bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical observation of menopause hormone therapy in postmenopausal women with euthyroid and mild subclinical hypothyroidism
Authors: Xu Wenxian , Huang Yizhou , Ma Linjuan , Chen Peiqiong , Li Saisai , Chu Ketan , Lan Yibing , Li Chunming , Song Yang , Ying Qian , Zhou Jianhong 
Published: January 2023

Abstract
Background
To evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT).

Methods
A retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25–75th percentile) age was 52 (49–54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6–18 month cycles, serum endocrine hormone and metabolic indices were reassessed.

Results
Compared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment.

Conclusion
MHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.
Mothers’ accounts of the impact of being in nature on postnatal wellbeing: a focus group study
Authors: Hall Katherine , Evans Jonathan , Roberts Rosa , Brown Richard , Barnes Christopher , Turner Katrina 
Published: January 2023

Abstract
Background
The postnatal period is a vulnerable time for mothers to experience stress and mental health difficulties. There is increasing evidence that spending time in nature is beneficial for wellbeing. Nature-based interventions have been developed to support mental health, but not specifically tailored for mothers during the postnatal period. Understanding mothers’ views and experiences of nature would help determine the suitability for and potential impact of such interventions on postnatal wellbeing.

Aims
To explore mothers’ views on the impact of spending time in nature on their postnatal mental wellbeing.

Methods
Focus groups were held with mothers of young children (under five), including mothers from migrant and refugee communities, mothers living with mental health difficulties, and disabled mothers. Data were analysed using reflexive thematic analysis.

Results
Four focus groups were held, with a total of 30 participants. Six themes were developed: (1) mothers’ experiences of what constitutes ‘nature’; (2) sensing nature improves wellbeing; (3) natural spaces facilitate human connection; (4) nature provides escape and relief from daily indoor stressors; (5) nature allows new perspectives; and (6) mothers face a variety of environmental, practical, psychological, physical, socioeconomic, and cultural barriers to spending time in nature during the postnatal period.

Conclusions
Mothers report significant benefits to their postnatal wellbeing when spending time in nature. Further research is warranted to understand whether nature-based interventions have the potential to support postnatal wellbeing, socially, mentally, and physically.
Synergistic antimalarial treatment of Plasmodium berghei infection in mice with dihydroartemisinin and Gymnema inodorum leaf extract
Authors: Ounjaijean Sakaewan , Somsak Voravuth 
Published: January 2023

Abstract
Background
Chemotherapy is crucial in the fight against malaria. The rise of resistance to most antimalarial medicines has been a serious hurdle to effective treatment. Artemisinin-based combination therapies (ACTs) are currently the most effective antimalarial medication. Malaria parasites are growing more resistant to ACTs, particularly in Southeast Asia. As a result, effective alternative antimalarials are in high demand. The leaf extract of Gymnema inodorum (GIE) has previously shown promise as an effective antimalarial. Therefore, this study evaluated the antimalarial potential of combination dihydroartemisinin (DHA) and GIE therapy against Plasmodium berghei in a mouse model.

Methods
The medications were evaluated using the standard 4-day test for determining the 50% effective dosage (ED50) of DHA and GIE on P. berghei ANKA (PbANKA). DHA and GIE were combined using a fixed-ratio approach, with DHA/GIE ED50s of 100/0, 80/20, 60/40, 40/60, 20/80, and 0/100, respectively.

Results
The ED50 against PbANKA was determined to be 2 mg/kg of DHA and 100 mg/kg of GIE. The 60/40 (DHA/GIE) ratio demonstrated significantly higher antimalarial activity than the other ratios (p < 0.001) against PbANKA, with 88.95% inhibition, suggesting synergistic efficacy (combination index (CI) = 0.68695). Furthermore, this ratio protected PbANKA-infected mice against loss of body weight and packed cell volume decline, leading to a longer survival time over 30 days.

Conclusion
Our results suggest that GIE could be an effective adjuvant to DHA that can enhance the antimalarial effects in the treatment of PbANKA-infected mice.
Clinical reasoning pattern used in oral health problem solving – A case study in Indonesian undergraduate dental students
Authors: Chrismawaty B. E. , Emilia O. , Rahayu G. R. , Ana I. D. 
Published: January 2023

Abstract
Background
Health professionals are known to use various combinations of knowledge and skills, such as critical thinking, clinical reasoning, clinical judgment, problem-solving, and decision-making, in conducting clinical practice. Clinical reasoning development is influenced by knowledge and experience, the more knowledge and experience, the more sophisticated clinical reasoning will be. However, clinical reasoning research in dentistry shows varying results .

Aims
This study aims to observe the clinical reasoning pattern of undergraduate dental students when solving oral health problems, and their accordance with their knowledge acquisition.

Material and methods
This qualitative study employed the think-aloud method and the result was assessed through verbal protocol analyses. Five respondents from final year dental undergraduate students were agreed to participate. A unique hypothetical clinical scenario was used as a trigger. The audio data were transcribed, interpreted, and categorized as a clinical reasoning pattern; and the concept maps created were assessed by a Structure of Learning Outcomes (SOLO) taxonomy as knowledge acquisition.

Results
Observations on clinical reasoning patterns and the level of knowledge acquisition in five undergraduate dental students showed varying results. They applied clinical reasoning patterns according to their knowledge acquisition during didactical phase. Learners with inadequate knowledge relied on guessing, meanwhile learners with adequate knowledge applied more sophisticated reasoning pattern when solving problems.

Conclusions
Various problem-solving strategies were encountered in this study, which corresponded to the level of knowledge acquisition. Dental institutions must set minimum standards regarding the acquisition of conceptual knowledge accompanied by improvement of clinical reasoning skills, as well as refinement of knowledge and procedural skills.
Students’ perception of asynchronous versus synchronous distance learning during COVID-19 pandemic in a medical college, southwestern region of Saudi Arabia
Authors: Alzahrani Hassan A. , Shati Ayed A. , Bawahab Mohammed A. , Alamri Abdulaziz A. , Hassan Bahaeldin , Patel Ayyub A. , Ahmad Mohammad Tauheed , El Maksoud Walid Abd , Alsaleem Mohammed A. 
Published: January 2023

Abstract
Background
COVID-19 preventive measures required a drastic shift to online teaching-learning in most of countries. Institutions used different combinations of live online lectures (synchronous) requiring students to attend the class in real-time, as well as recorded lectures uploaded by the instructors to be accessed by students as per their own convenience (asynchronous). We undertook this study to assess and compare the perceptions of students regarding their learning experiences in the synchronous versus asynchronous mode of instruction using their teaching-learning during the compulsory online mode of instruction at the peak of the COVID-19 pandemic.

Methodology
This cross-sectional questionnaire-based study received responses from 122 final-year medical students studying at the College of Medicine, King Khalid University, Abha, Saudi Arabia. An online 5-point Likert scale-based questionnaire was used to collect data regarding experience and perception towards synchronous and asynchronous learning. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. A P-value less than 0.05 was considered significant.

Result
All the students found both synchronous and asynchronous learning to be equally satisfying, enjoyable and comfortable. No statistically significant difference was found when both the methods were analyzed for enhancement of knowledge. The students opined that asynchronous learning helped them manage their time better whereas synchronous learning encouraged more interaction during the live lectures.

Conclusion
Overall, the students' perceptions regarding both synchronous and asynchronous online learning were positive. As both methods have their advantages/limitations, a mix of both synchronous and asynchronous methods may be adopted depending upon the content of the topic and the desired learning outcomes.
Opportunities and challenges of virtual reality-based interventions for patients with breast cancer: a systematic review
Authors: Yazdipour Alireza Banaye , Saeedi Soheila , Bostan Hassan , Masoorian Hoorie , Sajjadi Hasan , Ghazisaeedi Marjan 
Published: January 2023

Abstract
Background
Breast cancer is one of the most common cancers diagnosed worldwide and the second leading cause of death among women. Virtual reality (VR) has many opportunities and challenges for breast cancer patients' rehabilitation and symptom management. The purpose of this systematic review is to look into the benefits and drawbacks of VR interventions for breast cancer patients.

Methods
A systematic search was conducted on PubMed, Web of Science, Scopus, IEEE, and the Cochrane Library, from inception until February 6, 2022. The inclusion criteria were: (1) original studies without restriction in study design; (2) a study population consisting of patients with breast cancer; (3) any type of VR-based interventions (immersive and non-immersive); and (5) studies published in English. To assess the risk of bias, the Effective Public Health Practice Project (EPHPP) Tool was used.

Results
Eighteen articles were included in this systematic review. The result showed that VR could provide many opportunities for patients with breast cancer, including reducing anxiety, time perception, pain, fatigue, chemotherapy-related symptom distress levels, and depression severity, as well as improvement in the range of motion, strength, and function. Cybersickness symptoms, the weight of headsets and helmets, the quality of the visual image, and the cost of the equipment are some of the challenges in using this technology on these patients.

Conclusions
The systematic review showed that VR interventions have opportunities and challenges for patients with breast cancer. VR can be effective for rehabilitation and symptom management and is used in different stages of treatment to improve the condition of patients with breast cancer. However, before using it, the researcher should consider its challenges.
The impact of community-based health insurance on health service utilization and financial risk protection in Ethiopia
Authors: Alemayehu Yibeltal Kiflie , Dessie Ermias , Medhin Girmay , Birhanu Negalign , Hotchkiss David R. , Teklu Alula M. , Kiros Mizan 
Published: January 2023

Abstract
Background
Evidence on the effectiveness of community-based health insurance (CBHI) in low-income countries is inconclusive. This study assessed the impact of CBHI on health service utilization and financial risk protection in Ethiopia.

Methods
We conducted a comparative cross-sectional study nested within a larger national household survey in 2020. Data was collected from three groups of households—CBHI member households (n = 1586), non-member households from CBHI implementing woredas (n = 1863), and non-member households from non-CBHI implementing woredas (n = 789). Indicators of health service utilization, out-of-pocket health spending, catastrophic health expenditure, and impoverishment due to health spending among CBHI members were compared with non-members from CBHI implementing woredas and households from non-CBHI implementing woredas. Propensity score matching (PSM) was used to account for possible selection bias.

Results
The annual number of OPD visits per capita among CBHI member households was 2.09, compared to 1.53 among non-member households from CBHI woredas and 1.75 among households from non-CBHI woredas. PSM estimates indicated that CBHI members had 0.36 (95% CI: 0.25, 0.44) and 0.17 (95% CI: -0.04, 0.19) more outpatient department (OPD) visits per capita per year than their matched non-member households from CBHI-implementing and non-CBHI implementing woredas, respectively. CBHI membership resulted in a 28–43% reduction in annual OOP payments as compared to non-member households. CBHI member households were significantly less likely to incur catastrophic health expenditures (measured as annual OOP payments of more than 10% of the household’s total expenditure) compared to non-members (p < 0.01).

Conclusion
CBHI membership increases health service utilization and financial protection. CBHI proves to be an important strategy for promoting universal health coverage. Implementing CBHI in all woredas and increasing membership among households in woredas that are already implementing CBHI will further expand its benefits.
A novel polypeptide encoded by the circular RNA ZKSCAN1 suppresses HCC via degradation of mTOR
Authors: Song Runjie , Ma Shuoqian , Xu Jiajia , Ren Xin , Guo Peilan , Liu Huijiao , Li Peng , Yin Fan , Liu Mei , Wang Qiang , Yu Lei , Liu Jiali , Duan Binwei , Rahman Nafis A. , Wołczyński Sławomir , Li Guangming , Li Xiangdong 
Published: January 2023

Abstract
Background
hsa_circ_0001727 (circZKSCAN1) has been reported to be a tumor-associated circRNA by sponging microRNAs. Intriguingly, we found that circZKSCAN1 encoded a secretory peptide (circZKSaa) in the liver. The present study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression.

Methods
The circRNA profiling datasets (RNA-seq data GSE143233 and GSE140202) were reanalyzed and circZKSCAN1 was selected for further study. Mass spectrometry, polysome fractionation assay, dual-luciferase reporter, and a series of experiments showed that circZKSCAN1 encodes circZKSaa. Cell proliferation, apoptosis, and tumorigenesis in nude mice were examined to investigate the functions of circZKSaa. Mechanistically, the relationship between the circZKSaa and mTOR in HCC was verified by immunoprecipitation analyses, mass spectrometry, and immunofluorescence staining analyses.

Results
Receiver operating characteristic (ROC) analysis demonstrated that the secretory peptide circZKSaa encoded by circZKSCAN1 might be the potential biomarker for HCC tissues. Through a series of experiments, we found that circZKSaa inhibited HCC progression and sensitize HCC cells to sorafenib. Mechanistically, we found that the sponge function of circZKSCAN1 to microRNA is weak in HCC, while overexpression of circZKSaa promoted the interaction of FBXW7 with the mammalian target of rapamycin (mTOR) to promote the ubiquitination of mTOR, thereby inhibiting the PI3K/AKT/mTOR pathway. Furthermore, we found that the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5.

Conclusions
These results reveal that a novel circZKSCAN1-encoded peptide acts as a tumor suppressor on PI3K/AKT/mTOR pathway, and sensitizes HCC cells to sorafenib via ubiquitination of mTOR. These findings demonstrated that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.
Applying behaviour change models to policy-making: development and validation of the Policymakers’ Information Use Questionnaire (POLIQ)
Authors: Shikako Keiko , El Sherif Reem , Cardoso Roberta , Zhang Hao , Lai Jonathan , Mogo Ebele R. I. , Schuster Tibor 
Published: January 2023

AbstractBackgroundThe purpose of this study was to develop and validate the Policymakers’ Information Use Questionnaire (POLIQ) to capture the intention of individuals in decision-making positions, such as health policy-makers, to act on research-based evidence in order to inform theory and the application of behaviour change models to decision-making spheres.MethodsThe development and validation comprised three steps: item generation, qualitative face validation with cognitive debriefing and factorial construct validation. Confirmatory factor analysis was applied to estimate item–domain correlations for five predefined constructs relating to content, beliefs, behaviour, control and intent. Cronbach’s alpha coefficient was calculated to assess the overall consistency of questionnaire items with the predefined constructs. Participants in the item generation and face validation were health and policy researchers and two former decision-makers (former assistant deputy ministers) from the Canadian provincial level. Participants in the construct validation were 39 Canadian decision-makers at various positions of municipal, provincial and federal jurisdiction who participated in a series of policy dialogues focused on childhood disability.ResultsCognitive debriefing allowed for small adjustments in language for clarity, including simultaneous validation of the English and French questionnaires. Participants found that the questions were clear and addressed the domains being targeted. Internal consistency of items belonging to the respective questionnaire domains was moderate to high, with estimated Cronbach’s alpha values ranging from 0.67 to 0.84. Estimated item–domain correlations indicated moderate to high measurement performance for the domains norm, control and beliefs, whereas weak to moderate correlations resulted for the constructs content and intent. Estimated imprecision of factor loadings (95% confidence interval widths) was considerable for the questionnaire domains content and intent.ConclusionMeasuring decision-makers’ behaviour in relation to research evidence use is challenging. We provide initial evidence on face validity and appropriate measurement properties of the POLIQ based on a convenience sample of decision-makers in social and health policy. Larger validation studies and further psychometric property testing will support further utility of the POLIQ.
Healthcare costs of congenital cytomegalovirus (cCMV) disease in infants during the first two years of life: a retrospective German claims database analysis
Authors: Stephan Anna-Janina , de Lepper Marion , Wölle Regine , Luzak Agnes , Wang Wei , Jacob Christian , Schneider Kim Maren , Buxmann Horst , Goelz Rangmar , Hamprecht Klaus , Kummer Peter , Modrow Susanne , Greiner Wolfgang , Reuschenbach Miriam 
Published: January 2023

Abstract
Background
Congenital cytomegalovirus (cCMV) infection can cause severe neurological damage, growth retardation, hearing loss, and microcephaly in infants. We aimed at assessing healthcare costs of infants with recorded cCMV diagnosis in an administrative claims database in the first 2 years of life.

Methods
We conducted a retrospective, controlled cohort study using German claims data from the Institute for Applied Health Research Berlin (InGef) database. Incremental healthcare costs during the first and second year of life were assessed by matching (1:60) infants with cCMV diagnoses ≤ 90 days after birth (cCMV90 cohort) to infants without cCMV diagnosis (“representative” controls) and infants with cCMV diagnoses ≤ 21 days after birth plus specific symptoms (cCMV21-S) to infants without cCMV and any ICD-10-GM records (besides Z00-Z99) until 4th preventive health check-up (“healthy” controls). Due to missing data, mean imputation was applied for aids and remedies costs.

Results
We identified 54 and 24 infants born 2014–2018 for the cCMV90 and cCMV21-S cohorts, respectively. During the first year, mean (median) healthcare costs were significantly higher in cCMV90 cases vs. “representative” controls (€22,737 (€9759) vs. €3091 (€863), p < 0.001), with 87.2% inpatient costs. Healthcare costs for cCMV21-S cases compared to “healthy” controls were €34,498 (€20,924) vs. €680 (€569), p < 0.001. Differences decreased for both comparisons in the second year but remained statistically significant.

Conclusions
cCMV comprises a considerable economic burden for the German healthcare system (€19,646 to €33,818 higher mean costs for infants with recorded cCMV diagnosis in the first year of life). Attempts should be made to reduce this burden.
GRHL2-controlled gene expression networks in luminal breast cancer
Authors: Wang Zi , Coban Bircan , Wu Haoyu , Chouaref Jihed , Daxinger Lucia , Paulsen Michelle T. , Ljungman Mats , Smid Marcel , Martens John W. M. , Danen Erik H. J. 
Published: January 2023

AbstractGrainyhead like 2 (GRHL2) is an essential transcription factor for development and function of epithelial tissues. It has dual roles in cancer by supporting tumor growth while suppressing epithelial to mesenchymal transitions (EMT). GRHL2 cooperates with androgen and estrogen receptors (ER) to regulate gene expression. We explore genome wide GRHL2 binding sites conserved in three ER⍺/GRHL2 positive luminal breast cancer cell lines by ChIP-Seq. Interaction with the ER⍺/FOXA1/GATA3 complex is observed, however, only for a minor fraction of conserved GRHL2 peaks. We determine genome wide transcriptional dynamics in response to loss of GRHL2 by nascent RNA Bru-seq using an MCF7 conditional knockout model. Integration of ChIP- and Bru-seq pinpoints candidate direct GRHL2 target genes in luminal breast cancer. Multiple connections between GRHL2 and proliferation are uncovered, including transcriptional activation of ETS and E2F transcription factors. Among EMT-related genes, direct regulation of CLDN4 is corroborated but several targets identified in other cells (including CDH1 and ZEB1) are ruled out by both ChIP- and Bru-seq as being directly controlled by GRHL2 in luminal breast cancer cells. Gene clusters correlating positively (including known GRHL2 targets such as ErbB3, CLDN4/7) or negatively (including TGFB1 and TGFBR2) with GRHL2 in the MCF7 knockout model, display similar correlation with GRHL2 in ER positive as well as ER negative breast cancer patients. Altogether, this study uncovers gene sets regulated directly or indirectly by GRHL2 in luminal breast cancer, identifies novel GRHL2-regulated genes, and points to distinct GRHL2 regulation of EMT in luminal breast cancer cells.