bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between baseline LDL-C and prognosis among patients with coronary artery disease and advanced kidney disease
Authors: Wang Bo , Chen Shiqun , Liu Jin , Liang Yan , Meng Liangguang , Yan Xiaoming , Huang Haozhang , Chen Guanzhong , Huang Zhidong , Xu Danyuan , Li Min , Liang Jingjing , Liu Shuangxin , Chen Jiyan , Liu Yong , Tan Ning 
Published: May 2021

Abstract
Background
Lower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. The association between low baseline LDL-C (< 1.8 mmol/L) and mortality is unknown among patients with CAD and advanced kidney disease (AKD). The current study aimed to evaluate prognostic value of low baseline LDL-C level for all-cause death in these patients.

Methods
In this observational study, 803 CAD patients complicated with AKD (eGFR < 30 mL/min/1.73 m2) were enrolled between January 2008 to December 2018. Patients were divided into two groups (LDL-C < 1.8 mmol/L, n = 138; LDL-C ≥ 1.8 mmol/L, n = 665). We used Kaplan-Meier methods and Cox regression analyses to assess the association between baseline low LDL-C levels and long-term all-cause mortality.

Results
Among 803 participants (mean age 67.4 years; 68.5% male), there were 315 incidents of all-cause death during a median follow-up of 2.7 years. Kaplan–Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for full 24 confounders (e.g., age, diabetes, heart failure, and dialysis, etc.), multivariate Cox regression analysis revealed that lower LDL-C level (< 1.8 mmol/L) was significantly associated with higher risk of all-cause death (adjusted HR, 1.38; 95% CI, 1.01–1.89).

Conclusions
Our data demonstrated that among patients with CAD and AKD, a lower baseline LDL-C level (< 1.8 mmol/L) did not present a higher survival rate but was related to a worse prognosis, suggesting a cautiousness of too low LDL-C levels among patients with CAD and AKD.
Overexpression of TNFα induces senescence, autophagy and mitochondrial dysfunctions in melanoma cells
Authors: Tyciakova Silvia , Valova Valeria , Svitkova Barbora , Matuskova Miroslava 
Published: May 2021

Abstract
Background
Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine with both anti-tumorigenic and pro-tumorigenic activity, affecting tumor cell biology, the balance between cell survival and death. The final effect of TNFα is dependent on the type of malignant cells, with the potential to arrest cancer progression.

Methods
In order to explain the diverse cellular response to TNFα, we engineered melanoma and colorectal carcinoma cell lines stably overexpressing this cytokine.

Results
Under the TNFα overexpression, significant upregulation of two genes was observed: proinflammatory cytokine IL6 gene in melanoma cells A375 and gene for pro-apoptotic ligand TRAIL in colorectal carcinoma cells HT29, both mediated by TNFα/TNFR1 signaling. Malignant melanoma line A375 displayed also increased autophagy on day 3, followed by premature senescence on day 6. Both processes seem to be interconnected, following earlier apoptosis induction and deregulation of mitochondrial functions. We documented altered mitochondrial status, lowered ATP production, lowered mitochondrial mass, and changes in mitochondrial morphology (shortened and condensed mitochondria) both in melanoma and colorectal carcinoma cells. Overexpression of TNFα was not linked with significant affection of the subpopulation of cancer stem-like cells in vitro. However, we could demonstrate a decrease in aldehyde dehydrogenase (ALDH) activity up to 50%, which is associated with to the stemness phenotype.

Conclusions
Our in vitro study of direct TNFα influence demonstrates two distinct outcomes in tumor cells of different origin, in non-epithelial malignant melanoma cells of neural crest origin, and in colorectal carcinoma cells derived from the epithelium.
The effects of secondary iron overload and iron chelation on a radiation-induced acute myeloid leukemia mouse model
Authors: Chan Lap Shu Alan , Gu Lilly ChunHong , Wells Richard A. 
Published: May 2021

Abstract
Background
Patients with myelodysplastic syndrome (MDS) require chronic red blood cell (RBC) transfusion due to anemia. Multiple RBC transfusions cause secondary iron overload and subsequent excessive generation of reactive oxygen species (ROS), which leads to mutations, cell death, organ failure, and inferior disease outcomes. We hypothesize that iron loading promotes AML development by increasing oxidative stress and disrupting important signaling pathways in the bone marrow cells (BMCs). Conversely, iron chelation therapy (ICT) may reduce AML risk by lowering iron burden in the iron-loaded animals.

Methods
We utilized a radiation-induced acute myeloid leukemia (RI-AML) animal model. Iron overload was introduced via intraperitoneal injection of iron dextran, and iron chelation via oral gavage of deferasirox. A total of 86 irradiated B6D2F1 mice with various levels of iron burden were monitored for leukemia development over a period of 70 weeks. The Kaplan-Meier estimator was utilized to assess AML free survival. In addition, a second cohort of 30 mice was assigned for early analysis at 5 and 7 months post-irradiation. The BMCs of the early cohort were assessed for alterations of signaling pathways, DNA damage response and gene expression. Statistical significance was established using Student’s t-test or ANOVA.

Results
Iron loading in irradiated B6D2F1 mice accelerated RI-AML development. However, there was a progressive decrease in AML risk for irradiated mice with increase in iron burden from 7.5 to 15 to 30 mg. In addition, ICT decreased AML incidence in the 7.5 mg iron-loaded irradiated mice, while AML onset was earlier for the 30 mg iron-loaded irradiated mice that received ICT. Furthermore, analysis of BMCs from irradiated mice at earlier intervals revealed accelerated dysregulation of signaling pathways upon iron loading, while ICT partially mitigated the effects.

Conclusions
We concluded that iron is a promoter of leukemogenesis in vivo up to a peak iron dose, but further iron loading decreases AML risk by increasing cell death. ICT can partially mitigate the adverse effects of iron overload, and to maximize its benefit this intervention should be undertaken prior to the development of extreme iron overload.
Baseline spirometry parameters as predictors of airway hyperreactivity in adults with suspected asthma
Authors: Peled Michael , Ovadya David , Cohn Jennifer , Seluk Lior , Pullerits Teet , Segel Michael J. , Onn Amir 
Published: May 2021

Abstract
Background
Methacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been inconclusive. The test is time consuming and usually requires referral to specialized centers. Simple methods to predict AHR could help determine which patients should be referred to MCTs, thus avoiding unnecessary testing. Here we investigated the potential use of baseline spirometry variables as surrogate markers for AHR in adults with suspected asthma.

Methods
Baseline spirometry and MCTs performed between 2013 and 2019 in a large tertiary center were retrospectively evaluated. Receiver-operating characteristic curves for the maximal expiratory flow-volume curve indices (angle β, FEV1, FVC, FEV1/FVC, FEF50%, FEF25–75%) were constructed to assess their overall accuracy in predicting AHR and optimal cutoff values were identified.

Results
A total of 2983 tests were analyzed in adults aged 18–40 years. In total, 14% of all MCTs were positive (PC20 ≤ 16 mg/ml). All baseline spirometry parameters were significantly lower in the positive group (p < 0.001). FEF50% showed the best overall accuracy (AUC = 0.688) and proved to be useful as a negative predictor when applying FEF50% ≥ 110% as a cutoff level.

Conclusions
This study highlights the role of FEF50% in predicting AHR in patients with suspected asthma. A value of ≥ 110% for baseline FEF50% could be used to exclude AHR and would lead to a substantial decrease in MCT referrals.
A qualitative exploration of priorities for quality improvement amongst Aboriginal and Torres Strait Islander primary health care services
Authors:   With the LEAP Learning Community, Carlisle Karen , Matthews (Quandamooka) Veronica , Redman-MacLaren Michelle , Vine Kristina , Turner (Anmatyerre/Jaru) Nalita Nungarrayi , Felton-Busch Catrina , Taylor Judy , Thompson Sandra , Whaleboat Donald , Larkins Sarah 
Published: May 2021

AbstractBackgroundAchieving quality improvement in primary care is a challenge worldwide, with substantial gaps between best practice and actual practice. Within the context of Australia, Aboriginal and Torres Strait Primary Health Care (PHC) services have great variation across settings, structures and context. Research has highlighted how these contextual differences can critically influence the success of Quality Improvement (QI) interventions and outcomes. Less understood is the interaction between local context and other factors, which may impact the implementation of QI interventions. This paper aims to explore the strengths and challenges in QI for Aboriginal and Torres Strait Islander PHC services and their priorities for improvement.MethodsA multiple case study design was adopted, working with eight Aboriginal and Torres Strait Islander PHC services in Northern Territory, Queensland and Western Australia. Data were collected via a health service survey, semi-structured interviews with health service staff and service users and researcher observations, to explore QI and perceptions of care quality at the service level. Data reported here were analysed using an iterative thematic technique, within-case and across-case.ResultsA total of 135 interviews were conducted with health service staff, service users and community members. Participants emphasised the centrality of resilient community, committed workforce and valued Aboriginal and Torres Strait Islander team members in delivering care. A shared purpose around improving the health of community was a significant driver. Key challenges included staff turnover and shortages, a complex and overwhelming acute and chronic care workload, building relationships and trust between health services and the community. Service-suggested priority areas for improvement were categorised into five themes: i) cultural safety (community driving health and planning for culturally safe services); ii) community engagement (through clinical activities in the community); iii) shared ownership and a team approach around QI; iv) strengthening systems and consistent ways of doing things in the health service; and v) strengthening local workforce (and resources for a culturally safe workforce).ConclusionsThese findings advance understandings of relational, community and cultural factors which are identified priorities for the delivery of quality care in Aboriginal and Torres Strait Islander PHC services across varied contexts.
Costs associated with depression and obesity among cardiovascular patients: medical expenditure panel survey analysis
Authors: Tápias Felipe Saia , Otani Victor Henrique Oyamada , Vasques Daniel Augusto Corrêa , Otani Thais Zelia Santos , Uchida Ricardo Riyoiti 
Published: May 2021

AbstractBackgroundThere is a lack of information on the cost of depression associated with metabolic syndrome and cardiovascular diseases in the literature.MethodsWe evaluated the synergistic effects of depression and obesity on total expenditures for cardiovascular conditions using data from the Medical Expenditure Panel Survey (MEPS) database. We analyzed MEPS data from 1996 to 2017 comprising adult cardiovascular subjects. We categorized individuals following a combination of International Classification of Diseases ICD-9-CM and ICD-10 codes, and depression symptoms as evaluated using the Patient Health Questionnaire-2 (PHQ-2) depression screening tool. Our sample comprised cardiovascular patients aged 18 years and older, with a body mass index (BMI) between 18.5 and 60. Our study comprised unweighted sample of 96,697 (weighted sample of 938,835,031) adults, a US-nationwide representative sample of cardiovascular disease patients. The four response categories were: no depression; unrecognized depression; asymptomatic depression; and symptomatic depression. Our evaluated outcomes were total annual healthcare expenditures, including dental, emergency room, hospital outpatient, hospital inpatient, office-based, prescription, and home health care expenses.ResultsAsymptomatic and symptomatic depression was more frequent among obese individuals than in individuals with a normal BMI (p <  0.001). Total expenditure was highest among symptomatic depression individuals (17,536) and obese (9871) with cardiovascular disease. All the expenditure outcomes were significantly higher among symptomatic depression individuals than those without depression (p <  0.001), except for dental costs. All healthcare expenditures associated with obesity were higher compared to individuals with normal BMI withp <  0.001, except for emergency and home healthcare costs. Most importantly, among obese individuals, all healthcare expenditures were significantly higher (p <  0.001) in those with symptomatic depression than those without depression, except for dental costs, where the difference was not significant (0.899). Therefore, obesity and depression entail increased expenses in patients with cardiovascular disease.ConclusionsWe found incremental expenditures among unrecognized, asymptomatic, and symptomatic depressed individuals with obesity compared to non-depressed, non-obese subjects. However, these are preliminary results that should be further validated using different methodologies.
The association between insulin sensitivity indices, ECG findings and mortality: a 40-year cohort study
Authors: Moshkovits Yonatan , Rott David , Chetrit Angela , Dankner Rachel 
Published: May 2021

Abstract
Background
Type 2 Diabetes is a major risk factor for cardiovascular (CV) mortality. Insulin resistance can be evaluated non-invasively by insulin sensitivity indices (ISI) such as the Mcauley index (MCAi), which is a function of the fasting insulin and triglycerides. Currently, the association between ISIs and ECG findings and all-cause and CV mortality is still not established in a large scale and heterogeneous population.

Method
In a prospective study of the Israel cohort on Glucose Intolerance, Obesity and Hypertension (GOH) second phase (1979–1982) 1830 men and women were followed until December-2016 for CV-mortality and December-2019 for all-cause mortality. ECGs were recorded and OGTTs performed during baseline. ISIs were categorized into quartiles and evaluated against ECG findings and all-cause and CV-mortality.

Results
Mean age at baseline was 52.0 ± 8.1 years, and 75 (15.2%) and 47 (25.3%) participants in the upper quartiles (Q2-4) and the lower quartile (Q1) of the MCAi, presented with Ischemic changes on ECG respectively (p = 0.02). Multivariable analysis showed higher odds for ECG ischemic changes, for individuals in Q1-MCAi (adjusted-OR = 1.7, 95% CI 1.02–2.8), compared with Q2-4-MCAi, which attenuated when excluding individuals with diabetes (adjusted-OR = 1.6, 95% CI 0.9–2.7, p = 0.09).
Median follow up for all-cause and for cardiovascular mortality was 31 years and 37 years, respectively. Cox proportional-hazards regression showed an increased risk for all-cause mortality for individuals in Q1-MCAi (HR = 1.2, 95% CI 1.02–1.3) as well as an increased risk for CV-mortality (HR = 1.4, 95%CI 1.1–1.8) compared with Q2-4-MCAi. Individuals in Q4-Ln Homeostatic model assessment- Insulin Resistance (HOMA-IR) and Q1- Quantitative Insulin Sensitivity Check Index (QUICKI) also presented with increased risk for all-cause-mortality (HR = 1.2, 95%CI 1.04–1.4; and HR = 1.2, 95% CI 1.04–1.4, respectively). Other ISIs did not show significant associations with CV-mortality.

Conclusion
Higher insulin-resistance, according to the MCAi, associated with ECG-changes, and with greater risk for all-cause and CV-mortality over a 40-year follow-up. The MCAi may be considered as an early predictive and prognostic biomarker for CV-morbidity and mortality in adults.
Efficacy and safety of artemether–lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ethiopia: a systematic review and meta-analysis
Authors: Abamecha Abdulhakim , Yilma Daniel , Adissu Wondimagegn , Yewhalaw Delenasaw , Abdissa Alemseged 
Published: May 2021

AbstractBackgroundRegular monitoring of anti-malarial drug efficacy is vital for establishing rational malaria treatment guidelines and ensuring adequate treatment outcomes. This study aimed to synthesize the available evidence on the efficacy of artemether–lumefantrine for the management of uncomplicated falciparum malaria in Ethiopia.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Relevant published studies were searched from the databases (PubMed, Google Scholar and Clinical trial registry) on published artemether–lumefantrine therapeutic efficacy studies conducted in Ethiopia from 2004 to 2020. The retrieved studies were assessed for quality using the modified Newcastle Ottawa Scale for observational studies and modified Jadad scale for interventional studies. Risk of bias was also assessed by using ROBINS-I tool. OpenMeta-Analyst software was used for the statistical analysis. The review protocol is registered in PROSPERO, number CRD42020201859.ResultsFifteen studies (1523 participants) were included in the final analysis. The overall PCR-uncorrected pooled proportion of treatment success of artemether–lumefantrine therapy for uncomplicated falciparum malaria was 98.4% (95%CI 97.6–99.1). A random-effects model was used because of considerable heterogeneity [χ2 = 20.48,df(14),P = 0.011 and I2 = 31.65]. PCR-corrected pooled proportion of treatment success of artemether–lumefantrine therapy was 98.7% (95% CI 97.7–99.6). A random-effects model was used [χ2 = 7.37,df(6),P = 0.287 and I2 = 18.69]. Most studies included in the present review achieved a rapid reduction of fevers and parasitaemia between D0 and D3 of assessment. Adverse events were mostly mild and only two cases were reported as serious, but were not directly attributed to the drug.ConclusionThe present meta-analysis suggests that artemether–lumefantrine therapy is efficacious and safe in treating uncomplicated falciparum malaria in Ethiopia. However, owing to the high risk of bias in the included studies, strong conclusions cannot be drawn. Further high-quality RCTs assessing anti-malarial efficacy and safety should be performed to demonstrates strong evidence of changes in parasite sensitivity to artemether–lumefantrine in Ethiopia.
Embryo CHH hypermethylation is mediated by RdDM and is autonomously directed in Brassica rapa
Authors: Chakraborty Tania , Kendall Timmy , Grover Jeffrey W. , Mosher Rebecca A. 
Published: May 2021

AbstractBackgroundRNA-directed DNA methylation (RdDM) initiates cytosine methylation in all contexts and maintains asymmetric CHH methylation. Mature plant embryos show one of the highest levels of CHH methylation, and it has been suggested that RdDM is responsible for this hypermethylation. Because loss of RdDM inBrassica rapacauses seed abortion, embryo methylation might play a role in seed development. RdDM is required in the maternal sporophyte, suggesting that small RNAs from the maternal sporophyte might translocate to the developing embryo, triggering DNA methylation that prevents seed abortion. This raises the question of whether embryo hypermethylation is autonomously regulated by the embryo itself or influenced by the maternal sporophyte.ResultsHere, we demonstrate thatB. rapaembryos are hypermethylated in both euchromatin and heterochromatin and that this process requires RdDM. Contrary to the current models,B. rapaembryo hypermethylation is not correlated with demethylation of the endosperm. We also show that maternal somatic RdDM is not sufficient for global embryo hypermethylation, and we find no compelling evidence for maternal somatic influence over embryo methylation at any locus. Decoupling of maternal and zygotic RdDM leads to successful seed development despite the loss of embryo CHH hypermethylation.ConclusionsWe conclude that embryo CHH hypermethylation is conserved, autonomously controlled, and not required for embryo development. Furthermore, maternal somatic RdDM, while required for seed development, does not directly influence embryo methylation patterns.
Evaluating the impact of COVID-19 on rare disease support groups
Authors: McMullan Julie , Crowe Ashleen L. , Bailie Caitlin , McKnight Amy Jayne 
Published: May 2021

Abstract
Objectives
The impact of the current COVID-19 pandemic has been felt worldwide. Many vulnerable populations rely heavily on peer support provided by individual or collaborative groups. This study aimed to evaluate the impact of COVID-19 on groups supporting patients with a rare disease(s). Anecdotally the current pandemic significantly changed the way in which these groups operate and the services they can provide.

Data description
A targeted survey was conducted online with rare disease individual or collaborative groups. The results of the survey highlight the challenges individual and collaborative groups are facing during this pandemic and help to identify what support should be put in place to enable them to sustain their much-valued service through these trialing times. Groups have experienced an increase in calls to their helplines as well as followers to their websites and social media feeds. Groups are no longer meeting in person and so online meetings, webinars and zoom chats have become a regular occurrence. Fundraising was highlighted as an area of concern for such groups. It is hoped that this data might be used to highlight the support individual and collaborative groups require while also raising awareness of the value they bring to many.
Alpha 2-antiplasmin deficiency in a Sudanese child: a case report
Authors: Mohammed Bashir Abdrhman Bashir 
Published: May 2021

Abstract
Background
The plasma serine protease inhibitor alpha 2-antiplasmin (α2-AP, otherwise known as α2-plasmin inhibitor) is a rapid-acting plasmin inhibitor recently found in human plasma, which seems to have a significant role in the regulation of in vivo fibrinolysis. Congenital deficiency of α2-AP is extremely uncommon.

Case presentation
We report here a case of absolute deficiency of α2-AP in an 11-year-old Sudanese boy, who had a lifelong intermittent hemorrhagic tendency (gum bleeding, epistaxis, and exaggerated bleeding after trauma). Coagulation tests including prothrombin time, partial thromboplastin time, thrombin time, bleeding time, platelet count, clot retraction test, antithrombin, and factor VIII levels were within normal limits. Hepatic function tests and complete blood count were also normal. The main interesting finding in this patient was that the whole blood clot lysis was extremely fast, completed within 5–8 hours. The second abnormal finding is that the euglobulin clot lysis time was short. Nevertheless, the concentration of α2-AP in the patient's plasma was 0.2 IU/ml (reference range is 0.80–1.20 IU/ml). The addition of pooled plasma (with normal α2-AP) to the patient's whole blood corrected the accelerated fibrinolysis.

Conclusion
The study showed that α2-AP deficiency resulted in uninhibited fibrinolysis that caused the hemorrhagic tendency in this patient. Thus, this report demonstrates the significant role of α2-AP in coagulation.