bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets
Authors: Cai Chunyang , Meng Chunren , He Shuai , Gu Chufeng , Lhamo Thashi , Draga Deji , Luo Dawei , Qiu Qinghua 
Published: November 2022

AbstractBackgroundDiabetic retinopathy (DR), a specific neuron-vascular complication of diabetes, is a major cause of vision loss among middle-aged people worldwide, and the number of DR patients will increase with the increasing incidence of diabetes. At present, it is limited in difficult detection in the early stages, limited treatment and unsatisfactory treatment effects in the advanced stages.Main bodyThe pathogenesis of DR is complicated and involves epigenetic modifications, oxidative stress, inflammation and neovascularization. These factors influence each other and jointly promote the development of DR. DNA methylation is the most studied epigenetic modification, which has been a key role in the regulation of gene expression and the occurrence and development of DR. Thus, this review investigates the relationship between DNA methylation and other complex pathological processes in the development of DR. From the perspective of DNA methylation, this review provides basic insights into potential biomarkers for diagnosis, preventable risk factors, and novel targets for treatment.ConclusionDNA methylation plays an indispensable role in DR and may serve as a prospective biomarker of this blinding disease in its relatively early stages. In combination with inhibitors of DNA methyltransferases can be a potential approach to delay or even prevent patients from getting advanced stages of DR.
A systematic review and meta-analysis assessing antiretroviral therapy for treatment-experienced HIV adult patients using an optimized background therapy approach: is there evidence enough for a standardized third-line strategy?
Authors: Mocellin Lucas Pitrez , Ziegelmann Patricia Klarmann , Kuchenbecker Ricardo 
Published: November 2022

AbstractBackgroundThe World Health Organization (WHO) has identified the need for evidence on third-line antiretroviral therapy (ART) for adults living with HIV/AIDS, given that some controversy remains as to the best combinations of ART for experienced HIV-1-infected patients. Therefore, we conducted a systematic review and meta-analysis to (i) assess the efficacy of third-line therapy for adults with HIV/AIDS based on randomized controlled trials (RCT) that adopted the “new antiretroviral (ARV) + optimized background therapy (OBT)” approach and (ii) address the key issues identified in WHO’s guidelines on the use of third-line therapy.MethodsMEDLINE, EMBASE, LILACS, ISI Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for RCTs assessing third-line ARV therapy that used an OBT approach between 1966 and 2015. Data was extracted using an Excel-structured datasheet based on the Consolidated Standards of Reporting Trials (CONSORT) recommendations. The primary outcome of this meta-analysis was the proportion of patients reaching undetectable HIV RNA levels (< 50 copies/mL) at 48 weeks of follow-up. Included studies were evaluated using the Cochrane’s Risk of Bias assessment tool. Summarized evidence was rated according to the GRADE approach.ResultsEighteen trials assessing 9 new ARV + OBT combinations defined as third-line HIV therapy provided the efficacy data: 7 phase IIb trials and 11 phase III trials. Four of the 18 trials provided extension data, thus resulting in 14 trials providing 48-week efficacy data. In the meta-analysis, considering the outcome regarding the proportion of patients with a viral load below 50 copies/ml at 48 weeks, 9 out of 14 trials demonstrated the superiority of the new combination being studied (risk difference = 0.18, 95% CI 0.13–0.23). The same analysis stratified by the number of fully active ARVs demonstrated a risk difference of 0.29 (95% CI 0.12–0.46), 0.28 (95% CI 0.17–0.38) and 0.17 (95% CI 0.10–0.24) respectively from zero, one, and two or more active drugs strata. Nine of the 18 trials were considered to have a high risk of bias.ConclusionsEfficacy results demonstrated that the groups of HIV-experienced patients receiving the new ARV + OBT were more likely to achieve viral suppression when compared to the control groups. However, most of these trials may be at a high risk of bias. Thus, there is still not enough evidence to stipulate which combinations are the most effective for therapeutic regimens that are to be used sequentially due to documented multi-resistance.
Prevalence of hypertension and associated risks in hospitalized patients with COVID-19: a meta-analysis of meta-analyses with 1468 studies and 1,281,510 patients
Authors: Khairy Yousof , Naghibi Deniz , Moosavi Ahmad , Sardareh Mehran , Azami-Aghdash Saber 
Published: November 2022

Abstract
Background
Since the COVID-19 outbreak, preliminary research has shown that some risk-associated conditions increase death and severe complications of the disease, hypertension being one of them. Thus, numerous meta-analyses have been conducted to explore this issue. Therefore, this umbrella review aims to perform a meta-analysis of the meta-analyses to estimate the prevalence and associated risks of hypertension in patients with COVID-19.

Methods
PubMed, Scopus, Web of Knowledge, Embase, and Cochrane databases were searched for the published meta-analyses up to January 1, 2022. Google Scholar, citation check, reference check, and Grey literature were also manually searched. A random-effect model approach was used for analysis.

Results
The overall death rate was estimated at 12%. Hypertension was present in 25% of the patients as a comorbid disease. The overall RR for death, disease severity, and the possibility of ICU admission were estimated at 1.79 [1.68–1.89 with 95% CI], 1.74 [1.66–1.83 with 95% CI], and 1.91 [1.48–2.34 with 95% CI], respectively. The meta-regression results showed that being “male” significantly increases the risk of disease severity and ICU admission.

Conclusions
The results indicated that hypertension is a common comorbid disease in hospitalized patients with COVID-19, which significantly increases mortality risk, the severity of the disease, and the probability of ICU admission.

Systematic review registration
This study has been registered in PROSPERO (CRD42021231844).
The method for solving the extension of general of the split feasibility problem and fixed point problem of the cutter
Authors: Saechou Kanyanee , Kangtunyakarn Atid 
Published: November 2022

AbstractThis paper first introduces a new iterative method for weak and strong convergence theorem to demonstrate the estimation potential for a fixed point of the cutter and the finite general split feasibility problem. Consequently, the set of fixed points of a quasi-nonexpansive mapping and the finite general split feasibility problem, the constrained minimization problem, and the general constrained minimization problems are proved using our main results. Finally, we give two numerical examples to advocate our main results.
Evaluating an implementation model of evidence-based therapy for eating disorders in non-specialist regional mental health settings
Authors: Johnson Catherine , Cook Lesley , Cadman Kath , Andersen Thu , Williamson Paul , Wade Tracey D. 
Published: November 2022

AbstractBackgroundMany people with eating disorders (EDs) either do not access treatment, access it well after symptoms first start, or drop out of treatment. This study evaluated ways to improve early access to evidence-based interventions for those with EDs in a non-specialist community setting.MethodsIn an Australian regional community, links were formed between general medical practitioners and treatment providers (psychologists, mental health social workers and dietitians), who received ongoing training, feedback and support. Service users had access to 20–40 subsidised treatment sessions. Data were collected from 143 patients over 18 months. Our outcomes are reported according to the RE-AIM implementation framework: Reach (we measured uptake and treatment completion); Effectiveness (impact on disordered eating cognitions, body mass index, remission, and moderators of effectiveness including illness duration, previous treatment, presence of comorbidities, presence of a normative level of disordered eating, presence of any ED behaviours, weighing in treatment, multidisciplinary case conferencing, number of dietetic sessions); Adoption (drop-out and predictors); Implementation (barriers encountered); Maintenance (subsequent activity designed to embed new practices).ResultsTreatment was completed by 71%; significant large decreases in eating disorder cognitions were achieved; remission was obtained by 37% (intent-to-treat). Treatment completion was predicted by lower baseline levels of disordered eating, uptake of ≥ 3 dietetic sessions, and ≥ 2 team case conferences. Greater improvement over time was predicted by regular case conferencing and in-session weighing.ConclusionsImplementation of this model in a regional community setting produced completion rates and outcomes comparable to those found in specialist clinical trials of ED treatments. Service providers identified care coordination as the most important factor to connect users to services and help navigate barriers to ongoing treatment.Trial Registration:This research was an invited evaluation of a project implemented by the Australian Department of Health. The project did not introduce any new clinical practice but sought to improve access to evidence-based multidisciplinary treatment for people with EDs by removing four known systemic barriers: securing an accurate diagnosis, availability of multidisciplinary treatment, cost of treatment, and intensity of treatment. As such, the project did not require trial registration. Notwithstanding, this evaluation obtained ethics approval (Bellberry Human Research Ethics Committee, Application No: 2018-09-728-FR-1).
Saudi Arabian students in postgraduate dental programs: Investigating factors associated with burnout
Authors: Asiri Amal 
Published: November 2022

Background: Burnout related to emotional and physical study or work demands affects an individual’s performance and wellbeing. This study focused on Saudi Arabian dental residents studying in the United States and the United Kingdom who are faced with many challenges in the pursuit of a higher education degree. Methods: A survey including demographic and Maslach Burnout inventory (MBI) questions was distributed to assess this population’s level of burnout. The MBI has been widely used in the literature to assess three components of burnout: emotional exhaustion (EE), depersonalization (DEP), and (diminished) personal accomplishment (PA). Potential predictors of burnout level, tested for statistical significance, included: (1) country (US vs UK), (2) hours of work, (3) sponsorship status, (4) marital status (5) gender, and (6) prior work experience. Results: The number of participants from the UK was 29 and from the US was 64 (n=93). The total number of participants who completed the survey was 87. Using multiple regression analyses, those found to predict EE included hours of work, sponsorship status, and gender. Only gender was found to predict PA. None of the variables were predictive of DEP. Moreover, after controlling for the demographic variables, the country where studying did not help account for the level of burnout. Conclusion: In the literature, burnout was found to be prevalent among dental postgraduate students. This study suggests that Saudi Arabian dental residents experience high burnout due to emotional exhaustion when compared to other medical professionals. Moreover, Female residents are more likely to report experiencing burnout than their male counterparts. Limitations of the study, implications for practice and suggestions for further research are offered in the discussion.
Outward investment of Portuguese small and medium enterprises in the Central and Eastern European countries: motivations and challenges
Authors: Santos Eleonora , Moreira Jacinta 
Published: November 2022

Background: This paper identifies the determinant factors of Portuguese investment in Poland, Hungary, and the Czech Republic. We assume that investment abroad is motivated by business opportunities, and the quality-price ratio of the workforce. Methods: To this end, we used a qualitative methodology composed of 6 case studies, based on interviews and surveys with the managers of the Portuguese firms investing in those three economies. Results: Despite the business opportunities, Portuguese investment directed towards these economies is negligible, due, in part, to the geographic and cultural distance. However, the economic and political stability, combined with market size and growth potential are undeniable attraction factors for Portuguese investors. Small and medium enterprises (SMEs), due to their flexible conditions that allow changes in the activity, and the strong trend towards outsourcing, to the detriment of the manufacturing industry, are the primary focus of international investment. This trend, although common to several sectors, has shown greater dynamism in the banking and financial sector. Conclusions: The results suggest market-oriented investments aiming at growth and expansion. The vast Polish market is the one that most attracted Portuguese investors. The hybrid feature of some strategies can align with the cautious attitude towards the investment translated into cooperation agreements with financial institutions for funding, the market learning process, and the training of the personnel. The anticipation of the installation over potential competitors, the experience in production and international markets, the price-quality ratio, the capacity of product adaptation and the design were considered important sources of competitive advantage that motivated the investment. The greatest difficulties during this process were language and the complexity of legislation.
Política exterior y de CTI en Colombia: la diplomacia científica como frontera
Authors: Pineros Ayala Rafael , Echeverría-King Luisa F. , Andrade-Sastoque Ernesto 
Published: November 2022

La diplomacia científica (DC) se consolida como una propuesta ecléctica y de frontera entre la ciencia, la tecnología y la innovación (CTI), por un lado, y las Relaciones Internacionales y la política exterior, por el otro. ¿Cómo se articulan las políticas del sector ciencia y tecnología, y relaciones internacionales en Colombia en torno a la diplomacia científica? A partir de un análisis exploratorio y de naturaleza cualitativa-descriptiva de documentos de política pública en el período 2018-2022, se identifican las acciones de dc que Colombia ha implementado. Concluimos que se han dado pasos importantes y acelerados, pero persisten desafíos en materia de articulación y consolidación de la DC como una estrategia efectiva que facilite la consecución de objetivos tanto para el sector CTI, como de Relaciones Internacionales. Este artículo señala las bases conceptuales para comprender de manera situada la dc, algunas de sus críticas, y ubica la experiencia colombiana en perspectiva comparada con la de Brasil, México y Chile.
The cure rate after different treatments for mucosal leishmaniasis in the Americas: A systematic review
Authors: Carvalho Janaína de Pina , Silva Sarah Nascimento , Freire Mariana Lourenço , Alves Líndicy Leidicy , Souza Carolina Senra Alves de , Cota Gláucia 
Published: November 2022

Background
Mucosal or mucocutaneous leishmaniasis is the most severe form of tegumentary leishmaniasis due to its destructive character and potential damage to respiratory and digestive tracts. The current treatment recommendations are based on low or very low-quality evidence, and pentavalent antimonial derivatives remain strongly recommended. The aim of this review was to update the evidence and estimate the cure rate and safety profile of the therapeutic options available for mucosal leishmaniasis (ML) in the Americas.

Methodology
A systematic review was conducted in four different databases and by different reviewers, independently, to evaluate the therapeutic efficacy and toxicity associated with different treatments for ML. All original studies reporting cure rates in more than 10 patients from American regions were included, without restriction of design, language, or publication date. The risk of bias was assessed by two reviewers, using different tools according to the study design. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. The protocol for this review was registered at the International Prospective Register of Systematic Reviews, PROSPERO: CRD42019130708.

Principal findings
Twenty-seven original studies from four databases fulfilled the selection criteria. A total of 1,666 patients with ML were treated predominantly with pentavalent antimonials in Brazil. Other interventions, such as pentamidine, miltefosine, imidazoles, aminosidine sulfate, deoxycholate and lipidic formulations of amphotericin B (liposomal, lipid complex, colloidal dispersion), in addition to combinations with pentoxifylline, allopurinol or sulfa were also considered. In general, at least one domain with a high risk of bias was identified in the included studies, suggesting low methodological quality. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. It was confirmed that antimony is still the most used treatment for ML, with only moderate efficacy (possibly increased by combining with pentoxifylline). There is already evidence for the use of miltefosine for ML, with a cure rate similar to antimony, as observed in the only direct meta-analysis including 57 patients (OR: 1.2; 0.43–3.49, I2 = 0). It was possible to gather all descriptions available about adverse events reported during ML treatment, and the toxicity reflected the pattern informed in the manufacturers’ technical information.

Conclusions
This study provides an overview of the clinical experience in the Americas related to ML treatment and points out interventions and possible combinations that are eligible to be explored in future well-designed studies.
What factors contribute to the need for physical restraint in institutionalized residents in Taiwan?
Authors: Chien Ching-Fang , Huang Ling-Chun , Chang Yang-Pei , Lin Chung-Fen , Hsu Chih-Cheng , Yang Yuan-Han 
Published: November 2022

Background
In Taiwan, physical restraint is commonly used in institutions to protect residents from falling or injury. However, physical restraint should be used cautiously to avoid side effects, such as worse cognition, mobility, depression, and even death.

Objectives
To identify the rate of physical restraint and the associated risk factors in institutionalized residents in Taiwan.

Methods
A community-based epidemiological survey was conducted from July 2019 to February 2020 across 266 residential institutions. Among the estimated 6,549 residents being surveyed, a total of 5,752 finished the study. The questionnaires were completed by residents, his/her family or social workers. The cognition tests were conducted by specialists and a multilevel analysis approach was used to identify cognition/disability/medical history/special nursing care/BPSD risk factors for physical restraints.

Results
Of the 5,752 included institutionalized residents, 30.2% (1,737) had been previously restrained. Older age, lower education level, lower cognitive function, higher dependence, residents with cerebrovascular disease, pulmonary disease, dementia, and intractable epilepsy, all contributed to a higher physical restraint rate, while orthopedic disease and spinal cord injury were associated with a lower physical restraint rate. Furthermore, residents with special nursing care had a higher restraint rate. Residents with most of the behavior and psychological symptoms were also associated with an increased restraint rate.

Conclusions
We studied the rate of physical restraint and associated risk factors in institutionalized residents in Taiwan. The benefits and risks of physical restraint should be evaluated before application, and adjusted according to different clinical situations.
Feasibility of flow-related enhancement brain perfusion MRI
Authors: Glandorf Julian , Klimeš Filip , Voskrebenzev Andreas , Gutberlet Marcel , Kern Agilo Luitger , Kornemann Norman , Mahmoudi Nima , Wattjes Mike P. , Wacker Frank , Vogel-Claussen Jens 
Published: November 2022

Purpose
Brain perfusion imaging is of enormous importance for various neurological diseases. Fast gradient-echo sequences offering flow-related enhancement (FREE) could present a basis to generate perfusion-weighted maps. In this study, we obtained perfusion-weighted maps without contrast media by a previously described postprocessing algorithm from the field of functional lung MRI. At first, the perfusion signal was analyzed in fast low-angle shot (FLASH) and balanced steady-state free precession (bSSFP) sequences. Secondly, perfusion maps were compared to pseudo-continuous arterial spin labeling (pCASL) MRI in a healthy cohort. Thirdly, the feasibility of the new technique was demonstrated in a small selected group of patients with metastases and acute stroke.

Methods
One participant was examined with bSSFP and FLASH sequences at 1.5T and 3T, different flip angles and slice thicknesses. Twenty-five volunteers had bSSFP imaging and pCASL MRI. Three patients with cerebral metastases and one with acute ischemic stroke had bSSFP imaging and were compared to T1 post-contrast images and CT perfusion. Frequency analyses, SNR and perfusion contrast were compared at different flip angles and slice thicknesses. Regional correlations and Sorensen-Dice overlap were calculated in the healthy cohort. Dice overlap of the pathologies in the patient cohort were calculated.

Results
The bSSFP sequence presented detectable perfusion signal within brain vessel and parenchyma together with superior SNR compared to FLASH. Perfusion contrast and its corticomedullary differentiation increased with flip angle. Mean regional correlation was 0.36 and highly significant between FREE maps and pCASL and grey and white matter Dice match were 72% and 60% in the healthy cohort. Pathologies presented good overlap between FREE perfusion-weighted and T1 post-contrast images.

Conclusion
The feasibility of FREE brain perfusion imaging has been shown in a healthy cohort and selected patient cases with brain metastases and acute stroke. The study demonstrates a new approach for non-contrast brain perfusion imaging.