bluuebunny/crossref_metadata_2025_split huggingface dataset:
NPARS—A Novel Approach to Address Accuracy and Reproducibility in Genomic Data Science
Authors: Ma Li , Peterson Erich A. , Shin Ik Jae , Muesse Jason , Marino Katy , Steliga Matthew A. , Johann Donald J. 
Published: September 2021

Background: Accuracy and reproducibility are vital in science and presents a significant challenge in the emerging discipline of data science, especially when the data are scientifically complex and massive in size. Further complicating matters, in the field of genomic-based science high-throughput sequencing technologies generate considerable amounts of data that needs to be stored, manipulated, and analyzed using a plethora of software tools. Researchers are rarely able to reproduce published genomic studies.Results: Presented is a novel approach which facilitates accuracy and reproducibility for large genomic research data sets. All data needed is loaded into a portable local database, which serves as an interface for well-known software frameworks. These include python-based Jupyter Notebooks and the use of RStudio projects and R markdown. All software is encapsulated using Docker containers and managed by Git, simplifying software configuration management.Conclusion: Accuracy and reproducibility in science is of a paramount importance. For the biomedical sciences, advances in high throughput technologies, molecular biology and quantitative methods are providing unprecedented insights into disease mechanisms. With these insights come the associated challenge of scientific data that is complex and massive in size. This makes collaboration, verification, validation, and reproducibility of findings difficult. To address these challenges the NGS post-pipeline accuracy and reproducibility system (NPARS) was developed. NPARS is a robust software infrastructure and methodology that can encapsulate data, code, and reporting for large genomic studies. This paper demonstrates the successful use of NPARS on large and complex genomic data sets across different computational platforms.
The 10-Repeat 3′-UTR VNTR Polymorphism in the SLC6A3 Gene May Confer Protection Against Parkinson’s Disease: A Meta-analysis
Authors: Zeng Qiaoli , Ning Fan , Gu Shanshan , Zeng Qiaodi , Chen Riling , Peng Liuquan , Zou Dehua , Ma Guoda , Wang Yajun 
Published: September 2021

The dopamine transporter (DAT) is encoded by the SLC6A3 gene and plays an important role in the regulation of the neurotransmitter dopamine. The SLC6A3 gene contains several repetition alleles (3–11 repeats) of a 40-base pair variable number of tandem repeats (VNTR) in the 3′-untranslated region (3′-UTR), which may affect DAT expression levels. The 10-repeat (10R) allele could play a protective role against PD. However, inconsistent findings have been reported.Methods: A comprehensive meta-analysis was performed to accurately estimate the association between the 10R allele of the 3′-UTR VNTR in SLC6A3 and PD among four different genetic models.Results: This meta-analysis included a total of 3,142 patients and 3,496 controls. We observed a significant difference between patients and controls for the allele model (10R vs. all others: OR = 0.860, 95% CI: 0.771–0.958, P = 0.006), pseudodominant model (10R/10R + 10R/9R vs. all others: OR = 0.781, 95% CI: 0.641–0.952, P = 0.014) and pseudorecessive model (10R/10R vs. all others: OR = 0.858, 95% CI: 0.760–0.969, P = 0.013) using a fixed effects model. No significant differences were observed under the pseudocodominant model (10R/9R vs. all others: OR = 1.079, 95% CI: 0.945–1.233, P = 0.262). By subgroup analysis, the 10R, 10R/10R and 10R/9R genotypes were found to be significantly different from PD in Asian populations.Conclusion: Our findings suggest that the SLC6A3 10R may be a protective factor in susceptibility to PD.
Effects of Exercise Interventions on Immune Function in Children and Adolescents With Cancer and HSCT Recipients - A Systematic Review
Authors: Beller Ronja , Bennstein Sabrina Bianca , Götte Miriam 
Published: September 2021

BackgroundPediatric cancer patients are at high risk for life-threatening infections, therapy associated complications and cancer-related side effects. Exercise is a promising tool to support the immune system and reduce inflammation. The primary objective of this systematic review was to evaluate the effects of exercise interventions in pediatric cancer patients and survivors on the immune system.MethodsFor this systematic review (PROSPERO ID: CRD42021194282) we searched four databases (MEDLINE, Cochrane Library, ClinicalTrials.gov, SPORTDiscus) in June 2021. Studies with pediatric patients with oncological disease were included as main criterion. Two authors independently performed data extraction, risk of bias assessment, descriptive analysis and a direction ratio was calculated for all immune cell parameters.FindingsOf the 1448 detected articles, eight studies with overall n = 400 children and adolescents with cancer and n = 17 healthy children as controls aged 4-19 years met the inclusion criteria. Three randomized, four non-randomized controlled trials and one case series were analyzed descriptively. The exercise interventions had no negative adverse effects on the immune system. Statistically significant results indicated enhanced cytotoxicity through exercise, while changes in immune cell numbers did not differ significantly. Interventions further reduced days of in-hospitalization and reduced the risk of infections. Several beneficial direction ratios in immune parameters were identified favoring the intervention group.InterpretationExercise interventions for pediatric cancer patients and survivors had no negative but promising beneficial effects on the immune system, especially regarding cytotoxicity, but data is very limited. Further research should be conducted on the immunological effects of different training modalities and intensities, during various treatment phases, and for different pediatric cancer types. The direction ratio parameters given here may provide useful guidance for future clinical trials.Systemic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021194282, Prospero ID: CRD42021194282.
Real-Life Retention Rates and Reasons for Switching of Biological DMARDs in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
Authors: Bhushan Vandana , Lester Susan , Briggs Liz , Hijjawi Raif , Shanahan E. Michael , Pontifex Eliza , Ninan Jem , Hill Catherine , Cai Fin , Walker Jennifer , Goldblatt Fiona , Wechalekar Mihir D. 
Published: September 2021

Aims: To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data.Methods: Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients (n = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated “biologics” clinic in a tertiary hospital; the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences. The effect of covariates on switching risk was analysed by a conditional risk-set Cox proportional-hazards model. Treatment retention data was compared to a historical analysis (2002–2008).Results: The proportions remaining on treatment (retention) were similar, throughout follow-up, for the first, second and third b/tsDMARDs across all patients (p = 0.46). When compared to RA patients, the risk of b/tsDMARD failure was halved in PsA patients [Hazard Ratio (HR) = 0.50], but no different in AS patients (HR = 1.0). The respective restricted mean (95%CI) treatment durations, estimated at 5 years of follow-up, were 3.1 (2.9, 3.4), 4.1 (3.7, 4.6), and 3.3 (2.8, 3.9) years, for RA, PsA, and AS, respectively. Age, gender, disease duration, smoking status and the use of concomitant csDMARDS were not associated with the risk of bDMARD failure. The most common reasons for switching in the first and subsequent years were secondary (n = 62) and primary (n = 35) failure. Comparison with historical data indicated no substantive differences in switching of the first biologic for RA and PsA.Conclusion: Similar retention rates of the second and third compared to the first b/tsDMARD in RA, PsA, and AS support a strategy of differential b/tsDMARDs use informed by patient presentation. Despite greater availability of b/tsDMARDs with differing mechanisms of action, retention rates of the first b/tsDMARD remain similar to previous years.
Long-Term Impact of Interprofessional Medical Mission Service Trips in Sierra Leone
Authors: Tran Yen , Jarrett Jennie , Gardner Scott , Fernando James , Milliron Mark , Hong Lisa 
Published: September 2021

Objective: The purpose of this study was to evaluate the impact of capacity-building short-term mission service trips to Sierra Leone on local health education and perspectives.Methods: This was a prospective, mixed-methods study. During three mission trips between June 2017 and December 2019, health professional students taught multiple locally selected patient care-related topics. Local staff completed knowledge questionnaires and were surveyed or interviewed on mission service impact along with the cultural competence of missionaries. Mission team members completed the Intercultural Effectiveness Scale (IES) and surveys to determine their cultural competence.Results: After initial education, 90% passed the knowledge questionnaire with at least a 50% and the correct response rate was 57.9 vs. 66.7% after 6 months and 2.5 years, respectively (p = 0.40). Local staff ranked education/training as most valuable (84%) and highly desired (53%). Mean IES score and survey responses of both missionaries and local staff rated mission team cultural competence as average.Conclusions: Education-focused mission trips in Sierra Leone seem to have long-lasting benefits and a positive impact on local staff, though improved intercultural competence is needed.
The Role of β-Carotene in Colonic Inflammation and Intestinal Barrier Integrity
Authors: Cheng Junrui , Balbuena Emilio , Miller Baxter , Eroglu Abdulkerim 
Published: September 2021

Background: Carotenoids are naturally occurring pigments accounting for the brilliant colors of fruits and vegetables. They may display antioxidant and anti-inflammatory properties in humans besides being precursors to vitamin A. There is a gap of knowledge in examining their role within colonic epithelial cells. We proposed to address this research gap by examining the effects of a major dietary carotenoid, β-carotene, in the in vitro epithelial cell model.Methods: We examined the function of β-carotene in the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway. We conducted western blotting assays to evaluate expressions of TLR4 and its co-receptor, CD14. We also examined NF-κB p65 subunit protein levels in the model system. Furthermore, we studied the impact of β-carotene on the tight junction proteins, claudin-1, and occludin. We further carried out immunocytochemistry experiments to detect and visualize claudin-1 expression.Results: β-Carotene reduced LPS-induced intestinal inflammation in colonic epithelial cells. β-Carotene also promoted the levels of tight junction proteins, which might lead to enhanced barrier function.Conclusions: β-Carotene could play a role in modulating the LPS-induced TLR4 signaling pathway and in enhancing tight junction proteins. The findings will shed light on the role of β-carotene in colonic inflammation and also potentially in metabolic disorders since higher levels of LPS might induce features of metabolic diseases.
High Glycemic Diet Is Related to Brain Amyloid Accumulation Over One Year in Preclinical Alzheimer's Disease
Authors: Taylor Matthew K. , Sullivan Debra K. , Morris Jill K. , Vidoni Eric D. , Honea Robyn A. , Mahnken Jonathan D. , Burns Jeffrey M. 
Published: September 2021

Objective: To test the hypothesis that high glycemic diet is related to 1-year change in brain amyloid based on our prior cross-sectional evidence that high glycemic diet is associated with brain amyloid.Methods: This longitudinal, observational study assessed the relationship between reported habitual consumption of a high glycemic diet (HGDiet) pattern and 1-year brain amyloid change measured by Florbetapir F18 PET scans in 102 cognitively normal older adults with elevated or sub-threshold amyloid status that participated in a 1-year randomized, controlled exercise trial at the University of Kansas Medical Center in Kansas City.Results: Among all participants (n = 102), higher daily intake of the HGDiet pattern (β = 0.06, p = 0.04), sugar (β = 0.07, p = 0.01), and total carbohydrate (β = 0.06, p = 0.04) were related to more precuneal amyloid accumulation. These relationships in the precuneus were accentuated in participants with elevated amyloid at enrollment (n = 70) where higher intake of the HGDiet pattern, sugar, and carbohydrate were related to more precuneal amyloid accumulation (β = 0.11, p = 0.01 for all measures). In individuals with elevated amyloid, higher intake of the HGDiet pattern was also related to more amyloid accumulation in the lateral temporal lobe (β = 0.09, p &lt; 0.05) and posterior cingulate gyrus (β = 0.09, p &lt; 0.05) and higher sugar and carbohydrate intake were also related to more amyloid accumulation in the posterior cingulate gyrus (β = 0.10, p &lt; 0.05 for both measures).Conclusion: This longitudinal observational analysis suggests that a high glycemic diet relates to higher brain amyloid accumulation over 1 year in regions of the temporoparietal cortex in cognitively normal adults, particularly in those with elevated amyloid status. Further studies are required to assess whether there is causal link between a high glycemic diet and brain amyloid.Clinical Trial Registration:ClinicalTrials.gov, Identifier (NCT02000583).
Comparison of Dosimetric Benefits of Three Precise Radiotherapy Techniques in Nasopharyngeal Carcinoma Patients Using a Priority-Classified Plan Optimization Model
Authors: Wang Qiaoli , Qin Jiyong , Cao Ruixue , Xu Tianrui , Yan Jiawen , Zhu Sijin , Wu Jiang , Xu Guoqiang , Zhu Lixiu , Jiang Wei , Li Wenhui , Xiong Wei 
Published: September 2021

IntroductionAlthough intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and tomotherapy (TOMO) are broadly applied for nasopharyngeal carcinoma (NPC), the best technique remains unclear. Therefore, this study was conducted to address this issue.MethodsThe priority-classified plan optimization model was applied to IMRT, VMAT and TOMO plans in forty NPC patients according to the latest international guidelines. And the dosimetric parameters of planning target volumes (PTVs) and organs at risk (OARs) were compared among these three techniques. The Friedman M test in SPSS software was applied to assess significant differences.ResultsThe median PGTVnx coverage of IMRT was the lowest (93.5%, P &lt; 0.001) for all T categories. VMAT was comparable to TOMO in OARs clarified as priority I and II, and both satisfied the prescribed requirement. IMRT resulted in a relatively high dose for V25 and V30. Interestingly, subgroup analysis showed that the median PTV coverage of the three techniques was no less than 95% in the early T stage. The heterogeneity index (HI) of PGTVnx in VMAT was better than that in IMRT (P = 0.028). Compared to TOMO, VMAT showed a strong ability to protect eyesight and decrease low-dose radiation volumes. In the advanced T stage subgroup, TOMO numerically achieved the highest median PGTVnx coverage volume compared with VMAT and IMRT (93.61%, 91% and 90%, respectively). The best CI and HI of PCTV-1 were observed in TOMO. Furthermore, TOMO was better than VMAT for sparing the brain stem, spinal cord and temporal lobes (all P &lt; 0.05). However, the median V5, V10, V15, V20 and V25 were significantly higher with TOMO than with VMAT (all P &lt; 0.05).ConclusionIn the early T stage, VMAT provides a similar dose coverage and protection of OARs to IMRT, and there are no obvious advantages to choosing TOMO for NPC patients in the early T stage. TOMO may be recommended for patients in the advanced T stage due as it provides the largest dose coverage of PGTVnx and the best protection of the brain stem, spinal cord and temporal lobes. Additionally, more randomized clinical trials are needed for further clarification.
Bone Metastases of Glioblastoma: A Case Report and Review of the Literature
Authors: Zhang Wei , Cai Yuan-yuan , Wang Xiao-li , Wang Xiao-xiao , Li Yang , Han Gui-yan , Chu Yu-jing , Zhang Yun-xiang , Hao Fu-rong 
Published: September 2021

BackgroundGlioblastoma (GBM) is the most common primary intracranial tumor and originates from the small pool of adult neural stem and progenitor cells (NSPCs). According to the World Health Organization (WHO) classification of brain tumors, gliomas are classified into grades I–IV, and GBM is defined as the highest grade (IV). GBM can be disseminated by cerebrospinal fluid (CSF), but extracranial metastasis is rare. Additionally, the pathway and mechanism involved remain unclear.Case PresentationWe report a rare case of left temporal lobe GBM with multiple bone metastases and soft tissue metastasis. This 49-year-old right-handed man who was diagnosed with GBM underwent surgery on May 9, 2017, followed by radiochemotherapy in June 2017. On August 13, 2019, local relapse was found. Then, the patient received a second surgery but not radiochemotherapy. In November 2019, the patient was reported to be suffering from low back pain for nearly 1 month. On December 6, 2019, magnetic resonance imaging (MRI) of the thoracolumbar vertebrae and abdominal computed tomography (CT) confirmed metastases on the ninth posterior rib on the right, the third anterior rib on the left, and the T7 and T10 vertebrae and their appendages. CT-guided rib space-occupying puncture biopsy was performed, and GBM was identified by pathology.ConclusionWe should pay attention to extracranial metastasis of GBM. Timely detection and early treatment improve overall quality of patients’ life. The extracranial metastasis in this patient may have occurred through the spinal nerve root or intercostal nerve. Further clinical observations are required to clarify the pathway and mechanism involved.
Diagnostic and Prognostic Value of MicroRNAs in Metastasis and Recurrence of Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Qiu Ke , Song Yao , Rao Yufang , Liu Qiurui , Cheng Danni , Pang Wendu , Ren Jianjun , Zhao Yu 
Published: September 2021

MicroRNAs have been proven to make remarkable differences in the clinical behaviors of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically analyze whether differential expression levels of microRNAs are related to recurrence or metastasis in patients with HNSCC. A comprehensive search of the PubMed, EMBASE, and CENTRAL was conducted up to July 24th, 2021. Data were collected and combined from studies reporting recurrence-free survival (RFS) of HNSCC patients with high microRNA expression compared to those with low expression. Besides, studies providing necessary data for evaluating the diagnostic value of microRNAs for detecting recurrence and metastasis based on their expression levels were also included and combined. The pooled hazard ratio (HR) value for the outcomes of RFS in 1,093 HNSCC samples from 10 studies was 2.51 (95%CI: 2.13–2.96). A sensitivity of 0.79 (95% CI: 0.72–0.85) and specificity of 0.77 (95%CI: 0.68–0.83) were observed in three studies, of which 93 patients with recurrence and 82 nonrecurrence controls were included, and the area under the curve (AUC) was 0.85 (95% CI: 0.81–0.88). Additionally, high diagnostic accuracy of microRNAs in detecting lymph node metastasis (LNM) was also reported. In conclusion, two panels of microRNAs showed the potential to predict recurrence or diagnose recurrence in HNSCC patients, respectively, which could facilitate prognosis prediction and diagnosis of clinical behaviors in HNSCC patients.Systematic Review RegistrationPROSPERO (https://www.crd.york.ac.uk/prospero), identifier CRD42020161117.
A Role for Global DNA Methylation Level and IL2 Expression in the Transition From Acute to Chronic Low Back Pain
Authors: Eller Olivia C. , Glidden Nicole , Knight Brittany , McKearney Noelle , Perry Mallory , Bernier Carney Katherine M. , Starkweather Angela , Young Erin E. , Baumbauer Kyle M. 
Published: September 2021

Objectives: The transition from acute low back pain (aLBP) to chronic LBP (cLBP) results from a variety of factors, including epigenetic modifications of DNA. The aim of this study was to (1) compare global DNA (gDNA) methylation and histone acetylation at LBP onset between the aLBP and cLBP participants, (2) compare mRNA expression of genes with known roles in the transduction, maintenance, and/or modulation of pain between the aLBP and cLBP participants, (3) compare somatosensory function and pain ratings in our participants, and (4) determine if the aforementioned measurements were associated.Methods: A total of 220 participants were recruited for this prospective observational study following recent onset of an episode of LBP. We retained 45 individuals whose gDNA was of sufficient quality for analysis. The final sample included 14 participants whose pain resolved within 6 weeks of onset (aLBP),15 participants that reported pain for 6 months (cLBP), and 16 healthy controls. Participants were subjected to quantitative sensory testing (QST), blood was drawn via venipuncture, gDNA isolated, and global DNA methylation and histone acetylation, as well as mRNA expression of 84 candidate genes, were measured.Results: Individuals that develop cLBP display multimodal somatosensory hypersensitivity relative to aLBP participants. cLBP participants also had significantly lower global DNA methylation, which was negatively correlated with interleukin-2 (IL2) mRNA expression.Discussion: cLBP is characterized by somatosensory hypersensitivity, lower global DNA methylation, and higher IL2 expression level compared to those whose pain will resolve quickly (aLBP). These results suggest potential diagnostic and therapeutic relevance for global DNA methylation and IL2 expression in the pathology underlying the transition from acute to chronic LBP.