bluuebunny/crossref_metadata_2025_split huggingface dataset:
The trends in the incidence and thrombosis-related comorbidities of antiphospholipid syndrome: a 14-year nationwide population-based study
Authors: Yao Wei-Cheng , Leong Kam-Hang , Chiu Lu-Ting , Chou Po-Yi , Wu Li-Chih , Chou Chih-Yu , Kuo Chien-Feng , Tsai Shin-Yi 
Published: September 2022

Abstract
Background
This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database.

Methods
Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000–2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed.

Results
The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000–2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren’s syndrome, and polymyositis.

Conclusions
Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS.
Understanding the policy dynamics of COVID-19 vaccination in Ghana through the lens of a policy analytical framework
Authors: Atinga Roger A. , Koduah Augustina , Abiiro Gilbert Abotisem 
Published: September 2022

Abstract
Background
Ghana became the first African country to take delivery of the first wave of the AstraZeneca/Oxford vaccine from the COVAX facility. But why has this promising start of the vaccination rollout not translated into an accelerated full vaccination of the population? To answer this question, we drew on the tenets of a policy analytical framework and analysed the diverse interpretations, issue characteristics, actor power dynamics and political context of the COVID-19 vaccination process in Ghana.

Methods
We conducted a rapid online review of media reports, journal articles and other documents on debates and discussions of issues related to framing of the vaccination rollout, social constructions generated around vaccines, stakeholder power dynamics and political contentions linked to the vaccination rollout. These were complemented by desk reviews of parliamentary reports.

Results
The COVID-19 vaccination was mainly framed along the lines of public health, gender-centredness and universal health coverage. Vaccine acquisition and procurement were riddled with politics between the ruling government and the largest main opposition party. While the latter persistently blamed the former for engaging in political rhetoric rather than a tactical response to vaccine supply issues, the former attributed vaccine shortages to vaccine nationalism that crowded out fair distribution. The government’s efforts to increase vaccination coverage to target levels were stifled when a deal with a private supplier to procure 3.4 million doses of the Sputnik V vaccine collapsed due to procurement breaches. Amidst the vaccine scarcity, the government developed a working proposal to produce vaccines locally which attracted considerable interest among pharmaceutical manufacturers, political constituents and donor partners. Regarding issue characteristics of the vaccination, hesitancy for vaccination linked to misperceptions of vaccine safety provoked politically led vaccination campaigns to induce vaccine acceptance.

Conclusions
Scaling up vaccination requires political unity, cohesive frames, management of stakeholder interests and influence, and tackling contextual factors promoting vaccination hesitancy.
From raw data to a score: comparing quantitative methods that construct multi-level composite implementation strength scores of family planning programs in Malawi
Authors: Pattnaik Anooj , Mohan Diwakar , Zeger Scott , Kanyuka Mercy , Kachale Fannie , Marx Melissa A. 
Published: September 2022

Abstract
Background
Data that capture implementation strength can be combined in multiple ways across content and health system levels to create a summary measure that can help us to explore and compare program implementation across facility catchment areas. Summary indices can make it easier for national policymakers to understand and address variation in strength of program implementation across jurisdictions. In this paper, we describe the development of an index that we used to describe the district-level strength of implementation of Malawi’s national family planning program.

Methods
To develop the index, we used data collected during a 2017 national, health facility and community health worker Implementation Strength Assessment survey in Malawi to test different methods to combine indicators within and then across domains (4 methods—simple additive, weighted additive, principal components analysis, exploratory factor analysis) and combine scores across health facility and community health worker levels (2 methods—simple average and mixed effects model) to create a catchment area-level summary score for each health facility in Malawi. We explored how well each model captures variation and predicts couple-years protection and how feasible it is to conduct each type of analysis and the resulting interpretability.

Results
We found little difference in how the four methods combined indicator data at the individual and combined levels of the health system. However, there were major differences when combining scores across health system levels to obtain a score at the health facility catchment area level. The scores resulting from the mixed effects model were able to better discriminate differences between catchment area scores compared to the simple average method. The scores using the mixed effects combination method also demonstrated more of a dose–response relationship with couple-years protection.

Conclusions
The summary measure that was calculated from the mixed effects combination method captured the variation of strength of implementation of Malawi’s national family planning program at the health facility catchment area level. However, the best method for creating an index should be based on the pros and cons listed, not least, analyst capacity and ease of interpretability of findings. Ultimately, the resulting summary measure can aid decision-makers in understanding the combined effect of multiple aspects of programs being implemented in their health system and comparing the strengths of programs across geographies.
Performance evaluation of antigen detection rapid diagnostic test (Ag-RDT) for COVID-19 diagnosis in a primary healthcare center during the Shanghai COVID-19 quarantine period
Authors: Dong Lan , Li Wen-Fang , Jiang Ying 
Published: September 2022

Abstract
Background
Rapid and accurate detection of SARS-CoV-2 infection is the cornerstone of prompt patient care. However, the reliability of the antigen rapid diagnostic test (Ag-RDT) in the diagnosis of SARS-CoV-2 infection remains inconclusive.

Methods
We conducted a field evaluation of Ag-RDT performance during the Shanghai Coronavirus disease 2019 (COVID-19) quarantine and screened 7225 individuals visiting our Emergency Department. 83 asymptomatic SARS-CoV-2 (+) individuals were enrolled in the current study. Simultaneously, Ag-RDT was performed to evaluate its testing performance.

Results
For the Ag-RDT(−) cases, the average cycle threshold (Ct) values of the N gene were 27.26 ± 4.59, which were significantly higher than the Ct value (21.9 ± 4.73) of the Ag-RDT(+) individuals (p < 0.0001). The overall sensitivity of Ag-RDT versus that of RT-PCR was 43.37%. The Ag-RDT(+) individuals regarding the N gene’s Ct value were 16 cases in the < 20 range, 12 in 20–25, 5 in 25–30, and 3 in 30–35. The corresponding sensitivity was 84.21%, 52.17%, 21.74% and 16.67%, respectively. Meanwhile, sampling had a straight specificity of 100% regardless of the Ct value.

Conclusions
The Ag-RDT were extremely sensitive in asymptomatic COVID-19 individuals with a Ct value < 20.
A meta-analysis of colchicine in prevention of atrial fibrillation following cardiothoracic surgery or cardiac intervention
Authors: Zhao Hong , Chen Yueming , Mao Min , Yang Jun , Chang Jing 
Published: September 2022

Abstract
Background
Postoperative atrial fibrillation (POAF) is the most common complication after cardiothoracic surgery or cardiac intervention. Colchicine is an anti-inflammatory agent that was associated with improved cardiovascular outcomes. However, its effect on POAF prevention was inconsistent across studies. Therefore, the aim of this meta-analysis was to evaluate the efficacy of colchicine in prevention of POAF.

Methods
We searched PubMed, Embase, ClinicalTrials.gov, Cochrane Library database and Google Scholar for randomized controlled trials (RCTs), using terms "atrial fibrillation” and “colchicine". The primary end point was the occurrence of clinically diagnosed atrial fibrillation. The relative risk (RR) and 95% confidence interval (CI) were evaluated. Estimates were pooled using DerSimonian-Laird random-effects model. We also performed subgroup analyses based on the duration and dose of colchicine treatment.

Results
A total of 9 RCTs were included in this meta-analysis, enrolling a total of 2031 patients. Colchicine significantly reduces the incidence of POAF (RR 0.62; 95% CI, 0.52–0.74, P < 0.001, I2 = 0%). Subgroup analyses indicated that the protective effect of colchicine on POAF was almost the same (P = 0.71) in the long-duration group (RR 0.60; 95% CI, 0.48–0.75, P < 0.001, I2 = 0%) and the short-duration group (RR 0.65; 95% CI, 0.49–0.86, P < 0.001, I2 = 0%).

Conclusion
Colchicine is effective in preventing the occurrence of POAF. The efficacy of colchicine cannot be slightly increased over treatment duration, with no obvious adverse reactions.
APE1 redox function is required for activation of Yes-associated protein 1 under reflux conditions in Barrett’s-associated esophageal adenocarcinomas
Authors: Ballout Farah , Lu Heng , Chen Lei , Sriramajayam Kannappan , Que Jianwen , Meng Zhipeng , Wang Timothy C. , Giordano Silvia , Zaika Alexander , McDonald Oliver , Peng Dunfa , El-Rifai Wael 
Published: September 2022

Abstract
Background
Esophageal adenocarcinoma (EAC) is characterized by poor prognosis and low survival rate. Chronic gastroesophageal reflux disease (GERD) is the main risk factor for the development of Barrett’s esophagus (BE), a preneoplastic metaplastic condition, and its progression to EAC. Yes-associated protein 1 (YAP1) activation mediates stem-like properties under cellular stress. The role of acidic bile salts (ABS) in promoting YAP1 activation under reflux conditions remains unexplored.

Methods
A combination of EAC cell lines, transgenic mice, and patient-derived xenografts were utilized in this study. mRNA expression and protein levels of APE1 and YAP1 were evaluated by qRT-PCR, western blot, and immunohistochemistry. YAP1 activation was confirmed by immunofluorescence staining and luciferase transcriptional activity reporter assay. The functional role and mechanism of regulation of YAP1 by APE1 was determined by sphere formation assay, siRNA mediated knockdown, redox-specific inhibition, and co-immunoprecipitation assays.

Results
We showed that YAP1 signaling is activated in BE and EAC cells following exposure to ABS, the mimicry of reflux conditions in patients with GERD. This induction was consistent with APE1 upregulation in response to ABS. YAP1 activation was confirmed by its nuclear accumulation with corresponding up-regulation of YAP1 target genes. APE1 silencing inhibited YAP1 protein induction and reduced its nuclear expression and transcriptional activity, following ABS treatment. Further investigation revealed that APE1-redox-specific inhibition (E3330) or APE1 redox-deficient mutant (C65A) abrogated ABS-mediated YAP1 activation, indicating an APE1 redox-dependent mechanism. APE1 silencing or E3330 treatment reduced YAP1 protein levels and diminished the number and size of EAC spheroids. Mechanistically, we demonstrated that APE1 regulated YAP1 stability through interaction with β-TrCP ubiquitinase, whereas APE1-redox-specific inhibition induced YAP1 poly-ubiquitination promoting its degradation.

Conclusion
Our findings established a novel function of APE1 in EAC progression elucidating druggable molecular vulnerabilities via targeting APE1 or YAP1 for the treatment of EAC.
The role of oxidative stress in ovarian aging: a review
Authors: Yan Fei , Zhao Qi , Li Ying , Zheng Zhibo , Kong Xinliang , Shu Chang , Liu Yanfeng , Shi Yun 
Published: September 2022

AbstractOvarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.
CTCF and cohesin promote focal detachment of DNA from the nuclear lamina
Authors: van Schaik Tom , Liu Ning Qing , Manzo Stefano G. , Peric-Hupkes Daan , de Wit Elzo , van Steensel Bas 
Published: September 2022

Abstract
Background
Lamina-associated domains (LADs) are large genomic regions that are positioned at the nuclear lamina. It has remained largely unclear what drives the positioning and demarcation of LADs. Because the insulator protein CTCF is enriched at LAD borders, it was postulated that CTCF binding could position some LAD boundaries, possibly through its function in stalling cohesin and hence preventing cohesin invading into the LAD. To test this, we mapped genome–nuclear lamina interactions in mouse embryonic stem cells after rapid depletion of CTCF and other perturbations of cohesin dynamics.

Results
CTCF and cohesin contribute to a sharp transition in lamina interactions at LAD borders, while LADs are maintained after depletion of these proteins, also at borders marked by CTCF. CTCF and cohesin may thus reinforce LAD borders, but do not position these. CTCF binding sites within LADs are locally detached from the lamina and enriched for accessible DNA and active histone modifications. Remarkably, despite lamina positioning being strongly correlated with genome inactivity, this DNA remains accessible after the local detachment is lost following CTCF depletion. At a chromosomal scale, cohesin depletion and cohesin stabilization by depletion of the unloading factor WAPL quantitatively affect lamina interactions, indicative of perturbed chromosomal positioning in the nucleus. Finally, while H3K27me3 is locally enriched at CTCF-marked LAD borders, we find no evidence for an interplay between CTCF and H3K27me3 on lamina interactions.

Conclusions
These findings illustrate that CTCF and cohesin are not primary determinants of LAD patterns. Rather, these proteins locally modulate NL interactions.
Utilization of preventive services in a systemic lupus erythematosus population-based cohort: a Lupus Midwest Network (LUMEN) study
Authors: Chevet Baptiste , Figueroa-Parra Gabriel , Yang Jeffrey X. , Hocaoglu Mehmet , Osei-Onomah Shirley-Ann , Hulshizer Cassondra A. , Gunderson Tina M. , Cornec Divi , Barbour Kamil E. , Greenlund Kurt J. , Crowson Cynthia S. , Duarte-García Alí 
Published: September 2022

Abstract
Background
Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population.

Methods
All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations.

Results
We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85–1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58–0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13–1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96–1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11–2.87; and HR 3.19, 95% CI 2.31–4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12–1.54; and HR 2.06, 95% CI 1.38–3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81–1.69).

Conclusions
The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.
Robustness under parameter and problem domain alterations of Bayesian optimization methods for chemical reactions
Authors: Khondaker Rubaiyat Mohammad , Gow Stephen , Kanza Samantha , Frey Jeremy G , Niranjan Mahesan 
Published: September 2022

AbstractThe related problems of chemical reaction optimization and reaction scope search concern the discovery of reaction pathways and conditions that provide the best percentage yield of a target product. The space of possible reaction pathways or conditions is too large to search in full, so identifying a globally optimal set of conditions must instead draw on mathematical methods to identify areas of the space that should be investigated. An intriguing contribution to this area of research is the recent development of the Experimental Design for Bayesian optimization (EDBO) optimizer [1]. Bayesian optimization works by building an approximation to the true function to be optimized based on a small set of simulations, and selecting the next point (or points) to be tested based on an acquisition function reflecting the value of different points within the input space. In this work, we evaluated the robustness of the EDBO optimizer under several changes to its specification. We investigated the effect on the performance of the optimizer of altering the acquisition function and batch size, applied the method to other existing reaction yield data sets, and considered its performance in the new problem domain of molecular power conversion efficiency in photovoltaic cells. Our results indicated that the EDBO optimizer broadly performs well under these changes; of particular note is the competitive performance of the computationally cheaper acquisition function Thompson Sampling when compared to the original Expected Improvement function, and some concerns around the method’s performance for “incomplete” input domains.
Hydrocephalus: historical analysis and considerations for treatment
Authors: Hochstetler Alexandra , Raskin Jeffrey , Blazer-Yost Bonnie L. 
Published: September 2022

AbstractHydrocephalus is a serious condition that affects patients of all ages, resulting from a multitude of causes. While the etiologies of hydrocephalus are numerous, many of the acute and chronic symptoms of the condition are shared. These symptoms include disorientation and pain (headaches), cognitive and developmental changes, vision and sleep disturbances, and gait abnormalities. This collective group of symptoms combined with the effectiveness of CSF diversion as a surgical intervention for many types of the condition suggest that the various etiologies may share common cellular and molecular dysfunctions. The incidence rate of pediatric hydrocephalus is approximately 0.1–0.6% of live births, making it as common as Down syndrome in infants. Diagnosis and treatment of various forms of adult hydrocephalus remain understudied and underreported. Surgical interventions to treat hydrocephalus, though lifesaving, have a high incidence of failure. Previously tested pharmacotherapies for the treatment of hydrocephalus have resulted in net zero or negative outcomes for patients potentially due to the lack of understanding of the cellular and molecular mechanisms that contribute to the development of hydrocephalus. Very few well-validated drug targets have been proposed for therapy; most of these have been within the last 5 years. Within the last 50 years, there have been only incremental improvements in surgical treatments for hydrocephalus, and there has been little progress made towards prevention or cure. This demonstrates the need to develop nonsurgical interventions for the treatment of hydrocephalus regardless of etiology. The development of new treatment paradigms relies heavily on investment in researching the common molecular mechanisms that contribute to all of the forms of hydrocephalus, and requires the concerted support of patient advocacy organizations, government- and private-funded research, biotechnology and pharmaceutical companies, the medical device industry, and the vast network of healthcare professionals.