bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants
Authors: Borges Maria Carolina , Haycock Philip C. , Zheng Jie , Hemani Gibran , Holmes Michael V. , Davey Smith George , Hingorani Aroon D. , Lawlor Deborah A. 
Published: June 2022

Abstract
Background
Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization.

Methods
We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis).

Results
GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8–7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol.

Conclusions
We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses.
Impact of the ACOSOG Z0011 trial on surgical practice in Asian patients: trends in axillary surgery for breast cancer from a Korean Breast Cancer Registry analysis
Authors: Cha Chihwan , Kim Eun Young , Kim Sung Yong , Ryu Jai Min , Park Min Ho , Lee Seokwon , Suh Young-jin , Choi Nayeon , Hong Hanpyo , Kim Hyung Suk , Chung Min Sung ,   Korean Breast Cancer Society
Published: June 2022

Abstract
Background
Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients.

Methods
We collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in Korean cohort with that previously reported in a Dutch cohort.

Results
From KBCR data, 7478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier years at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to the Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 37.2 vs. 5.8%, p < 0.001).

Conclusions
This study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in the Dutch cohort.
The U.S. Global Gag Rule in Ethiopia: a foreign policy challenging domestic sexual and reproductive health and rights gains
Authors: Vernaelde Jamie M. 
Published: June 2022

Abstract
Background
Ethiopia’s government and civil society have driven crosscutting initiatives in the last 15 years to improve sexual and reproductive health outcomes, including passing a 2005 abortion law that facilitated reduced rates of maternal death due to unsafe abortion. However, both the government and nongovernmental organizations have relied on external funding for sexual and reproductive health and rights, particularly from the U.S. government, which has been Ethiopia’s largest global health donor. This article explores how the implementation and expansion of the 2017–2021 U.S. foreign policy “Protecting Life in Global Health Assistance,” also known as the Global Gag Rule—which attached itself to a nongovernmental organization’s funding—impacted sexual and reproductive health and rights, including safe abortion care, in Ethiopia.

Methods
This article is based on research conducted by PAI staff in Ethiopia in 2018 with follow-up in 2019. PAI held in-depth semistructured interviews with representatives of 30 organizations in Ethiopia’s capital, Addis Ababa. Among these groups were U.S.-based and non-U.S. nongovernmental organizations, including community-based organizations, non-U.S. government donors, and Ethiopian government officials.

Results
Nongovernmental organizations have been essential to sexual and reproductive health service provision and advocacy in Ethiopia. Because of the sector’s reliance on U.S. global health assistance, these organizations; their activities; and, consequently, the wider health system were negatively impacted by the Global Gag Rule. Certain vulnerable groups, particularly adolescents and youth, have traditionally relied on the private sector for sexual and reproductive health services. PAI’s research demonstrates that U.S. policy disrupted activities and service delivery, threatened the closure of private clinics, stalled mobile outreach, and impacted safe abortion training of health personnel. Additionally, the Global Gag Rule dismantled partnerships, affected non-U.S. government donors’ investments, and caused confusion that limited activities permissible under the policy.

Conclusions
The Trump administration’s Global Gag Rule forced non-U.S. organizations to choose between providing comprehensive care or losing U.S. global health assistance, ultimately impacting populations in need of services. Ethiopia provides a clear example of how the Global Gag Rule can threaten a country’s domestic health agenda by targeting nongovernmental organizations that are vital to health service delivery and safe abortion care.
Two decades of family planning in Ethiopia and the way forward to sustain hard-fought gains!
Authors: Kibret Mengistu Asnake , Gebremedhin Lia Tadesse 
Published: June 2022

AbstractFamily planning (FP) is a human right, and ensuring women’s access to FP is central to protecting the health and wellbeing of mothers and children. Over the past two decades, Ethiopia has made FP service more widely available, increasing the contraceptive prevalence rate from 8% in 2000 to 41% in 2019. This remarkable fivefold increase can be attributed to the country’s overall development, including investment in education (particularly for girls) and reduction in child marriage, as well as the adoption and implementation of several enabling FP policies and strategies. In Ethiopia, achieving universal access to sexual and reproductive health care services, information, and education, including FP, by 2030 means enhancing these effective government policies and programs. Achieving universal access requires increasing financial resources, including domestic financing through greater government commitment for commodity security and program implementation; strengthening public–private partnerships; and improving service delivery for populations that are hard to reach and/or in humanitarian crisis. The persistence of equity gaps due to regional and/or sociodemographic disparities and the low quality of FP service delivery challenge our progress in Ethiopia. The papers included in this supplement provide additional detail on the overall progress described in this commentary and highlight focal areas for improvement in responding to unmet needs. Current policies and services must adapt, maintain, and build upon these gains and focus on targeted actions in areas identified for improvement. We must sustain the hard-fought gains of the past decades and help shape the prosperous future we advocate for in our society by 2030 and beyond—Leaving No One Behind.
Ivermectin under scrutiny: a systematic review and meta-analysis of efficacy and possible sources of controversies in COVID-19 patients
Authors: Shafiee Arman , Teymouri Athar Mohammad Mobin , Kohandel Gargari Omid , Jafarabady Kyana , Siahvoshi Sepehr , Mozhgani Sayed-Hamidreza 
Published: June 2022

AbstractBackgroundWe conducted a systematic review and meta-analysis to evaluate the efficacy of ivermectin for COVID-19 patients based on current peer-reviewed RCTs and to address disputes over the existing evidence.MethodsMEDLINE (Pubmed), Scopus, Web of Science, Cochrane library, Google scholar and Clinicaltrials.gov were searched for RCTs assessing the efficacy of Ivermectin up to 20 February 2022. A systematic review and meta-analysis of studies was performed based on the PRISMA 2020 statement criteria.Results19 and 17 studies were included in this systematic review and meta-analysis, respectively. There was no significant difference in progression to severe disease (log OR − 0.27 [95% CI − 0.61 to 0.08], I2 = 42.29%), negative RT-PCR (log OR 0.25 [95% CI − 0.18–0.68], I2 = 58.73%), recovery (log OR 0.11 [95% CI − 0.22–0.45], I2 = 13.84%), duration of hospitalization (SMD − 0.40 [95% CI − 0.85–0.06], I2 = 88.90%), time to negative RT-PCR (SMD − 0.36 [95% CI − 0.89–0.17], I2 = 46.2%), and viral load (SMD -0.17 [95% CI -0.45 to 0.12], I^2 = 0%). It is worth noting that, based on low-certainty evidence, ivermectin may possibly reduce mortality (log OR − 0.67 [95% CI − 1.20 to − 0.13], I2 = 28.96%). However, studies with a higher risk of bias were more likely to indicate positive effects on the efficacy of this drug, according to our subgroup analyses based on study quality.ConclusionIvermectin did not have any significant effect on outcomes of COVID-19 patients and as WHO recommends, use of ivermectin should be limited to clinical trials.
Dietary inflammatory index and metabolic syndrome in US children and adolescents: evidence from NHANES 2001–2018
Authors: Jia Guhua , Wu Chieh-Chen , Su Chun-Hsien 
Published: June 2022

Abstract
Background
An increasing number of children and adolescents are affected by metabolic syndrome (MetS). Dietary inflammatory index (DII) was associated with MetS in adult population. This study aimed to determine the associations between DII scores, MetS, and MetS components among children and adolescents.

Methods
Data of children and adolescents in the National Health and Nutrition Examination Survey (NHANES) database 2001–2008 were obtained. DII was calculated for each participant based on the 24-h dietary recall interview. Univariate and multivariate logistic regression were conducted to determine the associations between DII, the other study variables and abnormal MetS components.

Results
A total of 5,656 US children and adolescents (mean age = 15.49) in the 2001–2018 NHANES database were included. After adjusting for all confounders in the multivariate analysis, the top DII quartile was significantly and independently associated with increased odds of high blood pressure (BP) (aOR = 2.27, 95% CI: 1.02–5.07) as compared with the lowest DII quartile. DII in quartile 2, 3 or 4 were not significantly associated with increased odds of MetS, high waist circumference (WC), low high density lipoprotein-cholesterol (HDL-c), triglyceride (TG) or fasting plasma glucose (FPG) as compared with the lowest quartile. In stratified analysis by recommended physical activity level for children and adolescents, no significant association was observed between higher DII and MetS.

Conclusions
Among US children and adolescents, high DII is associated with prevalent high BP but not MetS. The finding may contribute to future policymaking in promoting children’s health.
Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model
Authors: Areecheewakul Sudartip , Adamcakova-Dodd Andrea , Haque Ezazul , Jing Xuefang , Meyerholz David K. , O’Shaughnessy Patrick T. , Thorne Peter S. , Salem Aliasger K. 
Published: June 2022

Abstract
Background
It has been shown that copper oxide nanoparticles (CuO NPs) induce pulmonary toxicity after acute or sub-acute inhalation exposures. However, little is known about the biodistribution and elimination kinetics of inhaled CuO NPs from the respiratory tract. The purposes of this study were to observe the kinetics of pulmonary inflammation during and after CuO NP sub-acute inhalation exposure and to investigate copper (Cu) biodistribution and clearance rate from the exposure site and homeostasis of selected trace elements in secondary organs of BALB/c mice.

Results
Sub-acute inhalation exposure to CuO NPs led to pulmonary inflammation represented by increases in lactate dehydrogenase, total cell counts, neutrophils, macrophages, inflammatory cytokines, iron levels in bronchoalveolar lavage (BAL) fluid, and lung weight changes. Dosimetry analysis in lung tissues and BAL fluid showed Cu concentration increased steadily during exposure and gradually declined after exposure. Cu elimination from the lung showed first-order kinetics with a half-life of 6.5 days. Total Cu levels were significantly increased in whole blood and heart indicating that inhaled Cu could be translocated into the bloodstream and heart tissue, and potentially have adverse effects on the kidneys and spleen as there were significant changes in the weights of these organs; increase in the kidneys and decrease in the spleen. Furthermore, concentrations of selenium in kidneys and iron in spleen were decreased, pointing to disruption of trace element homeostasis.

Conclusions
Sub-acute inhalation exposure of CuO NPs induced pulmonary inflammation, which was correlated to Cu concentrations in the lungs and started to resolve once exposure ended. Dosimetry analysis showed that Cu in the lungs was translocated into the bloodstream and heart tissue. Secondary organs affected by CuO NPs exposure were kidneys and spleen as they showed the disruption of trace element homeostasis and organ weight changes.
Crowberry inhibits cell proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling in cholangiocarcinoma
Authors: Wang Xue , Zhou Xuebing , Zhang Ludan , Zhang Xin , Yang Chunyu , Piao Yingshi , Zhao Jinhua , Jin Lili , Jin Guihua , An Renbo , Ren Xiangshan 
Published: June 2022

Abstract
Background
Cholangiocarcinoma (CCA) is a rare biliary adenocarcinoma related to poor clinical prognosis. Crowberry is an herbal medicine used to control inflammatory diseases and reestablish antioxidant enzyme activity. Although crowberry shows significant therapeutic efficacy in various tumors and diseases, its anticancer effects and specific molecular mechanisms in CCA are poorly understood.

Aim of the study
This study was conducted to characterize crowberry effects on CCA cells behavior.

Materials and methods
The chemical profiles of crowberry extract was qualitatively analyzed by high-performance liquid chromatography (HPLC) and HPLC–tandem mass spectrometry. MTT, colony formation and EdU assays were performed to measure cell proliferation. The effect of crowberry treatment on CCA cell migration was assessed by wound healing and migration assays. Moreover, Hoechst staining assay and flow cytometry were performed to assess the cell apoptosis rate. Western blotting was used to assess the protein expression levels of key factors associated with apoptosis, the Akt signaling pathway, and the epithelial-mesenchymal transition. A xenograft model was established and immunohistochemical and H&E staining was performed to assess crowberry antitumor effects in vivo.

Results
Crowberry clearly inhibited CCA cells proliferation and migration in a dose-dependent manner and induced apoptosis in vitro. Crowberry inactivated the PI3K/Akt signaling pathway by regulating DEK in vitro and significantly inhibited tumor growth by downregulating the DEK expression in xenograft models.

Conclusion
Crowberry inhibits CCA cells proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling pathway inhibition in vitro and in vivo.

Graphical Abstract
Lifetime extension and the recent cause of death in Werner syndrome: a retrospective study from 2011 to 2020
Authors: Kato Hisaya , Koshizaka Masaya , Kaneko Hiyori , Maezawa Yoshiro , Yokote Koutaro 
Published: June 2022

Abstract
Background
Werner syndrome (WS) is an autosomal recessive premature ageing disease that causes accelerated ageing-like symptoms after puberty. Previous studies conducted in the late 2000s reported that malignant neoplasms and atherosclerotic diseases were the two leading causes of death, with life expectancies in the mid-50 s. However, the recent lifespan and cause of death in patients with WS remain unclear.

Objective
To clarify the latest lifespan and causes of death in patients with WS.

Method
We conducted a questionnaire-based survey in 2020 among the primary doctors of WS patients who were identified in previous nationwide surveys in Japan and clarified the following: the age of WS patients (age of death, if the patient had already died), sex, and cause of death. Patients who died in 2010 or earlier were excluded from the analysis.

Results
A total of 123 living patients were identified at the time of the survey in 2020. Fourteen WS patients died between 2011 and 2020, with a mean age of 59.0 ± 8.9 years (mean ± SD). The most common cause of death was non-epithelial tumours, accounting for eight deaths, while no patient died of atherosclerotic diseases.

Conclusions
Compared to previous studies, this study suggests that the lifespan of patients with WS has been extended. Although there were no deaths due to atherosclerotic diseases, non-epithelial tumours were still the leading cause of death. Further development of screening and treatment methods for these tumours is required.
Care burden and associated factors in caregivers of children with cancer
Authors: Chaghazardi Mahnaz , Janatolmakan Maryam , Rezaeian Shahab , Khatony Alireza 
Published: June 2022

Abstract
Background
Evidence suggests that many parents who care for their children with cancer are affected by the care burden due to the chronic nature of the disease. The aim of this study was to determine the burden of care level and its related factors in the caregivers of children with cancer.

Method
A total of 270 caregivers of children with cancer were included in this cross-sectional study by convenience sampling method. Data collection tools were a personal information form and the Novak & Guest’s Caregiver Burden Inventory. Data were analyzed by descriptive and inferential statistics (chi-square and univariate linear regression model).

Results
The mean ages of caregivers and patients were 35.7 ± 7.0 and 3.1 ± 1.6 years, respectively. The mean care burden was 68.4 ± 1.5 out of 120. About 50 and 36% of caregivers had moderate and severe care burden, respectively.

Conclusion
Caregivers had moderate to high care burden. A number of factors associated with care burden were identified. Health authorities need to take family-centered measures to reduce the burden of caregivers.
Association between periodontitis and ossification of the posterior longitudinal ligament: a case report
Authors: Tsuru Michiyo , Oosio Takayoshi , Higashi Teruyo , Nagata Kensei , Wada Kanichiro , Ishibashi Yasuyuki 
Published: June 2022

Abstract
Introduction
Ossification of the posterior longitudinal ligament in the spinal ligament compresses the spinal cord, causing various spinal nerve diseases. The ligament tissue is an important connective tissue in the joints, teeth, and spine, which, when torn and damaged, reduces the range of movement.

Case presentation
We report the treatment of periapical periodontitis and tooth preservation in a 41-year-old Japanese woman previously diagnosed with ossification of the posterior longitudinal ligament. She presented with widespread pain from the paranasal sinuses to the head caused by the onset of periapical periodontitis of the upper front tooth.

Discussion
The patient received an oral zinc supplement, which resolved periapical periodontitis over a 2-year follow-up period.

Conclusion
The findings from this case imply that, when patients with ossification of the posterior longitudinal ligament develop periapical periodontitis, they should be tested for zinc deficiency.