort among 18 distinct areas of Iran. This study was conducted on 130,570 adults 35 years and older. A structured questionnaire was applied to collect data. The concentration index (C) was used to quantify and decompose socioeconomic inequalities in drug use.

Results
The prevalence experience of drug use was 11.9%. The estimated C for drug use was − 0.021. The corresponding value of the C for women and men were − 0.171 and − 0.134, respectively. The negative values of the C suggest that drug use is more concentrated among the population with low socioeconomic status in Iran (p < 0.001). For women, socioeconomic status (SES) (26.37%), province residence (− 22.38%) and age (9.76%) had the most significant contribution to socioeconomic inequality in drug use, respectively. For men, SES (80.04%), smoking (32.04%) and alcohol consumption (− 12.37%) were the main contributors to socioeconomic inequality in drug use.

Conclusions
Our study indicated that drug use prevention programs in Iran should focus on socioeconomically disadvantaged population. Our finding could be useful for health policy maker to design and implement effective preventative programs to protect Iranian population against the drug use.
Improvement in functional gait parameters following corrective thoracolumbar surgery in children affected by Mucopolysaccharidosis 1 (Hurler syndrome)
Authors: Sundarapandian Rajkumar , Jones Simon , Broomfield Alexander , Hensman Pauline , Oxborrow Neil 
Published: June 2020

Abstract
Objective
Thoracolumbar kyphosis is a common indication for spinal surgery in children with Mucopolysaccharidosis. Functional outcome of spinal surgical intervention has never been published in patients with this rare disease. We present a cohort of patients with Mucopolysaccharidosis 1(Hurler syndrome) who underwent thoraco-lumbar spinal deformity correction and functional outcome assessed by pre-operative and post-operative gait analysis. This study represents the first attempt at presenting a functional assessment of surgical outcome in any Mucopolysaccharidosis subtype.

Methods
A retrospective analysis of prospectively collected data was carried out from 11 children diagnosed with this subtype of Mucopolysaccharidosis. All patients underwent thoracolumbar kyphosis correction between the years 2013 to 2016. Gait assessment was performed using GAITRite™ electronic walkway pre-operatively and post-operatively within 9 to 24 months from the index surgery. Walking distance, cadence and gait velocity were the three spatio-temporal parameters analysed. Wilcoxon signed rank test was used to analyse the data and P-Value ≤0.05 was deemed significant.

Results
There was a statistically significant improvement in walking distance in 9 out of 11 patient post-operatively with a mean increase of 232.06 cms (P = 0.05). There was marginal improvement in cadence by 6.33 steps/min post-operatively (P-value 0.79). Gait velocity also showed a marginal increase by 8.73 cms/sec post-operatively (P-value 0.32).

Conclusion
The results of our study suggest that correction of thoracolumbar kyphosis in children with Mucopolysaccharidosis 1 resulted in a significant improvement of walking distance with a trend towards improved gait in the other parameters. Post-operative change in cadence was not statistically significant suggesting that physiological maturation of gait had minimal effect in the specified post-operative assessment timeframe. This study emphasizes that outcomes of spinal surgery in children with Mucopolysaccharidosis 1 should be determined by functional measures aiming to maintain or improve quality of life.
Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis
Authors: Crisafulli Salvatore , Sultana Janet , Fontana Andrea , Salvo Francesco , Messina Sonia , Trifirò Gianluca 
Published: June 2020

AbstractBackgroundDuchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. A recent systematic review and meta-analysis of global DMD epidemiology is not available. This study aimed to estimate the global overall and birth prevalence of DMD through an updated systematic review of the literature.MethodsMEDLINE and EMBASE databases were searched for original research articles on the epidemiology of DMD from inception until 1st October 2019. Studies were included if they were original observational research articles written in English, reporting DMD prevalence and/or incidence along with the number of individuals of the underlying population. The quality of the studies was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases. To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using random-effects logistic models for overall and birth prevalence and within two different underlying populations (i.e. all individuals and in males only), separately. Heterogeneity was assessed using Cochran’s Q-test along with its derived measure of inconsistency I2.ResultsA total of 44 studies reporting the global epidemiology of DMD were included in the systematic review and only 40 were included in the meta-analysis. The pooled global DMD prevalence was 7.1 cases (95% CI: 5.0–10.1) per 100,000 males and 2.8 cases (95% CI: 1.6–4.6) per 100,000 in the general population, while the pooled global DMD birth prevalence was 19.8 (95% CI:16.6–23.6) per 100,000 live male births. A very high between-study heterogeneity was found for each epidemiological outcome and for all underlying populations (I2 > 90%). The test for funnel plot asymmetry suggested the absence of publication bias. Of the 44 studies included in this systematic review, 36 (81.8%) were assessed as being of medium and 8 (18.2%) of low quality, while no study was assessed as being of high quality.ConclusionsGenerating epidemiological evidence on DMD is fundamental to support public health decision-making. The high heterogeneity and the lack of high quality studies highlights the need to conduct better quality studies on rare diseases.
Utility of plasma Neurofilament light as a diagnostic and prognostic biomarker of the postural instability gait disorder motor subtype in early Parkinson’s disease
Authors: Ng Adeline Su Lyn , Tan Yi Jayne , Yong Alisa Cui Wen , Saffari Seyed Ehsan , Lu Zhonghao , Ng Ebonne Yulin , Ng Samuel Yong Ern , Chia Nicole Shuang Yu , Choi Xinyi , Heng Dede , Neo Shermyn , Xu Zheyu , Keong Nicole Chwee Har , Tay Kay Yaw , Au Wing Lok , Tan Louis Chew Seng , Tan Eng-King 
Published: June 2020

Abstract
Background
The main motor subtypes of Parkinson’s disease (PD) include tremor-dominant (TD) and postural instability gait disorder (PIGD), with varying disease course that warrant the development of biomarkers capable of predicting progression according to motor subtype. The PIGD subtype is associated with a poorer prognosis, hence identification of a biomarker associated with PIGD is clinically relevant. Neurofilament light (NfL) chain is a potential biomarker of disease severity in neurological disorders including PD. However, no study has investigated NfL and PD motor subtypes. Here, we aimed to investigate the diagnostic and prognostic utility of plasma NfL for PD motor subtypes in early Parkinson’s disease. Given the higher risk for cognitive and motor decline in PIGD, we hypothesized that plasma NfL is a potential biomarker for PIGD.

Methods
Plasma NfL was measured in 199 participants (149 PD and 50 healthy controls, HC) using an ultrasensitive single molecule array. Patients were classified into TD or PIGD based on MDS-UPDRS components. After 2 years, 115 patients were reassessed. Association between NfL and clinical measures in PIGD and TD at baseline and at 2-year follow-up were analysed.

Results
At baseline, plasma NfL levels were higher in PD than HC (8.8 ± 3.4 vs 16.2 ± 7.6 pg/ml, p < 0.0001), and differentiated PD from HC with a good diagnostic accuracy (AUC = 0.833, p < 0.001). At 2 years, NfL was higher in PIGD than TD (18.4 ± 14.5 vs 12.6 ± 4.4 pg/ml, p = 0.039). Within the PIGD group, higher NfL associated significantly with worse global cognition and UPDRS motor scores at baseline, and was able to predict motor and cognitive decline at a mean follow-up duration of 1.9 years, controlled for age, sex and disease duration.

Conclusions
In this longitudinal study, we demonstrated for the first time the potential utility of plasma NfL as a diagnostic and prognostic biomarker in PIGD even at early stages of PD. These important novel findings will require further confirmation in larger, longitudinal PD cohorts.
A survey of ivermectin resistance in Parascaris species infected foals in south-eastern Poland
Authors: Studzińska Maria Bernadeta , Sallé Guillaume , Roczeń-Karczmarz Monika , Szczepaniak Klaudiusz , Demkowska-Kutrzepa Marta , Tomczuk Krzysztof 
Published: June 2020

AbstractParascaris spp. are major gastro-intestinal nematodes that infect foals and can lead to respiratory symptoms, poor growth, and in some cases obstruction of the small intestine and death. Ivermectin resistance has been reported for Parascaris spp. in many countries. In Poland, the knowledge of the level of resistance against ivermectin in Parascaris spp. is limited. The aim of this study was to examine the efficacy of ivermectin against Parascaris spp. in foals from south-eastern Poland. Foals (n = 225 = reared in 7 stud farms) were treated orally with ivermectin paste. Faecal samples were collected from the rectum of each foal or from the environment straight after defaecation on 1 day prior and 2 weeks after deworming. A faecal egg count (FEC) was performed using the McMaster method with a minimum detection limit of 50 eggs/g. FEC reduction (FECR) was calculated using the Faecal Egg Count Reduction Test. The statistical analysis was limited to foals excreting more than 150 eggs/g before treatment and to stud farms with at least 6 foals excreting at or above this level. Confidence intervals were determined by 1000 bootstraps at farm level and the contribution of sex and age to FECR was quantified using a generalized equation estimation procedure. Parascaris spp. eggs were found in 40% of the foals. Following ivermectin treatment, Parascaris spp. eggs were identified in 28.4% of the foals. The mean estimated FECR ranged from 44% to 97% and average efficacy was 49.3%. FECR was more pronounced in older foals (P-values = 0. 003). The FECR was more pronounced in males than in females (P value = 0.028). This study is the first to indicate a reduced efficacy of ivermectin against Parascaris spp. in foals in Poland.
Long non-coding RNAs in ovarian granulosa cells
Authors: Tu Jiajie , Chen Yu , Li Zhe , Yang Huan , Chen He , Yu Zhiying 
Published: June 2020

AbstractGranulosa cells (GCs) are somatic cells surrounding oocytes within follicles and are essential for folliculogenesis. Pathological changes in GCs are found in several ovarian disorders. Recent reports have indicated that long non-coding RNAs (lncRNAs), which modulate gene expression via multiple mechanisms, are key regulators of the normal development of GCs, follicles, and ovaries. In addition, accumulating evidence has suggested that lncRNAs can be utilized as biomarkers for the diagnosis and prognosis of GC-related diseases, such as polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Therefore, lncRNAs not only play a role in GCs that are involved in normal folliculogenesis, but they may also be considered as potential candidate biomarkers and therapeutic targets in GCs under pathological conditions. In the future, a detailed investigation of the in vivo delivery or targeting of lncRNAs and large-cohort-validation of the clinical applicability of lncRNAs is required.