bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein
Authors: Tani Hideki , Kimura Miyuki , Tan Long , Yoshida Yoshihiro , Ozawa Tatsuhiko , Kishi Hiroyuki , Fukushi Shuetsu , Saijo Masayuki , Sano Kaori , Suzuki Tadaki , Kawasuji Hitoshi , Ueno Akitoshi , Miyajima Yuki , Fukui Yasutaka , Sakamaki Ippei , Yamamoto Yoshihiro , Morinaga Yoshitomo 
Published: January 2021

Abstract
Background
SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is now classified in the genus Coronavirus with closely related SARS-CoV. SARS-CoV-2 is highly pathogenic in humans and is classified as a biosafety level (BSL)-3 pathogen, which makes manipulating it relatively difficult due to its infectious nature.

Methods
To circumvent the need for BSL-3 laboratories, an alternative assay was developed that avoids live virus and instead uses a recombinant VSV expressing luciferase and possesses the full length or truncated spike proteins of SARS-CoV-2. Furthermore, to measure SARS-CoV-2 neutralizing antibodies under BSL2 conditions, a chemiluminescence reduction neutralization test (CRNT) for SARS-CoV-2 was developed. The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay (IFA).

Results
The CRNT, which used whole blood collected from hospitalized patients with COVID-19, was also examined. As a result, the inhibition of pseudotyped virus infection was specifically observed in both serum and whole blood and was also correlated with the results of the IFA.

Conclusions
In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2.
Long-chain saturated fatty acid species are not toxic to human pancreatic β-cells and may offer protection against pro-inflammatory cytokine induced β-cell death
Authors: Thomas Patricia , Leslie Kaiyven A. , Welters Hannah J. , Morgan Noel G. 
Published: January 2021

AbstractObesity is a major risk factor for type 2 diabetes (T2D) although the causal links remain unclear. A feature shared by both conditions however is systemic inflammation and raised levels of circulating fatty acids (FFA). It is widely believed that in obese individuals genetically prone to T2D, elevated levels of plasma FFA may contribute towards the death and dysfunction of insulin-producing pancreatic β-cells in a process of (gluco)lipotoxicity. In support of this, in vitro studies have shown consistently that long-chain saturated fatty acids (LC-SFA) are toxic to rodent β-cells during chronic exposure (> 24 h). Conversely, shorter chain SFA and unsaturated species are well tolerated, suggesting that toxicity is dependent on carbon chain length and/or double bond configuration. Despite the wealth of evidence implicating lipotoxicity as a means of β-cell death in rodents, the evidence that a similar process occurs in humans is much less substantial. Therefore, the present study has evaluated the effects of chronic exposure to fatty acids of varying chain length and degree of saturation, on the viability of human β-cells in culture. We have also studied the effects of a combination of fatty acids and pro-inflammatory cytokines. Strikingly, we find that LC-FFA do not readily promote the demise of human β-cells and that they may even offer a measure of protection against the toxic effects of pro-inflammatory cytokines. Therefore, these findings imply that a model in which elevated circulating LC-FFA play a direct role in mediating β-cell dysfunction and death in humans, may be overly simplistic.
Changing course: supporting a shift to environmental strategies in a state prevention system
Authors: Ballard Parissa J. , Pankratz Melinda , Wagoner Kimberly G. , Cornacchione Ross Jennifer , Rhodes Scott D. , Azagba Sunday , Song Eunyoung Y. , Wolfson Mark 
Published: January 2021

Abstract
Background
This study examines how the North Carolina state prevention system responded to a policy shift from individual-level prevention strategies to environmental strategies from the perspective of the organizations implementing the policy shift.

Methods
We use two data sources. First, we conducted interviews to collect qualitative data from key informants. Second, we used prevention provider agency expenditure data from the year the shift was announced and the following year.

Results
The interviews allowed us to identify effective features of policy change implementation in complex systems, such as the need for clear communication and guidance about the policy changes. Our interview and expenditure analyses also underscore variation in the level of guidance and oversight provided by implementing agencies to prevention providers.

Conclusions
Our analyses suggest that more active monitoring and oversight may have facilitated more consistent implementation of the policy shift toward greater use of environmental prevention strategies.
Context-acceptability theories: example of family planning interventions in five African countries
Authors: Webster Jayne , Krishnaratne Shari , Hoyt Jenna , Demissie Shiferaw Dechasa , Spilotros Nathaly , Landegger Justine , Kambanje Misozi , Pryor Shannon , Moseti Easterlina , Marcus Seth , Gnintoungbe Marius , Curry Dora , Hamon Jessie K. 
Published: January 2021

AbstractBackgroundFamily planning (FP) can lengthen birth intervals and potentially reduce the risk of foetal death, low birthweight, prematurity, and being small for gestational age. Effective FP is most easily achieved through access to and acceptability of modern contraceptive methods (MCMs). This study aimed to identify mechanisms of acceptability and the contexts in which they are triggered and to generate theories to improve the selection and implementation of effective interventions by studying an intervention integrating FP with childhood immunisation services.MethodsQualitative interpretative synthesis of findings from realist evaluations of FP interventions in five African countries was guided by an analytical framework. Empirical mechanisms of acceptability were identified from semi-structured interviews and focus group discussions with key stakeholders (N= 253). The context in which these mechanisms were triggered was also defined. Empirical mechanisms of acceptability were matched to constructs of a theoretical framework of acceptability. Context-acceptability theories (CATs) were developed, which summarised constructs of acceptability triggered for specific actors in specified contexts. Examples of interventions that may be used to trigger acceptability for these actors were described.ResultsSeven CATs were developed for contexts with strong beliefs in religious values and with powerful religious leaders, a traditional desire for large families, stigmatisation of MCM use, male partners who are non-accepting of FP, and rumours or experiences of MCM side effects. Acceptability mechanisms included alignment with values and beliefs without requiring compromise, actors’ certainty about their ability to avoid harm and make the intervention work, and understanding the intervention and how it works. Additionally, acceptability by one group of actors was found to alter the context, triggering acceptability mechanisms amongst others.ConclusionsThis study demonstrated the value of embedding realist approaches within implementation research. CATs are transferable theories that answer the question: given the context, what construct of acceptability does an intervention need to trigger, or more simply, what intervention do we need to apply here to achieve our outcomes? CATs facilitate transfer of interventions across geographies within defined contexts.
Using brain functional magnetic resonance imaging to evaluate the effectiveness of acupuncture combined with mirror therapy on upper limb function in patients with cerebral ischemic stroke: a study protocol for a randomized, controlled trial
Authors: Xu Mingzhu , Lin Run , Luo Jing , Tang Chunzhi , Wang Shuhui , Wong John , Wu Meng , Huang Jianting , Shi Peng , Gao Ang , Bai Yuqian , Xie Ying , Luo Jun , Yang Yunqiu , Cui Shaoyang 
Published: January 2021

Abstract
Background
Upper limb and hand motor dysfunction is one of the challenges in rehabilitation after cerebral ischemic stroke (CIS), and the clinical efficacy of rehabilitation needs to be improved. This study aims to combine Jin’s three-needle acupuncture (JTN) therapy with mirror therapy (MT) for hemiplegia after CIS, objectively evaluate the clinical effects and safety of JTN to treat upper limb dysfunction, and use functional magnetic resonance imaging (fMRI) of the brain to investigate the central mechanisms of the effects, which would provide a powerful evidence-based medical basis for further supporting the application of JTN combined with MT.

Methods/design
This trial will be a single-blind, randomized controlled study. Patients who meet the study criteria will be recruited and randomly assigned to either the combined treatment group (JTN+MT) or the JTN group. Both interventions will be conducted for 6 days per week and last for 4 weeks. The primary outcome will be the effective rate based on the Fugl–Meyer Assessment for Upper Extremity (FMA-UE). Other outcome measures will include scores on the motor assessment scale (MAS), action research arm test (ARAT), activities of daily living (ADL) scale, and fMRI analyses. For safety evaluation, adverse events will be observed and recorded.

Discussion
This study may help to identify the efficacy and safety of acupuncture combined with MT for upper limb dysfunction after CIS and explore the central mechanisms with brain fMRI.

Trial registration
Chinese Clinical Trial Registry ChiCTR-IOR-17012174. Registered on 5 April 2017.
Integration of sperm ncRNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance
Authors: Beck Daniel , Ben Maamar Millissia , Skinner Michael K. 
Published: January 2021

Abstract
Background
Environmentally induced epigenetic transgenerational inheritance of pathology and phenotypic variation has been demonstrated in all organisms investigated from plants to humans. This non-genetic form of inheritance is mediated through epigenetic alterations in the sperm and/or egg to subsequent generations. Although the combined regulation of differential DNA methylated regions (DMR), non-coding RNA (ncRNA), and differential histone retention (DHR) have been shown to occur, the integration of these different epigenetic processes remains to be elucidated. The current study was designed to examine the integration of the different epigenetic processes.

Results
A rat model of transiently exposed F0 generation gestating females to the agricultural fungicide vinclozolin or pesticide DDT (dichloro-diphenyl-trichloroethane) was used to acquire the sperm from adult males in the subsequent F1 generation offspring, F2 generation grand offspring, and F3 generation great-grand offspring. The F1 generation sperm ncRNA had substantial overlap with the F1, F2 and F3 generation DMRs, suggesting a potential role for RNA-directed DNA methylation. The DMRs also had significant overlap with the DHRs, suggesting potential DNA methylation-directed histone retention. In addition, a high percentage of DMRs induced in the F1 generation sperm were maintained in subsequent generations.

Conclusions
Many of the DMRs, ncRNA, and DHRs were colocalized to the same chromosomal location regions. Observations suggest an integration of DMRs, ncRNA, and DHRs in part involve RNA-directed DNA methylation and DNA methylation-directed histone retention in epigenetic transgenerational inheritance.
Circular RNAs in osteoarthritis: indispensable regulators and novel strategies in clinical implications
Authors: Zhang Wenchao , Qi Lin , Chen Ruiqi , He Jieyu , Liu Zhongyue , Wang Wanchun , Tu Chao , Li Zhihong 
Published: January 2021

AbstractOver the past decades, circular RNAs (circRNAs) have emerged as a hot spot and sparked intensive interest. Initially considered as the transcriptional noises, further studies have indicated that circRNAs are crucial regulators in multiple cellular biological processes, and thus engage in the development and progression of many diseases including osteoarthritis (OA). OA is a prevalent disease that mainly affects those aging, obese and post-traumatic population, posing as a major source of socioeconomic burden. Recently, numerous circRNAs have been found aberrantly expressed in OA tissues compared with counterparts. More importantly, circRNAs have been demonstrated to interplay with components in OA microenvironments, such as chondrocytes, synoviocytes and macrophages, by regulation of their proliferation, apoptosis, autophagy, inflammation, or extracellular matrix reorganization. Herein, in this review, we extensively summarize the roles of circRNAs in OA microenvironment, progression, and putative treatment, as well as envision the future directions for circRNAs research in OA, with the aim to provide a novel insight into this field.
Childhood DNA methylation as a marker of early life rapid weight gain and subsequent overweight
Authors: Robinson N. , Brown H. , Antoun Elie , Godfrey Keith M. , Hanson Mark A. , Lillycrop Karen A. , Crozier Sarah R. , Murray Robert , Pearce M. S. , Relton C. L. , Albani V. , McKay J. A. 
Published: January 2021

AbstractBackgroundHigh early postnatal weight gain has been associated with childhood adiposity; however, the mechanism remains unknown. DNA methylation is a hypothesised mechanism linking early life exposures and subsequent disease. However, epigenetic changes associated with high early weight gain have not previously been investigated. Our aim was to investigate the associations between early weight gain, peripheral blood DNA methylation, and subsequent overweight/obese. Data from the UK Avon Longitudinal study of Parents and Children (ALSPAC) cohort were used to estimate associations between early postnatal weight gain and epigenome-wide DNA CpG site methylation (Illumina 450 K Methylation Beadchip) in blood in childhood (n = 125) and late adolescence (n = 96). High weight gain in the first year (a change in weight z‐scores > 0.67), both unconditional (rapid weight gain) and conditional on birthweight (rapid thrive), was related to individual CpG site methylation and across regions using the meffil pipeline, with and without adjustment for cell type proportions, and with 5% false discovery rate correction. Variation in methylation at high weight gain-associated CpG sites was then examined with regard to body composition measures in childhood and adolescence. Replication of the differentially methylated CpG sites was sought using whole-blood DNA samples from 104 children from the UK Southampton Women’s Survey.ResultsRapid infant weight gain was associated with small (+ 1% change) increases in childhood methylation (age 7) for two distinct CpG sites (cg01379158 (NT5M) and cg11531579 (CHFR)). Childhood methylation at one of these CpGs (cg11531579) was also higher in those who experienced rapid weight gain and were subsequently overweight/obese in adolescence (age 17). Rapid weight gain was not associated with differential DNA methylation in adolescence. Childhood methylation at the cg11531579 site was also suggestively associated with rapid weight gain in the replication cohort.ConclusionsThis study identified associations between rapid weight gain in infancy and small increases in childhood methylation at two CpG sites, one of which was replicated and was also associated with subsequent overweight/obese. It will be important to determine whether loci are markers of early rapid weight gain across different, larger populations. The mechanistic relevance of these differentially methylated sites requires further investigation.
Alzheimer’s cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans
Authors: Moon Sohee , Kim Sujin , Mankhong Sakulrat , Choi Seong Hye , Vandijck Manu , Kostanjevecki Vesna , Jeong Jee Hyang , Yoon Soo Jin , Park Kyung Won , Kim Eun-Joo , Yoon Bora , Kim Hee Jin , Jang Jae-Won , Hong Jin Yong , Park Dong-Ho , Shaw Leslie M. , Kang Ju-Hee 
Published: January 2021

Abstract
Background
Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on β-amyloid (Aβ) positron emission tomography (PET) status comparing with these from two manual immunoassays, in Koreans.

Methods
Among 331 Korean participants enrolled from a prospective, 3-year longitudinal observational study of the validation cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD, 139 (29 CN, 58 SCD, 29 MCI, and 23 AD) provided CSF and 271 underwent baseline amyloid PET (n = 128 with overlapping CSF and Aβ-PET, and 143 without CSFs). Three annual cognitive and neuropsychiatric function tests were conducted. Aβ42, Aβ40, total-tau, and phosphorylated-tau181 were measured by Lumipulse fully automated immunoassay and two manual immunoassays (INNO-BIA AlzBio3, INNOTEST). Clinical utility of CSF biomarker cutoffs, based on 128 participants with Aβ-PET, was evaluated.

Results
Cognitive and neuropsychological scores differed significantly among the groups, with descending performance among CN>SCD>MCI>AD. Biomarker levels among immunoassays were strongly intercorrelated. We determined the Aβ-PET status in a subgroup without CSF (n = 143), and then when we applied CSF biomarker cutoffs determined based on the Aβ-PET status, the CSF biomarkers (cutoffs of 642.1 pg/mL for Aβ42, 0.060 for Aβ42/Aβ40, 0.315 for t-tau/Aβ42, and 0.051 for p-tau/Aβ42, respectively) showed good agreement with Aβ-PET (overall AUC ranges of 0.840–0.898). Use of the Aβ-PET-based CSF cutoffs showed excellent diagnostic discrimination between AD and CN (Aβ42, Aβ42/Aβ40, t-tau/Aβ42, and p-tau/Aβ42) with overall AUC ranges of 0.876–0.952. During follow-up, participants with AD-like CSF signature determined by Aβ-PET-based cutoffs from Lumipulse showed rapid progression of cognitive decline in 139 subjects, after adjustment for potential confounders, compared with those with a normal CSF signature.

Conclusion
CSF AD biomarkers measured by different immunoassay platforms show strong intercorrelated agreement with Aβ-PET in Koreans. The Korean-specific Aβ-PET-based CSF biomarker cutoffs measured by the Lumipulse assay strongly predicts progression of cognitive decline. The clinical utility of CSF biomarkers from fully-automated immunoassay platforms should be evaluated in larger, more diverse cohorts.
Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD)
Authors: Ridzuan Noridzzaida , Zakaria Norashikin , Widera Darius , Sheard Jonathan , Morimoto Mitsuru , Kiyokawa Hirofumi , Mohd Isa Seoparjoo Azmel , Chatar Singh Gurjeet Kaur , Then Kong-Yong , Ooi Ghee-Chien , Yahaya Badrul Hisham 
Published: January 2021

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.

Methods
In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD).

Results
Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD.

Conclusions
In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.
The role of vitamin D in autoimmune diseases: could sex make the difference?
Authors: Dupuis Maria Luisa , Pagano Maria Teresa , Pierdominici Marina , Ortona Elena 
Published: January 2021

AbstractOver the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.