bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the natural indirect effect and the mediation proportion via the product method
Authors: Cheng Chao , Spiegelman Donna , Li Fan 
Published: November 2021

Abstract
Background
The natural indirect effect (NIE) and mediation proportion (MP) are two measures of primary interest in mediation analysis. The standard approach for mediation analysis is through the product method, which involves a model for the outcome conditional on the mediator and exposure and another model describing the exposure–mediator relationship. The purpose of this article is to comprehensively develop and investigate the finite-sample performance of NIE and MP estimators via the product method.

Methods
With four common data types with a continuous/binary outcome and a continuous/binary mediator, we propose closed-form interval estimators for NIE and MP via the theory of multivariate delta method, and evaluate its empirical performance relative to the bootstrap approach. In addition, we have observed that the rare outcome assumption is frequently invoked to approximate the NIE and MP with a binary outcome, although this approximation may lead to non-negligible bias when the outcome is common. We therefore introduce the exact expressions for NIE and MP with a binary outcome without the rare outcome assumption and compare its performance with the approximate estimators.

Results
Simulation studies suggest that the proposed interval estimator provides satisfactory coverage when the sample size ≥500 for the scenarios with a continuous outcome and sample size ≥20,000 and number of cases ≥500 for the scenarios with a binary outcome. In the binary outcome scenarios, the approximate estimators based on the rare outcome assumption worked well when outcome prevalence less than 5% but could lead to substantial bias when the outcome is common; in contrast, the exact estimators always perform well under all outcome prevalences considered.

Conclusions
Under samples sizes commonly encountered in epidemiology and public health research, the proposed interval estimator is valid for constructing confidence interval. For a binary outcome, the exact estimator without the rare outcome assumption is more robust and stable to estimate NIE and MP. An R package is developed to implement the methods for point and variance estimation discussed in this paper.
Low-dose dobutamine cardiovascular magnetic resonance segmental strain study of early phase of intramyocardial hemorrhage rats
Authors: Xia Rui , He Bo , Zhu Tong , Zhang Yu , Chen Yushu , Wang Lei , Zhou Yang , Liao Jichun , Zheng Jie , Li Yongmei , Lv Fajin , Gao Fabao 
Published: November 2021

Abstract
Background
This study investigates the segmental myocardial strain of the early phase of intramyocardial hemorrhage (IMH) caused by reperfused myocardial infarction (MI) in rats by low-dose dobutamine (LDD) cardiovascular magnetic resonance (CMR) feature-tracking.

Methods
Nine sham rats and nine rats with 60-min myocardial ischemia followed by 48-h reperfusion were investigated using CMR, including T2*-mapping sequence and fast imaging with steady-state precession (FISP)–cine sequence. Another FISP–cine sequence was acquired after 2 min of dobutamine injection; the MI, IMH, and Non-MI (NMI) areas were identified. The values of peak radial strains (PRS) and peak circumferential strains (PCS) of the MI, IMH and NMI segments were acquired. The efficiency of PRS and PCS (EPRS and EPCS, respectively) were calculated on the basis of the time of every single heartbeat.

Results
The PRS, PCS, EPRS, and EPCS of the sham group increased after LDD injection. However, the PRS, PCS, EPRS, and EPCS of the IMH segment did not increase. Moreover, the PRS and PCS of the MI and NMI segments did not increase, but the EPRS and EPCS of these segments increased. The PRS, PCS, EPRS, and EPCS of the IMH segment were lower than those of the MI and NMI segments before and after LDD injection, but without a significant difference between MI segment and NMI segment before and after LDD injection.

Conclusions
LDD could help assess dysfunctions in segments with IMH, especially using the efficiency of strain. IMH was a crucial factor that decreased segmental movement and reserved function.
Circular RNA hsa_circ_0043278 inhibits breast cancer progression via the miR-455-3p/EI24 signalling pathway
Authors: Shi Yue , Liu Chong 
Published: November 2021

Abstract
Background
Breast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified.

Methods
The levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis.

Results
Hsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells.

Conclusion
Hsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.
Identification of a novel RPGR mutation associated with X-linked cone-rod dystrophy in a Chinese family
Authors: Wang Yafang , Liu Shu , Zhai Yuanqi , Liu Yang , Wan Xiaoling , Wang Wenqiu , Wang Fenghua , Sun Xiaodong 
Published: November 2021

Abstract
Background
Cone-rod dystrophy (CORD) is a group of inherited retinal dystrophies, characterized by decreased visual acuity, color vision defects, photophobia, and decreased sensitivity in the central visual field. Our study has identified a novel pathogenic variant associated with X-linked cone-rod dystrophy (XLCORD) in a Chinese family.

Methods
All six family members, including the proband, affected siblings, cousins and female carriers, have underwent thorough ophthalmic examinations. The whole exome sequencing was performed for the proband, followed by Sanger sequencing for spilt-sample validation. A mammalian expression vector (AAV-MCS) with mutated retinitis pigmentosa GTPase regulator (RPGR) sequence was expressed in HEK293 T cells. The mutated protein was verified by Western blotting and immunohistochemistry.

Results
A novel mutation in the RPGR gene (c.2383G > T, p.E795X) is identified to be responsible for CORD pathogenesis.

Conclusions
Our findings have expanded the spectrum of CORD-associated mutations in RPGR gene and serve as a basis for genetic diagnosis for X-linked CORD.
Adolescent psychiatric outpatient care rapidly switched to remote visits during the COVID-19 pandemic
Authors: Savilahti Emma M. , Lintula Sakari , Häkkinen Laura , Marttunen Mauri , Granö Niklas 
Published: November 2021

Abstract
Background
The COVID-19-pandemic and especially the physical distancing measures drastically changed the conditions for providing outpatient care in adolescent psychiatry.

Methods
We investigated the outpatient services of adolescent psychiatry in the Helsinki University Hospital (HUH) from 1/1/2015 until 12/31/2020. We retrieved data from the in-house data software on the number of visits in total and categorized as in-person or remote visits, and analysed the data on a weekly basis. We further analysed these variables grouped according to the psychiatric diagnoses coded for visits. Data on the number of patients and on referrals from other health care providers were available on a monthly basis. We investigated the data descriptively and with a time-series analysis comparing the pre-pandemic period to the period of the COVID-19 pandemic.

Results
The total number of visits decreased slightly at the early stage of the COVID-19 pandemic in Spring 2020. Remote visits sharply increased starting in 3/2020 and remained at a high level compared with previous years. In-person visits decreased in Spring 2020, but gradually increased afterwards. The number of patients transiently fell in Spring 2020.

Conclusions
Rapid switch to remote visits in outpatient care of adolescent psychiatry made it possible to avoid a drastic drop in the number of visits despite the physical distancing measures during the COVID-19 pandemic.
Cultural adaptation of mental health first aid guidelines for depression for Sri Lanka: a Delphi expert consensus study
Authors: Fernando Madhawee , Chandrasiri Amila , Dayabandara Madhubhashinee , Reavley Nicola J. 
Published: November 2021

Abstract
Background
Family and friends can play a key role in supporting a person with depression to seek professional help. However, they may lack the knowledge to do so. English-language guidelines for high-income countries have been developed to assist with this. The aim of this study was to adapt the English mental health first aid guidelines for helping a person with depression to the Sri Lankan context.

Methods
A Delphi expert consensus study involving mental health professionals and people with lived experience (either their own or as carers) was conducted. Participants were recruited from inpatient, outpatient and community care settings. The English-language questionnaire was translated into Sinhala and participants were asked to rate the importance of each item for inclusion in the guidelines for Sri Lanka.

Results
Data were collected over two survey rounds. A total of 115 panellists (23% male) consisting of 92 mental health professionals and 23 consumers and carers completed the Round 1 questionnaire. A total of 165 items were included in the final guidelines, with 156 adopted from the guidelines for English-speaking countries and 9 generated from the comments of panellists.

Conclusions
The adapted guidelines were similar to the English-language guidelines. However, new items reflecting culturally relevant approaches to autonomy-granting, communication and culture-specific manifestations of depression were reflected in the adapted version. Further research should explore the use of the adapted guidelines, including their incorporation into Mental Health First Aid Training.
Layering of a health, nutrition and sanitation programme onto microfinance-oriented self-help groups in rural India: results from a process evaluation
Authors: Irani Laili , Schooley Janine , Supriya  , Chaudhuri Indrajit 
Published: November 2021

Abstract
Background
The state of Bihar has been lagging behind Indian national averages on indicators related to maternal and child health, primarily due to lack of knowledge among mothers of young children on lifesaving practices and on where to seek services when healthcare is needed. Hence, the JEEViKA Technical Support Programme was established in 101 blocks to support the state rural livelihood entity, JEEViKA, in order to increase demand for and link rural families to existing health, nutrition and sanitation services. Programme activities were geared to those engaged in JEEViKA’s microfinance-oriented self-help groups. These groups were facilitated by a village-based community mobilizer who was trained on health, nutrition and sanitation-related topics which she later shared in self-help group meetings monthly and during ad hoc home visits. Further, a block-level health, nutrition and sanitation integrator was introduced within JEEViKA to support community mobilizers. Also, indicators were added into the existing monitoring system to routinely capture the layering of health, nutrition and sanitation activities.

Methods
A process evaluation was conducted from August–November 2017 which comprised of conducting 594 quantitative surveys with community mobilizers, from program and non-programme intervention blocks. Linear and logistic regressions were done to capture the association of at least one training that the community mobilizers received on knowledge of the topics learned and related activities they carried out.

Results
Community mobilizers who had received at least one training were more likely to have higher levels of knowledge on the topics they learned and were also more likely to carry out related activities, such as interacting with block-level integrators for guidance and support, routinely collect data on health, nutrition and sanitation indicators and spend time weekly on related activities.

Conclusions
Successful integration of health, nutrition and sanitation programming within a non-health programme such as JEEViKA is possible through trainings provided to dedicated staff in decentralized positions, such as community mobilizers. The findings of this evaluation hold great promise for engaging existing non-health, nutrition and sanitation systems that are serving vulnerable communities to become partners in working towards ensuring stronger health, nutrition and sanitation outcomes for all.
Improving body image at scale among Brazilian adolescents: study protocol for the co-creation and randomised trial evaluation of a chatbot intervention
Authors: Matheson E. L. , Smith H. G. , Amaral A. C. S. , Meireles J. F. F. , Almeida M. C. , Mora G. , Leon C. , Gertner G. , Ferrario N. , Suarez Battan L. , Linardon J. , Fuller-Tyszkiewicz M. , Diedrichs P. C. 
Published: November 2021

AbstractBackgroundBody image concerns are prevalent among Brazilian adolescents and can lead to poor psychological and physical health. Yet, there is a scarcity of culturally-appropriate, evidence-based interventions that have been evaluated and made widely available. Chatbot technology (i.e., software that mimics written or spoken human speech) offers an innovative method to increase the scalability of mental health interventions for adolescents. The present protocol outlines the co-creation and evaluation of a body image chatbot for Brazilian adolescents via a partnership between academics, industry organisations and the United Nations Children’s Fund (UNICEF).MethodsA two-armed fully remote randomised controlled trial will evaluate the chatbot’s effectiveness at improving body image and well-being. Adolescent girls and boys (N = 2800) aged 13–18 years recruited online will be randomly allocated (1:1) into either: 1) a body image chatbot or 2) an assessment-only control condition. Adolescents will engage with the chatbot over a 72-hour period onFacebook Messenger. Primary outcomes will assess the immediate and short-term impact of the chatbot on state- and trait-based body image, respectively. Secondary outcomes will include state- and trait-based affect, trait self-efficacy and treatment adherence.DiscussionThis research is the first to develop an evidence-informed body image chatbot for Brazilian adolescents, with the proposed efficacy trial aiming to provide support for accessible, scalable and cost-effective interventions that address disparities in body image prevalence and readily available resources.Trial registration numberNCT04825184, registered 30th March 2021.
Change in exposure of children to second-hand smoke with impact on children’s health and change in parental smoking habits after smoking ban in Bavaria – a multiple cross-sectional study
Authors: El Sharkawy Mohammed , Heinze Stefanie , Hendrowarsito Lana , Weinberger Alisa , Huß Jonas , Nennstiel Uta , Herr Caroline , Kutzora Susanne ,   for the GME Study Group, Doerk Wiltrud , Pfister Angelika , Sit-tig Ro S E Earie , Strauch Winfried , Thamm Heidi , Wunder Anita , FrießHesse Tatjana , Lang Franziska , Rudolph Dagmar , Schmid Roland , Winter Gudrun , Bockmann Isabella , Gampenrieder Christine , Motzet Margot , Schneider Elisabeth , Tontsch Traudl , Woelk Gerlinde , Kranebitter Sylvia , Mayrhofer Heidi , Rohrhirsch Gertraud , Weise Brigitte , Wolf Luisa , Baranek Kornelia , Koch-Singer Gitte , Kühnel Maximilian , Baghi Ladan , Bayer Otmar , von Kries Rüdiger , Bolte Gabriele , Fromme Hermann , Heißenhuber Annette , Hendrowarsito Lana , Herr Caroline , Kohlhuber Martina , Kuhn Joseph , Liebl Bernhard , Lüders Anja , Meyer Nicole , Mitschek Christine , Morlock Gabriele , Mosetter Michael , Nennstiel-Ratzel Uta , Twardella Dorothee , Wildner Manfred , Zirngibl Angelika 
Published: November 2021

AbstractBackgroundConcerns about smoking displacement from public places to private amenities aroused following smoking ban implementation in Bavaria in 2008. We analysed children’s exposure to second-hand smoke (SHS) before and after the ban, its effect on children’s health and prevalence of active smoking in adults.MethodsSix cross-sectional surveys (n = 32,443) on pre-school children in Bavaria were analysed, two surveys before the smoking ban in years 2004 and 2005 (S1 and S2) and four after the ban in 2008, 2012, 2014 and 2016 (S4, S6, S7 and S8). Using multivariable logistic regression, we analysed change in children’s intra- and extrauterine SHS exposure and its adverse health effects (Asthma, wheezing, bronchitis and neurodermatitis) as well as change in parental active smoking.ResultsThe response rates were 78% for S1, 73% for S2, 61% for S4, 62% for S6, 56% for S7 and 54% for S8. Odds of parents never smoked at home in presence of children increased significantly from before to after the ban with odds ratios (OR) 1.17 (CI95%1.01–1.35), 1.65 (CI95%1.39–1.95), 2.85 (CI95%2.32–3.51), 2.24 (CI95%1.84–2.72) and 3.66 (CI95%2.89–4.63) for S2, S4, S6, S7 and S8, respectively with S1 as reference. Compared to S4, odds of parents who were not actively smoking is significantly higher in S7 (OR = 1.13 (CI95%1.03–1.24)) and S8 (OR = 1.24 (CI95%1.13–1.36)). The odds of mothers who never smoked during pregnancy increased over time with OR = 1.22 (CI95%1.06–1.40) for S2 and 1.57 (CI95%1.33–1.86) for S8 compared to S1. Adverse health effects related to children’s exposure to SHS are significantly less in S8 compared to S1.ConclusionAfter 11 years of smoking ban in Bavaria, smoking displacement to homes was disproved. Exposure of children to SHS intrauterine and at home is decreasing. Number of parents who are not actively smoking is increasing over time. Prevalence of health problems in children related to exposure to SHS is decreasing.
Methodological issues in economic evaluations of disease prevention and health promotion: an overview of systematic and scoping reviews
Authors: Seleznova Yana , Alayli Adrienne , Stock Stephanie , Müller Dirk 
Published: November 2021

Abstract
Background
We aimed to provide a comprehensive overview of methodological challenges in economic evaluations of disease prevention and health promotion (DPHP)-measures.

Methods
We conducted an overview of reviews searching MEDLINE, EMBASE, NHS Economic Evaluation Database, Database of Promoting Health Effectiveness Reviews, Cochrane Database of Systematic Reviews (CDSR) and Database of Promoting Health Effectiveness Reviews (DOPHER) (from their inception to October 2021). We included both systematic and scoping reviews of economic evaluations in DPHP addressing following methodological aspects: (i) attribution of effects, (ii) outcomes, (iii) inter-sectoral (accruing to non-health sectors of society) costs and consequences and (iv) equity. Data were extracted according to the associated sub-criteria of the four methodological aspects including study design economic evaluation (e.g. model-based), type/scope of the outcomes (e.g. outcomes beyond health), perspective, cost categories related to non-health sectors of society, and consideration of equity (method of inclusion). Two reviewers independently screened all citations, full-text articles, and extracted data. A narrative synthesis without a meta-analysis or other statistical synthesis methods was conducted.

Results
The reviewing process resulted in ten systematic and one scoping review summarizing 494 health economic evaluations. A lifelong time horizon was adopted in about 23% of DPHP evaluations, while 64% of trial-based evaluations had a time horizon up to 2 years. Preference-based outcomes (36%) and non-health outcomes (8%) were only applied in a minority of studies. Although the inclusion of inter-sectoral costs (i.e. costs accruing to non-health sectors of society) has increased in recent years, these were often neglected (between 6 and 23% depending on the cost category). Consideration to equity was barely given in economic evaluations, and only addressed in six of the eleven reviews.

Conclusions
Economic evaluations of DPHP measures give only little attention to the specific methodological challenges related to this area. For future economic DPHP evaluations a tool with structured guidance should be developed.
This overview of reviews was not registered and a published protocol does not exist.