bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacist dispensing of the abortion pill in Canada: Diffusion of Innovation meets integrated knowledge translation
Authors: Munro Sarah , Wahl Kate , Soon Judith A. , Guilbert Edith , Wilcox Elizabeth S. , Leduc-Robert Genevieve , Ansari Nadra , Devane Courtney , Norman Wendy V. 
Published: August 2021

AbstractBackgroundSince Canadian drug regulatory approval of mifepristone for medical abortion in 2015 and its market availability in January 2017, the role of pharmacists in abortion provision has changed rapidly. We sought to identify the factors that influenced the initiation and provision of medical abortion from the perspectives of Canadian pharmacists, bridging two frameworks — Diffusion of Innovation in Health Service Organizations and integrated knowledge translation.MethodsWe conducted one-on-one semi-structured interviews with pharmacists residing in Canada who intended to stock and dispense mifepristone within the first year of availability. Our data collection, analysis, and interpretation were guided by reflexive thematic analysis and supported by an integrated knowledge translation partnership with pharmacy stakeholders.ResultsWe completed interviews with 24 participants from across Canada: 33% had stocked and 21% had dispensed mifepristone. We found that pharmacists were willing and able to integrate medical abortion care into their practice and that those who had initiated practice were satisfied with their dispensing experience. Our analysis indicated that several key Diffusion of Innovation constructs impacted the uptake of mifepristone, including: innovation (relative advantage, complexity and compatibility, technical support), system readiness (innovation-system fit, dedicated time, resources), diffusion and dissemination (expert opinion, boundary spanners, champions, social networks, peer opinions), implementation (external collaboration), and linkage. Participants’ experiences suggest that integrated knowledge translation facilitated evidence-based changes to mifepristone dispensing restrictions, and communication of those changes to front line pharmacists.ConclusionsWe illustrate how Diffusion of Innovation and integrated knowledge translation may work together as complimentary frameworks for implementation science research. Unlike in the USA, UK, and other highly regulated settings globally, pharmacists in Canada are permitted to dispense mifepristone for medical abortion. We contribute to literature that shows that mifepristone dispensed outside of hospitals, clinics, and medical offices is safe and acceptable to both patients and prescribers. This finding is of particular importance to the current COVID-19 pandemic response and calls for continued and equitable access to abortion care in primary practice.
Clinical and radiological outcomes in three-dimensional printing assisted revision total hip and knee arthroplasty: a systematic review
Authors: Zhang Rui , Lin Jiajun , Chen Fenyong , Liu Wenge , Chen Min 
Published: August 2021

AbstractBackgroundThis study investigates whether three-dimensional (3D) printing-assisted revision total hip/knee arthroplasty could improve its clinical and radiological outcomes and assess the depth and breadth of research conducted on 3D printing-assisted revision total hip and knee arthroplasty.MethodsA literature search was carried out on PubMed, Web of Science, EMBASE, and the Cochrane Library. Only studies that investigated 3D printing-assisted revision total hip and knee arthroplasty were included. The author, publication year, study design, number of patients, patients’ age, the time of follow-up, surgery category, Coleman score, clinical outcomes measured, clinical outcomes conclusion, radiological outcomes measured, and radiological outcomes conclusion were extracted and analyzed.ResultsTen articles were included in our review. Three articles investigated the outcome of revision total knee arthroplasty, and seven investigated the outcome of revision total hip arthroplasty. Two papers compared a 3D printing group with a control group, and the other eight reported 3D printing treatment outcomes alone. Nine articles investigated the clinical outcomes of total hip/knee arthroplasty, and eight studied the radiological outcomes of total hip/knee arthroplasty.Conclusion3D printing is being introduced in revision total hip and knee arthroplasty. Current literature suggests satisfactory clinical and radiological outcomes could be obtained with the assistance of 3D printing. Further long-term follow-up studies are required, particularly focusing on cost-benefit analysis, resource availability, and, importantly, the durability and biomechanics of customized prostheses using 3D printing compared to traditional techniques.
Using a BonE BiOPsy (BeBoP) to determine the causative agent in persons with diabetes and foot osteomyelitis: study protocol for a multicentre, randomised controlled trial
Authors: Gramberg Meryl Cinzía Tila Tamara , Lagrand Rimke Sabine , Sabelis Louise Willy Elizabeth , den Heijer Martin , de Groot Vincent , Nieuwdorp Max , Kortmann Willemijn , Sieswerda Elske , Peters Edgar Josephus Gerardus 
Published: August 2021

AbstractBackgroundDiabetic foot osteomyelitis (DFO) poses a major disease burden. It can generally be treated with long-term antibacterial therapy. International guidelines recommend to base antibacterial therapy choices on percutaneous bone biopsy culture, while in practice, therapy is frequently based on (less invasive) ulcer bed cultures. It is currently unknown if treatment outcomes of DFO differ depending on the chosen diagnostic strategy.MethodsThe BeBoP trial is a multicentre; randomised controlled; physician-, researcher- and subject-blinded; clinical trial comparing two diagnostic strategies in persons with DFO. Culture-directed antibacterial therapy will be based on either percutaneous bone biopsy culture results (intervention group) or ulcer bed biopsy culture results (comparison group). We will enrol 80 subjects with diabetes mellitus (≥ 18 years) and DFO, and we will use block randomisation stratified per centre to randomise them in a 1:1 allocation. The primary outcome is remission of DFO 12 months after enrolment. The secondary outcomes are the time to remission, signs of inflammation or ulceration at the primary location of infection at 6 and 12 months, microbiological and molecular profiles of culture outcomes, surgical interventions including amputation, total antibacterial therapy duration, infection-free survival days, adverse events, quality of life and survival. We will compare the outcomes by intention-to-treat and per-protocol analysis.DiscussionWe aim to compare clinical remission in persons with DFO treated with antibacterial therapy based on either percutaneous bone biopsy culture results or ulcer bed biopsy culture results.Trial registrationNetherlands Trial RegisterNL 7582. Registered on 05 March 2019
Comparing the effects of self-selected MUsic versus predetermined music on patient ANXiety prior to gynaecological surgery: the MUANX randomized controlled trial
Authors: Reynaud D. , Bouscaren N. , Lenclume V. , Boukerrou M. 
Published: August 2021

AbstractBackgroundAnxiety is frequently observed in the preoperative setting. The negative impact of preoperative anxiety is well known. In the context of gynaecological surgery, anxiety is exacerbated by the fact that the intervention can have catastrophic repercussions on a woman’s body image, sexuality, and psycho-affective well-being. Music listening is increasingly used as an alternative therapy for minimizing preoperative anxiety. Personal preferences, familiarity, and popularity may be key elements for an optimal relaxation response to music.This study aimed to determine whether listening to self-selected music decreases preoperative anxiety in women scheduled to undergo gynaecologic surgery compared with predetermined music from an application (MUSIC CARE®).MethodsThe MUANX study was a single-blind, monocentric, parallel, superiority, randomized controlled trial. A total of 174 women were included and randomized in two groups between August 2017 and September 2018. Patients in the intervention group listened to the personal music playlist that they had created before being hospitalized. Patients in the control group listened to the predetermined playlist on the MUSIC CARE® application. All patients received standard nursing care and listened to 20 min of music 1 h before surgery. Anxiety scores were assessed before and after the music session using Spielberger’s State-Trait Anxiety Inventory (STAI).ResultsThe mean age of the 171 evaluated patients was 41.5 years (SD = 10.0 years). Before the music session, the STAI state anxiety score was similar in the control group (M = 38.8, SD = 11.9) and the intervention group (M = 39.0, SD = 13.1). After the music session, this score had significantly decreased in both the control group (M = −7.2, SD = 9.0) and the intervention group (M = −5.5, SD = 6.6), with no significant difference in score reduction between groups. Physiological parameters were unchanged after the music session. No significant differences in postoperative measurements (pain intensity, hospitalization duration) were observed between the two groups.ConclusionSelf-selected music is as effective as predetermined music for reducing patient anxiety before gynaecological surgery. As it has no side effects and is easily applicable in gynaecological surgical services, this non-drug intervention may be proposed by healthcare professionals in the management of preoperative anxiety.Trial registrationThe MUANX trial (MUsic therapy on ANXiety) is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT03226834. Registered on 24 July 2017.https://clinicaltrials.gov/ct2/show/NCT03226834?term=muanx&draw=2&rank=1
Simplified binomial estimation of human malaria transmission exposure distributions based on hard classification of where and when mosquitoes are caught: statistical applications with off-the-shelf tools
Authors: Killeen Gerry F. , Monroe April , Govella Nicodem J. 
Published: August 2021

AbstractThe impacts and limitations of personal protection measures against exposure to vectors of malaria and other mosquito-borne pathogens depend on behavioural interactions between humans and mosquitoes. Therefore, understanding where and when they overlap in time and space is critical. Commonly used approaches for calculating behaviour-adjusted estimates of human exposure distribution deliberately use soft classification of where and when people spend their time, to yield nuanced and representative distributions of mean exposure to mosquito bites across entire human populations or population groups. However, these weighted averages rely on aggregating individual-level data to obtain mean human population distributions across the relevant behavioural classes for each time increment, so they cannot be used to test for variation between individuals. Also, these summary outcomes are quite complex functions of the disaggregated data, so they do not match the standard binomial or count distributions to which routine off-the-shelf statistical tools may be confidently applied. Fortunately, the proportions of exposure to mosquito bites that occur while indoors or asleep can also be estimated in a simple binomial fashion, based on hard classification of human location over a given time increment, as being either completely indoors or completely outdoors. This simplified binomial approach allows convenient analysis with standard off-the-shelf logistic regression tools, to statistically assess variations between individual humans, human population subsets or vector species. Such simplified binomial estimates of behavioural interactions between humans and mosquitoes should be more widely used for estimating confidence intervals around means of these indicators, comparing different vector populations and human population groups, and assessing the influence of individual behaviour on exposure patterns and infection risk. Also, standard sample size estimation techniques may be readily used to estimate necessary minimum experimental scales and data collection targets for field studies recording these indicators as key outcomes. Sample size calculations for field studies should allow for natural geographic variation and seasonality, taking advantage of rolling cross-sectional designs to survey and re-survey large numbers of separate study locations in a logistically feasible manner.
First exposure to rituximab is associated to high rate of anti-drug antibodies in systemic lupus erythematosus but not in ANCA-associated vasculitis
Authors: Faustini Francesca , Dunn Nicky , Kharlamova Nastya , Ryner Malin , Bruchfeld Annette , Malmström Vivianne , Fogdell-Hahn Anna , Gunnarsson Iva 
Published: August 2021

Abstract
Background
Anti-drug antibodies (ADAs) can impact on the efficacy and safety of biologicals, today used to treat several chronic inflammatory conditions. Specific patient groups may be more prone to develop ADAs. Rituximab is routinely used for ANCA-associated vasculitis (AAV) and as off-label therapy for systemic lupus erythematosus (SLE), but data on occurrence and predisposing factors to ADAs in these diseases is limited.

Objectives
To elucidate the rate of occurrence, and risk factors for ADAs against rituximab in SLE and AAV.

Methods
ADAs were detected using a bridging electrochemiluminescent (ECL) immunoassay in sera from rituximab-naïve (AAV; n = 41 and SLE; n = 62) and rituximab-treated (AAV; n = 22 and SLE; n = 66) patients. Clinical data was retrieved from medical records. Disease activity was estimated by the SLE Disease Activity Index-2000 (SLEDAI-2 K) and the Birmingham Vasculitis Activity Score (BVAS).

Results
After first rituximab cycle, no AAV patients were ADA-positive compared to 37.8% of the SLE patients. Samples were obtained at a median (IQR) time of 5.5 (3.7–7.0) months (AAV), and 6.0 (5.0–7.0) months (SLE). ADA-positive SLE individuals were younger (34.0 (25.9–40.8) vs 44.3 (32.7–56.3) years, p = 0.002) and with more active disease (SLEDAI-2 K 14.0 (10.0–18.5) vs. 8.0 (6.0–14), p = 0.0017) and shorter disease duration (4.14 (1.18–10.08) vs 9.19 (5.71–16.93), p = 0.0097) compared to ADA-negative SLE. ADAs primarily occurred in nephritis patients, were associated with anti-dsDNA positivity but were not influenced by concomitant use of corticosteroids, cyclophosphamide or previous treatments.
Despite overall reduction of SLEDAI-2 K (12.0 (7.0–16) to 4.0 (2.0–6.7), p < 0.0001), ADA-positive individuals still had higher SLEDAI-2 K (6.0 (4.0–9.0) vs 4.0 (2.0–6.0), p = 0.004) and their B cell count at 6 months follow-up was higher (CD19 + % 4.0 (0.5–10.0) vs 0.5 (0.4–1.0), p = 0.002). At retreatment, two ADA-positive SLE patients developed serum sickness (16.7%), and three had infusion reactions (25%) in contrast with one (5.2%) serum sickness in the ADA-negative group.

Conclusions
In contrast to AAV, ADAs were highly prevalent among rituximab-treated SLE patients already after the first course of treatment and were found to effect on both clinical and immunological responses. The high frequency in SLE may warrant implementations of ADA screening before retreatment and survey of immediate and late-onset infusion reactions.
EHMT2 promotes the pathogenesis of hepatocellular carcinoma by epigenetically silencing APC expression
Authors: Guo Yuan , Zhao Yan-Rong , Liu Huan , Xin Yang , Yu Jian-Zhi , Zang Yun-Jin , Xu Qing-guo 
Published: August 2021

AbstractBackgroundHepatocellular carcinoma (HCC), the second leading cause of cancer death worldwide, alone accounts for over half (466,100) of new cancer cases and 422,100 deaths based on the average year incidence rates of 2009 to 2011 in China. Due to unclear and complex underlying mechanisms for HCC development, effective therapy for HCC is still unavailable. The Wnt–β-catenin pathway is a critical contributor of HCC pathogenesis: 40–70% of HCCs from patients harbor the nuclear accumulation of β-catenin protein. However, the mechanisms for β-catenin activation are not fully understood.MethodsThe deletion of EHMT2 in Hep3B and Huh1 cells was achieved by transiently transfecting cells with pX459 plasmids, which carry EHMT2 specific small guide RNA (sgRNA) sequences for Cas9 protein. All experiments were performed in triplicate and repeated more than three times.ResultsIn the present study, we observed thatEHMT2(but notEHMT1) mRNA and protein levels were significantly elevated in HCC compared with normal controls. Next, the results of Ki67 staining, as well as MTT, soft-agar and xenograft assays, in wild-type andEHMT2−/−Hep3B and Huh1 cancer stem cells collectively revealed that the elevation of EHMT2 expression is required for the tumorigenesis of HCC. Meanwhile, we found that elevated EHMT2 expression contributes to the activation of Wnt–β-catenin signaling: deletion ofEHMT2in Hep3B or Huh1 cells promoted the cytoplasmic localization of β-catenin and restrained the expression of Wnt–β-catenin signaling targets such asMyc,CCND1,MMP-7, etc. We demonstrated that EMHT2 directly mediates the H3K9me2 methylation of theAPCpromoter to epigenetically silence its expression. More intriguingly, our findings also showed that UNC0642, a specific inhibitor of EHMT2, exhibits anti-tumorigenesis effects in HCC both in vitro and in vivo, which were largely abolished by deletion ofEHMT2or overexpression ofAPCin Hep3B and Huh1 cells.ConclusionAltogether, our observations emphasize that the EHMT2–APC axis is a critical contributor to Wnt–β-catenin pathway activation in HCC, and UNC0642 may be a potential candidate for target drug treatment of HCC.
Parental stress around ophthalmological health conditions: a systematic review of literature protocol
Authors: Souza-Silva Julio Cesar , Martins Cleusa Alves , Garciazapata Marco Túlio Antônio , Barbosa Maria Alves 
Published: August 2021

AbstractBackgroundParents can be psychologically impacted when their children are diagnosed with eye diseases, such as blindness, strabismus, and eye cancer. Stress can reduce the quality of parental care and may be linked to the deterioration of parents’ and children’s mental and physical health and family dynamics. No systematic literature review on parental stress in ophthalmology has been found to provide evidence synthesis capable of stimulating and defining new studies and thereby promoting research in this field. To address this important gap, the present review aims to synthesize evidence about approaches, methods, instruments, and results from research regarding ophthalmology-related parental stress.MethodsPrimary epidemiological observational studies should be original in addressing parental stress caused by ophthalmological health conditions in children. They should present the characteristics of the study population and the clinical and ophthalmic characterizations of children.MEDLINE (via Ovid), EMBASE, PsycINFO, Google Scholar, and gray literature (PsycEXTRA, NTIS, and OpenSINGLE) will be searched. Controlled vocabulary, Boolean operators, and defined search strategies will be used. There will be no restrictions on the studies’ publication language, which will be selected in two screening stages. Two reviewers will independently retrieve full-text studies, assess methodological quality, and extract data. Data available through December 2021 will be considered for inclusion.DiscussionThe socioeconomic characterization of the participants, the identification of which ophthalmological diseases have been studied in relation to parental stress, and the knowledge of each instrument and methodology peculiarities potentially contribute to this study. The results may promote the development or enhancement of public policies focused on this specific theme, thereby providing the means for potential improvement of the physical and mental health of parents and children with eye diseases.Systematic review registrationPROSPEROCRD42018094972
Roles of physical exercise in neurodegeneration: reversal of epigenetic clock
Authors: Xu Miao , Zhu JiaYi , Liu Xian-Dong , Luo Ming-Ying , Xu Nan-Jie 
Published: August 2021

AbstractThe epigenetic clock is defined by the DNA methylation (DNAm) level and has been extensively applied to distinguish biological age from chronological age. Aging-related neurodegeneration is associated with epigenetic alteration, which determines the status of diseases. In recent years, extensive research has shown that physical exercise (PE) can affect the DNAm level, implying a reversal of the epigenetic clock in neurodegeneration. PE also regulates brain plasticity, neuroinflammation, and molecular signaling cascades associated with epigenetics. This review summarizes the effects of PE on neurodegenerative diseases via both general and disease-specific DNAm mechanisms, and discusses epigenetic modifications that alleviate the pathological symptoms of these diseases. This may lead to probing of the underpinnings of neurodegenerative disorders and provide valuable therapeutic references for cognitive and motor dysfunction.
The role of personality, social economic and prevention strategy effects on health-related quality of life among people living with HIV/AIDS
Authors: Wang Xiaowen , Luo Hongbing , Yao Enlong , Tang Renhai , Dong Wenbin , Liu Fuyong , Liang Jun , Li Huilan , Xiao Minyang , Zhang Zuyang , Niu Jin , Song Lijun , Fu Liru , Li Xuehua , Qian Shicong , Guo Qing , Song Zhizhong 
Published: August 2021

Abstract
Background
HIV/AIDS has transformed into a chronic controllable but not yet curable infectious disease as other chronic diseases to some extent. The additional of so called fourth 90% that included the improved health-related quality of life (HRQoL) for people living with HIV (PLWHIV) required solutions beyond antiretroviral therapy and viral load suppression. This study will explore the role of personality, social economic and prevention strategy effection on HRQoL among people living with HIV/AIDS.

Methods
A cross-sectional study was conducted among PLWHIV aged more than 16 years old in the 10 municipalities in Yunnan Province, China from October 2019 to May 2020, enrolling total 1997 participants. Individual-level HRQoL data were measured by 12-item Short Form Health Survey (SF-12) and EuroQol Five Dimensions Questionnaire (EQ-5D-5L). We assembled municipal-level data about social economic from Yunnan Statistical Yearbook in 2020 and strategy practice information from the self-evaluation system. We used the principal component analysis to build the social economic and strategy effect on each area respectively and one-way ANOVA was used to perform univariate analysis to identify the predictors with significant differences. Finally we used multi-level model (MLM) to explore the personality, social economic and strategy effects in health-related quality of life among PLWHIV.

Results
The global score for quality of life measured using EQ-5D-5L had an estimated mean score (standard deviation, SD) of 0.901 ± 0.146. The HRQoL score measured using PCS-12 had an estimated mean score (SD) of 46.62 ± 8.55. The mean MCS-12 score (SD) was estimated to be 47.80 ± 9.71. The area-level predictors explained a proportion of 13.6–17.2% for the between-area variation of the HRQoL scores, regardless of the total HRQoL, physical component and mental component. The impacts of stigma (P < 0.01), social support (P < 0.001), anxiety (P < 0.001), depression (P < 0.05) and social economic status (P < 0.05) on HRQoL at the individual-level were significantly different. The plots visualized the impact of individual-level factors on a respondent’s HRQoL was modified by the area-level characteristics.

Conclusions
The study identified the possible strategy determinant of individual HRQoL of PLWHIV and also the area effect on HRQoL. Stigma, social support, anxiety, depression and social economic status were the individual-level determinants on HRQoL. These could be a valuable resource for evaluating the overall health of the areas and help improve local decision making.

Graphic abstract