bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the challenges and opportunities of public engagement with fundamental biology
Authors: Clements-Brod Naomi , Holmes Leah , Rawlins Emma L. 
Published: September 2022

ABSTRACT
The Human Developmental Biology Initiative (HDBI) is a Wellcome-funded research consortium involving scientists based in institutions across the UK and Europe. It aims to pioneer new technologies and techniques to answer fundamental questions about human development and could, therefore, eventually improve treatments for fertility, birth defects and developmental diseases, as well as aiding regenerative medicine. HDBI research relies on human fetal and embryonic tissues donated following pregnancy terminations or fertility treatment. The situations in which these tissues are donated, their use in research and the potential healthcare impacts of this work all present complex ethical and moral questions that are of interest not only to scientists but also to the public. As such, HDBI's public engagement programme ‘What makes us human?’ aspires to test new ways of engaging the public with fundamental biology. In this brief Perspective, we provide an overview of this public engagement approach, exploring its challenges and opportunities, and outline our longer-term plans. We hope that by sharing our experiences we will encourage and enable others to organise similarly experimental public engagement, even if their research is very fundamental or potentially controversial.
Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice
Authors: Lee Katie J. , Rambault Lisa , Bou-Gharios George , Clegg Peter D. , Akhtar Riaz , Czanner Gabriela , van ‘t Hof Rob , Canty-Laird Elizabeth G. 
Published: September 2022

ABSTRACT
The osteogenesis imperfecta murine (oim) model with solely homotrimeric (α1)3 type I collagen, owing to a dysfunctional α2(I) collagen chain, has a brittle bone phenotype, implying that the (α1)2(α2)1 heterotrimer is required for physiological bone function. Here, we comprehensively show, for the first time, that mice lacking the α2(I) chain do not have impaired bone biomechanical or structural properties, unlike oim homozygous mice. However, Mendelian inheritance was affected in male mice of both lines, and male mice null for the α2(I) chain exhibited age-related loss of condition. Compound heterozygotes were generated to test whether gene dosage was responsible for the less-severe phenotype of oim heterozygotes, after allelic discrimination showed that the oim mutant allele was not downregulated in heterozygotes. Compound heterozygotes had impaired bone structural properties compared to those of oim heterozygotes, albeit to a lesser extent than those of oim homozygotes. Hence, the presence of heterotrimeric type I collagen in oim heterozygotes alleviates the effect of the oim mutant allele, but a genetic interaction between homotrimeric type I collagen and the oim mutant allele leads to bone fragility.
Acute frataxin knockdown in induced pluripotent stem cell-derived cardiomyocytes activates a type I interferon response
Authors: Cotticelli M. Grazia , Xia Shujuan , Truitt Rachel , Doliba Nicolai M. , Rozo Andrea V. , Tobias John W. , Lee Taehee , Chen Justin , Napierala Jill S. , Napierala Marek , Yang Wenli , Wilson Robert B. 
Published: September 2022

ABSTRACT
Friedreich ataxia, the most common hereditary ataxia, is a neuro- and cardio-degenerative disorder caused, in most cases, by decreased expression of the mitochondrial protein frataxin. Cardiomyopathy is the leading cause of premature death. Frataxin functions in the biogenesis of iron-sulfur clusters, which are prosthetic groups that are found in proteins involved in many biological processes. To study the changes associated with decreased frataxin in human cardiomyocytes, we developed a novel isogenic model by acutely knocking down frataxin, post-differentiation, in cardiomyocytes derived from induced pluripotent stem cells (iPSCs). Transcriptome analysis of four biological replicates identified severe mitochondrial dysfunction and a type I interferon response as the pathways most affected by frataxin knockdown. We confirmed that, in iPSC-derived cardiomyocytes, loss of frataxin leads to mitochondrial dysfunction. The type I interferon response was activated in multiple cell types following acute frataxin knockdown and was caused, at least in part, by release of mitochondrial DNA into the cytosol, activating the cGAS-STING sensor pathway.
Association of Accelerometer-Measured Physical Activity and Sedentary Time with Epigenetic Markers of Aging
Authors: Spartano Nicole L. , Wang Ruiqi , Yang Qiong , Chernofsky Ariel , Murabito Joanne M. , Vasan Ramachandran S. , Levy Daniel , Beiser Alexa S. , Seshadri Sudha 
Published: September 2022

ABSTRACT

Introduction/Purpose
Physical activity may influence chronic disease risk, in part, through epigenetic mechanisms. Previous studies have demonstrated that an acute bout of physical activity can influence DNA methylation status. Few studies have explored the relationship between habitual, accelerometer-measured physical activity or sedentary time with epigenetic markers of aging.

Methods
We used linear regression to examine cross-sectional associations of accelerometer-measured physical activity and sedentary time with extrinsic and intrinsic epigenetic age acceleration (EEAA and IEAA) models and GrimAge measured from blood samples from Framingham Heart Study participants with accelerometry and DNA methylation data (n = 2435; mean age, 54.9 ± 14.3; 46.0% men). Residuals of Hannum-, Horvath-, and GrimAge-predicted epigenetic age were calculated by regressing epigenetic age on chronological age. We took into account blood cell composition for EEAA, IEAA, and AdjGrimAge. Moderate to vigorous physical activity was log-transformed to normalize its distribution. Adjustment models accounted for family structure, age, sex, smoking status, cohort–laboratory indicator, and accelerometer wear time. We additionally explored adjustment for body mass index (BMI).

Results
Walking 1500 more steps per day or spending 3 fewer hours sedentary was associated with >10 months lower GrimAge biological age (or ~1 month lower AdjGrimAge, after adjusting for blood cells, P < 0.05). Every 5 min·d−1 more moderate to vigorous physical activity was associated with 19–79 d of lower GrimAge (4–23 d lower using EEAA or AdjGrimAge, P < 0.01). Adjusting for BMI attenuated these results, but all statistically significant associations with AdjGrimAge remained.

Conclusions
Greater habitual physical activity and lower sedentary time were associated with lower epigenetic age, which was partially explained by BMI. Further research should explore whether changes in physical activity influence methylation status and whether those modifications influence chronic disease risk.
Adapting Bruner’s 3-Tier Theory to Improve Teacher Trainees’ Conceptual Knowledge for Teaching Integers at the Basic School
Authors: Aduko Edmund Anamboi , Armah Robert Benjamin 
Published: September 2022

<p style="text-align: justify;">The focus of this action research was to adapt Bruner’s 3-tier theory to enhance conceptual knowledge of teacher trainees on integer operations. It looks into how learners' conceptual knowledge of integer operations changes over time, as well as their attitudes toward using the 3-tier model. Eighty-two (82) teacher trainees, who were in their first year semester one of the 2020/2021 academic year were purposely selected for the study. Data was collected using test and semi-structured interviews. The study found that using Bruner’s 3-tier theory contributed to substantial gains in conceptual knowledge on integers operations among learners. It was also found that learners proffered positive compliments about the Concrete-Iconic-Symbolic (C-I-S) construct of lesson presentation and how it built their understanding to apply knowledge on integers operations. Learners also largely proffered positive image about C-I-S construct as it aroused interest and activated unmotivated learners. On these bases, the study concludes that lessons presentations should mirror C-I-S construct in order to alleviate learning difficulties encountered on integer operations. To do this, the study suggests that workshops on lesson presentation using C-I-S construct be organized for both subject tutors, mentors and lead mentors to re-equip their knowledge and to buy-in the idea among others.</p>
Implementing large-scale data quality validation in a national arthroplasty registry to improve compliance
Authors: Boulton Christopher , Harrison Carol , Wilton Timothy , Armstrong Richard , Young Elaine , Pegg Derek , Wilkinson J. Mark 
Published: September 2022

Data of high quality are critical for the meaningful interpretation of registry information. The National Joint Registry (NJR) was established in 2002 as the result of an unexpectedly high failure rate of a cemented total hip arthroplasty. The NJR began data collection in 2003. In this study we report on the outcomes following the establishment of a formal data quality (DQ) audit process within the NJR, within which each patient episode entry is validated against the hospital unit’s Patient Administration System and vice-versa. This process enables bidirectional validation of every NJR entry and retrospective correction of any errors in the dataset. In 2014/15 baseline average compliance was 92.6% and this increased year-on-year with repeated audit cycles to 96.0% in 2018/19, with 76.4% of units achieving > 95% compliance. Following the closure of the audit cycle, an overall compliance rate of 97.9% was achieved for the 2018/19 period. An automated system was initiated in 2018 to reduce administrative burden and to integrate the DQ process into standard workflows. Our processes and quality improvement results demonstrate that DQ may be implemented successfully at national level, while minimizing the burden on hospitals. Cite this article: Bone Jt Open 2022;3(9):716–725.
Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing
Authors: Menzies Stefanie K. , Litschka-Koen Thea , Edge Rebecca J. , Alsolaiss Jaffer , Crittenden Edouard , Hall Steven R. , Westhorpe Adam , Thomas Brent , Murray James , Shongwe Nondusimo , Padidar Sara , Lalloo David G. , Casewell Nicholas R. , Pons Jonathan , Harrison Robert A. 
Published: September 2022

Background
Snakebite is a major public health concern in Eswatini, where treatment relies upon one antivenom—SAIMR Polyvalent. Although effective in treating snakebite, SAIMR Polyvalent is difficult to source outside its manufacturing country (South Africa) and is dauntingly expensive. We compared the preclinical venom-neutralising efficacy of two alternative antivenoms with that of SAIMR Polyvalent against the lethal and tissue-destructive effects of venoms from five species of medically important snakes using in vivo murine assays. The test antivenoms were ‘Panafrican’ manufactured by Instituto Clodomiro Picado and ‘PANAF’ manufactured by Premium Serums & Vaccines.

Principal findings
In vivo murine preclinical studies identified both test antivenoms were equally or more effective than SAIMR Polyvalent at neutralising lethal and tissue-destructive effects of Naja mossambica venom. Both test antivenoms were less effective than SAIMR Polyvalent at neutralising the lethal effects of Bitis arietans, Dendroaspis polylepis, Hemachatus haemachatus and Naja annulifera venoms, but similarly effective at neutralising tissue damage induced by B. arietans and H. haemachatus venoms.
In vitro immunological assays identified that the titres and toxin-specificities of immunoglobulins (iGs) in the test antivenoms were comparable to that of SAIMR Polyvalent. Plasma clotting disturbances by H. haemachatus and N. mossambica were neutralised by the test antivenoms, whereas SAIMR Polyvalent failed to neutralise this bioactivity of N. mossambica venom. B. arietans SVMP activity was equally reduced by all three antivenoms, and H. haemachatus and N. mossambica PLA2 activities were neutralised by all three antivenoms.

Conclusions
While both Panafrican and PANAF antivenoms exhibited promising preclinical efficacies, both were less poly-specifically effective than SAIMR Polyvalent in these murine assays. The efficacy of these antivenoms against the lethal and tissue-destructive effects of N. mossambica venom, the most common biting species in Eswatini, identify that Panafrican and PANAF antivenoms offer effective alternatives to SAIMR Polyvalent for the treatment of snakebite in Eswatini, and potentially for neighbouring countries.
Patient perceptions by race of educational animations about living kidney donation made for a diverse population
Authors: Keller Maria M. , Lucas Todd , Cadzow Renee , Feeley Thomas , Tumiel Berhalter Laurene , Kayler Liise 
Published: September 2022

Introduction
This qualitative study sought to identify potential design and delivery alterations to inform cultural adaptation of educational animations about living donor kidney transplantation (LDKT)–previously developed for a diverse population–to better fit Black Americans’ needs.

Methods
We conducted a secondary analysis of 88 transcripts derived from interviews and focus groups conducted with diverse target users (62 kidney failure patients, 36 prior/potential donors, and 11 care partners) to develop 12 animations about LDKT, named KidneyTIME. Statements were abstracted and coded pertaining to cognitive and communication barriers to LDKT, and the perceived value of using the videos to learn and share the information with social network members using content analysis. Incidence counts of each content code were also calculated to assess differences between Black and non-Black patients.

Results
Cognitive barrier codes included lack of knowledge, ambivalence, and concern for donor. Communication barrier codes included reluctance and difficulty talking about LDKT. Cognitive facilitating codes included attention-getting, efficient learning, manageable content, emotional impact, and new knowledge. Communication facilitating codes included delivery through many dissemination channels and broadly shareable. Compared to non-black patients (n = 33) Black patients (n = 29) more often stated concern for donor and reluctance/difficulty talking about LDKT as barriers, and less often stated efficient learning and manageable content as facilitators.

Conclusion
Findings highlight the value of LDKT informational content that is visually appealing, digestible, non-threatening, and highly shareable. Heterogeneity may exist when considering access and intervention preferences in using KidneyTIME videos and highlight a potential for further cultural targeting or tailoring.
Proximal tubular renal dysfunction among HIV infected patients on Tenofovir versus Tenofovir sparing regimen in western Kenya
Authors: Karoney Mercy Jelagat , Koech Mathew Kirtptonui , Njiru Evangeline Wawira , Owino Ong’or Willis Dixon 
Published: September 2022

Introduction
Tenofovir Disoproxil Fumarate (TDF) is the most widely used Anti-Retroviral Therapy (ART) drug due to its potency, safety profile and World Health Organization (WHO) recommendation. TDF causes proximal tubular renal dysfunction (PTRD) leading to Fanconi syndrome, acute kidney injury and chronic kidney disease. Modest rates (2–4%) of TDF related toxicity based on estimated Glomerular Filtration Rate (GFR) have been described, while TDF-induced PTRD has been reported to be 22%. TDF toxicity is more likely among African patients, it is reversible and TDF may be renal dosed in patients with dysfunction. The objective of this study was to assess proximal tubular renal dysfunction, global renal function, and their determinants among patients on TDF versus TDF-sparing regimen.

Methods
This was a cross-sectional study among people living with HIV/AIDS (PLWHA) attending the Academic Model Providing Access to Healthcare (AMPATH) program. The primary outcome of interest in this study was PTRD while the secondary outcome of interest was estimated GFR. PTRD was defined as any two of beta-2 microglobulin in urine, metabolic acidosis, normoglycemic glucosuria and fractional excretion of phosphate. Student’s t-test, chi-square and their non-parametric equivalents were used to test for statistical significance. Univariate and multivariate logistic regression analysis was carried out.

Results
A total of 516 participants were included in the final analysis, 261 on TDF while 255 were on TDF-sparing regimens. The mean (SD) age of all participants was 41.5 (12.6) years with majority being female (60.3%). The proportion of PTRD was 10.0% versus 3.1% in the TDF compared to TDF-sparing group (P<0.001). Mean estimated GFR was 112.8 (21.5) vs 109.7 (21.9) ml/min/1.73mm3 (P = 0.20) for the TDF compared to TDF-sparing group. TDF users were more likely to have PTRD compared to non-TDF users, adjusted Odds Ratio (AOR) 3.0, 95% CI 1.12 to 7.75.

Conclusion
There was significant PTRD in the TDF compared to TDF-sparing group without significant difference in estimated GFR. The clinical significance of these findings may not be clear in the short term.
Mentoring future mentors in undergraduate medical education
Authors: Ong Yun Ting , Quek Chrystie Wan Ning , Pisupati Anushka , Loh Eleanor Kei Ying , Venktaramana Vaishnavi , Chiam Min , Krishna Lalit Kumar Radha 
Published: September 2022

BackgroundEfforts to support flagging mentoring programs facing shortages of experienced clinical mentors have had an unexpected and welcome effect. Supplementing traditional mentoring programs with peer-mentoring have not only addressed gaps in practice, structure, support and mentee oversight but have offered mentees charged with peer-mentoring duties the opportunity to take on mentoring roles under senior supervision. This study evaluates the experiences of peer-mentors within a local research mentoring program to better understand and advance this endeavor.MethodsSemi-structured interviews and post-interview surveys based on recent reviews on mentoring were employed. Adapting the Systematic Evidence Based Approach, data was analysed using thematic and content analysis. Results were combined using the Jigsaw Perspective to ensure that key elements of the different mentoring stages were identified.ResultsThe interviews and surveys revealed the following domains: Motivation, Initiation, Practicing, and Mentoring Environment.ConclusionThese findings provide novel insight into a structured framework that may help guide the experiences, training, assessment, and oversight of peer-mentors beyond the auspices of our local program. These general observations will equip host organizations with the direction they need to take in designing and executing peer-mentoring training and assessment programs of their own. Whilst the stages of peer-mentoring need further evaluation and an effective means of assessment and support pivotal, we believe our findings suggest that peer-mentoring may not only help to address the shortfall in mentors but is an invaluable learning experience that prepares and instils key values, beliefs and principles in young would-be mentors.
Modeling spatial determinants of initiation of breastfeeding in Ethiopia: A geographically weighted regression analysis
Authors: Hailegebreal Samuel , Haile Yosef , Seboka Binyam Tariku , Enyew Ermias Bekele , Shibiru Tamiru , Mekonnen Zeleke Abebaw , Mengiste Shegaw Anagaw 
Published: September 2022

Background
The World Health Organization (WHO) encourages breastfeeding to begin within the first hour after birth in order to save children’s lives. In Ethiopia, different studies are done on the prevalence and determinants of breastfeeding initiation, up to our knowledge, the spatial distribution and the spatial determinants of breast feeding initiation over time are not investigated. Therefore, the objectives of this study were to assess spatial variation and its spatial determinant of delayed initiation of breastfeeding in Ethiopia using Geographically Weighted Regression (GWR).

Methods
A cross-sectional study was undertaken using the nationally representative 2016 Ethiopian Demographic and Health Survey (EDHS) dataset. Global Moran’s I statistic was used to measure whether delayed breastfeeding initiation was dispersed, clustered, or randomly distributed in study area. Ordinary Least Squares (OLS) regression was used to identify factors explaining the geographic variation in delayed breastfeeding initiation. Besides, spatial variability of relationships between dependent and selected predictors was investigated using geographically weighted regression.

Result
A total weighted sample of 4169 children of aged 0 to 23 months was included in this study. Delayed initiation of breastfeeding was spatially varies across the country with a global Moran’s I value of 0.158 at (p-value<0.01). The hotspot (high risk) areas were identified in the Amhara, Afar, and Tigray regions. Orthodox religion, poor wealth index, caesarian section, baby postnatal checkup, and small size of a child at birth were spatially significant factors for delayed breastfeeding initiation in Ethiopia.

Conclusion
In Ethiopia initiation of breastfeeding varies geographically across region. A significant hotspot was identified in the Amhara, Afar, and Tigray regions. The GWR analysis revealed that orthodox religion, poor wealth index, caesarian section, baby postnatal checkup, and small birth weight were spatially significant factors.
Emotion-focused coping mediates the relationship between COVID-related distress and compulsive buying
Authors: Kovács Lilla Nóra , Katzinger Eva , Yi Sunghwan , Demetrovics Zsolt , Maraz Aniko , Kökönyei Gyöngyi 
Published: September 2022

Background and aims
COVID-19 posits psychological challenges worldwide and has given rise to nonadaptive behavior, especially in the presence of maladaptive coping. In the current study, we assessed whether the relationship between COVID-related distress and compulsive buying is mediated by task-focused and emotion-focused coping. We also examined whether these associations were invariant over time as the pandemic unfolded.

Methods
Self-report surveys were administered online in the United States in the first six months of the pandemic (March–October 2020) in sampling batches of 25 participants every three days, resulting in a total sample of N = 1,418 (40% female, mean age = 36.6). We carried out structural equation modeling to assess whether the relationship between distress related to COVID-19 and compulsive buying is mediated by task-focused and emotion-focused coping. Time was used as a grouping variable based on events related to the pandemic in the U.S. to calculate model invariance across three time periods.

Results
The results indicated significant mediation between distress, emotion-focused coping, and compulsive buying, but not between task-focused coping and compulsive buying. The mediation model showed excellent fit to the data (χ² = 1119.377, df = 420, RMSEA = 0.059 [0.055–0.064], SRMR = 0.049, CFI = 0.951, TLI = 0.947). Models were not invariant across the three examined time periods.

Conclusions
Our results indicate that compulsive buying is more likely to occur in relation to emotion-focused coping as a response to COVID-related distress than in relation to task-focused coping, especially during periods of increasing distress. However, model paths varied during the course of the pandemic.