bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of intestinal and systemic inflammatory biomarkers with immune reconstitution in HIV+ patients on ART
Authors: Ruiz-Briseño Mariana del Rocio , De Arcos-Jiménez Judith Carolina , Ratkovich-González Sarah , Sánchez-Reyes Karina , González-Hernández Luz A. , Andrade-Villanueva Jaime F. , Alvarez-Zavala Monserrat 
Published: October 2020

Abstract
Background
HIV infection is characterized by CD4+ T-cells depletion related to gut damage, microbial translocation, immune activation and intestinal and systemic low-grade inflammation. With the use of antiretroviral treatment, these alterations in HIV+ patients reach similar levels to HIV- controls. However, almost 20% patients have deficient immune reconstitution of CD4+ T-cells, which make them more susceptible to develop non-AIDS and AIDS comorbidities.

Methods
HIV+ patients on ART, with sustained virologic control were grouped according to their immune reconstitution as: immunological responders (n = 18) and immunological non-responders (n = 18); also, HIV- controls were enrolled (n = 14). CD4+ and CD8+ T-cell activation (HLA-DR+ and CD38+ single and co-expression) were measured by flow cytometry. Serum levels of sCD14, sCD163, lipopolysaccharide, I-FABP, sST2, as well as fecal levels of calprotectin, lactoferrin and secretory IgA were evaluated by ELISA. Levels of C-reactive protein were determined by a high sensibility singleplex bead-based immunoassay. Serum and fecal concentrations of proinflammatory cytokines were quantified by multiplex bead-based immunoassay.

Results
HLA-DR+ and CD38+ co-expression, as well as median fluorescence intensity in CD4+ and CD8+ T-cells subpopulations was greater in immunological non-responders group, after normalization and fold change calculation. Similarly, this group presented higher levels of sCD14, C-reactive protein, as well as fecal calprotectin and lactoferrin. Furthermore, both HIV+ groups showed elevated levels of proinflammatory cytokines in stool.

Conclusions
Our data suggests that despite the virologic control, HIV+ patients under treatment with deficient immune reconstitution showed elevation of both innate and T-cells immune activation, as well as intestinal and systemic inflammation. However, some patients with CD4+ T-cells count above 350 cells/μL also presented these alterations. Future studies are necessary to evaluate the dynamics of multiple systemic and intestinal biomarkers in diverse types of HIV+ patients, as such as their clinical impact.
The pharmaceutical practice of mask distribution by pharmacists in Taiwan’s community pharmacies under the Mask Real-Name System, in response to the COVID-19 outbreak
Authors: Lin Che-huei , Lin Ya-Wen , Wang Jong-yi , Lin Ming-hung 
Published: October 2020

Abstract
Background
Pharmacists hold to their promise to foster, implement and promote the health of the population and to prevent disease, given their knowledge, skills, and proximity to the locals. The objective of this study was to foster equality and cost-effectiveness in the distribution and sale of masks to all Taiwanese citizens, in response to the COVID-19 pandemic.

Methods
All 6336 special community pharmacies participating in the NHI (National Health Insurance) served as mask-selling sites. Access to masks by citizens was determined and controlled, based on the weekly rationing of the number of purchasable masks per citizen and the last digit of their NHI card number. Masks were available on different weekdays for holders of cards ending with odd and even numbers, except on Sundays, when everyone was eligible to buy a mask.

Results
Implementing the program has provided equal access to masks for all citizens across Taiwan. It has stabilized the pricing of masks and mitigated the public’s anxiety of a perceived likely market shortage.

Conclusion
The community pharmacy-based approach to the distribution of prevention face masks to citizens represents a new and innovative engagement of pharmacists in public health promotion and protection initiatives. Community pharmacies can greatly improve the efficiency, reliability, and cost-saving of the distribution of public health resources to local communities, especially in the face of an epidemic.
LTBP1 plays a potential bridge between depressive disorder and glioblastoma
Authors: Fu Xiaojun , Zhang Pei , Song Hongwang , Wu Chenxing , Li Shengzhen , Li Shouwei , Yan Changxiang 
Published: October 2020

Abstract
Background
Glioblastoma multiforme (GBM) is the most malignant tumor in human brain. Diagnosis and treatment of GBM may lead to psychological disorders such as depressive and anxiety disorders. There was no research focusing on the correlation between depressive/anxiety disorder and the outcome of GBM. Thus, the aim of this study was to investigate the possibility of depressive/anxiety disorder correlated with the outcome of GBM patients, as well as the overlapped mechanism bridge which could link depressive/anxiety disorders and GBM.

Methods
Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) were used to investigate the psychological condition of GBM patients in our department. To further explore the potential mechanism, bioinformatic methods were used to screen out genes that could be indicators of outcome in GBM, followed by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein–protein interaction (PPI) analysis. Further, cellular experiments were conducted to evaluate the proliferation, migration capacity of primary GBM cells from the patients.

Results
It was revealed that patients with higher PHQ-9 and GAD-7 scores had significantly worse prognosis than their lower-scored counterparts. Bioinformatic mining revealed that LTBP1 could be a potential genetic mechanism in both depressive/anxiety disorder and GBM. Primary GBM cells with different expression level of LTBP1 should significantly different proliferation and migration capacity. GO, KEGG analysis confirmed that extracellular matrix (ECM) was the most enriched function of LTBP1. PPI network showed the interaction of proteins altered by LTBP1. Hub genes COL1A2, COL5A1 and COL10A1, as well as mesenchymal marker CD44 and Vimentin were statistically higher expressed in LTBP1 high group; while proneural marker E-cadherin was significantly higher expressed in low LTBP1 group.

Conclusion
There is closely correlation between depressive/anxiety disorders and GBM. LTBP1 could be a potential bridge linking the two diseases through the regulation of ECM.
Designing and piloting a generic research architecture and workflows to unlock German primary care data for secondary use
Authors: Bahls Thomas , Pung Johannes , Heinemann Stephanie , Hauswaldt Johannes , Demmer Iris , Blumentritt Arne , Rau Henriette , Drepper Johannes , Wieder Philipp , Groh Roland , Hummers Eva , Schlegelmilch Falk 
Published: October 2020

Abstract
Background
Medical data from family doctors are of great importance to health care researchers but seem to be locked in German practices and, thus, are underused in research. The RADAR project (Routine Anonymized Data for Advanced Health Services Research) aims at designing, implementing and piloting a generic research architecture, technical software solutions as well as procedures and workflows to unlock data from family doctor’s practices. A long-term medical data repository for research taking legal requirements into account is established. Thereby, RADAR helps closing the gap between the European countries and to contribute data from primary care in Germany.

Methods
The RADAR project comprises three phases: (1) analysis phase, (2) design phase, and (3) pilot. First, interdisciplinary workshops were held to list prerequisites and requirements. Second, an architecture diagram with building blocks and functions, and an ordered list of process steps (workflow) for data capture and storage were designed. Third, technical components and workflows were piloted. The pilot was extended by a data integration workflow using patient-reported outcomes (paper-based questionnaires).

Results
The analysis phase resulted in listing 17 essential prerequisites and guiding requirements for data management compliant with the General Data Protection Regulation (GDPR). Based on this list existing approaches to fulfil the RADAR tasks were evaluated—for example, re-using BDT interface for data exchange and Trusted Third Party-approach for consent management and record linkage. Consented data sets of 100 patients were successfully exported, separated into person-identifying and medical data, pseudonymised and saved. Record linkage and data integration workflows for patient-reported outcomes in the RADAR research database were successfully piloted for 63 responders.

Conclusion
The RADAR project successfully developed a generic architecture together with a technical framework of tools, interfaces, and workflows for a complete infrastructure for practicable and secure processing of patient data from family doctors. All technical components and workflows can be reused for further research projects. Additionally, a Trusted Third Party-approach can be used as core element to implement data privacy protection in such heterogeneous family doctor’s settings. Optimisations identified comprise a fully-electronic consent recording using tablet computers, which is part of the project’s extension phase.
Classification models using circulating neutrophil transcripts can detect unruptured intracranial aneurysm
Authors: Poppenberg Kerry E. , Tutino Vincent M. , Li Lu , Waqas Muhammad , June Armond , Chaves Lee , Jiang Kaiyu , Jarvis James N. , Sun Yijun , Snyder Kenneth V. , Levy Elad I. , Siddiqui Adnan H. , Kolega John , Meng Hui 
Published: October 2020

AbstractBackgroundIntracranial aneurysms (IAs) are dangerous because of their potential to rupture. We previously found significant RNA expression differences in circulating neutrophils between patients with and without unruptured IAs and trained machine learning models to predict presence of IA using 40 neutrophil transcriptomes. Here, we aim to develop a predictive model for unruptured IA using neutrophil transcriptomes from a larger population and more robust machine learning methods.MethodsNeutrophil RNA extracted from the blood of 134 patients (55 with IA, 79 IA-free controls) was subjected to next-generation RNA sequencing. In a randomly-selected training cohort (n = 94), the Least Absolute Shrinkage and Selection Operator (LASSO) selected transcripts, from which we constructed prediction models via 4 well-established supervised machine-learning algorithms (K-Nearest Neighbors, Random Forest, and Support Vector Machines with Gaussian and cubic kernels). We tested the models in the remaining samples (n = 40) and assessed model performance by receiver-operating-characteristic (ROC) curves. Real-time quantitative polymerase chain reaction (RT-qPCR) of 9 IA-associated genes was used to verify gene expression in a subset of 49 neutrophil RNA samples. We also examined the potential influence of demographics and comorbidities on model prediction.ResultsFeature selection using LASSO in the training cohort identified 37 IA-associated transcripts. Models trained using these transcripts had a maximum accuracy of 90% in the testing cohort. The testing performance across all methods had an average area under ROC curve (AUC) = 0.97, an improvement over our previous models. The Random Forest model performed best across both training and testing cohorts. RT-qPCR confirmed expression differences in 7 of 9 genes tested. Gene ontology and IPA network analyses performed on the 37 model genes reflected dysregulated inflammation, cell signaling, and apoptosis processes. In our data, demographics and comorbidities did not affect model performance.ConclusionsWe improved upon our previous IA prediction models based on circulating neutrophil transcriptomes by increasing sample size and by implementing LASSO and more robust machine learning methods. Future studies are needed to validate these models in larger cohorts and further investigate effect of covariates.
Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes
Authors: Lai Yun-Ru , Chen Meng Hsiang , Lin Wei Che , Chiu Wen-Chan , Cheng Ben-Chung , Chen Jung-Fu , Tsai Nai-Wen , Huang Chih-Cheng , Lu Cheng-Hsien 
Published: October 2020

Abstract
Background
Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes.

Methods
The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value).

Results
A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS.

Conclusions
Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.
Determinants of disease activity change over time in Enthesitis related arthritis: effect of structured outcome monitoring and clinical decision support
Authors: Tirelli Francesca , Xiao Rui , Brandon Timothy G. , Burnham Jon M. , Chang Joyce C. , Weiss Pamela F. 
Published: October 2020

Abstract
Background
We aimed to test if standardized point-of-care outcome monitoring and clinical decision support (CDS), as compared to standard care, improves disease activity and patient-reported pain in children with enthesitis-related arthritis (ERA).

Methods
This was a retrospective cohort study of outcomes of children with ERA after phased implementation of I) standardized outcome monitoring with CDS for polyarticular JIA, and II) CDS for ERA, compared to a pre-intervention group of historical controls. We used multivariable mixed-effects models for repeated measures to test whether implementation phase or other disease characteristics were associated with change over time in disease activity, as measured by the clinical juvenile arthritis disease activity score (cJADAS), and pain.

Results
One hundred fifty-two ERA patients (41% incident cases) were included with a median age of 14.9 years. Implementation of standardized outcome monitoring or ERA-specific CDS did not result in significant differences in cJADAS or pain over time compared to the pre-intervention cohort. Higher cJADAS at the index visit, pain and more tender entheses were significantly associated with higher cJADAS scores over time (all p < 0.01), while biologic use was associated with lower cJADAS (p = 0.02). Regardless of intervention period, incident ERA cases had a greater rate of cJADAS improvement over time compared to prevalent cases (p < 0.01), but pain persisted over time among both incident and prevalent cases.

Conclusions
There was no significant effect of point-of-care outcome monitoring or CDS interventions on disease activity or pain over time in children with ERA in this single center study. Future efforts to improve disease outcomes using standardized outcome monitoring and CDS will need to consider the importance of addressing pain as a target in addition to spondyloarthritis-specific disease activity metrics.
Chronic stress, epigenetics, and adipose tissue metabolism in the obese state
Authors: Xiao Yang , Liu Dongmin , Cline Mark A. , Gilbert Elizabeth R. 
Published: October 2020

AbstractIn obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders.
Evaluation of duplicated reference genes for quantitative real-time PCR analysis in genome unknown hexaploid oat (Avena sativa L.)
Authors: Yang Zheng , Wang Kai , Aziz Usman , Zhao Cuizhu , Zhang Meng 
Published: October 2020

Abstract
Background
Oat (Avena sativa L.), a hexaploid crop with unknown genome, has valuable nutritional, medicinal and pharmaceutical uses. However, no suitable RGs (reference genes) for qPCR (quantitative real-time PCR) has been documented for oat yet. Single-copy gene is often selected as RG, which is challengeable or impactable in unexplored polyploids.

Results
In this study, eleven candidate RGs, including four duplicated genes, were selected from oat transcriptome. The stability and the optimal combination of these candidate RGs were assessed in 18 oat samples by using four statistical algorithms including the ΔCt method, geNorm, NormFinder and BestKeeper. The most stable RGs for “all samples”, “shoots and roots of seedlings”, “developing seeds” and “developing endosperms” were EIF4A (Eukaryotic initiation factor 4A-3), UBC21 (Ubiquitin-Conjugating Enzyme 21), EP (Expressed protein) and EIF4A respectively. Among these RGs, UBC21 was a four-copy duplicated gene. The reliability was validated by the expression patterns of four various genes normalized to the most and the least stable RGs in different sample sets.

Conclusions
Results provide a proof of concept that the duplicated RG is feasible for qPCR in polyploids. To our knowledge, this study is the first systematic research on the optimal RGs for accurate qPCR normalization of gene expression in different organs and tissues of oat.
Development of a novel and rapid phenotype-based screening method to assess rice seedling growth
Authors: Vlaminck Lena , Sang-Aram Chananchida , Botterman Deborah , Uy Christine Jewel C. , Harper Mary Kay , Inzé Dirk , Gheysen Godelieve , Depuydt Stephen 
Published: October 2020

AbstractBackgroundRice (Oryza sativa) is one of the most important model crops in plant research. Despite its considerable advantages, (phenotypic) bioassays for rice are not as well developed as forArabidopsis thaliana. Here, we present a phenotype-based screening method to study shoot-related parameters of rice seedlings via an automated computer analysis.ResultsThe phenotype-based screening method was validated by testing several compounds in pharmacological experiments that interfered with hormone homeostasis, confirming that the assay was consistent with regard to the anticipated plant growth regulation and revealing the robustness of the set-up in terms of reproducibility. Moreover, abiotic stress tests using NaCl and DCMU, an electron transport blocker during the light dependent reactions of photosynthesis, confirmed the validity of the new method for a wide range of applications. Next, this method was used to screen the impact of semi-purified fractions of marine invertebrates on the initial stages of rice seedling growth. Certain fractions clearly stimulated growth, whereas others inhibited it, especially in the root, illustrating the possible applications of this novel, robust, and fast phenotype-based screening method for rice.ConclusionsThe validated phenotype-based and cost-efficient screening method allows a quick and proper analysis of shoot growth and requires only small volumes of compounds and media. As a result, this method could potentially be used for a whole range of applications, ranging from discovery of novel biostimulants, plant growth regulators, and plant growth-promoting bacteria to analysis of CRISPR knockouts, molecular plant breeding, genome-wide association, and phytotoxicity studies. The assay system described here can contribute to a better understanding of plant development in general.
Management of liver trauma in urban university hospitals in India: an observational multicentre cohort study
Authors: Sinha Yash , Khajanchi Monty U. , Prajapati Ramlal P. , Dharap Satish , Soni Kapil Dev , Kumar Vineet , Mahindrakar Santosh , Roy Nobhojit 
Published: October 2020

AbstractBackgroundLow- and middle-income countries (LMICs) contribute to 90% of injuries occurring in the world. The liver is one of the commonest organs injured in abdominal trauma. This study aims to highlight the demographic and management profile of liver injury patients, presenting to four urban Indian university hospitals in India.MethodsThis is a retrospective registry-based study. Data of patients with liver injury either isolated or concomitant with other injuries was used using the ICD-10 code S36.1 for liver injury. The severity of injury was graded based on the World Society of Emergency Surgery (WSES) grading for liver injuries.ResultsA total of 368 liver injury patients were analysed. Eighty-nine percent were males, with road traffic injuries being the commonest mechanism. As per WSES liver injury grade, there were 127 (34.5%) grade I, 96 (26.1%) grade II, 70 (19.0%) grade III and 66 (17.9%) grade IV injuries. The overall mortality was 16.6%. Two hundred sixty-two patients (71.2%) were managed non-operatively (NOM), and 106 (38.8%) were operated. 90.1% of those managed non-operatively survived.ConclusionIn this multicentre cohort of liver injury patients from urban university hospitals in India, the commonest profile of patient was a young male, with a blunt injury to the abdomen due to a road traffic accident. Success rate of non-operative management of liver injury is comparable to other countries.