bluuebunny/crossref_metadata_2025_split huggingface dataset:
“UNTARGETING” AUTOANTIBODIES USING GENOME EDITING, A PROOF-OF-CONCEPT STUDY
Authors: Keppeke Gerson Dierley , Diogenes Larissa , Gomes Kethellen , Andrade Luis Eduardo Coelho 
Published: October 2022

AbstractAutoantibodies are useful biomarkers of autoimmune diseases and some have direct pathogenic role. Current standard therapies for elimination of specific B/plasma-cell clones are not fully efficient. In this proof-of-concept study, we used the CRISPR/Cas9 genome-editing system to knockout V(D)J rearrangements that produce pathogenic autoantibodiesin vitro.HEK293T cell lines were established with stable expression of two monoclonal antibodies, a humanized anti-dsDNA (clone 3H9) and a human-derived anti-nAChR-α1-subunit (clone B12L). For each clone, five CRISPR/Cas9 guided-RNAs (T-gRNAs) were designed to target the heavy chain CDR2/3 variable regions. After CRISPR/Cas9 editing, levels of secreted immunoglobulins were evaluated, in addition to 3H9 anti-dsDNA reactivity by ELISA and B12L anti-AChR reactivity using cells overexpressing mouse genes of AChR-α1/β1/δ/γ/ε-subunits.The T-gRNAs decreased the expression of the heavy chain to ∼50-60%, compared to >90% in Non-Target-gRNA. Levels of secreted IgG and reactivity to the respective target antigens decreased ∼90% and ∼95% after knockout with the T-gRNAs compared to Non-Target-gRNA for clones 3H9 and B12L, respectively. Sequencing indicated the presence ofindelsat the Cas9 cut-site, which could lead to codon jam, the likely cause of the knockout. Additionally, remaining secreted 3H9 antibodies presented variable reactivity to dsDNA among the five T-gRNA, suggesting that the exact Cas9 cut-site andindelsmay further interfere with antibody-antigen interaction.CRISPR/Cas9 genome-editing was very effective to knockout the Heavy-Chain-IgG genes, considerably affecting the secretion and binding capacity of the autoantibodiesin vitro, warranting application of this concept toin vivomodels as a potential novel therapeutic approach for autoantibody-mediated diseases.Highlights➢Autoantibodies can have a direct pathogenic role in some autoimmune diseases.➢Elimination of specific B/plasma-cell clones is not attainable with current therapies.➢CRISPR/Cas9 allows targeting of specific DNA sites, such as V(D)J rearrangements.➢CRISPR/Cas9 genome-editing was very effective in knocking out the heavy chain of autoantibodies.➢Indels introduced at Cas9 cut site interfered with autoantibody-antigen interaction.
Overweight and Obesity among Women at Reproductive Age in Cambodia: Data Analysis of Cambodia Demographic and Health Survey 2014
Authors: Um Samnang , Yom An , Muir Jonathan A. , Sopheab Heng 
Published: October 2022

ABSTRACTIntroductionOverweight and obesity increase the risk of cardiovascular disease, type 2 diabetes mellitus, hypertension, stroke, and some type of cancers, and maternal health globally. In Cambodia, the prevalence of overweight and obesity among women aged 15-49 years increased from 6% in 2000 to 18% in 2014, becoming a public health burden. We examined socio-demographic and behavioral factors associated with overweight and/or obesity among women of reproductive age in Cambodia.MethodsWe analyzed existing data from the 2014 Cambodia Demographic and Health Survey (CDHS) that used a two-stage stratified cluster sampling design. Data analysis was restricted to non-pregnant women, resulting in an analytic sample of 10,818 women. Multivariable logistic regressions that accounted for the CDHS sampling design were performed using STATA V16 to examine factors associated with overweight and obesity.ResultsPrevalence of overweight and obesity among non-pregnant women of reproductive age were 15.2% and 2.8% respectively. Factors independently associated with increased odds of overweight and/or obesity including women aged 20-29 years with adjusted odds ratio [AOR=2.4; 95% CI: 1.6-3.6], 30-39 years [AOR=4.6; 95% CI: 3.0-6.9], and 40-49 years [AOR=6.6; 95% CI: 4.3-10.1], married women [AOR=1.8; 95% CI: 1.3-2.7], urban residence [AOR=1.3; 95% CI: 1.1-1.5], and women having at least 4 children [AOR=1.7; 95% CI: 1.2-2.5]. The following factors were associated with decreased odds of overweight and obesity: completed at least secondary education [AOR=0.7; 95% CI: 0.6-0.8], agricultural work [AOR=0.7; 95% CI: 0.5-0.8], and manual labor work [AOR=0.7; 95% CI: 0.6-0.9].ConclusionsIncreased age, married women, living in urban residence, and having at least four children were the main risk factors associated with overweight and/or obesity. Conversely, higher education, working in agriculture, and working in manual labor were negatively associated with overweight and/or obesity. Cambodia’s non-communicable disease (NCD) public health programs should consider these characteristic for targeting interventions to further reduce overweight and/or obesity in the coming years.
Reporting of medication adherence in randomized controlled trials of pharmacological interventions for SARS-CoV-2: a cross-sectional analysis
Authors: Lee C K , Otunla A , Brennan  , Aronson JK , Nunan D 
Published: October 2022

AbstractBackgroundAdherence to pharmacological interventions in clinical trials is crucial for correct estimation of beneficial and adverse effects, including trials of SARS-CoV-2. The Template for Intervention Description and Replication (TIDieR) – a 12-item extension of the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines – includes two items (11 and 12) that address intervention adherence reporting in trial publications.ObjectiveTo assess compliance with TIDieR items 11 and 12 of randomised controlled trials (RCTs) of interventions in SARS-CoV-2 infection published in five selected journals during 2021.MethodsWe assessed SARS-CoV-2 pharmacological RCTs published in theAnnals of Internal Medicine, The BMJ, JAMA, The Lancet, andThe New England Journal of Medicinein 2021 for compliance with TIDieR items 11 and 12. Item 11 was assessed in two parts: 11a—how intervention adherence was assessed; 11b—if any strategies were used to maintain or improve how intervention adherence was maintained or improved. Item 12 assessed the extent to which the intervention was delivered as planned. We calculated raw adherence and proportional (weighted) adherence for pharmacological and comparator interventions where available.ResultsWe found 75 eligible RCTs, of which 28 (37%) reported results related to SARS-CoV-2 vaccinations. Compliance with items 11a and 12 could be assessed in 71 of these 75. Of those 71 RCTs, 37 (52%, 95% confidence interval 40–64%) were compliant with reporting of item 11a. Seven RCTs had a strategy to assess compliance with item 11b, and only three (43%, 9–82%) of those complied with item 11b reporting. Of the 71 RCTs, 70 complied with reporting of item 12. Only one of the 71 RCTs (1.4%, 0–7.6%) fully complied with TIDieR items 11a, 11b, and 12. Compliance varied across journals.ConclusionsRCTs of SARS-CoV-2 pharmacological interventions published in high-impact medical journals complied variably with reporting of intervention adherence, even though the journals endorse CONSORT. The implications for interpretation, application, and replication of findings based on these publications warrant consideration.
A study on the nonlinear dynamics of ASEAN financial integration
Authors: Le Thai-Ha , Vo Long Hai , Taghizadeh-Hesary Farhad 
Published: October 2022

PurposeThis study examines the co-integration relationships between Association of Southeast Nations (ASEAN) stock indices as a way to assess the feasibility of policy initiatives to strengthen market integration in ASEAN and identify implications for portfolio investors.Design/methodology/approachThe authors employ threshold co-integration tests and a non-linear autoregressive distributed lag (NARDL) model to study the asymmetric dynamics of ASEAN equity markets. The study’s data cover the 2009–2022 period for seven member states: Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand and Vietnam.FindingsThe authors find evidence supporting co-integration relationships; adjustment toward equilibrium is asymmetric in the short run and symmetric in the long run for these countries. While co-movement in ASEAN equity markets seems encouraging for initiatives seeking to foster financial integration in regional economies, the benefits for international portfolio diversification appear to be neutralized.Originality/valueThe issue of stock market integration is important among policymakers, investors and academics. This study examines the level of stock market integration in ASEAN during the 2009–2022 period. For this purpose, advanced co-integration techniques are applied to different frequencies of data (daily, weekly and monthly) for comparison and completeness. The empirical analysis of this study is conducted using the Enders and Siklos (2001) co-integration and threshold adjustment procedure. This advanced co-integration technique is superior compared to other co-integration techniques by permitting asymmetry in the adjustment toward equilibrium.
Understandings of mild cognitive impairment (MCI): a survey study of public and professional perspectives
Authors: Yemm Heather , Peel Elizabeth , Brooker Dawn 
Published: October 2022

Purpose
This paper aims to report the findings of a survey study exploring perceptions about cognitive impairment. These findings are relevant to public health campaigns and education programmes.

Design/methodology/approach
A survey exploring respondents’ views and knowledge about mild cognitive impairment (MCI) was circulated via UK networks. A total of 417 respondents completed the survey, including people living with cognitive impairment (n = 10), care partners (n = 23), older adults (n = 83), younger adults (n = 83), general health-care professionals (n = 96), dementia specialist health-care professionals (n = 48) and dementia specialists (n = 40).

Findings
Respondents were more confident in their knowledge about dementia than cognitive impairment but wanted more information about both conditions. Younger adults were uncertain about many aspects of MCI, and were the most likely to view MCI as a normal part of ageing. Diet (45.1%, n = 188) and personal behaviour (63.8%, n = 266) were the least endorsed possible causes of MCI, suggesting a lack of awareness of lifestyle choices as risk factors for MCI.

Originality/value
The results highlight the need to provide education and awareness raising about MCI to enable people to seek help in a timely manner and be able to make informed lifestyle choices that may reduce their risk of MCI and dementia. Implementing education about MCI and dementia in schools is a key target, as younger people were the most uncertain or misinformed about these topics. It is clear that further public health initiatives around MCI are both warranted and welcomed by the general public.
Contribution of calcium dysregulation to impaired coronary artery contraction in Zucker diabetic fatty rats
Authors: Liu Lin , Yang Hui , Kuang Su‐Juan , Zhang Li , Zhou Meng‐Yuan , Zeng Peng , Zhang Meng‐Zhen , Rao Fang , Zhou Zhi‐Ling , Deng Chun‐Yu 
Published: October 2022

AbstractDiabetic coronary artery injury is closely associated with Ca2+ dysregulation, although the underlying mechanism remains unclear. This study explored the role and mechanism of Ca2+ handling in coronary artery dysfunction in type 2 diabetic rats. Zucker diabetic fatty (ZDF) rats were used as the type 2 diabetes mellitus model. The contractility of coronary artery rings induced by KCl, CaCl2, 5‐HT and U46619 was significantly lower in ZDF rats than in Zucker lean rats. Vasoconstriction induced by 5‐HT and U46619 was greatly inhibited by nifedipine. However, in the presence of 1 μM nifedipine or in the Ca2+‐free KH solution containing 1 μM nifedipine, there was no difference in the vasoconstriction between Zucker lean and ZDF rats. Store‐operated calcium channels (SOCs) were not involved in coronary vasoconstriction. The downregulation of contractile proteins and the upregulation of synthesized proteins were in coronary artery smooth muscle cells (CASMCs) from ZDF rats. Metformin reversed the reduction of vasoconstriction in ZDF rats. Taken together, L‐type calcium channel is important for regulating the excitation–contraction coupling of VSMCs in coronary arteries, and dysregulation of this channel contributes to the decreased contractility of coronary arteries in T2DM.
The politicisation of internet privacy regulation
Authors: ANTOINE ELISE 
Published: October 2022

AbstractDespite a rich body of literature on politicisation, knowledge of this process and its driving forces remains limited. Specifically, little empirical analysis has been carried out to assess the impact of focusing events on politicisation within global and seemingly technical venues of policy‐making. Building on existing studies, I conceptualise politicisation as a combination of three components: (1) issue salience, (2) actor expansion and (3) actor diversity. I test the impact of focusing events on the politicisation of one of the most pressing global policy issues of our age: internet regulation, specifically regarding global data protection and internet privacy rules. I use a systematic analysis of news media coverage over a 20‐year period, resulting in an original dataset of 2,100 news articles. Controlling for different factors, my findings reveal that focusing events do contribute to politicisation in technical venues, in particular regarding the actors involved in debates.
7% sodium citrate (with benzyl alcohol) as catheter lock: Dedication or obsession?
Authors: Ash Stephen R. 
Published: October 2022

AbstractThe standard heparin lock for dialysis catheters in US dialysis units is 1000 units/ml, though its use has significant limitations and problems. The alternative catheter lock of 4% sodium citrate is used in some patients, but a 7% solution would maintain catheter patency better than the 4% concentration. In spite of the failure of two prior catheter locks to become widely used in the US (highly concentrated citrate and Zuragen™), Ash Access worked with a compounding pharmacy to produce 7% sodium citrate with preservative in single‐patient use frangible vials, at a reasonable cost to users. The product had early acceptance by a number of dialysis units and hospitals, but then follow‐up orders were few. Where the project goes from here is unclear.
Men's experiences of antenatal care services in low‐income and middle‐income countries: A qualitative systematic review
Authors: Chiang Ron Kai Quan , Shorey Shefaly 
Published: October 2022

AbstractBackgroundMen's involvement in antenatal care is critical for the family's overall well‐being, yet remains low in many low‐income and middle‐income countries. The goal of this study was to consolidate and synthesize currently available literature on men's experiences of antenatal care services in low‐income and middle‐income countries.MethodsPubMed, CINAHL, Embase, PsycINFO, and Scopus were searched through December 2020. Qualitative studies were included exploring the antenatal care experiences of men whose pregnant partners utilized antenatal care services, regardless of ethnicity, race, and education levels. Studies examining men's participation in antenatal care that specifically focused on certain conditions such as the human immunodeficiency virus, known pregnancy complications, as well as contraception/fertility treatment, were excluded. Quality appraisal of the included studies was conducted using the Critical Appraisal Skills Program checklist, and Sandelowski and Barroso's two‐step approach was used to meta‐summarize and meta‐synthesize the extracted data.ResultsFour themes were derived from the 27 studies included: (a) Factors enabling men's participation in antenatal care; (b) Barriers affecting men's participation in antenatal care; (c) Men's self‐perceived care roles; and (d) Recommendations to improve men's involvement.ConclusionsMen's involvement in antenatal care depended on community perceptions, traditional gender roles, and work commitments. Although men often regarded antenatal care services as exclusive to women, some expressed their willingness to participate. Current findings highlight the need for community educational programs, male role models, and training of healthcare providers to improve men's participation.
Diallyl trisulfide alleviates chemotherapy sensitivity of ovarian cancer via the AMPK/SIRT1/PGC1α pathway
Authors: Wang Zhaojun , Yan Yi , Lou Yijie , Huang Xiaoyan , Liu Lijian , Weng Zhuofan , Cui Yusheng , Wu Xinyue , Cai Huijun , Chen Xiaohui , Ji Yunxi 
Published: October 2022

AbstractPlatinum‐based chemotherapy promotes drug resistance in ovarian cancer. We investigated the antichemoresistance characteristics of diallyl trisulfide (DATS) in cisplatin‐resistant ovarian cancer cells, in vitro and in vivo. Previous preclinical studies have revealed that DATS regulates distinct hallmark cancer‐signaling pathways. The cell cycle pathway is the most investigated signaling pathway in DATS. Additionally, post‐DATS treatment has been found to promote proapoptotic capacity through the regulation of intrinsic and extrinsic apoptotic pathway components. In the present study, we found that treating cisplatin‐sensitive and cisplatin‐resistant ovarian cell lines with DATS inhibited their proliferation and reduced their IC50. It induced cell apoptosis and promoted oxidative phosphorylation through the regulation of the AMPK/SIRT1/PGC1α pathway, OXPHOS, and enhanced chemotherapy sensitivity. DATS treatment alleviated glutamine consumption in cisplatin‐resistant cells. Our findings highlight the role of DATS in overcoming drug resistance in ovarian cancer in vitro and in vivo. In addition, we elucidated the role of the AMPK/SIRT1/PGC1α signaling pathway as a potential target for the treatment of drug‐resistant ovarian cancer.
Rapid treatment of endophthalmitis with intravitreal antibiotics is associated with better vision outcomes
Authors: Michael Eugene , Welch Sarah , Niederer Rachael L 
Published: October 2022

AbstractBackgroundTo discover whether the timing of intravitreal antibiotics, from the time of presentation to injection, affects the visual outcomes of patients with endophthalmitis from all causes.MethodsA retrospective study of consecutive patients managed at Auckland District Health Board between 1 January 2004 and 1 July 2021. The main outcome measure was final visual acuity at follow‐up and the proportion of subjects with severe vision loss (≤6/60).ResultsThree hundred and seventy‐four eyes were included in the study, with a median age of 69.7 years at presentation; 192 subjects (51.6%) were female. The median presenting visual acuity was hand movements and hypopyon was present in 194 subjects (51.9%). Cataract surgery was the most frequent aetiology in 115 subjects (30.7%), followed by intravitreal anti‐vascular endothelial growth factor injections in 89 subjects (23.8%) and endogenous endophthalmitis in 54 subjects (14.4%). Median time to injection of intravitreal antibiotics was 3.5 h (Interquartile range 2–6). On multivariate analysis, early treatment with intravitreal antibiotics was associated with better visual outcome, particularly for those treated within 2 h, while poor presenting visual acuity and culture‐positive endophthalmitis were associated with worse outcomes.ConclusionRapid intravitreal antibiotic administration is associated with better final visual acuity outcomes, particularly for those receiving treatment within 2 h of presentation. Patients with severe vision loss on presentation, benefit the most with improved final visual acuity following expedited treatment.
Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics
Authors: Home Philip D. , McCrimmon Rory J. , Rosenstock Julio , Blüher Matthias , Pegelow Katrin , Melas‐Melt Lydie , Djaballah Khier , Giorgino Francesco ,   the SoliMix trial investigators
Published: October 2022

AbstractAimTo report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics.MethodsSoliMix (EudraCT 2017‐003370‐13) compared once‐daily iGlarLixi (a fixed‐ratio combination of insulin glargine 100 U/mL and the glucagon‐like peptide‐1 receptor agonist lixisenatide) with twice‐daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function.ResultsNo evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P > 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P = 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events.ConclusionsTreatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well‐tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.
Invariant chain of the MAIT‐TCR vα7.2‐Jα33 as a novel diagnostic biomarker for keloids
Authors: Nurzat Yeltai , Zhu Zhu , Zhang Yixin , Xu Heng 
Published: October 2022

AbstractKeloids are pathological scars that invade normal surrounding tissue without self‐limitation, causing pain, itching, cosmetic disfigurement, etc. Knowledge of the molecular mechanisms underlying keloids remains unclear; thus, there are no available biomarkers for its diagnosis, resulting in a diagnostic accuracy of only 81%, which may be resolved by seeking an effective biomarker. Given that keloids possess pathogenic features similar to those of autoimmune skin disease, this study aimed to utilise the single‐cell V(D)J sequencing method to identify a potential biomarker and clarify the underlying biological mechanisms. Single‐cell V(D)J sequencing was used to detect T cell receptor (TCR) diversity between keloid patients and healthy donors using peripheral blood samples, the results of which were further validated using reverse transcription‐polymerase chain reaction (RT‐PCR). Flow cytometry was used to analyse the mucosal‐associated invariant T (MAIT) cell percentage, cytokine production, and activation marker expression levels in peripheral blood samples of keloid patients and normal donors. An immunofluorescence test was used to quantitatively analyse the distribution of MAIT cells in scar and healthy donor skin tissues. Single‐cell V(D)J sequencing analysis showed that the usage frequency of the TRAJ33‐one invariant chain of the TCR of MAIT cells was decreased in keloid patients. This result was validated by RT‐PCR, which showed that significantly lower TCR Vα7.2‐Jα33 was expressed in keloid patients compared with that in healthy donors and hypertrophic scar patients (p < 0.05). Flow cytometry and immunofluorescence tests further verified that MAIT cells decreased significantly both in the peripheral blood sample and lesions of keloid patients compared with those of healthy controls (p < 0.05). MAIT cells from keloid patients secreted less interferon (IFN)‐γ than those from the healthy controls and hypertrophic scar group (p < 0.001). The percentage of PLZF+ MAIT cells was lowest in the peripheral blood samples of keloid patients (p < 0.05). The percentage of IL‐18+ MAIT cells was lower in the peripheral blood samples of keloid patients compared with that in healthy donors (p < 0.05). These findings indicate that MAIT cells could be associated with keloids and may serve as potential biomarkers or therapeutic targets in the diagnosis of keloids.