bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functionality of technical working groups in enabling evidence-informed decision-making within Malawi's Ministry of Health: a cross-sectional qualitative study
Authors: Sakala Melody , Chawani Marlen Stacey , Kazanga-Chiumia Isabel , Hara Hleziwe , Abdullahi Leila , Kambalame Dzinkambani , Banda Josephine , Mitambo Collins , Terlouw Anja , Oronje Rose 
Published: June 2023

Abstract
Background
The roles and functionality of technical working groups (TWGs) in the health sectors vary across countries, still they aim to support government and ministries in formulating evidence-informed recommendations for policies and facilitate dialogue and alignment of activities among stakeholders within the health sector. Thus, TWGs have a role in enhancing the functionality and effectiveness of the health system structure. However, in Malawi, the functionality of TWGs and how they utilize research evidence to contribute to decision-making is not monitored. This study sought to understand the TWGs' performance and functionality in enabling evidence-informed decision-making (EIDM) in Malawi's health sector.

Methods
A cross-sectional descriptive qualitative study. Data were collected through interviews, documents review and observation of three TWG meetings. Qualitative data were analysed using a thematic approach. The WHO-UNICEF Joint Reporting Form (JRF) was used to guide the assessment of TWG functionality.

Results
TWG functionality varied in the Ministry of Health (MoH) in Malawi. The reasons for those perceived to be functioning well included meeting frequently, diverse representation of members, and that their recommendations to MoH were usually considered when decisions were made. For the TWGs that were perceived as not functioning well, the main reasons included lack of funding, periodic meetings and discussions that needed to provide clear decisions on the actions to be taken. In addition, evidence was recognized as important in decision-making, and research was valued by decision-makers within the MoH. However, some of the TWGs lacked reliable mechanisms for generating, accessing and synthesizing research. They also needed more capacity to review and use the research to inform their decisions.

Conclusions
TWGs are highly valued and play a critical role in strengthening EIDM within the MoH. Our paper highlights the complexity and barriers of TWG functionality in supporting pathways for health policy-making in Malawi. These results have implications for EIDM in the health sector. This suggests that the MoH should actively develop reliable interventions and evidence tools, strengthen capacity-building and increase funding for EIDM.
Stakeholder perceptions and experiences from the implementation of the Gratuité user fee exemption policy in Burkina Faso: a qualitative study
Authors: Banke-Thomas Aduragbemi , Offosse Marie-Jeanne , Yameogo Pierre , Manli Astrid Raissa , Goumbri Aude , Avoka Cephas , Boxshall Matt , Eboreime Ejemai 
Published: June 2023

Abstract
Background
In 2016, the Gratuité policy was initiated by the Government of Burkina Faso to remove user fees for maternal, newborn, and child Health (MNCH) services. Since its inception, there has not been any systematic capture of experiences of stakeholders as it relates to the policy. Our objective was to understand the perceptions and experiences of stakeholders regarding the implementation of the Gratuité policy.

Methods
We used key informant interviews (KIIs) and focus group discussions (FGDs) to engage national and sub-national stakeholders in the Centre and Hauts-Bassin regions. Participants included policymakers, civil servants, researchers, non-governmental organizations in charge of monitoring the policy, skilled health personnel, health facility managers, and women who used MNCH services before and after the policy implementation. Topic guides aided sessions, which were audio recorded and transcribed verbatim. A thematic analysis was used for data synthesis.

Results
There were five key themes emerging. First, majority of stakeholders have a positive perception of the Gratuité policy. Its implementation approach is deemed to have strengths including government leadership, multi-stakeholder involvement, robust internal capacity, and external monitoring. However, collateral shortage of financial and human resources, misuse of services, delays in reimbursement, political instability and health system shocks were highlighted as concerns that compromise the government's objective of achieving universal health coverage (UHC). However, many beneficiaries were satisfied at the point of use of MNHC services, though Gratuité did not always mean free to the service users. Broadly, there was consensus that the Gratuité policy has contributed to improvements in health-seeking behavior, access, and utilization of services, especially for children. However, the reported higher utilization is leading to some perceived increased workload and altered health worker attitude.

Conclusions
There is a general perception that the Gratuité policy is achieving what it set out to do, which is to increase access to care by removing financial barriers. While stakeholders recognized the intention and value of the Gratuité policy, and many beneficiaries were satisfied at the point of use, inefficiencies in its implementation undermines progress. As the country moves towards the goal of realizing UHC, reliable investment in the Gratuité policy is needed.
Knowledge level and access barriers related to sexual and reproductive health information among youth with disabilities in China: a cross-sectional study
Authors: Qi Wenjuan , Li Hongyan , Lian Qiguo , Zuo Xiayun , Yu Chunyan , Lou Chaohua , Tu Xiaowen 
Published: June 2023

Abstract
Background
Youth with disabilities have the same right to sexual and reproductive health (SRH) as their peers without disabilities. However, their needs and rights are often ignored. Little is known about the knowledge, needs and access barriers related to SRH information among youth with different types of disabilities in China.

Methods
A cross-sectional survey was carried out among 473 unmarried youth aged 15–24 with visual, hearing, physical disabilities in both urban and rural areas in China.

Results
Out of a maximum possible score of 100, respondent’s median score ranged from 30 to 50 for knowledge related to sexual physiology, STIs/HIV/AIDS and contraception. For these three categories of knowledge, respondents with hearing and physical disabilities or from rural areas scored lower than their counterparts with visual disabilities or from urban areas. The multivariate analyses showed that the residential area and education level were strong correlates of knowledge among respondents with visual and hearing disabilities. Other significant correlates were age for respondents with visual impairment and physical impairment, and single child status in the family and father’s education level for respondents with hearing impairment. Sources of and barriers and preferences in accessing SRH information differed by type of disabilities, residential areas and gender. In general, school teachers were the primary and most preferred sources of SRH knowledge, followed by the Internet, peers/friends and parents. Unaware of where to get accurate information and feeling embarrassed to seek information were the two most frequently mentioned barriers in accessing SRH information.

Conclusion
Respondents had poor knowledge of SRH and limited access to SRH information, especially those from rural areas. Efforts should be made to promote school and family-based sexuality education tailored for youth with different types of disabilities.
Managers perception of hospital employees’ effort-reward imbalance
Authors: Heming Meike , Siegrist Johannes , Erschens Rebecca , Genrich Melanie , Hander Nicole R. , Junne Florian , Küllenberg Janna K. , Müller Andreas , Worringer Britta , Angerer Peter 
Published: June 2023

Abstract
Objective
Hospitals are frequently associated with poor working conditions that can lead to work stress and increase the risk for reduced employee well-being. Managers can shape and improve working conditions and thereby, the health of their teams. Thus, as a prerequisite, managers need to be aware of their employees’ stress levels. This study had two objectives: At first, it aimed to test the criterion validity of the Effort-Reward Imbalance (ERI) questionnaire measuring psychosocial workload in hospital employees. Secondly, mean scales of the ERI questionnaire filled in by employees were compared with mean scales of an adapted ERI questionnaire, in which managers assessed working conditions of their employees.

Methods
Managers (n = 141) from three hospitals located in Germany assessed working conditions of their employees with an adapted external, other-oriented questionnaire. Employees (n = 197) of the mentioned hospitals completed the short version of the ERI questionnaire to assess their working conditions. Confirmatory factor analyses (CFA) were applied to test factorial validity, using the ERI scales for the two study groups. Criterion validity was assessed with multiple linear regression analysis of associations between ERI scales and well-being among employees.

Results
The questionnaires demonstrated acceptable psychometric properties in terms of internal consistency of scales, although some indices of model fit resulting from CFA were of borderline significance. Concerning the first objective, effort, reward, and the ratio of effort-reward imbalance were significantly associated with well-being of employees. With regard to the second objective, first tentative findings showed that managers’ ratings of their employees’ effort at work was quite accurate, whereas their reward was overestimated.

Conclusions
With its documented criterion validity the ERI questionnaire can be used as a screening tool of workload among hospital employees. Moreover, in the context of work-related health promotion, managers’ perceptions of their employees’ workload deserve increased attention as first findings point to some discrepancies between their perceptions and those provided by employees.
Integration of transcriptomics and proteomics to elucidate inhibitory effect and mechanism of rosmarinic acid from Perilla frutescens (L.) Britt. in treating Trichophyton mentagrophytes
Authors: Xu Yang-ding , Guo Yu-jie , Mao He-rong , Xiong Zhi-xiang , Luo Meng-yu , Luo Rui-qi , Lu Shan , Huang Lu , Hong Yi 
Published: June 2023

Abstract
Background
Dermatophyte caused by Trichophyton mentagrophytes is a global disease with a growing prevalence that is difficult to cure. Perilla frutescens (L.) Britt. is an edible and medicinal plant. Ancient books of Traditional Chinese Medicine and modern pharmacological studies have shown that it has potential anti-fungi activity. This is the first study to explore the inhibitory effects of compounds from P. frutescens on Trichophyton mentagrophytes and its mechanism of action coupled with the antifungal activity in vitro from network pharmacology, transcriptomics and proteomics.

Methods
Five most potential inhibitory compounds against fungi in P. frutescens was screened with network pharmacology. The antifungal activity of the candidates was detected by a broth microdilution method. Through in vitro antifungal assays screening the compound with efficacy, transcriptomics and proteomics were performed to investigate the pharmacological mechanisms of the effective compound against Trichophyton mentagrophytes. Furthermore, the real-time polymerase chain reaction (PCR) was applied to verify the expression of genes.

Results
The top five potential antifungal compounds in P. frutescens screened by network pharmacology are: progesterone, luteolin, apigenin, ursolic acid and rosmarinic acid. In vitro antifungal assays showed that rosmarinic acid had a favorable inhibitory effect on fungi. The transcriptomic findings exhibited that the differentially expressed genes of fungus after rosmarinic acid intervention were mainly enriched in the carbon metabolism pathway, while the proteomic findings suggested that rosmarinic acid could inhibit the average growth of Trichophyton mentagrophytes by interfering with the expression of enolase in the glycolysis pathway. Comparison of real-time PCR and transcriptomics results showed that the trends of gene expression in glycolytic, carbon metabolism and glutathione metabolic pathways were identical. The binding modes and interactions between rosmarinic acid and enolase were preliminary explored by molecular docking analysis.

Conclusion
The key findings of the present study manifested that rosmarinic acid, a medicinal compound extracted from P. frutescens, had pharmacological activity in inhibiting the growth of Trichophyton mentagrophytes by affecting its enolase expression to reduce metabolism. Rosmarinic acid is expected to be an efficacious product for prevention and treatment of dermatophytes.
Achondroplasia natural history study (CLARITY): 60-year experience in orthopedic surgery from four skeletal dysplasia centers
Authors: Nahm Nickolas J. , Mackenzie W. G. Stuart , Mackenzie William G. , Gough Ethan , Hashmi S. Shahrukh , Hecht Jacqueline T. , Legare Janet M. , Little Mary Ellen , Modaff Peggy , Pauli Richard M. , Rodriguez-Buritica David F. , Serna Maria Elena , Smid Cory J. , Hoover-Fong Julie , Bober Michael B. 
Published: June 2023

AbstractBackgroundThe purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.ResultsInformation from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. 12.7% (n = 175) of patients underwent spine surgery at a mean age at first surgery of 22.4 ± 15.3 years old. The median age was 16.7 years old (0.1–67.4). 21.2% (n = 291) of patients underwent lower extremity surgery at a mean age at first surgery of 9.9 ± 8.3 years old with a median age of 8.2 years (0.2–57.8). The most common spinal procedure was decompression (152 patients underwent 271 laminectomy procedures), while the most common lower extremity procedure was osteotomy (200 patients underwent 434 procedures). Fifty-eight (4.2%) patients had both a spine and lower extremity surgery. Specific risk factors increasing the likelihood of orthopedic surgery included: patients with hydrocephalus requiring shunt placement having higher odds of undergoing spine surgery (OR 1.97, 95% CI 1.14–3.26); patients having a cervicomedullary decompression also had higher odds of undergoing spine surgery (OR 1.85, 95% CI 1.30–2.63); and having lower extremity surgery increased the odds of spine surgery (OR 2.05, 95% CI 1.45–2.90).ConclusionsOrthopedic surgery was a common occurrence in achondroplasia with 29.7% of patients undergoing at least one orthopedic procedure. Spine surgery (12.7%) was less common and occurred at a later age than lower extremity surgery (21.2%). Cervicomedullary decompression and hydrocephalus with shunt placement were associated with an increased risk for spine surgery. The results from CLARITY, the largest natural history study of achondroplasia, should aid clinicians in counseling patients and families about orthopedic surgery.
Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer’s Disease drug candidate
Authors: Nemergut Michal , Marques Sérgio M. , Uhrik Lukas , Vanova Tereza , Nezvedova Marketa , Gadara Darshak Chandulal , Jha Durga , Tulis Jan , Novakova Veronika , Planas-Iglesias Joan , Kunka Antonin , Legrand Anthony , Hribkova Hana , Pospisilova Veronika , Sedmik Jiri , Raska Jan , Prokop Zbynek , Damborsky Jiri , Bohaciakova Dasa , Spacil Zdenek , Hernychova Lenka , Bednar David , Marek Martin 
Published: June 2023

AbstractBackgroundApolipoprotein E (ApoE) ε4 genotype is the most prevalent risk factor for late-onset Alzheimer’s Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by the C112R mutation, the molecular mechanism of its proteinopathy is unknown.MethodsHere, we reveal the molecular mechanism of ApoE4 aggregation using a combination of experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering and molecular dynamics simulations. Treatment of ApoE ε3/ε3 and ε4/ε4 cerebral organoids with tramiprosate was used to compare the effect of tramiprosate on ApoE4 aggregation at the cellular level.ResultsWe found that C112R substitution in ApoE4 induces long-distance (> 15 Å) conformational changes leading to the formation of a V-shaped dimeric unit that is geometrically different and more aggregation-prone than the ApoE3 structure. AD drug candidate tramiprosate and its metabolite 3-sulfopropanoic acid induce ApoE3-like conformational behavior in ApoE4 and reduce its aggregation propensity. Analysis of ApoE ε4/ε4 cerebral organoids treated with tramiprosate revealed its effect on cholesteryl esters, the storage products of excess cholesterol.ConclusionsOur results connect the ApoE4 structure with its aggregation propensity, providing a new druggable target for neurodegeneration and ageing.Graphic Abstract
Targeting CXCR4 abrogates resistance to trastuzumab by blocking cell cycle progression and synergizes with docetaxel in breast cancer treatment
Authors: Liu Shuying , Xie Shelly M. , Liu Wenbin , Gagea Mihai , Hanker Ariella B. , Nguyen Nguyen , Singareeka Raghavendra Akshara , Yang-Kolodji Gloria , Chu Fuliang , Neelapu Sattva S. , Marchese Adriano , Hanash Samir , Zimmermann Johann , Arteaga Carlos L. , Tripathy Debasish 
Published: June 2023

Abstract
Background
Although trastuzumab and other HER2-targeted therapies have significantly improved survival in patients with HER2 overexpressed or amplified (HER2+) breast cancer, a significant proportion of patients do not respond or eventually develop clinical resistance. Strategies to reverse trastuzumab resistance remain a high clinical priority. We were the first to report the role of CXCR4 in trastuzumab resistance. The present study aims to explore the therapeutic potential of targeting CXCR4 and better understand the associated mechanisms.

Methods
Immunofluorescent staining, confocal microscopy analysis, and immunoblotting were used to analyze CXCR4 expression. BrdU incorporation assays and flow cytometry were used to analyze dynamic CXCR4 expression. Three-dimensional co-culture (tumor cells/breast cancer-associated fibroblasts/human peripheral blood mononuclear cells) or antibody-dependent cellular cytotoxicity assay was used to mimic human tumor microenvironment, which is necessary for testing therapeutic effects of CXCR4 inhibitor or trastuzumab. The FDA-approved CXCR4 antagonist AMD3100, trastuzumab, and docetaxel chemotherapy were used to evaluate therapeutic efficacy in vitro and in vivo. Reverse phase protein array and immunoblotting were used to discern the associated molecular mechanisms.

Results
Using a panel of cell lines and patient breast cancer samples, we confirmed CXCR4 drives trastuzumab resistance in HER2+ breast cancer and further demonstrated the increased CXCR4 expression in trastuzumab-resistant cells is associated with cell cycle progression with a peak in the G2/M phases. Blocking CXCR4 with AMD3100 inhibits cell proliferation by downregulating mediators of G2-M transition, leading to G2/M arrest and abnormal mitosis. Using a panel of trastuzumab-resistant cell lines and an in vivo established trastuzumab-resistant xenograft mouse model, we demonstrated that targeting CXCR4 with AMD3100 suppresses tumor growth in vitro and in vivo, and synergizes with docetaxel.

Conclusions
Our findings support CXCR4 as a novel therapeutic target and a predictive biomarker for trastuzumab resistance in HER2+ breast cancer.
Providing office workers with height-adjustable workstation to reduce and interrupt workplace sitting time: protocol for the Stand Up for Healthy Aging (SUFHA) cluster randomized controlled trial
Authors: Júdice Pedro B. , Silva Hélio , Teno Sabrina C. , Monteiro Patrícia , Silva Marlene N. , Carraça Eliana V. , Santos Inês , Pereira Sara , Luz Filipe , Viegas Patrícia C. , Oliveira Jorge , Santos Isabel F. , Palmeira António L. 
Published: June 2023

Abstract
Background
Sedentary behavior (SB) has been linked to several negative health outcomes. Therefore, reducing SB or breaking up prolonged periods of SB improves functional fitness, food consumption, job satisfaction, and productivity. Reducing SB can be achieved by introducing a health-enhancing contextual modification promoted by a sit-stand desk in the workplace. The primary goal will be to test the effectiveness of this intervention in reducing and breaking up SB, while improving health outcomes in office-based workers during a 6-month intervention.

Methods
A two-arm (1:1), superiority parallel-group cluster RCT will be conducted to evaluate the effectiveness of this intervention in a sample of office-based workers from a university in Portugal. The intervention will consist of a psychoeducation session, motivational prompts, and contextual modification promoted by a sit-stand desk in the workplace for 6 months. The control group will work as usual in their workplace, with no contextual change or prompts during the 6-month intervention. Three assessment points will be conducted in both groups, pre-intervention (baseline), post-intervention, and a 3-month follow-up. The primary outcomes include sedentary and physical activity-related variables, which will be objectively assessed with 24 h monitoring using the ActivPAL for 7 days. The secondary outcomes include (a) biometric indices as body composition, body mass index, waist circumference, and postural inequalities; and (b) psychosocial variables such as overall and work-related fatigue, overall discomfort, life/work satisfaction, quality of life, and eating behavior. Both the primary and secondary outcomes will be assessed at each assessment point.

Discussion
This study will lean on the use of a sit-stand workstation for 6 months, prompted by an initial psychoeducational session and ongoing motivational prompts. We will aim to contribute to this topic by providing robust data on alternating sitting and standing postures in the workplace.

Trial registration
The trial was prospectively registered, and the details are at: https://doi.org/10.17605/OSF.IO/JHGPW; Registered 15 November 2022. OSF Preregistration.