bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confounding factors in profiling of locus-specific human endogenous retrovirus (HERV) transcript signatures in primary T cells using multi-study-derived datasets
Authors: Hamann Martin V. , Adiba Maisha , Lange Ulrike C. 
Published: April 2023

Abstract
Background
Human endogenous retroviruses (HERV) are repetitive sequence elements and a substantial part of the human genome. Their role in development has been well documented and there is now mounting evidence that dysregulated HERV expression also contributes to various human diseases. While research on HERV elements has in the past been hampered by their high sequence similarity, advanced sequencing technology and analytical tools have empowered the field. For the first time, we are now able to undertake locus-specific HERV analysis, deciphering expression patterns, regulatory networks and biological functions of these elements. To do so, we inevitable rely on omics datasets available through the public domain. However, technical parameters inevitably differ, making inter-study analysis challenging. We here address the issue of confounding factors for profiling locus-specific HERV transcriptomes using datasets from multiple sources.

Methods
We collected RNAseq datasets of CD4 and CD8 primary T cells and extracted HERV expression profiles for 3220 elements, resembling most intact, near full-length proviruses. Looking at sequencing parameters and batch effects, we compared HERV signatures across datasets and determined permissive features for HERV expression analysis from multiple-source data.

Results
We could demonstrate that considering sequencing parameters, sequencing-depth is most influential on HERV signature outcome. Sequencing samples deeper broadens the spectrum of expressed HERV elements. Sequencing mode and read length are secondary parameters. Nevertheless, we find that HERV signatures from smaller RNAseq datasets do reliably reveal most abundantly expressed HERV elements. Overall, HERV signatures between samples and studies overlap substantially, indicating a robust HERV transcript signature in CD4 and CD8 T cells. Moreover, we find that measures of batch effect reduction are critical to uncover genic and HERV expression differences between cell types. After doing so, differences in the HERV transcriptome between ontologically closely related CD4 and CD8 T cells became apparent.

Conclusion
In our systematic approach to determine sequencing and analysis parameters for detection of locus-specific HERV expression, we provide evidence that analysis of RNAseq datasets from multiple studies can aid confidence of biological findings. When generating de novo HERV expression datasets we recommend increased sequence depth ( > = 100 mio reads) compared to standard genic transcriptome pipelines. Finally, batch effect reduction measures need to be implemented to allow for differential expression analysis.
Human cells with osteogenic potential in bone tissue research
Authors: Dvorakova Jana , Wiesnerova Lucie , Chocholata Petra , Kulda Vlastimil , Landsmann Lukas , Cedikova Miroslava , Kripnerova Michaela , Eberlova Lada , Babuska Vaclav 
Published: April 2023

AbstractBone regeneration after injury or after surgical bone removal due to disease is a serious medical challenge. A variety of materials are being tested to replace a missing bone or tooth. Regeneration requires cells capable of proliferation and differentiation in bone tissue. Although there are many possible human cell types available for use as a model for each phase of this process, no cell type is ideal for each phase. Osteosarcoma cells are preferred for initial adhesion assays due to their easy cultivation and fast proliferation, but they are not suitable for subsequent differentiation testing due to their cancer origin and genetic differences from normal bone tissue. Mesenchymal stem cells are more suitable for biocompatibility testing, because they mimic natural conditions in healthy bone, but they proliferate more slowly, soon undergo senescence, and some subpopulations may exhibit weak osteodifferentiation. Primary human osteoblasts provide relevant results in evaluating the effect of biomaterials on cellular activity; however, their resources are limited for the same reasons, like for mesenchymal stem cells. This review article provides an overview of cell models for biocompatibility testing of materials used in bone tissue research.
The magnitude and associated factors of coagulation abnormalities among liver disease patients at the University of Gondar Comprehensive Specialized Hospital Northwest, Ethiopia, 2022
Authors: Melkamu Abateneh , Woldu Berhanu , Sitotaw Chomaw , Seyoum Masresha , Aynalem Melak 
Published: April 2023

Abstract
Background
Liver disease is any condition that affects the liver cells and their function. It is directly linked to coagulation disorders since most coagulation factors are produced by the liver. Therefore, this study aimed to assess the magnitude and associated factors of coagulation abnormalities among liver disease patients.

Methods
A cross-sectional study was conducted from August to October 2022 among 307 consecutively selected study participants at the University of Gondar Comprehensive Specialized Hospital. Sociodemographic and clinical data were collected using a structured questionnaire and data extraction sheet, respectively. About 2.7 mL of venous blood were collected and analyzed by the Genrui CA51 coagulation analyzer. Data were entered into Epi-data and exported to STATA version 14 software for analysis. The finding was described in terms of frequencies and proportions. Factors associated with coagulation abnormalities were analyzed by bivariable and multivariable logistic regression.

Result
In this study, a total of 307 study participants were included. Of them the magnitude of prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) were 68.08% and 63.51%, respectively. The presence of anaemia (AOR = 2.97, 95% CI: 1.26, 7.03), a lack of a vegetable feeding habit (AOR = 2.98, 95% CI: 1.42, 6.24), no history of blood transfusion (AOR = 3.72, 95% CI: 1.78, 7.78), and lack of physical exercise (AOR = 3.23, 95% CI: 1.60, 6.52) were significantly associated with prolonged PT. While the presence of anaemia (AOR = 3.02; 95% CI: 1.34, 6.76), lack of vegetable feeding habit (AOR = 2.64; 95% CI: 1.34, 5.20), no history of blood transfusion (AOR = 2.28; 95% CI: 1.09, 4.79), and a lack of physical exercise (AOR = 2.35; 95% CI: 1.16, 4.78) were significantly associated with abnormal APTT.

Conclusion
Patients with liver disease had substantial coagulation problems. Being anemic, having a transfusion history, lack of physical activity, and lack of vegetables showed significant association with coagulopathy. Therefore, early detection and management of coagulation abnormalities in liver disease patients are critical.
Monetary valuation of COVID-19 informal care: caregivers’ willingness to pay and willingness to accept
Authors: Ramezani-Doroh Vajiheh , Karimi Faride , Rangchian Maryam , Hamidi Yadolah 
Published: April 2023

AbstractBackgroundInformal care can reduce hospitalization frequency and time, elevate bed turnover, and increase the health systems' capacity. This type of care has shown meaningful value in managing many cases through the COVID-19 pandemic. The present study aimed to identify determinants of monetary valuation of informal care and the burden of this care on the COVID-19 patients’ caregivers.MethodsThrough a cross-sectional phone survey from June to September 2021 in Sanandaj city, the west of Iran, COVID-19 patients and their caregivers (Each Group No. 425) were separately interviewed. A simple probabilistic sampling method was applied. Two questionnaires were developed and used after validation. Monetary valuation of informal caregivers was done using Willingness to pay (WTP) and willingness to accept (WTA). Double hurdle regressions were used to determine related variables to WTP/WTA. R software was used for the data analysis.ResultsThe total mean (Standard Deviation) of WTP and WTA were $12.02(28.73), $10.30(15.43) USD. Most respondents put a zero value on informal care by WTA (243(57.18%) and WTP [263 (61.88%)]. Caregivers’ Employment, and being spouse/child of the care recipient increased the probability of reporting a positive value for WTP (p-value < 0.0001, p-value = 0.011 respectively) and WTA (p-value = 0.004, p-value < 0.0001 respectively). An increase in the number of caring days decreased the probability of reporting positive WTA (p-value = 0.001) and increased the mean of lnWTP (p-value = 0.044). Perceived difficulty in doing indoor activities and perceived difficulty in doing outdoor activities decreased lnWTA mean (p-value = 0.002) and lnWTP mean (p-value = 0.043) respectively.ConclusionsIncreasing caregivers’ self-efficacy and facilitating their involvement in the caring process could be facilitated through flexible work status, educational programs, and interventions on decreasing their burnout.
Identification of serum exosomal metabolomic and proteomic profiles for remote ischemic preconditioning
Authors: Du Yang , Qiu Rui , Chen Lei , Chen Yuewen , Zhong Zhifeng , Li Peng , Fan Fangcheng , Cheng Yong 
Published: April 2023

Abstract
Background
Remote ischemic preconditioning (RIPC) refers to a brief episode of exposure to potential adverse stimulation and prevents injury during subsequent exposure. RIPC has been shown to increase tolerance to ischemic injury and improve cerebral perfusion status. Exosomes have a variety of activities, such as remodeling the extracellular matrix and transmitting signals to other cells. This study aimed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection.

Methods
Sixty adult male military personnel participants were divided into the control group (n = 30) and the RIPC group (n = 30). We analyzed the differential metabolites and proteins in the serum exosomes of RIPC participants and control subjects.

Results
Eighty-seven differentially expressed serum exosomal metabolites were found between the RIPC and control groups, which were enriched in pathways related to tyrosine metabolism, sphingolipid metabolism, serotonergic synapses, and multiple neurodegeneration diseases. In addition, there were 75 differentially expressed exosomal proteins between RIPC participants and controls, which involved the regulation of insulin-like growth factor (IGF) transport, neutrophil degranulation, vesicle-mediated transport, etc. Furthermore, we found differentially expressed theobromine, cyclo gly-pro, hemopexin (HPX), and apolipoprotein A1 (ApoA1), which are associated with neuroprotective benefits in ischemia/reperfusion injury. In addition, five potential metabolite biomarkers, including ethyl salicylate, ethionamide, piperic acid, 2, 6-di-tert-butyl-4-hydroxymethylphenol and zerumbone, that separated RIPC from control individuals were identified.

Conclusion
Our data suggest that serum exosomal metabolites are promising biomarkers for RIPC, and our results provide a rich dataset and framework for future analyses of cerebral ischemia‒reperfusion injury under ischemia/reperfusion conditions.
Unexpectedly high incidence of Kawasaki Disease in a Canadian Atlantic Province- an 11-year retrospective descriptive study
Authors: Alkanhal Abdulrahman , Saunders Joseph , Altammar Fajer , Huber Adam M. , Lynk Andrew , MacLeod Alison , Ortiz-Alvarez Oliva , Adams Meighan , Ramsey Suzanne , Stringer Elizabeth , Warren Andrew , Lang Bianca 
Published: April 2023

Abstract
Background
Kawasaki Disease (KD) is the leading cause of acquired heart disease in children in developed countries with a variable incidence worldwide. Previous studies reported an unexpectedly high incidence of KD in the Canadian Atlantic Provinces. The goals of our study were to validate this finding in the province of Nova Scotia and to carefully review patients’ characteristics and disease outcomes.

Methods
This was a retrospective review of all children < 16 years old from Nova Scotia diagnosed with KD between 2007–2018. Cases were identified using a combination of administrative and clinical databases. Clinical information was collected retrospectively by health record review using a standardized form.

Results
Between 2007–2018, 220 patients were diagnosed with KD; 61.4% and 23.2% met the criteria for complete and incomplete disease, respectively. The annual incidence was 29.6 per 100,000 children < 5 years. The male to female ratio was 1.3:1 and the median age was 3.6 years. All patients diagnosed with KD in the acute phase received intravenous immunoglobulin (IVIG); 23 (12%) were refractory to the first dose. Coronary artery aneurysms were found in 13 (6%) patients and one patient died with multiple giant aneurysms.

Conclusion
We have confirmed an incidence of KD in our population which is higher than that reported in Europe and other regions of North America despite our small Asian population. The comprehensive method to capture patients may have contributed to the detection of the higher incidence. The role of local environmental and genetic factors also deserves further study. Increased attention to regional differences in the epidemiology of KD may improve our understanding of this important childhood vasculitis.
TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder
Authors: You Yun-Fan , Chen Man , Tang Yue , Yu Wen-Xiang , Pang Xiao-Wei , Chu Yun-Hui , Zhang Hang , Shang Ke , Deng Gang , Zhou Luo-Qi , Yang Sheng , Wang Wei , Xiao Jun , Tian Dai-Shi , Qin Chuan 
Published: April 2023

AbstractNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are activated and play a pivotal role in response to tissue injury. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by microglia and promotes microglial activation, survival and phagocytosis. Here, we identify a critical role for TREM2 in microglial activation and function during AQP4-IgG and complement-induced demyelination. TREM2-deficient mice had more severe tissue damage and neurological impairment, as well as fewer oligodendrocytes with suppressed proliferation and maturation. The number of microglia clustering in NMOSD lesions and their proliferation were reduced in TREM2-deficient mice. Moreover, morphology analysis and expression of classic markers showed compromised activation of microglia in TREM2-deficient mice, which was accompanied by suppressed phagocytosis and degradation of myelin debris by microglia. These results overall indicate that TREM2 is a key regulator of microglial activation and exert neuroprotective effects in NMOSD demyelination.
Graphical Abstract
Effects of backward walking exercise using lower body positive pressure treadmill on knee symptoms and physical function in individuals with knee osteoarthritis: a protocol for RCT
Authors: Almutairi Sattam M. , Almutairi Marzouq K. , Alotaibi Mansour M. , Alshehri Mohammed , Alenazi Aqeel M. 
Published: April 2023

Abstract
Objectives
The primary aim is to compare the effects of backward walking exercise to forward walking exercise on knee pain, knee functions, and thigh muscle strength in individuals with mild to moderate knee osteoarthritis using lower body positive pressure, in addition to mobility functions, balance, and self-reported health status.

Methods
The study is a single blind randomized clinical trial with two independent groups. This study will enroll 26 participants with mild to moderate knee osteoarthritis. The participants will be randomized into either experimental group (backward walking exercise) or control group (forward walking exercise). Both groups will use lower body positive pressure treadmill for walking exercise. Both groups will perform regular conventional exercise and worm-up exercise before walking exercise. The treatment will be three times a week for six weeks. Walking session will be up to 30 min each session. Data collection will be collected during pre- and post- intervention including primary outcomes including numeric pain rating scale (NPRS), knee injury and osteoarthritis outcome score (KOOS), and thigh muscle strength test. The secondary outcomes include five times sit to stand test (FTSTS), 3-meter backward walk test (3MBWT), timed up and go test (TUG), four square step test (FSST), functional reach test (FRT), 10-meter walk test (10-MWT), six minute walk test (6MWT), medical outcomes study short form 12 (SF-12), patient health questionnaire -9 (PHQ-9), and rapid assessment of physical activity (RAPA). An independent t-test will be used to evaluate the effect of treatment on the outcome measures.

Results
Not applicable.

Conclusion
Using lower body positive pressure may have promising results against knee osteoarthritis. Moreover, walking backward exercise using lower body positive pressure might add more benefits to individuals with knee osteoarthritis and help clinicians in decision making.
Trial registration: This study was registered in ClinicalTrails.gov (ID: NCT05585099).
Psychosocial model of burnout among humanitarian aid workers in Bangladesh: role of workplace stressors and emotion coping
Authors: Foo Cheryl Yunn Shee , Tay Alvin Kuowei , Yang Yexinyu , Verdeli Helen 
Published: April 2023

Abstract
Background
While trauma exposure is an established predictor of poor mental health among humanitarian aid workers (HAWs), less is known about the role of psychosocial work-related factors. This study aims to establish a psychosocial model for burnout and psychological distress in HAWs that tests and compares the effects of adversity exposure and workplace stressors in combination, and explores the potential mediating role of individual coping styles.

Methods
Path analysis and model comparison using cross-sectional online survey data were collected from full-time international and local HAWs in Bangladesh between December 2020 and February 2021. HAWs self-reported on exposure to adversities, workplace psychosocial stressors (Third Copenhagen Psychosocial Questionnaire), coping styles (Coping Inventory for Stressful Situations), burnout (Maslach Burnout Inventory—Human Services Survey), and psychological distress (Kessler-6).

Results
Among N = 111 HAWs, 30.6%, 16.4%, 12.7%, and 8.2% screened positive for moderate psychological distress (8 ≤ Kessler-6 ≤ 12), emotional exhaustion (EE ≥ 27), depersonalization (DP ≥ 13), and severe psychological distress (K-6 ≥ 13), respectively. 28.8% reported a history of mental disorder. The preferred model showed distinct pathways from adversity exposure and workplace stressors to burnout, with negative emotion-focused coping and psychological distress as significant intervening variables. While greater exposure to both types of stressors were associated with higher levels of burnout and distress, workplace stressors had a stronger association with psychological outcomes than adversity exposure did (β = .52, p ≤ .001 vs. β = .20, p = .032). Workplace stressors, but not adversities, directly influenced psychological distress (β = .45, p ≤ .001 vs. β = −.01, p = .927). Demographic variables, task-focused and avoidance-focused coping were not significantly associated with psychological outcomes.

Conclusions
Compared to exposure to adversities, workplace stressors primarily influenced occupational stress syndromes. Reducing workplace stressors and enhancing adaptive coping may improve psychological outcomes in humanitarian staff.
Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice
Authors: Taylor Peter N. , Lansdown Andrew , Witczak Justyna , Khan Rahim , Rees Aled , Dayan Colin M. , Okosieme Onyebuchi 
Published: April 2023

Abstract
Background
Thyroid hormones are key determinants of health and well-being. Normal thyroid function is defined according to the standard 95% confidence interval of the disease-free population. Such standard laboratory reference intervals are widely applied in research and clinical practice, irrespective of age. However, thyroid hormones vary with age and current reference intervals may not be appropriate across all age groups. In this review, we summarize the recent literature on age-related variation in thyroid function and discuss important implications of such variation for research and clinical practice.

Main text
There is now substantial evidence that normal thyroid status changes with age throughout the course of life. Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations. Free triiodothyronine (FT3) levels fall with age and appear to play a role in pubertal development, during which it shows a strong relationship with fat mass. Furthermore, the aging process exerts differential effects on the health consequences of thyroid hormone variations. Older individuals with declining thyroid function appear to have survival advantages compared to individuals with normal or high-normal thyroid function. In contrast younger or middle-aged individuals with low-normal thyroid function suffer an increased risk of adverse cardiovascular and metabolic outcomes while those with high-normal function have adverse bone outcomes including osteoporosis and fractures.

Conclusion
Thyroid hormone reference intervals have differential effects across age groups. Current reference ranges could potentially lead to inappropriate treatment in older individuals but on the other hand could result in missed opportunities for risk factor modification in the younger and middle-aged groups. Further studies are now needed to determine the validity of age-appropriate reference intervals and to understand the impact of thyroid hormone variations in younger individuals.