bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives on mental health services for medical students at a Ugandan medical school
Authors: Kihumuro Raymond Bernard , Kaggwa Mark Mohan , Nakandi Rachael Mukisa , Kintu Timothy Mwanje , Muwanga David Richard , Muganzi David Jolly , Atwau Pius , Ayesiga Innocent , Acai Anita , Najjuka Sarah Maria , Najjuma Josephine Nambi , Frazier-Koussai Susan , Ashaba Scholastic , Harms Sheila 
Published: October 2022

Abstract
Background
University-based mental health services for medical students remain a challenge, particularly in low-income countries, due to poor service availability. Prior studies have explored the availability of mental health services in high-income countries but little is known about mental health services in countries in sub-Saharan Africa, such as Uganda. Medical students are at a higher risk of developing mental health challenges during their course of study as compared with other students. Thus, there is a need for well-structured mental health services for this group of students. The aim of this study was to explore perspectives on mental health services for medical students at a public University in Uganda.

Methods
This was a qualitative study where key informant interviews were conducted among purposively selected university administrators (n = 4), student leaders (n = 4), and mental health employees of the university (n = 3), three groups responsible for the mental well-being of medical students at a public university in Uganda. Interviews were audio-recorded, transcribed, and thematically analyzed to identify relevant themes.

Results
The working experience of university administrators and mental health providers was between eight months to 20 years, while student leaders had studied at the university for over four years. We identified five broad themes: (1) Burden of medical school: A curriculum of trauma, (2) Negative coping mechanisms and the problem of blame, (3) The promise of services: Mixed Messages, (4) A broken mental health system for students, and (5) Barriers to mental health services.

Conclusion
Distinguishing between psychological distress that is anticipated because of the subject matter in learning medicine and identifying those students that are suffering from untreated psychiatric disorders is an important conceptual task for universities. This can be done through offering education about mental health and well-being for administrators, giving arm’s length support for students, and a proactive, not reactive, approach to mental health. There is also a need to redesign the medical curriculum to change the medical education culture through pedagogical considerations of how trauma informs the learning and the mental health of students.
Cost-effectiveness of folic acid therapy for primary prevention of stroke in patients with hypertension
Authors: Zhang Tiantian , Liang Zhuoru , Lin Tengfei , Cohen David J. , Arrieta Alejandro , Wang Xiaobin , Qin Xianhui , Wang Binyan , Huo Yong , Liu Gordon G. , Jiang Jie , Zhang Zugui 
Published: October 2022

Abstract
Background
For hypertensive patients without a history of stroke or myocardial infarction (MI), the China Stroke Primary Prevention Trial (CSPPT) demonstrated that treatment with enalapril-folic acid reduced the risk of primary stroke compared with enalapril alone. Whether folic acid therapy is an affordable and beneficial treatment strategy for the primary prevention of stroke in hypertensive patients from the Chinese healthcare sector perspective has not been thoroughly explored.

Methods
We performed a cost-effectiveness analysis alongside the CSPPT, which randomized 20,702 hypertensive patients. A patient-level microsimulation model based on the 4.5-year period of in-trial data was used to estimate costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for enalapril-folic acid vs. enalapril over a lifetime horizon from the payer perspective.

Results
During the in-trial follow-up period, patients receiving enalapril-folic acid gained an average of 0.016 QALYs related primarily to reductions in stroke, and the incremental cost was $706.03 (4553.92 RMB). Over a lifetime horizon, enalapril-folic acid treatment was projected to increase quality-adjusted life years by 0.06 QALYs or 0.03 life-year relative to enalapril alone at an incremental cost of $1633.84 (10,538.27 RMB), resulting in an ICER for enalapril-folic acid compared with enalapril alone of $26,066.13 (168,126.54 RMB) per QALY gained and $61,770.73 (398,421.21 RMB) per life-year gained, respectively. A probabilistic sensitivity analysis demonstrated that enalapril-folic acid compared with enalapril would be economically attractive in 74.5% of simulations at a threshold of $37,663 (242,9281 RMB) per QALY (3x current Chinese per capita GDP). Several high-risk subgroups had highly favorable ICERs < $12,554 (80,976 RMB) per QALY (1x GDP).

Conclusions
For both in-trial and over a lifetime, it appears that enalapril-folic acid is a clinically and economically attractive medication compared with enalapril alone. Adding folic acid to enalapril may be a cost-effective strategy for the prevention of primary stroke in hypertensive patients from the Chinese health system perspective.
Laparoscopy assisted abomasal cannulation in cadavers of bovine fetuses
Authors: Gurgel Heytor Jales , de Oliveira Monteiro Francisco Décio , Barroso João Pedro Monteiro , de Sousa Loise Araújo , dos Santos Gabriela Melo Alves , da Cunha Rossy Kayan , da Silva Verena Siqueira , do Espirito Santo Fernandes Camila , Silva Carla Rozilene Guimarães , dos Santos Albuquerque Rodrigo , Borges Luisa Pucci Bueno , Araújo Luiz Henrique Vilela , dos Santos Daniele Lira , da Câmara Barros Felipe Farias Pereira , Teixeira Pedro Paulo Maia 
Published: October 2022

Abstract
Background
Due to the complexity of ruminant digestion, cannulation of organs of the digestive tract has been carried out in order to advance the understanding of digestive physiology, nutrient degradability, gastrointestinal diseases and biotechnological research. The abomasal cannulation is interesting for nutritional studies, especially in suckling calves, to obtain fluid and abomasal content, evaluation of abomasal flow and function, and infusion of nutrients and drugs when it is intended to reach high concentrations in the organ. Conventionally, access and cannulation of digestive organs of ruminants has been performed by laparotomy, a method often criticized and classified as cruel by some sectors related to ethics and animal welfare. The aim of this present study is to describe and standardize a minimally invasive by laparoscopy assisted abomasal cannulation in bovine fetuses (cadavers), which had been previously slaughtered by accident and would be discarded in local slaughterhouses.

Results
The abomasal cannulation technique was feasible, simple and did not present major difficulties. The surgical time for cannulation of the abomasum, from the insertion of the trocars to the completion of the technique with fixation of the organ to the abdominal wall, ranged from 9 to 27 min, with an average of 15.5 ± 6.62 min.

Conclusions
The Laproscopic assisted abomasal cannulation in bovine fetuses was feasible and safe with minimal tissue injury to the abdominal wall and with short surgical time. More studies in the clinical routine related to minimally invasive abomasal content collection, abomasopexy and abomasotomy are required in order to demonstrate its impact and importance in bovine clinic.
Automated measurement of malaria parasitaemia among asymptomatic blood donors in Malawi using the Sysmex XN-31 analyser: could such data be used to complement national malaria surveillance in real time?
Authors: Kayange Michael , M’baya Bridon , Hwandih Talent , Saker Jarob , Coetzer Thérèsa L. , Münster Marion 
Published: October 2022

Abstract
Background
The recent worldwide increase in malaria cases highlights the need for renewed efforts to eliminate malaria. The World Health Organization advocates that malaria surveillance becomes a core intervention. Current methods to estimate the malaria burden rely on clinical malaria case reports and surveys of asymptomatic parasite infection mainly from children  < 5 years. In this study the hypothesis was that screening blood donors for malaria parasites would provide real-time information on the asymptomatic reservoir of parasites in the adult population and mirror other surveillance data.

Methods
This study was conducted in Malawi, a high malaria burden country, at the Malawi Blood Transfusion Service, which collects blood units at donation sites countrywide. A secondary analysis was conducted on data obtained from a prior Sysmex XN-31 analyser malaria diagnostic evaluation study utilizing residual donor blood samples. XN-31 malaria results, donor age, sex, geographical location, and collection date, were analysed using standard statistical methods.

Results
The malaria parasite prevalence in blood donors was 11.6% (614/5281 samples) increasing seasonally from December (8.6%) to April (18.3%). The median age was 21 years and 45.9% of donors were from urban areas, which showed a lower prevalence compared to non-urban regions. The Central administrative region had the highest and the Northern region the lowest malaria parasite prevalence. The donors were predominantly male (80.2%), 13.1% of whom had malaria parasites, which was significantly higher (p < 0.0001) than for female donors (7.4%). Multivariable logistic regression analysis showed that age, location, and collection month were significant predictors of malaria positivity in males, whereas in females only location was significant. There was no gender difference in parasite density nor gametocyte carriage.

Conclusions
This study demonstrates the powerful utility of screening blood donors for malaria parasites using the XN-31, which not only improves the safety of blood transfusion, but provides valuable complementary surveillance data for malaria control, especially targeting males, who are generally excluded from periodic household surveys. Blood donations are sourced countrywide, year-round, and thus provide dynamic, real-time information on the malaria burden. Furthermore, the XN-31 identifies the asymptomatic human reservoir of infectious gametocytes, which must be targeted to eliminate malaria.
Temperature-related mortality and associated vulnerabilities: evidence from Scotland using extended time-series datasets
Authors: Wan Kai , Feng Zhiqiang , Hajat Shakoor , Doherty Ruth M. 
Published: October 2022

Abstract
Background
Adverse health impacts have been found under extreme temperatures in many parts of the world. The majority of such research to date for the UK has been conducted on populations in England, whilst the impacts of ambient temperature on health outcomes in Scottish populations remain largely unknown.

Methods
This study uses time-series regression analysis with distributed lag non-linear models to characterise acute relationships between daily mean ambient temperature and mortality in Scotland including the four largest cities (Aberdeen, Dundee, Edinburgh and Glasgow) and three regions during 1974–2018. Increases in mortality risk under extreme cold and heat in individual cities and regions were aggregated using multivariate meta-analysis. Cold results are summarised by comparing the relative risk (RR) of death at the 1st percentile of localised temperature distributions compared to the 10th percentile, and heat effects as the RR at the 99th compared to the 90th percentile.

Results
Adverse cold effects were observed in all cities and regions, and heat effects were apparent in all cities and regions. Aggregate all-cause mortality risk in Scotland was estimated to increase by 9% (95% confidence interval, CI: 8%, 11%) under extreme cold and 4% (CI: 3%, 5%) under extreme heat. The elderly had the highest RR under both extreme cold and heat. Males experienced greater cold effects than females, whereas the reverse was true with heat effects, particularly among the elderly. Those who were unmarried had higher RR than those married under extreme heat, and the effect remained after controlling for age. The younger population living in the most deprived areas experienced higher cold and heat effects than in less deprived areas. Deaths from respiratory diseases were most sensitive to both cold and heat exposures, although mortality risk for cardiovascular diseases was also heightened, particularly in the elderly. Cold effects were lower in the most recent 15 years, which may be linked to policies and actions in preventing the vulnerable population from cold impacts. No temporal trend was found with the heat effect.

Conclusions
This study assesses mortality risk associated with extreme temperatures in Scotland and identifies those groups who would benefit most from targeted actions to reduce cold- and heat-related mortalities.
Intervention time decides the status of autophagy, NLRP3 activity and apoptosis in macrophages induced by ox‐LDL
Authors: Zheng Liang , Xu Hongbiao , Zheng Fufu , Lai Yuanhui , Li Jie , Lv Weiming , Hu Zuojun , Wang Wenjian 
Published: October 2022

Abstract
Background
It has been determined through extensive studies that autophagy, the Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and apoptotic responses in macrophages jointly contribute to atherogenesis and its development in the presence of lipid abnormalities. Few studies have investigated in full-scale if the intervention time for lipids abnormality or NLRP3 activation have a significant effect on autophagy, NLRP3 or the apoptotic status in macrophages.

Methods
Human THP-1 monocyte-derived macrophages were established by challenging THP-1 monocytes with 80 µg/ml oxidized low-density lipoprotein (ox-LDL) for specific durations. Foam cell formation was observed by Oil Red O (ORO) staining. Western blots were employed to determine protein expression. Transmission electron microscope (TEM) and immunofluorescence microscopy were applied to observe the autophagic status of cells. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL).

Results
The cells were treated with ox-LDL for 12 h and 36 h, which were considered to represent early and advanced stages of atherogenesis for this study. The results showed that inhibition of ox-LDL phagocytosis by cytochalasin D in the early stage improved autophagic status, reduced NLRP3 activation and the apoptotic response significantly. In contrast, cytochalasin D had little effect on blocking the detrimental effect of ox-LDL at the advanced stage. Moreover, the changes in autophagy, apoptosis and NLRP3 expression after treatment with small interfering (si) RNA targeting NLRP3 in the early and advanced stages of atherogenesis were consistent with the above data.

Conclusions
Interventions against lipid disorders or inflammatory reactions in the early or advanced stages of atherogenesis may have different results depending on when they are applied during the process of atherosclerotic pathogenesis. These results may help improve therapeutic strategies for atherosclerosis prevention. Furthermore, a healthy lifestyle should still be recommended as the most important and inexpensive measure to prevent atherogenesis.
HB-EGF upregulates StAR expression and stimulates progesterone production through ERK1/2 signaling in human granulosa-lutein cells
Authors: Cheng Jung-Chien , Han Xiaoyu , Meng Qingxue , Guo Yanjie , Liu Boqun , Song Tinglin , Jia Yuanyuan , Fang Lanlan , Sun Ying-Pu 
Published: October 2022

Abstract
Background
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) belongs to the epidermal growth factor (EGF) family of growth factors. HB-EGF and its receptors, epidermal growth factor receptor (EGFR) and HER4, are expressed in the human corpus luteum. HB-EGF has been shown to regulate luteal function by preventing cell apoptosis. Steroidogenesis is the primary function of the human corpus luteum. Steroidogenic acute regulatory protein (StAR) plays a critical role in steroidogenesis. StAR expression and progesterone (P4) production in human granulosa-lutein (hGL) cells have been shown to be upregulated by a ligand of EGFR, amphiregulin. However, whether HB-EGF can achieve the same effects remains unknown.

Methods
A steroidogenic human ovarian granulosa-like tumor cell line, KGN, and primary culture of hGL cells obtained from patients undergoing in vitro fertilization treatment were used as experimental models. The underlying molecular mechanisms mediating the effects of HB-EGF on StAR expression and P4 production were explored by a series of in vitro experiments.

Results
Western blot showed that EGFR, HER2, and HER4 were expressed in both KGN and hGL cells. Treatment with HB-EGF for 24 h induced StAR expression but did not affect the expression of steroidogenesis-related enzymes, P450 side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase, and aromatase. Using pharmacological inhibitors and a siRNA-mediated knockdown approach, we showed that EGFR, HER4, but not HER2, were required for HB-EGF-stimulated StAR expression and P4 production. In addition, HB-EGF-induced upregulations of StAR expression and P4 production were mediated by the activation of the ERK1/2 signaling pathway.

Conclusion
This study increases the understanding of the physiological role of HB-EGF in human luteal functions.
Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia
Authors: Polli Andrea , Hendrix Jolien , Ickmans Kelly , Bakusic Jelena , Ghosh Manosij , Monteyne Dora , Velkeniers Brigitte , Bekaert Bram , Nijs Jo , Godderis Lode 
Published: October 2022

AbstractBackgroundCatechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulatingCOMTand its influence on inflammatory markers and symptoms in patients with CFS/FM.Methods.A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680COMTpolymorphisms and perform haplotype estimation, DNA methylation in theCOMTgene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β).Results.COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients.DiscussionOur results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.
CRISPR-KRISPR: a method to identify on-target and random insertion of donor DNAs and their characterization in knock-in mice
Authors: Tanaka Masayuki , Yokoyama Keiko , Hayashi Hideki , Isaki Sanae , Kitatani Kanae , Wang Ting , Kawata Hisako , Matsuzawa Hideyuki , Gurumurthy Channabasavaiah B. , Miura Hiromi , Ohtsuka Masato 
Published: October 2022

AbstractCRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 μg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.
APOE ε4-dependent effects on the early amyloid pathology in induced neurons of patients with Alzheimer’s disease
Authors: Kim Hongwon , Kim Siyoung , Cho Byounggook , Shin Jaein , Kim Jongpil 
Published: October 2022

Abstract
Background
The ε4 allele of apolipoprotein E (APOE ε4) is the strongest known genetic risk factor for late-onset Alzheimer’s disease (AD), associated with amyloid pathogenesis. However, it is not clear how APOE ε4 accelerates amyloid-beta (Aβ) deposition during the seeding stage of amyloid development in AD patient neurons.

Methods
AD patient induced neurons (iNs) with an APOE ε4 inducible system were prepared from skin fibroblasts of AD patients. Transcriptome analysis was performed using RNA isolated from the AD patient iNs expressing APOE ε4 at amyloid-seeding and amyloid-aggregation stages. Knockdown of IGFBP3 was applied in the iNs to investigate the role of IGFBP3 in the APOE ε4-mediated amyloidosis.

Results
We optimized amyloid seeding stage in the iNs of AD patients that transiently expressed APOE ε4. Remarkably, we demonstrated that Aβ pathology was aggravated by the induction of APOE ε4 gene expression at the amyloid early-seeding stage in the iNs of AD patients. Moreover, transcriptome analysis in the early-seeding stage revealed that IGFBP3 was functionally important in the molecular pathology of APOE ε4-associated AD.

Conclusions
Our findings suggest that the presence of APOE ε4 at the early Aβ-seeding stage in patient iNs is critical for aggravation of sporadic AD pathology. These results provide insights into the importance of APOE ε4 expression for the progression and pathogenesis of sporadic AD.
Antiproliferative activity of standardized herbal phytopreparation from Asclepias subulata
Authors: González Gutiérrez Francisco Humberto , Rascón Valenzuela Luisa Alondra , Meneses Sagrero Salvador Enrique , Dias-Silva Marcelo J. , Valenzuela Antelo Olivia , Velazquez Carlos , Vilegas Wagner , Robles Zepeda Ramón Enrique 
Published: October 2022

Background: Several studies have shown that active compounds of Asclepias subulata (cardenolides) have antiproliferative effect on human cancer cells. Cardenolides isolated from A. subulata can be used as active chemical markers to elaborate phytopharmaceutical preparations. The aim of this work was to evaluate the antiproliferative effect of a standardized extract of the aerial parts, based on Asclepias subulata cardenolides. Methods: Four standardized extracts were prepared by HPLC-DAD depending on the concentration of calotropin and the antiproliferative activity was measured for the MTT assay, on the A549, MCF-7, HeLa, PC3 and ARPE cell lines. The concentrations of calotropin used for the standardization of the extracts were 10, 7.6, 5 and 1 mg/dL. Results: Standardization of the A. subulata extract based on calotropin at 7.6 mg/g dry weight was achieved and the antiproliferative activity was evaluated over A549, HeLa and MCF-7 cell lines, obtaining proliferation percentages of 3.8 to 13.4%. Conclusions: The standardized extracts of A. subulata at different concentrations of calotropin showed antiproliferative activity against all the cell lines evaluated. The greatest effect was observed against the HeLa cell line.