bluuebunny/crossref_metadata_2025_split huggingface dataset:
The WHO-TDR Dissemination and Implementation Massive Open Online Course (MOOC): Evaluation and Lessons Learned from Eight Low-and Middle-Income Countries.
Authors: Rakhra Ashlin , Hooley Cole , Fort Meredith , Weber Mary Beth , Price LeShawndra , Nguyen Hoa L. , Ramirez Manuel , Muula Adamson S. , Hosseinipour Mina , Apusiga Kingsley , Davila-Roman Victor , Gyamfi Joyce , Adjei Kezia Gladys Amaning , Andesia Josephine , Fitzpatrick Annette , Launois Pascal , Baumann Ana A. 
Published: March 2022

Abstract
Introduction Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle-income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, we report on the feasibility of this MOOC, which was implemented during the SARS COVID-19 pandemic from April- November 2020.Methods Participants completed pre- and post- training questionnaires to assess self-reported D&I competencies, general research skills, and research mentor access and quality. D&I competencies were measured by use of a scale developed for a US-based training program, with change in competency scores assessed by paired t test. We used univariate statistics to analyze the data for all other outcomes.Results Of the 247 participants enrolled, 32 (13%) completed all MOOC components. D&I competency scores suggest improvement for those who had complete pre- and post-assessments. Trainee’s average score on the full competency scale improved 1.45 points (0-5 scale) from pre- to post-test; all four subscales also showed evidence of improvements. There were small but not significant increases in competencies for grant writing, proposal/ manuscript writing and presentations from pre- to post-test assessment. 40% of trainees reported access to a research mentor and 12% reported access to a D&I specific mentor. Participants reported barriers (e.g., unstable internet access and challenges due to COVID-19) and facilitators (e.g., topical interests, collaboration with colleagues) to completing the MOOC.ConclusionsAlthough COVID-19 affected program usage and completion, the MOOC was feasible and effective, showing that among LMIC participants completing the course, there was improvement in D&I competency scores. Recommendations for future D&I trainings in LMICs should include 1) adding more topic specific modules (i.e., NCD research, general research skills) for scalability; 2) fostering more collaboration with participants across LMICs; and 3) establishing partnerships with D&I mentors for course participants.
Impact of the size of CRISPR-Cas gene cassettes on the packaging efficiency and transduction titer of lentiviral vectors
Authors: Fan Minghui , Berkhout Ben , Herrera-Carrillo Elena 
Published: March 2022

Abstract
BackgroundCRISPR-Cas technology has revolutionized the use of genome-editing in studies on diverse biological topics. Lentiviral vectors (LVs) have been widely used for the generation of stably transduced cells that durably express the Cas protein and guide RNA (gRNA), the key components of the CRISPR-Cas editing system. This delivery system allows sustained gene expression in dividing and non-dividing cells in vitro and in vivo and LVs can be pseudo-typed with a variety of envelope proteins to establish a broad tropism for a range of target cells. A major challenge on the use of LVs in clinical settings is the requirement to obtain vector stocks of a sufficiently high titer. The endonuclease encoded by Streptococcus pyogenes Cas9 (SpCas9) is the most widely used CRISPR endonuclease for genome engineering, but it has an important limitation because of its relatively large size (∼4.1 kb coding sequence) that may hamper the delivery by means of viral vector systems. Smaller Cas endonucleases have been developed more recently, but these systems still need to be validated in specific experimental settings.ResultsThis work aimed to assess the impact of the CRISPR-Cas transgene size on the production of LVs and their ability to transduce cells. We observed that the LV transduction efficiency measured on the SupT1 T cell line dropped dramatically for RNA transcripts approaching 8 kb, e.g. a further increase of 1 kb reduced the transduction efficiency by more than 5-fold. As the number of produced virus particles was not affected, this means that the use of larger transgenes may cause the production of more empty virion particles. ConclusionsThis study confirmed that the transfer efficiency decreased for CRISPR-Cas genes above a certain size. One of the strategies to avoid the restricted RNA packaging can be the use of smaller CRISPR-Cas systems or the inclusion of truncated versions of the regulatory sequences like the promoters that are needed for efficient expression of the transgenes. This work has implications for the design of effective CRISPR-Cas editing therapies that use viral vectors, LVs in particular.
Stereotactic Body Radiotherapy versus Radiofrequency Ablation as Initial Treatment of Small Hepatocellular Carcinoma
Authors: Shin Hwang Sik , Cheon Gab Jin , Jun Baek Gyu , Kim Young Don , Yoo Jeong-Ju , Kim Sang Gyune , Kim Young Seok , Jeong Soung Won , Jang Jae Young , Kim Hong Soo , Suk Ki Tae , Kim Dong Joon , Lee Sae Hwan 
Published: March 2022

Abstract
Background/Aim: Resection or ablative therapy is not indicated for many patients with hepatocellular carcinoma (HCC) because of advanced cirrhosis or the tumor location. Stereotactic body radiotherapy (SBRT) may be an alternative treatment for these patients. This study compared the therapeutic effects of radiofrequency ablation (RFA) and SBRT in patients with small (≤ 3 cm) HCCs.Methods: Data of HCC patients who underwent SBRT or RFA as an initial treatment at four tertiary referral hospitals between March 2011 and February 2017 were reviewed. The patient inclusion criteria were a single nodule measuring ≤ 3 cm in size and not suitable for resection.Results: SBRT and RFA were performed for 72 (SBRT group) and 134 (RFA group) patients, respectively. The 1-, 3- and 5-year overall survival (OS) rates were 97.0%, 80.3%, and 80.3%, respectively, in the SBRT group compared with 98.5%, 83.9%, and 80.8%, respectively, in the RFA group, with no significant differences between the groups (P = 0.81). The estimated five-year local control (LC) rate was 68.1% in the SBRT group and 73.1% in the RFA group (P = 0.81). In the SBRT group analysis, both SBRT alone (n=34) and SBRT combined with transarterial chemoembolization (n=38) showed no difference with RFA in OS (p = 0.72) or LC rate (p = 0.95).Conclusion: SBRT is an effective and safe treatment method for small HCCs, with survival and tumor recurrence rates similar to those of RFA.
Wear Modelling of the Thread Pair in a Planetary Roller Screw Mechanism
Authors: Ma Shangjun , Xu Qianjin , Li Chuangchuang , Zhang Jianxin , Liu Geng 
Published: March 2022

Abstract
Based on the contact characteristics of helical surfaces and the coexistence of rolling and sliding at the screw-roller interface, a forecast model of thread pair using Archard wear theory is proposed. To obtain the wear depth and the wear volume of the screw raceway in the whole effective stroke, a test rig of thread wear is developed to obtain the wear rate that can be used to fit the values of the stress index and speed index. The area coefficient is further deduced to reflect the real wear condition. The calculation method of the relative sliding speed, coordinate transformation and load distribution are provided, the finite element (FE) model is established, and the transient dynamic simulation of thread wear is implemented to verify the correctness of the wear model. The relative error is less than 9% between the FE model and proposed model by comparing the wear depths and wear volumes, which indicates the wear model proposed in this paper is valid and can be used to forecast the thread wear of the PRSM. Finally, the wear behavior of the thread pair is preliminarily discussed based on the FE model.
Raw triaxial wrist accelerometer-measured physical activity in mid-age Australian adults
Authors: Mielke Gregore Iven , Burton Nicola W , Brown Wendy J 
Published: March 2022

Abstract
Background: Raw accelerometry data can provide valuable insights into specific attributes of physical activity, such as time spent in intensity-specific activity. The aim of this study was to describe physical activity assessed with raw triaxial wrist-worn accelerometers in mid-age Australian adults.Methods: Data were from a sub-sample of a population–based cohort of mid-age adults living in Brisbane, Australia (N=767). Participants (mean age: 60.4; SD:7.1 years) wore a triaxial accelerometer (Actigraph wGT3X-BT) on the non-dominant wrist during waking hours for seven consecutive days. Data were included if wear time was at least 600 min/day over at least four days (n=700). Total physical activity, expressed as acceleration in gravitational equivalent units (1mg=0.001g), and time spent in moderate-vigorous intensity physical activity (MVPA; >100 mg) using different bout criteria (non-bouted, 1-, 5-, and 10-min bouts) were calculated. Results: Mean acceleration was 23.2 mg (SD: 7.5) and did not vary by gender (men: 22.4; women: 23.7; p-value: 0.073) or education (p-value: 0.375). On average, mean acceleration was 10% (2.5 mg) lower per decade of age from age 55y. The median durations in non-bouted, 1-min, 5-min and 10-min MVPA bouts were, respectively, 68 (25th-75th: 45-99), 26 (25th-75th: 12-46), 10 (25th-75th: 3-24) and 8 (25th-75th: 0-19) min/day.Conclusion: This is one of the first population-based cohort studies to provide a detailed description of raw accelerometer physical activity in mid-age adults in Australia. Such data can be used to investigate how different patterns and intensities of physical activity vary across the day/week and influence health outcomes.
Effect of epigenetic activating of Dlk1-Dio3 imprinted cluster on miR-370 expression due to folate deficiency during nerve development
Authors: Chang Shaoyan , Min Jie , Lu Xiaolin , Zhang Qingyu , Shaofang Shangguan , Zhang Ting , Wang Li 
Published: March 2022

Abstract
Proper Dlk1-Dio3 imprinting plays a critical role in embryogenesis, and folic acid deficiency may affect the imprinting of this locus through epigenetic regulation. However, whether and how folic acid directly impacts the imprinting status of Dlk1-Dio3 to affect neural development remain unclear. Here, we found decreased IG-DMR methylation in the folate-deficient encephalocele in humans, suggesting that abnormal Dlk1-Dio3 imprinting status is related to neural tube defects (NTDs) caused by folate deficiency. Similar results were obtained with folate-deficient embryonic stem cells. By miRNA chip analysis, folic acid deficiency led to changes in multiple miRNAs, including the upregulation of 14 miRNAs located in the Dlk1-Dio3 locus. Real-time PCR confirmed that six of these miRNAs were upregulated, especially miR-370. In contrast to normal embryonic development, in which expression of miR-370 is highest at E9.5, the abnormally high and sustained expression of miRNA-370 in folate-deficient E13.5 embryos may contribute to NTDs. In addition, we found that DNMT3A is a direct target gene of miR-370 in neural cells, and that the high levels of miR-370 may inhibit cell migration by downregulating DNMT3A. Finally, in the folate-deficient mouse model, Dlk1-Dio3 epigenetic activation was found in fetal brain tissue, along with the upregulation of miR-370 and the downregulation of DNMT3A. Collectively, our findings demonstrate a pivotal role of folate in the epigenetic regulation of Dlk1-Dio3 imprinting during neurogenesis, revealing an elegant mechanism for the activation of Dlk1-Dio3 locus miRNAs in folic acid deficiency.
Absence of microbiome triggers extensive changes in the transcriptional profile of Hermetia illucens during larval ontology
Authors: Auger Laurence , Bouslama Sidki , Deschamps Marie-Hélène , Vandenberg Grant , Derome Nicolas 
Published: March 2022

Abstract
Black soldier fly larvae (BSF, Hermetia illucens) have gained much attention for their industrial use as biowaste recyclers and as a new source of animal proteins. The functional effect that microbiota has on insect health and growth performance remains largely unknown. This study clarifies the role of microbiota in BSF ontogeny by investigating the differential genomic expression of BSF larvae in axenic conditions (i.e., germfree) relative to non-axenic (conventional) conditions. We used RNA-seq to measure differentially expressed transcripts between axenic and conventional condition using DESeq2 at day 4, 12 and 20 post-hatching. Gene expression was significantly up or down-regulated for 2476 transcripts mapped in gene ontology functions, and axenic larvae exhibited higher rate of down-regulated functions. Up-regulated microbiota-dependant transcriptional gene modules included the immune system, the lipid metabolism, and the nervous system. Expression profile showed a shift in late larvae (day 12 and 20), exposing a significant temporal effect on gene expression. These results provide the first evidence of host functional genes regulated by microbiota in the BSF larva, further demonstrating the importance of host-microbiota interactions on host ontology and health. These results open the door to optimization of zootechnical properties in alternative animal protein production, biowaste revalorization and recycling.
Habitat quality influences trade-offs in animal movement along the exploration-exploitation continuum
Authors: SMITH JOSHUA , KEITER DAVID , SWEENEY STEVEN , MILLER RYAN , SCHLICHTING PETER , BEASLEY JAMES 
Published: March 2022

Abstract
To successfully establish itself in a novel environment, an animal must make an inherent trade-off between knowledge accumulation and exploitation of knowledge gained (i.e., the exploration-exploitation dilemma) to ensure survival. To evaluate how habitat quality affects the spatio-temporal scale of switching between exploration and exploitation during home range establishment, we conducted experimental trials to compare resource selection and four space-use metrics of translocated animals to those of reference individuals using reciprocal translocations between habitat types of differing quality. We selected wild pigs (Sus scrofa) as a model species to investigate hypotheses related to the movement behavior of translocated individuals because they are a globally distributed large mammal that is often translocated within their introduced range to facilitate recreational hunting, which is a primary mechanism contributing to the extensive range expansion of this species. Individuals translocated to higher quality habitat exhibited smaller exploratory movements and began exploiting resources more quickly than those introduced to lower quality areas, although those in lower-quality areas demonstrated an increased rate of selection for preferred habitat as they gained knowledge of the landscape. Our data demonstrate that habitat quality mediates the spatial and temporal scale at which animals respond behaviorally to novel environments, and how these processes may determine the success of population establishment.
Development of a predictive risk stratification tool to identify population over 45 at risk of new-onset stroke in seven years
Authors: Wang Yaoling , Jiang Gege , Hou Niuniu , Chen Minfang , Wang Liping , Li Wei 
Published: March 2022

Abstract
Background and Purpose: With the aging of society, stroke has become a vital health problem for the middle-aged and elderly. Amounts of stroke's new risk factors have been found recently. It is necessary to develop a predictive risk stratification tool containing multi-dimensional risk factors for identifying high-risk people.Methods: The study included 5844 people (Age≥45) who participated in the China Health and Retirement Longitudinal Study, in 2011 and follow-up to 2018. Randomly divided the population into training and validation set by 1:1. Lasso Cox screened predictors for new-onset stroke. Developed a nomogram and stratified the population according to the score calculated in the nomogram through the X-tile program. Internal and external verification of nomogram was performed by ROC and calibration curves, and the Kaplan-Meier method was applied to identify the performance of the risk stratification system.Results: Lasso COX regression screened out 13 candidate predictors from 50 risk factors. Finally, nine predictors, including low physical performance, triglyceride-glucose index, etc., were included in the nomogram. The nomogram's overall performance was good in both internal and external validation (AUCs of three-year, five-year, seven-year in the training set was 0.71, 0.71, 0.71, and 0.67, 0.65, 0.66 in the validation set, respectively). The nomogram was proven to could excellently discriminate between low-, moderate-, and high-risk groups with the 7-year new-onset stroke of 3.36%, 8.32%, and 20.13%, respectively (P<0.001).Conclusions: This research developed a clinical predictive risk stratification tool that can effectively identify the different risks of new-onset stroke incidents in 7-years in the middle-aged and elderly Chinese.
Second and third harmonic generation of asymmetrical Gaussian potential quantum dot
Authors: Ghanbari Ahmad , Birooni Raziyeh 
Published: March 2022

Abstract
In the current work, we have studied the second and third harmonic generation in asymmetrical Gaussian potential quantum dot subjected to the applied electric field. To do this, confined wave function together with energies of electron in an effective mass approximation framework were obtained. Apply these, the analytic expression for the second- and third harmonic generation are determined using a compact density matrix approach and an iterative procedure. According to the results, it is found that applying an electric field, enhances the peak values of the second- and third harmonic generation and redshifts the peak position of their spectrum. Our calculations indicate that increases the radius of quantum dot causes enhances the values of -harmonic generation and redshifts the peak positions of photon energy. It means by optimizing the confinement potential, the maximum –harmonic generation can be obtained. It should be noted that the structural parameters have a significant effect on the –harmonic generation in the considered system.
Weight loss outcomes achieved by adults accessing an online programme offered as part of Public Health England’s ‘Better Health’ campaign.
Authors: Avery Amanda , Toon Josef , Geneva Martina , Sharpe Paul , lavin Jacquie , Bennett Sarah 
Published: March 2022

Abstract
Effective use of health technology may offer a scalable solution to the obesity pandemic. Online digital programmes provide a convenient and flexible way for more people to access regular support. This service evaluation aims to determine whether adults accessing an online weight management programme via a national campaign are successful in losing weight. Data was analysed for adults registering with Slimming World’s online programme using a discounted membership offered as part of PHE’s ‘Better Health’ campaign between July and December 2020. Last-weight carried forward was used to calculate weight outcomes for participants who had the opportunity to complete 12-weeks and recorded ≥ one weight besides baseline. Engagement was determined using number of online weekly weights recorded with high engagers having weight data for ≥ 9 occasions. Socioeconomic status was assessed using postcode data. Resubscription and uploaded weight data were used to determine numbers who continued beyond the offer period. 27,248 adults (5.3% males) with mean age 41.0 ± 11.4years met inclusion criteria. Mean baseline BMI was 33.4 ± 6.8 kg/m2 (29.2% 30-34.9, 18.3% 35-39.9 and 15.1% >40 kg/m2). Mean weight loss at 12 weeks was 2.7 (± 3) kg representing a mean loss of 3% (± 3.1) body weight with 42.3% achieving ≥ 3% and 22.1% weight loss ≥ 5%. Median number of weigh-ins was six. Men had greater weight losses compared to women (p < 0.001). High engagers, both men and women, achieved greater weight losses (p < 0.001). Absolute weight loss was associated with joining BMI (rs=-0.15, p < 0.001) but for % weight change only small differences were seen (max effect size = 0.03) and no differences in weight change for high engagers between different baseline BMI categories (p > 0.05). 30.9% were in the lowest two IMD quintiles and absolute and percentage weight change did not differ across deprivation quintiles (p > 0.05). 34.9% continued to access the online support after the offer period. This service evaluation shows that an online programme, offered as part of a national campaign, can offer effective support to a large number of people with different starting BMIs and from different socioeconomic backgrounds. An increased level of engagement leads to better weight losses.
Feasibility Study Protocol: Investigating Family Reported Outcome Measures (FROMs) in the Estimation of Societal Value of Advanced Therapeutic Medicinal Products (ATMPs)
Authors: Brilliant Charles , Finlay Andrew , Salek Sam , Shah Rubina , Laing Hamish 
Published: March 2022

Abstract
BackgroundAdvance Therapeutic Medicinal Products (ATMPs) are a novel class of therapeutics to provide more effective treatment of conditions or diseases that have not responded to conventional treatment. However, ATMPs are generally very expensive, limiting their availability. Indicated conditions are usually chronic and severe and can have an impact beyond the patient themselves, impairing the lives of partners and other family members. This family impact is a major secondary burden of disease that is often ignored. The Family Reported Outcome Measure (FROM-16) is the first generic questionnaire designed to measure the impact of any chronic disease on the quality of life of family members or partners of patients. It is simple-to-use and non-burdensome for those completing it.We aim to validate the FROM-16 instrument in the setting of patients receiving ATMPs by recruiting family members to complete FROM-16 and Global Health Score questionnaire and undergo a semi-structured interview.MethodsUp to 30 patients of any age who are preparing for, or who have received, ATMP treatment and their family members aged 18 years or older, attending NHS providers within the Midland-Wales Advanced Therapy Treatment Centre will be recruited into this study. Family members will be asked to complete the FROM-16 and Global Health Score questionnaires, provide basic demographic information and complete a short semi-structured interview. The interview will provide data to contextualise the FROM-16 responses and allow construct and content validity to be assessed. Themes of experience will be identified from interview transcripts. The FROM-16 responses will be evaluated for total score, domain score, and individual item score. Reliability of responses between and within domains will be assessed by intraclass correlation. DiscussionCollecting FROM data reliably is important for demonstrating the wider impact of disease and the extended value of treatments. We hypothesise that collecting FROMs using the FROM-16 tool is a valid method to measure this impact in the setting of patients receiving ATMPs and if so, could provide evidence in future of the overall quality of life impact on the partners and family members of such patients and greater understanding of the wider societal value of these costly treatments. Trial RegistrationThis trial has been adopted onto the NIHR portfolio (I.D. 51376) and registered with www.ClinicalTrials.gov (#NCT05141318) in December 2021.