bluuebunny/crossref_metadata_2025_split huggingface dataset:
A care coordinator screening strategy to address health harming legal needs
Authors: Berg Daniel , Setrini Alice , Chan Kathy , Cibulskis Ann , Ameji Kulsum , Hinami Keiki 
Published: February 2022

Abstract
Background
Medical legal partnerships provide an opportunity to help address various social determinants of health; however, the traditional practice of screening patients during clinical encounters is limited by the capacity of busy clinicians. Our medical legal partnership utilized care coordinators trained by the legal service attorneys to screen patients outside of clinical encounters for health harming legal needs. The goal of our study was to demonstrate that our novel model could successfully identify and refer patients of a safety-net healthcare system to appropriate legal services.

Methods
We conducted a mixed methods evaluation of the program. Data was collected during the implementation period of the program from March 2017 to August 2018. Operational data collected included number of patients screened, number of referrals to the legal partner, source and reason for referrals. Return on investment was calculated by subtracting program costs from the total reimbursement to the health system from clients’ insurance benefits secured through legal services.

Results
During the 18-month study, 29,268 patients were screened by care coordinators for health harming legal needs, with 492 patients (1.7%) referred for legal assistance. Of the 133 cases closed in 2017, all clients were invited to participate in a telephone interview; 63 pre-consented to contact, 33 were successfully contacted and 23 completed the interview. The majority (57%) reported a satisfactory resolution of their legal barrier to health. This was accompanied by an improvement in self-reported health with a decrease of patients reporting less than optimal health from 16 (89%) prior to intervention to 8 (44%) after intervention [risk ratio (95% confidence interval): 0.20 (0.04, 0.91)]. Patients also reported improvements in general well-being for themselves and their family. The healthcare system recorded a 263% return on investment.

Conclusions
In our medical legal partnership, screening for health harming legal needs by care coordinators outside of a clinical encounter allowed for efficient screening in a high risk population. The legal services intervention was associated with improvements in self-reported health and family well-being when compared to previous models. The return on investment was substantial.
Drug therapy-related problem management in Nigeria community pharmacy – process evaluation with simulated patient
Authors: Segun Showande Johnson , Damilola Lawal Sodiq 
Published: February 2022

Abstract
Background
Unresolved drug therapy-related problems (DTRPs) have economic and clinical consequences and are common causes of patients’ morbidity and mortality. This study evaluated the ability of community pharmacists to identify and resolve DTRPs and assessed the perceived barriers to DTRP identification and resolution.

Methods
A cross-sectional study which employed the use of three simulated patients (SPs) visit to 36 selected community pharmacies in 11 local government areas in Ibadan, Nigeria. The SPs played the role of a patient with prescription for multiple ailments (23-year-old male), type 2 diabetes and hypertensive patient with medication packs (45-year-old male) and hypertensive patient with gastric ulcer with a prescription (37-year-old female). They re-enacted three rehearsed vignettes when they spoke with the pharmacists. A five-member panel of experts predetermined the DTRPs present in the vignettes (n = 11), actions to take to investigate the DTRPs (n = 9) and recommendations to resolve the DTRPs (n = 9). Pharmacists’ perceived barriers to the identification and resolution of DTRPs were assessed with a self-administered questionnaire. The percentage ability to detect and resolve DTRPs was determined and classified as poor ability (≤30%), fair ability (> 30 - ≤50%), moderate ability (> 50 - ≤70%) and high ability (> 70%).

Results
One hundred and eight visits were made by the three SPs to the pharmacies. In total, 4.42/11 (40.2%) DTRPs were identified, 3.50/9 (38.9%) actions were taken, and 3.94/9 (43.8%) recommendations were made to resolve the identified DTRPs. The percentage ability of the community pharmacists to detect and resolve DTRPs varied slightly from one vignette to another (vignette 1–49.3%, vignette 2–39.1%, vignette 3–38.8%). But overall, it was fair (40.9%). Pharmacists’ perceived barriers to DTRP detection and resolution included lack of access to patient’s/client’s medical history and lack of software for DTRP detection.

Conclusions
The community pharmacists displayed fair ability in detecting and resolving DTRPs. Several barriers preventing the optimal performance of pharmacist in DTRP identification and resolution were identified including inaccessibility of patient’s/client’s medical history. The regulatory authority of pharmacy education and practice in Nigeria need to mount Continuing Education Program to address this deficit among community pharmacists.
Functional genomics elucidates regulatory mechanisms of Parkinson’s disease-associated variants
Authors: Chen Rui , Liu Jiewei , Li Shiwu , Li Xiaoyan , Huo Yongxia , Yao Yong-Gang , Xiao Xiao , Li Ming , Luo Xiong-Jian 
Published: February 2022

Abstract
Background
Genome-wide association studies (GWASs) have identified multiple risk loci for Parkinson’s disease (PD). However, identifying the functional (or potential causal) variants in the reported risk loci and elucidating their roles in PD pathogenesis remain major challenges. To identify the potential causal (or functional) variants in the reported PD risk loci and to elucidate their regulatory mechanisms, we report a functional genomics study of PD.

Methods
We first integrated chromatin immunoprecipitation sequencing (ChIP-Seq) (from neuronal cells and human brain tissues) data and GWAS-identified single-nucleotide polymorphisms (SNPs) in PD risk loci. We then conducted a series of experiments and analyses to validate the regulatory effects of these (i.e., functional) SNPs, including reporter gene assays, allele-specific expression (ASE), transcription factor (TF) knockdown, CRISPR-Cas9-mediated genome editing, and expression quantitative trait loci (eQTL) analysis.

Results
We identified 44 SNPs (from 11 risk loci) affecting the binding of 12 TFs and we validated the regulatory effects of 15 TF binding-disrupting SNPs. In addition, we also identified the potential target genes regulated by these TF binding-disrupting SNPs through eQTL analysis. Finally, we showed that 4 eQTL genes of these TF binding-disrupting SNPs were dysregulated in PD cases compared with controls.

Conclusion
Our study systematically reveals the gene regulatory mechanisms of PD risk variants (including widespread disruption of CTCF binding), generates the landscape of potential PD causal variants, and pinpoints promising candidate genes for further functional characterization and drug development.
Comprehensive pan-cancer analysis on CBX3 as a prognostic and immunological biomarker
Authors: Niu Hongjuan , Chen Peiqiong , Fan Lu , Sun Boyu 
Published: February 2022

Abstract
Background
Increased evidence supports the relationship between chromobox protein homolog 3 (CBX3) and tumorigenesis of some cancers. However, the role of CBX3 in pan-cancers remains poorly defined. In the research, we aimed to investigate the prognostic value and the immunological functions of CBX3.

Results
We explored the potential oncogenic roles of CBX3 in mRNA and protein levels based on the diverse databases, including the expression, the correlation with prognosis, tumor microenvironment (TME), DNA methylation, protein phosphorylation and enrichment analysis across all TCGA tumors. The results show that CBX3 is overexpressed in multiple cancers, and significant correlations exist between high expression and adverse prognosis in most tumor patients. We observed an enhanced phosphorylation level in uterine corpus endometrial carcinoma, colon cancer and lung adenocarcinoma. A distinct relationship was also found between CBX3 expression and TME, including immune infiltration of tumor-infiltrating lymphocytes and cancer-associated fibroblasts, immune score or matrix score, immune checkpoints. The correlative transcription factors and miRNAs of CBX3-binding hub genes were analyzed to investigate the molecular mechanism. Moreover, alcoholism and alteration of DNA cellular biology may be involved in the functional mechanisms of CBX3.

Conclusion
The first pan-cancer study offers a relatively comprehensive cognition on the oncogenic roles of CBX3 as a prognostic and immunological marker in various malignant tumors.
Nifuroxazide ameliorates pulmonary fibrosis by blocking myofibroblast genesis: a drug repurposing study
Authors: Gan Cailing , Zhang Qianyu , Liu Hongyao , Wang Guan , Wang Liqun , Li Yali , Tan Zui , Yin Wenya , Yao Yuqin , Xie Yongmei , Ouyang Liang , Yu Luoting , Ye Tinghong 
Published: February 2022

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease with a complex pathogenesis and high mortality. The development of new drugs is time-consuming and laborious; therefore, research on the new use of old drugs can save time and clinical costs and even avoid serious side effects. Nifuroxazide (NIF) was originally used to treat diarrhoea, but more recently, it has been found to have additional pharmacological effects, such as anti-tumour effects and inhibition of inflammatory diseases related to diabetic nephropathy. However, there are no reports regarding its role in pulmonary fibrosis.MethodsThe therapeutic effect of NIF on pulmonary fibrosis in vivo was measured by ELISA, hydroxyproline content, H&E and Masson staining, immunohistochemistry (IHC) and western blot. Immune cell content in lung tissue was also analysed by flow cytometry. NIF cytotoxicity was evaluated in NIH/3T3 cells, human pulmonary fibroblasts (HPFs), A549 cells and rat primary lung fibroblasts (RPLFs) using the MTT assay. Finally, an in vitro cell model created by transforming growth factor-β1 (TGF-β1) stimulation was assessed using different experiments (immunofluorescence, western blot and wound migration assay) to evaluate the effects of NIF on the activation of NIH/3T3 and HPF cells and the epithelial-mesenchymal transition (EMT) and migration of A549 cells.ResultsIn vivo, intraperitoneal injection of NIF relieved and reversed pulmonary fibrosis caused by bleomycin (BLM) bronchial instillation. In addition, NIF inhibited the expression of a variety of cellular inflammatory factors and immune cells. Furthermore, NIF suppressed the activation of fibroblasts and EMT of epithelial cells induced by TGF-β1. Most importantly, we used an analytical docking experiment and thermal shift assay to further verify that NIF functions in conjunction with signal transducer and activator of transcription 3 (Stat3). Moreover, NIF inhibited the TGF-β/Smad pathway in vitro and decreased the expression of phosphorylated Stat3 in vitro and in vivo.ConclusionTaken together, we conclude that NIF inhibits and reverses pulmonary fibrosis, and these results support NIF as a viable therapeutic option for IPF treatment.Graphic Abstract
Overexpression of CBS/H2S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44
Authors: Zhang Yuyang , Chen Shanwen , Zhu Jing , Guo Shihao , Yue Taohua , Xu Hao , Hu Jianwen , Huang Zhihao , Chen Zeyang , Wang Pengyuan , Liu Yucun 
Published: February 2022

Abstract
Background
The role of hydrogen sulfide (H2S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H2S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H2S exerts an inhibitory effect on colon cancer cell proliferation and metastasis.

Methods
Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H2S was detected by H2S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA–protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions.

Results
Overexpression of CBS and exogenous H2S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H2S axis on colon cancer cells.

Conclusions
Overexpression of CBS and exogenous provision of H2S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1.
Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice
Authors: SheelaNair Arya , Romanczuk Aleksandra S. , Aogo Rosemary A. , Haldar Rohit Nemai , Lansink Lianne I. M. , Cromer Deborah , Salinas Yandira G. , Guy R. Kiplin , McCarthy James S. , Davenport Miles P. , Haque Ashraful , Khoury David S. 
Published: February 2022

Abstract
Background
Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation.

Methods
In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication.

Results
These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal.

Conclusions
Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
Correlation of cholesteryl ester metabolism to pathogenesis, progression and disparities in colorectal Cancer
Authors: Liu Zhirong , Gomez Christian R. , Espinoza Ingrid , Le Thuy Phuong T. , Shenoy Veena , Zhou Xinchun 
Published: February 2022

Abstract
Background
Colorectal cancer (CRC) is one of the most common cancers worldwide characterized by disparities in age, gender, race and anatomic sites. The mechanism underlying pathogenesis, progression and disparities of CRC remains unclear. This study aims to reveal the association of expression levels of enzymes related to cholesteryl ester (CE) metabolism with pathogenesis, progression and disparities of CRC.

Methods
The differences in gene expression levels were analyzed for enzymes in CE synthesis (acyl CoA: cholesterol acyltransferase 1 and 2, ACAT1, and ACAT2), and in CE hydrolysis (neutral cholesterol ester hydrolase, NCEH1 and lysosomal acid lipase, LAL) on TNMplot platform between CRC and normal colorectal tissues (NCT) in a large cohort. The differences in protein expression levels for these enzymes were determined by Immunochemistry (IHC) performed on tissue microarray containing 96 pairs of CRC and benign colorectal tissues (BCT) from different patient populations. The expression level represented as IHC score of each enzyme was compared between CRC and BCT in entire population and populations stratified by race, gender and anatomic sites. Student’s t-test, Fisher exact test and ANOVA were used for data analysis. Significant p value was set at P<0.05.

Results
The gene expression level of ACAT1 was significantly lower in CRC than in NCT (P = 2.15e-119). The gene expression level of ACAT2 was not statistically different between CRC and NCT. The gene expression level of LIPA (encoding LAL) was significantly higher in CRC than in NCT (P = 2.01e-14). No data was found for the gene expression level of NCEH1. The IHC score of ACAT1was significantly lower in CRC than in BCT in all studied populations and in sub site of colon, but not in that of rectum. The IHC score of ACAT2 was not statistically different between CRC and BCT. IHC score of NCEH1 was significantly higher in CRC than in BCT only in African American (AA) population. The IHC score of LAL was significantly higher in CRC than in BCT in all studied populations and in all sub sites. In addition, decreased ACAT1 in CRC significantly correlated to progression of CRC: the lower IHC score of ACAT1, the more advanced clinical stage of CRC will be.

Conclusions
This study revealed that altered expression levels in enzymes related to CE metabolism highly correlate to the pathogenesis, clinical progression and disparities of CRC. The results will add revenue in elucidating mechanisms underlying progression of CRC, and shed light on seeking biomarkers and exploring therapeutic targets for CRC in a new direction.
Assessing the psychometric properties of the Chinese return-to-work self-efficacy questionnaire using Rasch model analysis
Authors: Liu Feng , Zhang Zhenxiang , Lin Beilei , Ping Zhiguang , Mei Yongxia 
Published: February 2022

Abstract
Background
Self-efficacy is a significant predictor of return to work and affects the confidence of survivors to return to work after illness. The Return-to-work self-efficacy (RTW-SE) questionnaire is a self-report questionnaire to assess confidence in returning to work with good reliability and validity. The aim of this study was to translate and cross-culturally adapt the RTW-SE questionnaire into Chinese and examine the psychometric properties among young and middle-aged stroke survivors using Rasch model analysis.

Methods
The cross-cultural adaptation and translation procedures followed a dual-translation approach. The psychometric properties of the RTW-SE questionnaire were examined using Rasch model analysis by Winsteps software. The unidimensionality and local independence were analyzed by principal component analysis of the residuals (PCAR) and standardized residual correlations.Category diagnostics were performed for scale function, and the item fit, reliability, and separation were also validated. Item-person maps were used to examine the distribution and matching of item’s location and person ability. Finally, the differential item functioning (DIF) was used to measure gender-related group equivalence.

Results
A total of 366 participants aged 23–59 years were recruited from three communities in Zhengzhou. The RTW-SE questionnaire demonstrated unidimensionality and a 5-point Likert rating scale was more appropriate to investigate young and middle-aged stroke survivors’self-efficacy. There was a good fit for the items with both person and item reliabilities greater than 0.8 and separation indices of 3.75 and 3.94, respectively. The item location was identified from the item-person map as not covering person ability, but the scale did not have an age-related DIF.

Conclusions
The results confirm evidence of appropriate psychometric properties of the RTW-SE questionnaire and can be used as a reliable and validated instrument for measuring self-efficacy to return to work in young and middle-aged Chinese patients with stroke.
Health-related quality of life in individuals with genital herpes: a systematic review
Authors: Devine Angela , Xiong Xiuqin , Gottlieb Sami Lynne , de Mello Maeve Britto , Fairley Christopher K. , Ong Jason J. 
Published: February 2022

Abstract
Background
There is a significant global burden of herpes simplex virus (HSV) related genital ulcer disease yet little is known about its impact on quality of life. This systematic review aimed to identify studies that quantitatively evaluated the effect of genital herpes on various aspects of health-related quality of life.

Methods
Six databases were searched (MEDLINE, EMBASE, NHS Economic Evaluation Database, Health Technology Assessment, Database of Abstracts of Reviews of Effects, Web of Science Core Collection) for primary quality of life and economic evaluations of genital herpes from January 1, 2000 to January 7, 2021. Qualitative studies or those without primary data were excluded. Two authors independently extracted data from the publications. The study’s registration number with PROSPERO was CRD42021239410.

Findings
We identified 26 relevant publications: 19 presented primary quality of life data, and seven were economic evaluations. The primary studies presented a range of condition-specific tools for describing the quality of life in individuals with genital herpes, but only one study used a direct valuation that could be used to generate utility weights. All economic evaluations of HSV infection were from high-income country settings. Most (6 of 7) focused on neonatal HSV infection with utilities adopted from studies prior to 2000.

Interpretation
The extant literature on genital herpes-related quality of life is limited and requires updating. We recommend future studies be conducted in geographic- and population- diverse settings, and use preference-based condition-specific or generic-instruments to better inform economic modelling.