bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of complete atypical femur fracture with Oral bisphosphonate exposure beyond three years
Authors: Lo Joan C. , Neugebauer Romain S. , Ettinger Bruce , Chandra Malini , Hui Rita L. , Ott Susan M. , Grimsrud Christopher D. , Izano Monika A. 
Published: December 2020

Abstract
Background
Bisphosphonate (BP) therapy has been associated with atypical femur fracture (AFF). However, the threshold of treatment duration leading to increased AFF risk is unclear. In a retrospective cohort of older women initiating BP, we compared the AFF risk associated with treatment for at least three years to the risk associated with treatment less than three years.

Methods
We used observational data from a large population of female members of an integrated healthcare system who initiated oral BP during 2002–2014. Women were retrospectively followed for incident AFF confirmed by radiologic adjudication. Demographic data, pharmacologic exposures, comorbidity, bone density, and fracture history were ascertained from electronic health records. Inverse probability weighting was used to estimate risk differences comparing the cumulative incidence (risk) of AFF if women discontinued BP within three years to the cumulative incidence of AFF if women continued BP for three or more years, adjusting for potential time-dependent confounding by the aforementioned factors.

Results
Among 87,820 women age 45–84 years who initiated BP (mean age 68.6, median T-score − 2.6, 14% with prior major osteoporotic fracture), 16,180 continued BP for three or more years. Forty-six confirmed AFFs occurred during follow-up in the two groups. AFF-free survival was greater for BP treatment < 3 years compared to treatment ≥3 years (p = 0.004 comparing areas under survival curves). At five years, the risk of AFF was 27 per 100,000 (95% confidence interval, CI: 8–46) if women received BP treatment < 3 years and 120 per 100,000 (95% CI: 56–183) if women received BP treatment ≥3 years (risk difference 93 per 100,000, 95% CI: 30–160). By ten years, the risks were 27 (95% CI: 8–46) and 363 (95% CI: 132–593) per 100,000 for BP treatment < 3 and ≥ 3 years, respectively (risk difference 336 per 100,000, 95% CI: 110–570).

Conclusions
Bisphosphonate treatment for 3 or more years was associated with greater risk of AFF than treatment for less than 3 years. Although AFFs are uncommon among BP-treated women, this increased risk should be considered when counseling women about long-term BP use. Future studies should further characterize the dose-response relationship between BP duration and incident AFF and identify patients at highest risk.
Axial pelvic tilt in direct anterior Total hip Arthroplasty using a traction table
Authors: Aichmair A. , Dominkus M. , Hofstaetter J. G. 
Published: December 2020

Abstract
Background
Direct anterior approach total hip arthroplasty may be undertaken on a traction table, but the effects that patient positioning can have on axial pelvic tilt (aPT) are unknown. The aim of this study was to assess the degree of error from patient positioning on the traction table during anterior minimally-invasive surgery (AMIS) THA.

Methods
Patients were included who underwent direct anterior THA via the AMIS technique at a single institution between 11/2018 and 03/2019. Axial pelvic tilt was measured (a) in the supine position on the operating table, and (b) after positioning on the traction table, by the same consultant surgeon in all cases.

Results
In the above-mentioned study period, 50 patients (F: 32; M: 18) with an average age of 60.6 ± 13.6 (range: 26.5 to 88.3) years, and an average BMI of 27.2 ± 5.0 (range: 17.9 to 41.5) kg/m2 met the inclusion criteria. When measured in supine position, the average aPT was − 0.2 ± 1.7 (range: − 5.6 to 3.8) degrees. After positioning on the traction table, the average aPT was − 3.5 ± 2.1 (− 8.5 to 1.6) degrees (p < 0.001). In patients with an aPT of more than 5 degrees, the caput-collum-diaphyseal (CCD) angle was significantly lower (125 ± 11° vs. 134 ± 8°, p = 0.007).

Conclusion
This study raises awareness for the potential risk of aPT during positioning of the patient on the traction table, commonly used during direct anterior THA via the AMIS technique.
Planning peer assisted learning (PAL) activities in clinical schools
Authors: Burgess Annette , van Diggele Christie , Roberts Chris , Mellis Craig 
Published: December 2020

AbstractPeer Assisted Learning (PAL) is well accepted as an educational method within health professional education, involving a process of socialisation among students. PAL activities provide a framework whereby students are permitted to practice and develop their healthcare and teaching skills. However, the success of PAL activities is dependent upon two key factors: the “agency” of the individual students, that is, their willingness to participate; and importantly, the “affordance” of the activity, that is, the invitational quality provided by the clinical school. The purpose of this paper is to assist healthcare educators and administrators responsible for curriculum design, course co-ordination, and educational research, in developing their own PAL activities. Health professional students and junior health professionals leading or participating in PAL activities may also find the paper useful. Based on the authors’ collective experience, and relevant literature, we provide practical tips for the design, implementation and evaluation of PAL activities.
Effectiveness of blended learning versus lectures alone on ECG analysis and interpretation by medical students
Authors: Viljoen Charle André , Millar Rob Scott , Manning Kathryn , Burch Vanessa Celeste 
Published: December 2020

Abstract
Background
Most medical students lack confidence and are unable to accurately interpret ECGs. Thus, better methods of ECG instruction are being sought. Current literature indicates that the use of e-learning for ECG analysis and interpretation skills (ECG competence) is not superior to lecture-based teaching. We aimed to assess whether blended learning (lectures supplemented with the use of a web application) resulted in better acquisition and retention of ECG competence in medical students, compared to conventional teaching (lectures alone).

Methods
Two cohorts of fourth-year medical students were studied prospectively. The conventional teaching cohort (n = 67) attended 4 hours of interactive lectures, covering the basic principles of Electrocardiography, waveform abnormalities and arrhythmias. In addition to attending the same lectures, the blended learning cohort (n = 64) used a web application that facilitated deliberate practice of systematic ECG analysis and interpretation, with immediate feedback. All participants completed three tests: pre-intervention (assessing baseline ECG competence at start of clinical clerkship), immediate post-intervention (assessing acquisition of ECG competence at end of six-week clinical clerkship) and delayed post-intervention (assessing retention of ECG competence 6 months after clinical clerkship, without any further ECG training). Diagnostic accuracy and uncertainty were assessed in each test.

Results
The pre-intervention test scores were similar for blended learning and conventional teaching cohorts (mean 31.02 ± 13.19% versus 31.23 ± 11.52% respectively, p = 0.917). While all students demonstrated meaningful improvement in ECG competence after teaching, blended learning was associated with significantly better scores, compared to conventional teaching, in immediate (75.27 ± 16.22% vs 50.27 ± 17.10%, p <  0.001; Cohen’s d = 1.58), and delayed post-intervention tests (57.70 ± 18.54% vs 37.63 ± 16.35%, p <  0.001; Cohen’s d = 1.25). Although diagnostic uncertainty decreased after ECG training in both cohorts, blended learning was associated with better confidence in ECG analysis and interpretation.

Conclusion
Blended learning achieved significantly better levels of ECG competence and confidence amongst medical students than conventional ECG teaching did. Although medical students underwent significant attrition of ECG competence without ongoing training, blended learning also resulted in better retention of ECG competence than conventional teaching. Web applications encouraging a stepwise approach to ECG analysis and enabling deliberate practice with feedback may, therefore, be a useful adjunct to lectures for teaching Electrocardiography.
The effect of active occupational stress management on psychosocial and physiological wellbeing: a pilot study
Authors: Jukic Tomislav , Ihan Alojz , Strojnik Vojko , Stubljar David , Starc Andrej 
Published: December 2020

AbstractBackgroundThe aim of the study was to address the working population with an occupational stress prevention program using mHealth solution and encourage them for healthy lifestyle choices.MethodsSeventeen participants were randomized from the corporate setting. A 24alife app with a good compliance program was selected. Test battery has been designed to test the physical readiness, psychological evaluation and biological blood markers for stress. Participants were followed up after 30, 60 and 90 days, respectively, within the intervention period. Weight of participants was tracked three times per month. Univariate analysis compared the continuous variables by One-Way Repeated-Measures ANOVA test when the data were normally distributed, or Wilcoxon rank sum test for abnormal distribution of variables.ResultsParticipants used the app with a compliance rate of 94.1%. The psychological evaluation revealed higher motivation for work, lower burnout scores and participants gave subjective responses of better general wellbeing. Some of the participants lost up to four kg of body mass. Physical readiness has also improved.ConclusionsResults of mHealth projects on corporate could include primary health care institutions and health ministry to extend the existing system to patients’ pockets where they can monitor their disease and increase the ability of self-care.
Rural context, single institution prospective outcomes after enhanced recovery colorectal surgery protocol implementation
Authors: Smucker Levi , Victory Jennifer , Scribani Melissa , Oceguera Luis , Monzon Raul 
Published: December 2020

Abstract
Background
Rural hospitals face unique challenges to adopting Enhanced Recovery protocols after colorectal surgical procedures. There are few examples of successful implementation in the United States, and fewer yet of prospective, outcomes-based trials.

Methods
This study drew data from elective bowel resection prospectively collected, retrospectively analyzed cases 2 years prior (n = 214) and 3 years after (n = 224) implementing an ERAS protocol at a small, rural health network in upstate New York. Primary outcomes were cost, length-of-stay, readmission rate, and complications.

Results
The implementation required changes and buy-in at multiple levels of the institution. There was a statistically significant reduction in mean length of stay (6.9 versus 5.1 days) and per-patient savings to hospital ($3000) after implementation of ERAS protocol. There was no significant change in rate of 30-day readmissions or complications.

Conclusions
The authors conclude that for rural-specific barriers to implementation of Enhanced Recovery protocols there are specific organizational strategies that can ultimately yield sustainable endpoints.
Balancing revenue generation with capacity generation: case distribution, financial impact and hospital capacity changes from cancelling or resuming elective surgeries in the US during COVID-19
Authors: Tonna Joseph E. , Hanson Heidi A. , Cohan Jessica N. , McCrum Marta L. , Horns Joshua J. , Brooke Benjamin S. , Das Rupam , Kelly Brenna C. , Campbell Alexander John , Hotaling James 
Published: December 2020

AbstractBackgroundTo increase bed capacity and resources, hospitals have postponed elective surgeries, although the financial impact of this decision is unknown. We sought to report elective surgical case distribution, associated gross hospital revenue and regional hospital and intensive care unit (ICU) bed capacity as elective surgical cases are cancelled and then resumed under simulated trends of COVID-19 incidence.MethodsA retrospective, cohort analysis was performed using insurance claims from 161 million enrollees from the MarketScan database from January 1, 2008 to December 31, 2017. COVID-19 cases were calculated using Institute for Health Metrics and Evaluation models. Centers for Disease Control (CDC) reports on the number of hospitalized and intensive care patients by age estimated the number of cases seen in the ICU, the reduction in elective surgeries and the financial impact of this from historic claims data, using a denominator of all inpatient revenue and outpatient surgeries.ResultsAssuming 5% infection prevalence, cancelling all elective procedures decreases ICU overcapacity from 160 to 130%, but these elective surgical cases contribute 78% (IQR 74, 80) (1.1 trillion (T) US dollars) to inpatient hospital plus outpatient surgical gross revenue per year. Musculoskeletal, circulatory and digestive category elective surgical cases compose 33% ($447B) of total revenue.ConclusionsProcedures involving the musculoskeletal, cardiovascular and digestive system account for the largest loss of hospital gross revenue when elective surgery is postponed. As hospital bed capacity increases following the COVID-19 pandemic, restoring volume of these elective cases will help maintain revenue. In these estimates, adopting universal masking would help to avoid overcapacity in all states.
Crystal structure of the yeast heterodimeric ADAT2/3 deaminase
Authors: Liu Xiwen , Chen Ruoyu , Sun Yujie , Chen Ran , Zhou Jie , Tian Qingnan , Tao Xuan , Zhang Zhang , Luo Guan-zheng , Xie Wei 
Published: December 2020

Abstract
Background
The adenosine-to-inosine (A-to-I) editing in anticodons of tRNAs is critical for wobble base-pairing during translation. This modification is produced via deamination on A34 and catalyzed by the adenosine deaminase acting on tRNA (ADAT) enzyme. Eukaryotic ADATs are heterodimers composed of the catalytic subunit ADAT2 and the structural subunit ADAT3, but their molecular assemblies and catalytic mechanisms are largely unclear.

Results
Here, we report a 2.8-Å crystal structure of Saccharomyces cerevisiae ADAT2/3 (ScADAT2/3), revealing its heterodimeric assembly and substrate recognition mechanism. While each subunit clearly contains a domain resembling their prokaryotic homolog TadA, suggesting an evolutionary gene duplication event, they also display accessory domains for additional structural or functional purposes. The N-lobe of ScADAT3 exhibits a positively charged region with a potential role in the recognition and binding of tRNA, supported by our biochemical analysis. Interestingly, ScADAT3 employs its C-terminus to block tRNA’s entry into its pseudo-active site and thus inactivates itself for deamination despite the preservation of a zinc-binding site, a mechanism possibly shared only among yeasts.

Conclusions
Combining the structural with biochemical, bioinformatic, and in vivo functional studies, we propose a stepwise model for the pathway of deamination by ADAT2/3. Our work provides insight into the molecular mechanism of the A-to-I editing by the eukaryotic ADAT heterodimer, especially the role of ADAT3 in catalysis.
An optimized base editor with efficient C-to-T base editing in zebrafish
Authors: Zhao Yu , Shang Dantong , Ying Ruhong , Cheng Hanhua , Zhou Rongjia 
Published: December 2020

AbstractBackgroundZebrafish is a model organism widely used for the understanding of gene function, including the fundamental basis of human disease, enabled by the presence in its genome of a high number of orthologs to human genes. CRISPR/Cas9 and next-generation gene-editing techniques using cytidine deaminase fused with Cas9 nickase provide fast and efficient tools able to induce sequence-specific single base mutations in various organisms and have also been used to generate genetically modified zebrafish for modeling pathogenic mutations. However, the editing efficiency in zebrafish of currently available base editors is lower than other model organisms, frequently inducing indel formation, which limits the applicability of these tools and calls for the search of more accurate and efficient editors.ResultsHere, we generated a new base editor (zAncBE4max) with a length of 5560 bp following a strategy based on the optimization of codon preference in zebrafish. Our new editor effectively created C-to-T base substitution while maintaining a high product purity at multiple target sites. Moreover, zAncBE4max successfully generated the Twist2 p.E78K mutation in zebrafish, recapitulating pathological features of human ablepharon macrostomia syndrome (AMS).ConclusionsOverall, the zAncBE4max system provides a promising tool to perform efficient base editing in zebrafish and enhances its capacity to precisely model human diseases.
SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1
Authors: Tian Cong , Lang Tingyuan , Qiu Jiangfeng , Han Kun , Zhou Lei , Min Daliu , Zhang Zhiqi , Qi Dachuan 
Published: December 2020

AbstractBackgroundCancer stem cells (CSCs) have been recognized as an important drug target, however, the underlying mechanisms have not been fully understood. SKP1 is a traditional drug target for cancer therapy, while, whether SKP1 promotes colorectal cancer (CRC) stem cells (CRC-SCs) and the underlying mechanisms have remained elusive.MethodsHuman CRC cell lines and primary human CRC cells were used in this study. Gene manipulation was performed by lentivirus system. The mRNA and protein levels of target genes were examined by qRT-PCR and western blot. The sphere-forming and in vitro migration capacities were determined by sphere formation and transwell assay. The self-renewal was determined by limiting dilution assay. The tumorigenicity and metastasis of cancer cells were examined by xenograft model. The promoter activity was examined by luciferase reporter assay. Nuclear run-on and Chromatin immunoprecipitation-PCR (ChIP-PCR) assay were employed to examine the transcription and protein-DNA interaction. Co-immunoprecipitation assay was used to test protein–protein interaction. The relationship between gene expression and survival was analyzed by Kaplan–meier analysis. The correlation between two genes was analyzed by Spearman analysis. Data are represented as mean ± SD and the significance was determined by Student’sttest.ResultsSKP1 was upregulated in CRC-SCs and predicted poor prognosis of colon cancer patients. Overexpression of SKP1 promoted the stemness of CRC cells reflected by increased sphere-forming, migration and self-renewal capacities as well as the expression of CSCs markers. In contrast, SKP1 depletion produced the opposite effects. SKP1 strengthened YAP activity and knockdown of YAP abolished the effect of SKP1 on the stemness of CRC cells. SKP1 suppressed RASSF1 at both mRNA and protein level. Overexpression of RASSF1 abolished the effect of SKP1 on YAP activity and CRC stemness.ConclusionOur results demonstrated that SKP1 suppresses RASSF1 at both mRNA and protein level, attenuates Hippo signaling, activates YAP, and thereby promoting the stemness of CRC cells.
Infant sex modifies associations between placental malaria and risk of malaria in infancy
Authors: Kakuru Abel , Roh Michelle E. , Kajubi Richard , Ochieng Teddy , Ategeka John , Ochokoru Harriet , Nakalembe Miriam , Clark Tamara D. , Ruel Theodore , Staedke Sarah G. , Chandramohan Daniel , Havlir Diane V. , Kamya Moses R. , Dorsey Grant , Jagannathan Prasanna 
Published: December 2020

Abstract
Background
Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.

Methods
Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin–piperaquine (DP) or Sulfadoxine–pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (> 0–20% high powered fields [HPFs] with pigment), or severe past PM (> 20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM.

Results
There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00–1.71, p = 0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89–1.83, p = 0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45–3.25, p < 0.001), but not female infants (aIRR 0.74, 95% CI 0.46–1.20, p = 0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM.

Conclusion
PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk.
Trial registration ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622