bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of structural injury patterns in peripapillary retinal nerve fibre layer and retinal ganglion cell layer in ethambutol-induced optic neuropathy
Authors: Sheng Wen-Yan , Su Ling-Ya , Ge Wei , Wu Shuang-Qing , Zhu Li-Wei 
Published: March 2021

Abstract
Background
We investigated structural injury patterns in the peripapillary retinal nerve fibre layer (p-RNFL) and ganglion cell inner plexiform layer (GCIPL) caused by ethambutol treatment.

Methods
Sixty-four patients undergoing ethambutol treatment at Zhejiang Chinese Medicine and Western Medicine Integrated Hospital were recruited. Fourteen (14) exhibited visual dysfunction (abnormal group), and the remaining 50 had no visual dysfunction (subclinical group). The thickness of the p-RNFL, total macular retina layer and GCIPL were measured using Cirrus-HD Optical coherence tomography (Cirrus-HD OCT, Cirrus high-definition optical coherence tomography), and compared with 60 healthy, age-matched controls.

Results
The p-RNFL thickness was similar in both subclinical and control groups. When compared with the control group, p-RNFL thickness in the abnormal group was significantly increased in the inferior and superior quadrants (GEE, P = 0.040, P = 0.010 respectively). In contrast with the subclinical group, p-RNFL thickness in the inferior quadrant was increased in the abnormal group (GEE, P = 0.047). The GCIPL thickness in the inferonasal and inferior sectors was significantly deceased in the subclinical group when compared with controls (GEE, P = 0.028, P = 0.047, respectively). The average and minimum value of GCIPL thickness, and thickness in the superonasal, inferior, inferotemporal, superotemporal and superior sectors were significantly decreased in the abnormal group when compared with controls (GEE, P = 0.016, P = 0.001, P = 0.028, P = 0.010, P = 0.012, P = 0.015, P = 0.010, respectively). The cube average macular thickness (CAMT) in the abnormal group was significantly thinner than controls (GEE, P = 0.027).

Conclusions
GCIPL measurements using Cirrus-HD OCT detected retinal ganglion cell layer loss following ethambutol treatment, before visual dysfunction occurred.
Common mental disorders and HIV status in the context of DREAMS among adolescent girls and young women in rural KwaZulu-Natal, South Africa
Authors: Mthiyane Nondumiso , Harling Guy , Chimbindi Natsayi , Baisley Kathy , Seeley Janet , Dreyer Jaco , Zuma Thembelihle , Birdthistle Isolde , Floyd Sian , McGrath Nuala , Tanser Frank , Shahmanesh Maryam , Sherr Lorraine 
Published: March 2021

Abstract
Background
HIV affects many adolescent girls and young women (AGYW) in South Africa. Given the bi-directional HIV and mental health relationship, mental health services may help prevent and treat HIV in this population. We therefore examined the association between common mental disorders (CMD) and HIV-related behaviours and service utilisation, in the context of implementation of the combination DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored and Safe) HIV prevention programme in rural uMkhanyakude district, KwaZulu-Natal. DREAMS involved delivering a package of multiple interventions in a single area to address multiple sources of HIV risk for AGYW.

Methods
We analysed baseline data from an age-stratified, representative cohort of 13–22 year-old AGYW. We measured DREAMS uptake as a count of the number of individual-level or community-based interventions each participant received in the last 12 months. CMD was measured using the validated Shona Symptom Questionnaire, with a cut off score ≥ 9 indicating probable CMD. HIV status was ascertained through home-based serotesting. We used logistic regression to estimate the association between CMD and HIV status adjusting for socio-demographics and behaviours.

Results
Probable CMD prevalence among the 2184 respondents was 22.2%, increasing steadily from 10.1% among 13 year-old girls to 33.1% among 22 year-old women. AGYW were more likely to report probable CMD if they tested positive for HIV (odds ratio vs. test negative: 1.88, 95% confidence interval: 1.40–2.53). After adjusting for socio-demographics and behaviours, there was evidence that probable CMD was more prevalent among respondents who reported using multiple healthcare-related DREAMS interventions.

Conclusion
We found high prevalence of probable CMD among AGYW in rural South Africa, but it was only associated with HIV serostatus when not controlling for HIV acquisition risk factors. Our findings highlight that improving mental health service access for AGYW at high risk for HIV acquisition might protect them. Interventions already reaching AGYW with CMD, such as DREAMS, can be used to deliver mental health services to reduce both CMD and HIV risks. There is a need to integrate mental health education into existing HIV prevention programmes in school and communities.
Longitudinal study of MRI and functional outcome measures in facioscapulohumeral muscular dystrophy
Authors: Wang Leo H. , Shaw Dennis W. W. , Faino Anna , Budech Christopher B. , Lewis Leann M. , Statland Jeffrey , Eichinger Katy , Tapscott Stephen J. , Tawil Rabi N. , Friedman Seth D. 
Published: March 2021

Abstract
Background
Facioscapulohumeral muscular dystrophy (FSHD) is a patchy and slowly progressive disease of skeletal muscle. For MRI to be a useful biomarker in an FSHD clinical trial, it should reliably detect changes over relatively short time-intervals (~ 1 year). We hypothesized that fatty change over the study course would be most likely in muscles already demonstrating disease progression, and that the degree of MRI burden would be correlated with function.

Methods
We studied 36 patients with FSHD and lower-extremity weakness at baseline. Thirty-two patients returned in our 12-month longitudinal observational study. We analyzed DIXON MRI images of 16 lower-extremity muscles in each patient and compared them to quantitative strength measurement and ambulatory functional outcome measures.

Results
There was a small shift to higher fat fractions in the summed muscle data for each patient, however individual muscles demonstrated much larger magnitudes of change. The greatest increase in fat fraction was observed in muscles having an intermediate fat replacement at baseline, with minimally (baseline fat fraction < 0.10) or severely (> 0.70) affected muscles less likely to progress. Functional outcome measures did not demonstrate marked change over the interval; however, overall MRI disease burden was correlated with functional outcome measures. Direct comparison of the tibialis anterior (TA) fat fraction and quantitative strength measurement showed a sigmoidal relationship, with steepest drop being when the muscle gets more than ~ 20% fatty replaced.

Conclusions
Assessing MRI changes in 16 lower-extremity muscles across 1 year demonstrated that those muscles having an intermediate baseline fat fraction were more likely to progress. Ambulatory functional outcome measures are generally related to overall muscle MRI burden but remain unchanged in the short term. Quantitative strength measurement of the TA showed a steep loss of strength when more fatty infiltration is present suggesting that MRI may be preferable for following incremental change or modulation with drug therapy.
Effects of mouth breathing on facial skeletal development in children: a systematic review and meta-analysis
Authors: Zhao Ziyi , Zheng Leilei , Huang Xiaoya , Li Caiyu , Liu Jing , Hu Yun 
Published: March 2021

Abstract
Background
Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children.

Methods
An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Inclusion criteria were children under 18 years of age with maxillofacial deformities due to mouth breathing. The risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. The included indicators were SNA, SNB, ANB, SN-OP, SN-PP, PP-MP, SNGoGn, MP-H, 1-NA, 1. NA, 1. NB, 1-NB, Overjet, Overbite, SPAS, PAS, and C3-H. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion.

Results
Following full-text evaluations for eligibility, 10 studies were included in the final quantitative synthesis. In Sagittal direction, SNA (MD: − 1.63, P < 0.0001), SNB (MD: − 1.96, P < 0.0001) in mouth-breathing children was lower than that in nasal-breathing children. ANB (MD: 0.90, P < 0.0001), 1. NA (MD: 1.96, P = 0.009), 1-NA (MD: 0.66, P = 0.004), and 1-NB (MD: 1.03, P < 0.0001) showed higher values in children with mouth breathing. In vertical direction, SN-PP (MD: 0.68, P = 0.0050), SN-OP (MD: 3.05, P < 0.0001), PP-MP (MD: 4.92, P < 0.0001) and SNGoGn (MD: 4.10, P < 0.0001) were higher in mouth-breathing individuals. In airway, SPAS (MD: − 3.48, P = 0.0009), PAS (MD: − 2.11, P < 0.0001), and C3-H (MD: − 1.34, P < 0.0001) were lower in mouth breathing group.

Conclusions
The results showed that the mandible and maxilla rotated backward and downward, and the occlusal plane was steep. In addition, mouth breathing presented a tendency of labial inclination of the upper anterior teeth. Airway stenosis was common in mouth-breathing children.
Trial registration crd-register@york.ac.uk, registration number CRD42019129198.
Commercial sex work among university students: a case study of four public universities in Ghana
Authors: Gbagbo Fred Yao , Gbagbo Josephine Akosua 
Published: March 2021

Abstract
Background
Despite its criminalization in Ghana, commercial sex work dates back to ancient societies and occurs in various forms within communities. The authors examined commercial sex work in selected public Universities in Ghana to inform policy and program decisions for safer sex at the universities in Ghana.

Methods
The study was an exploratory-mixed-method design. Respondents were identified using purposive and snowballing techniques while semi-structured questionnaires and in-depth interviews were used for data collection between 2017and 2019. Quantitative data were analyzed using Statistical Package for Social Sciences version 23 and qualitative data analyzed thematically.

Results
Findings show that there is a proliferation of commercial sex work on university campuses in Ghana for financial, material, and emotional gains. Student sex workers have devised various strategies to combine academic work and sex work. Prospective customers are solicited by hanging out in drinking bars and nightclubs in and around university campuses at night and/or leaving contact details with pimps to be contacted for services. Brothels are also springing up in and around the university campuses in the form of movie houses and student sex workers convert their hostel rooms into brothels. Price negotiation is based on the environment, duration, the sex workers' perceived safety of the sexual act, customer's preferences for styles, and positions adopted for sex.

Conclusion
There is a need for further studies in this area and a multi-sectoral approach for appropriate policy and program interventions to regulate the practice on campus.
Assessment of the Adjusted Clinical Groups system in Dutch primary care using electronic health records: a retrospective cross-sectional study
Authors: Girwar Shelley-Ann M. , Fiocco Marta , Sutch Stephen P. , Numans Mattijs E. , Bruijnzeels Marc A. 
Published: March 2021

Abstract
Background
Within the Dutch health care system the focus is shifting from a disease oriented approach to a more population based approach. Since every inhabitant in the Netherlands is registered with one general practice, this offers a unique possibility to perform Population Health Management analyses based on general practitioners’ (GP) registries. The Johns Hopkins Adjusted Clinical Groups (ACG) System is an internationally used method for predictive population analyses. The model categorizes individuals based on their complete health profile, taking into account age, gender, diagnoses and medication. However, the ACG system was developed with non-Dutch data. Consequently, for wider implementation in Dutch general practice, the system needs to be validated in the Dutch healthcare setting. In this paper we show the results of the first use of the ACG system on Dutch GP data. The aim of this study is to explore how well the ACG system can distinguish between different levels of GP healthcare utilization.

Methods
To reach our aim, two variables of the ACG System, the Aggregated Diagnosis Groups (ADG) and the mutually exclusive ACG categories were explored. The population for this pilot analysis consisted of 23,618 persons listed with five participating general practices within one region in the Netherlands. ACG analyses were performed based on historical Electronic Health Records data from 2014 consisting of primary care diagnoses and pharmaceutical data. Logistic regression models were estimated and AUC’s were calculated to explore the diagnostic value of the models including ACGs and ADGs separately with GP healthcare utilization as the dependent variable. The dependent variable was categorized using four different cut-off points: zero, one, two and three visits per year.

Results
The ACG and ADG models performed as well as models using International Classification of Primary Care chapters, regarding the association with GP utilization. AUC values were between 0.79 and 0.85. These models performed better than the base model (age and gender only) which showed AUC values between 0.64 and 0.71.

Conclusion
The results of this study show that the ACG system is a useful tool to stratify Dutch primary care populations with GP healthcare utilization as the outcome variable.
Expression of a recombinant FLT3 ligand and its emtansine conjugate as a therapeutic candidate against acute myeloid leukemia cells with FLT3 expression
Authors: Zhang Dengyang , Guo Yao , Zhao Yuming , Yu Liuting , Chang Zhiguang , Pei Hanzhong , Huang Junbin , Chen Chun , Xue Hongman , Xu Xiaojun , Pan Yihang , Li Ningning , Zhu Chengming , Zhao Zhizhuang Joe , Yu Jian , Chen Yun 
Published: March 2021

AbstractBackgroundMost patients with acute myeloid leukemia (AML) remain uncurable and require novel therapeutic methods. Gain-of-function FMS-like tyrosine kinase 3 (FLT3) mutations are present in 30–40% of AML patients and serve as an attractive therapeutic target. In addition, FLT3 is aberrantly expressed on blasts in > 90% of patients with AML, making the FLT3 ligand-based drug conjugate a promising therapeutic strategy for the treatment of patients with AML. Here,E. coliwas used as a host to express recombinant human FLT3 ligand (rhFL), which was used as a specific vehicle to deliver cytotoxic drugs to FLT3 + AML cells.MethodsRecombinant hFL was expressed and purified from induced recombinant BL21 (DE3)E. coli. Purified rhFL and emtansine (DM1) were conjugated by anN-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) linker. We evaluated the potency of the conjugation product FL-DM1 against FLT3-expressing AML cells by examining viability, apoptosis and the cell cycle. The activation of proteins related to the activation of FLT3 signaling and apoptosis pathways was detected by immunoblotting. The selectivity of FL-DM1 was assessed in our unique HCD-57 cell line, which was transformed with the FLT3 internal tandem duplication mutant (FLT3-ITD).ResultsSoluble rhFL was successfully expressed in the periplasm of recombinantE. coli. The purified rhFL was bioactive in stimulating FLT3 signaling in AML cells, and the drug conjugate FL-DM1 showed activity in cell signaling and internalization. FL-DM1 was effective in inhibiting the survival of FLT3-expressing THP-1 and MV-4-11 AML cells, with half maximal inhibitory concentration (IC50) of 12.9 nM and 1.1 nM. Additionally, FL-DM1 induced caspase-3-dependent apoptosis and arrested the cell cycle at the G2/M phase. Moreover, FL-DM1 selectively targeted HCD-57 cells transformed by FLT3-ITD but not parental HCD-57 cells without FLT3 expression. FL-DM1 can also induce obvious apoptosis in primary FLT3-positive AML cells ex vivo.ConclusionsOur data demonstrated that soluble rhFL can be produced in a bioactive form in the periplasm of recombinantE. coli. FL can be used as a specific vehicle to deliver DM1 into FLT3-expressing AML cells. FL-DM1 exhibited cytotoxicity in FLT3-expressing AML cell lines and primary AML cells. FL-DM1 may have potential clinical applications in treating patients with FLT3-positive AML.
Absence of EpCAM in cervical cancer cells is involved in slug induced epithelial-mesenchymal transition
Authors: Liu Xian , Feng Qian , Zhang Yanru , Zheng PengSheng , Cui Nan 
Published: March 2021

Abstract
Background
Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study.

Methods
RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation.

Results
Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis.

Conclusions
These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin.
Trends in access to anti‐malarial treatment in the formal private sector in Uganda: an assessment of availability and affordability of first‐line anti‐malarials and diagnostics between 2007 and 2018
Authors: Kibira Denis , Ssebagereka Anthony , van den Ham Hendrika A. , Opigo Jimmy , Katamba Henry , Seru Morries , Reed Tim , Leufkens Hubert G. , Mantel-Teeuwisse Aukje K. 
Published: March 2021

Abstract
Background
Malaria is the single largest cause of illness in Uganda. Since the year 2008, the Global Fund has rolled out several funding streams for malaria control in Uganda. Among these are mechanisms aimed at increasing the availability and affordability of artemisinin-based combination therapy (ACT). This paper examines the availability and affordability of first-line malaria treatment and diagnostics in the private sector, which is the preferred first point of contact for 61% of households in Uganda between 2007 and 2018.

Methods
Cross-sectional surveys were conducted between 2007 and 2018, based on a standardized World Health Organization/Health Action International (WHO/HAI) methodology adapted to assess availability, patient prices, and affordability of ACT medicines in private retail outlets. A minimum of 30 outlets were surveyed per year as prescribed by the standardized methodology co-developed by the WHO and Health Action International. Availability, patient prices, and affordability of malaria rapid diagnostic tests (RDTs) was also tracked from 2012 following the rollout of the test and treat policy in 2010. The median patient prices for the artemisinin-based combinations and RDTs was calculated in US dollars (USD). Affordability was assessed by computing the number of days’ wages the lowest-paid government worker (LPGW) had to pay to purchase a treatment course for acute malaria.

Results
Availability of artemether/lumefantrine (A/L), the first-line ACT medicine, increased from 85 to100% in the private sector facilities during the study period. However, there was low availability of diagnostic tests in private sector facilities ranging between 13% (2012) and 37% (2018). There was a large reduction in patient prices for an adult treatment course of A/L from USD 8.8 in 2007 to USD 1.1 in 2018, while the price of diagnostics remained mostly stagnant at USD 0.5. The affordability of ACT medicines and RDTs was below one day’s wages for LPGW.

Conclusions
Availability of ACT medicines in the private sector medicines retail outlets increased to 100% while the availability of diagnostics remained low. Although malaria treatment was affordable, the price of diagnostics remained stagnant and increased the cumulative cost of malaria management. Malaria stakeholders should consolidate the gains made and consider the inclusion of diagnostic kits in the subsidy programme.
Measuring health inequalities: a systematic review of widely used indicators and topics
Authors: Albert-Ballestar Sergi , García-Altés Anna 
Published: March 2021

Abstract
Background
According to many conceptual frameworks, the first step in the monitoring cycle of health inequalities is the selection of relevant topics and indicators. However, some difficulties may arise during this selection process due to a high variety of contextual factors that may influence this step. In order to help accomplish this task successfully, a comprehensive review of the most common topics and indicators for measuring and monitoring health inequalities in countries/regions with similar socioeconomic and political status as Catalonia was performed.

Methods
We describe the processes and criteria used for selecting health indicators from reports, studies, and databases focusing on health inequalities. We also describe how they were grouped into well-known health topics. The topics were filtered and ranked by the number of indicators they accounted for.

Results
We found 691 indicators used in the study of health inequalities. The indicators were grouped into 120 topics, 34 of which were selected for having five indicators or more. Most commonly found topics in the list include “Life expectancy”, “Infant mortality”, “Obesity and overweight (BMI)”, “Mortality rate”, “Regular smokers/tobacco consumption”, “Self-perceived health”, “Unemployment”, “Mental well-being”, “Cardiovascular disease/hypertension”, “Socioeconomic status (SES)/material deprivation”.

Conclusions
A wide variety of indicators and topics for the study of health inequalities exist across different countries and organisations, although there are some clear commonalities. Reviewing the use of health indicators is a key step to know the current state of the study of health inequalities and may show how to lead the way in understanding how to overcome them.