bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lay knowledge of cardiovascular disease and risk factors in three communities in Accra, Ghana: a cross-sectional survey
Authors: Sanuade Olutobi Adekunle , Kushitor Mawuli Komla , Awuah Raphael Baffour , Asante Paapa Yaw , Agyemang Charles , de-Graft Aikins Ama 
Published: December 2021

ObjectivesCardiovascular disease is a major cause of morbidity and mortality in Ghana, and urban poor communities are disproportionately affected. Research has shown that knowledge of cardiovascular disease (CVD) is the first step to risk reduction. This study examines knowledge of CVD and risk factors and determinants of CVD knowledge in three urban poor communities in Accra, Ghana.MethodsUsing the Cardiovascular Disease Risk Factors Knowledge Level Scale, which has been validated in Ghana, we conducted a cross-sectional survey with 775 respondents aged 15–59 years. CVD knowledge was computed as a continuous variable based on correct answers to 27 questions, and each correct response was assigned one point. Linear regression was used to determine the factors associated with CVD knowledge.ResultsThe mean age of the participants was 30.3±10.8 years and the mean knowledge score was 19.3±4.8. About one-fifth of participants were living with chronic diseases. Overall, 71.1% had good CVD knowledge, and 28.9% had moderate or poor CVD knowledge. CVD knowledge was low in the symptoms and risk factor domains. A larger proportion received CVD knowledge from radio and television. The determinants of CVD knowledge included ethnicity, alcohol consumption, self-reported health and sources of CVD knowledge. CVD knowledge was highest among a minority Akan ethnic group, those who were current alcohol consumers and those who rated their health as very good/excellent, compared with their respective counterparts. CVD knowledge was significantly lower among those who received information from health workers and multiple sources.ConclusionThis study underscores the need for health education programmes to promote practical knowledge on CVD symptoms, risks and treatment. We outline health systems and community-level barriers to good CVD knowledge and discuss the implications for developing context-specific and culturally congruent CVD primary prevention interventions.
Cost effectiveness of screening for intracranial aneurysms among patients with bicuspid aortic valve: a Markov modelling study
Authors: Chen Jigang , Han Mingyang , Feng Xin , Peng Fei , Tong Xin , Niu Hao , Zhang Danfeng , Liu Aihua 
Published: December 2021

ObjectiveBicuspid aortic valve (BAV) is common and 7.7%–9.8% of patients with BAV have intracranial aneuryms (IAs) which might lead to a devastating subarachnoid haemorrhage (SAH). We aimed to evaluate different screening and follow-up strategies using magnetic resonance angiography for IAs among patients with BAV.MethodsA decision-analytic model was built to evaluate the costs and effectiveness of different management strategies from the Chinese healthcare payer’s perspective. The evaluated strategies included natural history without screening for possible IAs, regular screening and no follow-up for detected IAs, and regular screening with regular follow-up (Screen strategy/Follow-up strategy). Base case calculation, as well as probabilistic, one-way, and two-way sensitivity analyses, were performed.ResultsAccording to the base case calculation, natural history had the least cost and effectiveness while Every 5 years (y)/Annual gained the highest cost and effectiveness. Every 10y/Biennial was cost effective when compared with Every 10y/Every 5y under the willingness-to-pay threshold of ¥211 743 (US$30 162). Probabilistic sensitivity analysis showed that Every 10y/Biennial was superior in 88.3% of the cases when compared with Every 10y/Every 5y. One-way and two-way sensitivity analyses proved that Every 10y/Biennial was the dominant strategy under most circumstances.ConclusionsScreening for possible IAs among patients with BAV and follow-up for detected IAs would increase the effectiveness. Every 10y/Biennial was the optimal strategy from the Chinese healthcare payer’s perspective.
Health actor approaches to financing universal coverage strategies for pneumococcal and rotavirus immunisation programmes in low-income and middle-income countries: a scoping review protocol
Authors: Ogundele Oluwasegun Jko , Fadel Shaza , Braitstein Paula , Di Ruggiero Erica 
Published: December 2021

IntroductionSustainable financing of immunisation programmes is an important step towards universal coverage of life-saving vaccines. Yet, financing mechanisms for health programmes could have consequences on the design of universal approaches to immunisation coverage. Effective implementation of immunisation interventions necessitates investigating the roles of institutions and power on interventions. This review aims to understand how sustainable financing and equitable immunisation are conceptualised by health actors like Gavi, and government-related entities across low-income and middle-income countries (LMICs) and how financing mechanisms can affect universal coverage of vaccines.Methods and analysisThis study protocol outline a scoping review of the peer-reviewed and the grey literature, using established methodological framework for scoping review. Literature will be identified through a comprehensive search of multiple databases and grey literature. All peer-reviewed implementation research studies from the year 2002 addressing financing and universal coverage of immunisation programmes for the pneumococcal conjugated vaccine and rotavirus vaccines immunisation interventions will be included and grey literature published in/after the year 2015. For the study scope, population, concept and context are defined: Population as international and national health stakeholders financing immunisation programmes; Concept as implementation research on pneumococcal conjugate and rotavirus vaccination interventions; and Context as LMICs. Findings will be quantitatively summarised to provide an overview and narratively synthesised and analysed. Studies that do not use implementation research approaches, frameworks or models will be excluded.Ethics and disseminationEthics approval is not required for this scoping review. Findings and recommendations will be presented to implementation researchers and health stakeholders.
Sexual health promotion messages for young people in Netflix most-watched series content (2015–2020): mixed-methods analysis study
Authors: Tauty Solenne , Martin Philippe , Bourmaud Aurélie , Chapoton Boris , de La Rochebrochard Elise , Alberti Corinne 
Published: December 2021

IntroductionSexual health is a major issue for young people, and there is a need to promote it. Sexual health promotion messages may be included in Netflix series that are widely watched by young people, with important emotional dimensions in scenarios.ObjectiveThe aim of this study is to investigate the explicit sexual health promotion messages integrated in Netflix series popular among young people, and to describe them and how they are delivered.MethodsWe selected two types of Netflix series, aimed at young people: (1) series whose synopsis is mainly about sexual health and (2) all-subject series. We extracted data from 65 episodes of 6 of the most-watched Netflix series. We used a data extraction grid on EpiData. We analysed sexual health themes and sexual health promotion messages. We described the series and listed all the sexual health and other health themes discussed. For each promotion message, we described scene contents and extracted dialogues.ResultsWe found 62 promotion messages in the 6 analysed series. The two series that highlight sexual health in their synopsis account for 81% (n=50/62) of these identified promotion messages. Messages mainly focus on sexual harassment and violence (19%), on sexually transmitted infections protection (18%) and on contraception (15%). Messages are mainly delivered as verbal information, and mostly feature 16–18 years old characters in school. Analysis highlighted four main points concerning scenarios in these series: (1) there are different ways to deliver sexual health promotion messages; (2) there is depiction of negative value judgements and gender norms; (3) some information may be incomplete or misleading and (4) risky behaviours are represented.ConclusionNetflix series incorporate diverse sexual health promotion messages for young people. Further research could assess how these messages are perceived and whether they increase the knowledge, skills and positive health behaviours of young people.
Efficacy and safety of low-dose versus high-dose hydrocortisone to treat hypotension in neonates: a protocol for a systematic review and meta-analysis
Authors: Sushko Katelyn , Al-Rawahi Nada , Watterberg Kristi , Van Den Anker John , Litalien Catherine , Lacroix Jacques , Razak Abdul , Samiee-Zafarghandy Samira 
Published: December 2021

BackgroundImpaired adrenal function is a well-described entity in critically ill term and preterm neonates with systemic hypotension. The standard treatment for neonatal hypotension includes volume expanders and vasopressors. Recent evidence supports the use of glucocorticoids for the primary or rescue treatment of neonatal hypotension associated with impaired adrenal function. However, inconsistency regarding the prescribed dosing regimen to provide the best balance between efficacy and safety in this vulnerable population remains an area of concern.MethodsWe will conduct a systematic review and meta-analysis to evaluate low-dosing compared with high-dosing regimens of hydrocortisone for the treatment of hypotension in critically ill term, preterm and very low birth weight neonates. Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Web of Science will be searched from inception to November 2021. Study screening and selection will be completed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Our primary outcomes will be (1) an improvement in end-organ perfusion, defined as an increase in blood pressure along with an increase in urine output or a reduction in serum lactate and (2) mortality prior to discharge. Our secondary outcomes will be the development of (1) major neurosensory abnormality, (2) bronchopulmonary dysplasia and (3) the occurrence of adverse events.DiscussionHydrocortisone may be beneficial in the treatment of hypotension associated with impaired adrenal function among critically ill neonates. However, its optimal dosing to balance desired efficacy with the risk of adverse events is yet to be determined. Our systematic review and meta-analysis aims to address this evidence gap, providing valuable knowledge for a large audience, including guideline developers, policy-makers and clinicians.PROSPERO registration numberThis protocol is submitted for registration to the international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).
Distinct exhaustion features of T lymphocytes shape the tumor-immune microenvironment with therapeutic implication in patients with non-small-cell lung cancer
Authors: Kim Chang Gon , Kim Gamin , Kim Kyung Hwan , Park Seyeon , Shin Sunhye , Yeo Dahee , Shim Hyo Sup , Yoon Hong In , Park Seong Yong , Ha Sang-Jun , Kim Hye Ryun 
Published: December 2021

BackgroundReinvigoration of T-cell exhaustion with antibodies has shown promising efficacy in patients with non-small-cell lung cancer (NSCLC). However, the characteristics of T-cell exhaustion with regard to tumor-infiltrating lymphocytes (TILs) are poorly elucidated in NSCLC. Here, we investigated the exhaustion status of TILs in NSCLC patients at the intraindividual and interindividual levels.MethodsWe obtained paired peripheral blood, normal adjacent tissues, peritumoral tissues, and tumor tissues from 96 NSCLC patients. Features of T-cell exhaustion were analyzed by flow cytometry. T cells were categorized according to their programmed cell death-1 (PD-1) expression (PD-1high, PD-1int, and PD-1neg cells). Patients were classified based on the presence or absence of discrete PD-1high CD8+ TILs. Production of effector cytokines by CD8+ TILs was measured after T-cell stimulation with or without antibodies against immune checkpoint receptors.ResultsProgressive T-cell exhaustion with marked expression of exhaustion-related markers and diminished production of effector cytokines was observed in PD-1high CD8+ TILs compared with PD-1int and PD-1neg CD8+ TILs. Patients with distinct PD-1high CD8+ TILs (PD-1high expressers) exhibited characteristics associated with a favorable anti-PD-1 response compared with those without these lymphocytes (non-PD-1high expressers). Combined inhibition of dual immune checkpoint receptors further restored effector cytokine production by CD8+ TILs following T-cell stimulation. PD-1high CD8+ T lymphocyte populations in the peripheral blood and tumors were significantly correlated.ConclusionsT-cell exhaustion was differentially regulated among individual patients and was prominent in a subgroup of NSCLC patients who may benefit from PD-1 blockade or combined blockade of other immune checkpoint receptors.
Clinical outcomes following major trauma for patients with a diagnosis of depression: a large UK database analysis
Authors: Large Jamie , Naumann David N , Fellows Jodie , Connor Clare , Ahmed Zubair 
Published: December 2021

BackgroundMore than a quarter of the UK population are affected by depression during their lifetime. For major trauma patients, postinjury depression can result in poorer long-term outcomes, but there is limited evidence regarding outcomes for patients with pre-existing depression. This study investigated the relationship between a diagnosis of depression prior to hospital admission and clinical outcomes after major trauma.MethodsTrauma patients at a UK major trauma center were identified during a 6.5-year period using the Trauma Audit and Research Network database. Patients with Injury Severity Score >15 who did not die in the emergency department (ED) were included. Logistic regression models were used to compare in-hospital mortality (excluding ED), requirement for surgery, and length of stay (LOS) between those with depression and those without.ResultsThere were 4602 patients included in the study and 6.45% had a diagnosis of depression. Depression was associated with a significant reduction in mortality (OR 0.54, 95% CI 0.30 to 0.91; p=0.026). However, patients with depression were more likely to have longer LOS (OR 124, 95% CI 8.5 to 1831; p<0.001) and intensive care unit LOS (OR 9.69, 95% CI 3.14 to 29.9; p<0.001). Patients with depression were also more likely to undergo surgery (OR 1.36, 95% CI 1.06 to 1.75; p=0.016).DiscussionA pre-existing diagnosis of depression has complex association with clinical outcomes after major trauma, with reduced mortality but longer LOS and higher likelihood of surgical intervention. Further prospective investigations are warranted to inform optimal management strategies for major trauma patients with pre-existing depression.Level of evidenceIII.
Implications for the hierarchy problem, inflation and geodesic motion from fiber fabric of spacetime
Authors: Nam Cao H. 
Published: December 2021

AbstractIn this paper, we represent a resolution for the hierarchy problem where the inverse size of the extra dimension and the fundamental Planck scale would all be of the order of the TeV scale by proposing a fiber fabric of spacetime. The origin of the large hierarchy is essentially due to the $$\cosh $$
cosh
function which is physically originated from the dynamics of the horizontal metric in the vacuum of non-zero energy. In addition, the fiber fabric of spacetime allows us to resolve elegantly and naturally the problems of the chirality fermions and stabilizing potential for the size of the extra dimension, which are usually encountered in the higher dimensional theories. Then, we explore the inflation with the modulus of the extra dimension identified as the inflaton where our slow-roll inflationary model belongs to the E-model class with $$n=1$$

n
=
1

. We calculate the main inflationary observables which are consistent with the present experiments. Finally, we study how the geodesic motion of neutral test particles gets modified from the extension of spacetime. We compute the radius of the photon sphere, the innermost stable circular orbit, the perihelion shift, the light bending angle, and the observables of the strong gravitational lensing and the retrolensing phenomenon. By comparing the predicted values with the experimental observations, we determine the constraints on the fiber fabric of spacetime.
Too Good to Be True? Evaluation of Colonoscopy Sensitivity Assumptions Used in Policy Models
Authors: Rutter Carolyn M. , Nascimento de Lima Pedro , Lee Jeffrey K. , Ozik Jonathan 
Published: December 2021

Abstract

Background:
Models can help guide colorectal cancer screening policy. Although models are carefully calibrated and validated, there is less scrutiny of assumptions about test performance.

Methods:
We examined the validity of the CRC-SPIN model and colonoscopy sensitivity assumptions. Standard sensitivity assumptions, consistent with published decision analyses, assume sensitivity equal to 0.75 for diminutive adenomas (&lt;6 mm), 0.85 for small adenomas (6–10 mm), 0.95 for large adenomas (≥10 mm), and 0.95 for preclinical cancer. We also selected adenoma sensitivity that resulted in more accurate predictions. Targets were drawn from the Wheat Bran Fiber study. We examined how well the model predicted outcomes measured over a three-year follow-up period, including the number of adenomas detected, the size of the largest adenoma detected, and incident colorectal cancer.

Results:
Using standard sensitivity assumptions, the model predicted adenoma prevalence that was too low (42.5% versus 48.9% observed, with 95% confidence interval 45.3%–50.7%) and detection of too few large adenomas (5.1% versus 14.% observed, with 95% confidence interval 11.8%–17.4%). Predictions were close to targets when we set sensitivities to 0.20 for diminutive adenomas, 0.60 for small adenomas, 0.80 for 10- to 20-mm adenomas, and 0.98 for adenomas 20 mm and larger.

Conclusions:
Colonoscopy may be less accurate than currently assumed, especially for diminutive adenomas. Alternatively, the CRC-SPIN model may not accurately simulate onset and progression of adenomas in higher-risk populations.

Impact:
Misspecification of either colonoscopy sensitivity or disease progression in high-risk populations may affect the predicted effectiveness of colorectal cancer screening. When possible, decision analyses used to inform policy should address these uncertainties.
See related commentary by Etzioni and Lange, p. 702
Transcription Factor FOSL1 Enhances Drug Resistance of Breast Cancer through DUSP7-Mediated Dephosphorylation of PEA15
Authors: Li Lin , Wang Nan , Xiong Youyi , Guo Guangcheng , Zhu Mingzhi , Gu Yuanting 
Published: December 2021

Abstract

Breast cancer is one of the commonest malignancies in women with first occurrence and fifth mortality in the world. However, drug resistance has always been a major obstacle to cancer treatment. Transcription factors have been reported to have close association with drug resistance of tumors. Recently, by analyzing the data from Gene Expression Omnibus database (GSE76540), we found that transcription factor FOS like 1, AP-1 transcription factor subunit (FOSL1) was significantly upregulated in the transcriptome of doxorubicin-resistant breast cancer cells compared with that in sensitive parental cells. Therefore, we aim to explore the regulatory mechanism of FOSL1 in affecting the drug resistance of breast cancer cells. FOSL1 expression in doxorubicin-resistant breast cancer cells was firstly examined through qRT-PCR, and then its influence on the drug resistance of breast cancer cells was explored through a series of in vitro and in vivo mechanism assays. Results showed that FOSL1 promoted the drug resistance of breast cancer cells to doxorubicin both in intro and in vivo. It positively regulated the transcription of dual specificity phosphatase 7 (DUSP7) in breast cancer doxorubicin-resistant cells and DUSP7 also enhanced the drug resistance of breast cancer cells. Furthermore, FOSL1 promoted the dephosphorylation of proliferation and apoptosis adaptor protein 15 (PEA15) through DUSP7. In conclusion, it was verified that FOSL1 promoted the drug resistance in breast cancer through DUSP7-mediated dephosphorylation of PEA15.

Implications:
These initial findings suggest that the FOSL1/DUSP7/PEA15 pathway may provide a theoretical guidance for breast cancer treatment.
Variant Identification in BARD1, PRDM9, RCC1, and RECQL in Patients with Ovarian Cancer by Targeted Next-generation Sequencing of DNA Pools
Authors: Suszynska Malwina , Ratajska Magdalena , Galka-Marciniak Paulina , Ryszkowska Aleksandra , Wydra Dariusz , Debniak Jaroslaw , Jasiak Anna , Wasag Bartosz , Cybulski Cezary , Kozlowski Piotr 
Published: December 2021

Abstract

Several ovarian cancer susceptibility genes have been discovered, but more are likely to exist. In this study, we aimed to analyze knowledge-based selected genes, that is, BARD1, PRDM9, RCC1, and RECQL, in which pathogenic germline variants have been reported in patients with breast and/or ovarian cancer. As deep sequencing of DNA samples remains costly, targeted next-generation sequencing of DNA pools was utilized to screen the exons of BARD1, PRDM9, RCC1, and RECQL in approximately 400 Polish ovarian cancer cases. A total of 25 pools of 16 samples (including several duplicated samples with known variants) were sequenced on the NovaSeq6000 and analyzed with SureCall (Agilent) application. The set of variants was filtrated to exclude spurious variants, and, subsequently, the identified rare genetic variants were validated using Sanger sequencing. No pathogenic mutation was found within the analyzed cohort of patients with ovarian cancer. Validation genotyping of filtered rare silent and missense variants revealed that the majority of them were true alterations, especially those with a higher mutation quality value. The high concordance (R2 = 0.95) of population allele frequency for 44 common SNPs in the European control population (gnomAD) and our experiment confirmed the reliability of pooled sequencing. Mutations in BARD1, PRDM9, RCC1, and RECQL do not contribute substantially to the risk of ovarian cancer. Pooled DNA sequencing is a cost-effective and reliable method for the initial screening of candidate genes; however, it still requires validation of identified rare variants.

Prevention Relevance:
BARD1, PRDM9, RCC1, and RECQL are not high/moderate-risk ovarian cancer susceptibility genes. Pooled sequencing is a reliable and cost-effective method to detect rare variants in candidate genes.