bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of empagliflozin in patients with type 2 diabetes and established cardiovascular disease in China
Authors: Ramos Mafalda , Men Peng , Wang Xu , Ustyugova Anastasia , Lamotte Mark 
Published: August 2021

AbstractBackgroundIn several cardiovascular outcome trials (CVOTs), empagliflozin (SGLT-2 inhibitor), sitagliptin (DPP-4 inhibitor) and liraglutide (GLP-1 receptor agonist) + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and liraglutide + SoC based on the respective CVOT.MethodsThe IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease (HbA1c, BMI, blood pressure, lipids) were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and liraglutide + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk adjustments to calibrate the CDM were obtained after a trial and error process to match as closely the observed and CDM-predicted outcomes. The drug-specific treatment effects were considered up until HbA1c reached 8.5% and treatment switch occurred. After this switch, the United Kingdom Prospective Diabetes Study 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal bolus insulin were applied. The analysis was conducted from the perspective of the Chinese healthcare system applying 3% discounting. The time horizon was lifelong.ResultsEmpagliflozin + SoC provides additional Quality Adjusted Life years (QALY + 0.564) for an incremental cost of 42,497RMB (US$6053) compared to sitagliptin + SoC, resulting in an Incremental Cost Utility Ratio of 75,349RMB (US$10,732), thus below the willingness-to-pay threshold of 212,676RMB, corresponding to three times the Gross Domestic Product in China (2019). Compared to liraglutide + SoC, empagliflozin + SoC use leads to 0.211QALY gained and cost savings of 71,427RMB (US$10,173) and is as such dominant. Scenario and probabilistic sensitivity analyses demonstrated the robustness of the results.ConclusionResults suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and liraglutide + SoC at a willingness-to-pay threshold of 212,676RMB ($30,292)/QALY.
Strategies for reducing out of pocket payments in the health system: a scoping review
Authors: Jalali Faride Sadat , Bikineh Parisa , Delavari Sajad 
Published: August 2021

AbstractBackgroundDirect out-of-pocket payments (OOP) are among the most important financing mechanisms in many health systems, especially in developing countries, adversely affecting equality and leading vulnerable groups to poverty. Therefore, this scoping review study was conducted to identify the strategies involving OOP reduction in health systems.MethodsArticles published in English on strategies related to out-of-pocket payments were Searched and retrieved in the Web of Science, Scopus, PubMed, and Embase databases between January 2000 and November 2020, following PRISMA guidelines. As a result, 3710 papers were retrieved initially, and 40 were selected for full-text assessment.ResultsOut of 40 papers included, 22 (55%) and 18 (45%) of the study were conducted in developing and developed countries, respectively. The strategies were divided into four categories based on health system functions: health system stewardship, creating resources, health financing mechanisms, and delivering health services.As well, developing and developed countries applied different types of strategies to reduce OOP.ConclusionThe present review identified some strategies that affect the OOP payments According to the health system functions framework. Considering the importance of stewardship, creating resources, the health financing mechanisms, and delivering health services in reducing OOP, this study could help policymakers make better decisions for reducing OOP expenditures.
Perceptions of family, community and religious leaders and acceptability for minimal invasive tissue sampling to identify the cause of death in under-five deaths and stillbirths in North India: a qualitative study
Authors: Das Manoja Kumar , Arora Narendra Kumar , Kaur Gurkirat , Malik Prikanksha , Kumari Mahisha , Joshi Shipra , Rasaily Reeta , Chellani Harish , Gaikwad Harsha , Debata Pradeep , Meena K. R. 
Published: August 2021

Abstract
Background
Minimal invasive tissue sampling (MITS) has emerged as a suitable alternative to complete diagnostic autopsy (CDA) for determination of the cause of death (CoD), due to feasibility and acceptability issues. A formative research was conducted to document the perceptions of parents, community and religious leaders on acceptability of MITS.

Methods
This qualitative study was conducted at and around the Safdarjung Hospital, Delhi, India. Participants for in-depth interview included the parents who had either child or neonatal death or stillbirth and the key community and religious representatives. The focus group discussions (FGDs) involved community members. Process of obtaining consent for MITS was observed. Data were analyzed inductively manually for emerging themes and codes.

Results
A total of 104 interviews (parents of deceased children, neonates or stillbirths, n = 93; community members, n = 8 and religious leaders, n = 7), 8 FGDs (n = 72) were conducted and process of obtaining consent for MITS (n = 27) was observed. The participants were positive and expressed willingness to accept MITS. The key determinants for acceptance of MITS were: (1) understanding and willingness to know the cause of death or stillbirth, (2) experience of the healthcare received and trust, (3) the religious and sociocultural norms. Parents and community favored for MITS over CDA when needed, especially where in cases with past stillbirths and child deaths. The experience of treatment, attitude and communication from healthcare providers emerged as important for consent. The decision making process was collective involving the elders and family. No religious leader was against the procedure, as both, the respect for the deceased and need for medical care were satisfied.

Conclusions
Largely, MITS appeared to be acceptable for identifying the causes of child deaths and stillbirths, if the parents and family are counseled appropriately considering the sociocultural and religious aspects. They perceived the quality of care, attitude and communication by the healthcare providers as critical factors for acceptance of MITS.
Implementing work-related Mental health guidelines in general PRacticE (IMPRovE): a protocol for a hybrid III parallel cluster randomised controlled trial
Authors: Mazza Danielle , Chakraborty Samantha , Camões-Costa Vera , Kenardy Justin , Brijnath Bianca , Mortimer Duncan , Enticott Joanne , Kidd Michael , Trevena Lyndal , Reid Sharon , Collie Alex 
Published: August 2021

Abstract
Background
The Clinical Guideline for the Diagnosis and Management of Work-related Mental Health Conditions in General Practice (the Guideline) was published in 2019. The objective of this trial is to implement the Guideline in general practice.

Trial design
Implementing work-related Mental health conditions in general PRacticE is a hybrid III, parallel cluster randomised controlled trial undertaken in Australia. Its primary aim is to assess the effectiveness of a complex intervention on the implementation of the Guideline in general practice. Secondary aims are to assess patient health and work outcomes, to evaluate the cost-effectiveness of the trial, and to develop a plan for sustainability.

Methods
A total of 86 GP clusters will be randomly allocated either to the intervention arm, where they will receive a complex intervention comprising academic detailing, enrolment in a community of practice and resources, or to the control arm, where they will not receive the intervention. GP guideline concordance will be assessed at baseline and 9 months using virtual simulated patient scenarios. Patients who meet the eligibility criteria (>18years, employed, and receiving care from a participating GP for a suspected or confirmed work-related mental health condition) will be invited to complete surveys about their health and work participation and provide access to their health service use data. Data on health service use and work participation compensation claim data will be combined with measures of guideline concordance and patient outcomes to inform an economic evaluation. A realist evaluation will be conducted to inform the development of a plan for sustainability.

Results
We anticipate that GPs who receive the intervention will have higher guideline concordance than GPs in the control group. We also anticipate that higher concordance will translate to better health and return-to-work outcomes for patients, as well as cost-savings to society.

Conclusions
The trial builds on a body of work defining the role of GPs in compensable injury, exploring their concerns, and developing evidence-based guidelines to address them. Implementation of these guidelines has the potential to deliver improvements in GP care, patient health, and return-to-work outcomes.

Trial registration
ACTRN12620001163998, November 2020
Minocycline black bone disease in arthroplasty: a systematic review
Authors: Steadman William , Brown Zak , Wall Christopher J. 
Published: August 2021

Abstract
Background
Minocycline black bone disease is a rare finding that can cause concern when unexpectedly encountered during routine arthroplasty. Prolonged minocycline use can cause selective staining of subchondral bone, whilst peri-articular soft tissue and cartilage appear uninvolved.

Methods
A systematic review according to PRISMA guidelines was performed to identify all reported cases in the literature.

Results
Including the patient we present, eleven cases of minocycline black bone disease encountered during arthroplasty have been reported in the literature. All cases have had an excellent outcome, with no complications reported to date.

Conclusions
Minocycline black bone disease can be a concerning intra-operative finding when unexpectedly encountered during routine arthroplasty, but should not affect the operative plan. Surgeons should exclude alternative causes of bone discolouration when the history is unclear.
Aortic prosthetic size predictor in aortic valve replacement
Authors: Vo Anh Tuan , Nakajima Tomomi , Nguyen Trang Thi Thu , Nguyen Nguyen Thoi Hai , Le Nga Bich , Cao Tri Huu , Nguyen Dinh Hoang 
Published: August 2021

Abstract
Background
Patient-prosthesis mismatch (PPM) is a major concern in aortic valve replacement (AVR) and leads to perioperative morbidity and rehospitalization. Predicting aortic annulus diameter pre-procedurally is crucial to managing patients with high-risk of PPM.

Objectives
To compare preoperative measurements of aortic annulus from echocardiography and CT scan with surgical sizing and develop an imaging-based algorithm to predict PPM.

Methods
From January 2017 to December 2020, patients underwent AVR at a teaching hospital were examined. The relationship between imaging measurements with operative values was assesed using scatter plots and Pearson’s correlation coefficient. Univariable linear regression was then used to build the predictive model.

Results
A total of 144 patients underwent AVR during the study period. Suture types and surgical approaches were not significantly associated with prosthesis size. CT scan-based measurements showed strong correlation with prosthesis size: mean diameter (R = 0.79), perimeter-derived diameter (R = 0.76), and area-derived diameter (R = 0.75). Mechanical valve and tissue valve shared similar correlation coefficients. Prosthesis size predictive models based on CT scan were 12.89 + 0.335 × d for mean diameter, 13.275 + 0.315 × d for perimeter-derived diameter and 13.626 + 0.309 × d for area-derived diameter.

Conclusions
Preoperative CT scan measurements are a reliable predictor of aortic prosthesis size. Transthoracic echocardiography is a possible alternative, though it is highly performer-dependent and unable to represent the aortic annulus fully. Together, these two imaging modalities can be used to quantitatively anticipate PPM preoperatively.
Two methoxy derivatives of resveratrol, 3,3′,4,5′-tetramethoxy-trans-stilbene and 3,4′,5-trimethoxy-trans-stilbene, suppress lipopolysaccharide-induced inflammation through inactivation of MAPK and NF-κB pathways in RAW 264.7 cells
Authors: Zhou Chunxiu , Zhang Xutao , Ruan Cheng-Chao , Cheang Wai San 
Published: August 2021

Abstract
Background
3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and 3,4′,5-trimethoxy-trans-stilbene (3,4′,5-TMS) are two methoxy derivatives of resveratrol. Previous researches have proved that resveratrol and its analogues have anti-inflammatory effect through suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. This study aims to study whether 3,3′,4,5′-TMS and 3,4′,5-TMS alleviate inflammation and the underlying mechanism.

Methods
RAW 264.7 macrophage cells were treated with lipopolysaccharide (LPS) to induce inflammation and pretreated with 3,3′,4,5′-TMS or 3,4′,5-TMS. Cell viability was measured with the 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Nitric oxide (NO) release was detected by Griess reagent. The secretions of pro-inflammatory cytokines were assessed by ELISA kits. Protein expressions of signaling molecules were determined by Western blotting. Reactive oxygen species (ROS) production was detected by fluorescence staining and malondialdehyde (MDA) assay.

Results
3,3′,4,5′-TMS and 3,4′,5-TMS suppressed LPS-induced NO release and pro-inflammatory cytokines (IL-6 and TNF-α) secretions in a dose-dependent manner in RAW 264.7 cells. 3,3′,4,5′-TMS and 3,4′,5-TMS significantly down-regulated the LPS-induced expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and partially suppressed the activation of MAPK (phosphorylation of p38, JNK, ERK), and NF-κB (phosphorylation of IKKα/β, p65 and IκBα) signaling pathways; where phosphorylation of ERK and p65 was mildly but not significantly decreased by 3,3′,4,5′-TMS. LPS-induced NF-κB/p65 nuclear translocation was inhibited by both 3,3′,4,5′-TMS and 3,4′,5-TMS. Moreover, both resveratrol derivatives decreased the ROS levels.

Conclusions
3,3′,4,5′-TMS and 3,4′,5-TMS significantly suppress LPS-induced inflammation in RAW 264.7 cells through inhibition of MAPK and NF-κB signaling pathways and also provide anti-oxidative effect. This study reveals potential therapeutic applications of 3,3′,4,5′-TMS and 3,4′,5-TMS for inflammatory diseases.
Outcomes of community-based suicide prevention program in primary health care of Iran
Authors: Azizi Hosein , Fakhari Ali , Farahbakhsh Mostafa , Esmaeili Elham Davtalab , Mirzapour Mohammad 
Published: August 2021

Abstract
Background
Suicidal management and prevention in communities, especially in its first stages, is an effective intervention for the health systems. However, in numerous societies most cases go undetected. Primary Health Care (PHC) is an effective place for the management of Suicide Prevention Programs (SPP). In Malekan County, a health community assessment found suicide as the most important health problem. A regional SPP was performed for suicide prevention during 2014–2017.

Methods
This study was carried out in six steps: (1) Establishing a research team, (2) Improving a registry for suicidal behaviors (SBs), (3) Identifying local determinants of SBs, (4) Training healthcare providers, (5) Follow-up and monitoring of SBs, and (6) Public awareness campaigns. Our ultimate goal was to lower the rates of suicide, and suicide attempt (SA) by 15 and 20 %, respectively. Multiple logistic regression was used to estimate the adjusted odds ratios and the 95% confidence intervals.

Results
A total of 821 SAs and 32 suicides were identified. The gender distribution for suicides was 70% males whereas SAs were 64% among females. The majority of suicides occurred in spring 18 (56.25%) while summer was the most common season among SAs 288 (35.8%). Almost 62 and 75% of suicides and SAs have used hanging and poisoning methods, respectively. Hanging increased suicide risk significantly (OR: 8.5, 95% CI 2.9–76.99). During the study, 93 life-skill and parenting education sessions were held. The incidence rates of suicide and SA decreased from 11.22, and 203 per 100,000 in 2013 to 2.63, and 157 in 2017, respectively. Similarly, the re-attempt to SAs ratio decreased from 12% to 2013 to 6.7% in 2017. Moreover, more than 8% of SBs were collected from adjacent Counties.

Conclusions
At the study end, suicide, SA, and re-attempt were lowered by 75%, 22%, and 42%, respectively. The practical framework that achieved in this study could be used as a basis for developing future SPPs and suicide researches in the Iranian context. Furthermore, the various socio-economic and socio-cultural challenges highlight the need to consider a wide range of contextual factors when developing an SPP.
NUAK2 and RCan2 participate in the p53 mutant pro-tumorigenic network
Authors: Mammarella Eleonora , Zampieri Carlotta , Panatta Emanuele , Melino Gerry , Amelio Ivano 
Published: August 2021

AbstractMost inactivating mutations in TP53 gene generates neomorphic forms of p53 proteins that experimental evidence and clinical observations suggest to exert gain-of-function effects. While massive effort has been deployed in the dissection of wild type p53 transcriptional programme, p53 mutant pro-tumorigenic gene network is still largely elusive. To help dissecting the molecular basis of p53 mutant GOF, we performed an analysis of a fully annotated genomic and transcriptomic human pancreatic adenocarcinoma to select candidate players of p53 mutant network on the basis their differential expression between p53 mutant and p53 wild-type cohorts and their prognostic value. We identified NUAK2 and RCan2 whose p53 mutant GOF-dependent regulation was further validated in pancreatic cancer cellular model. Our data demonstrated that p53R270H can physically bind RCan2 gene locus in regulatory regions corresponding to the chromatin permissive areas where known binding partners of p53 mutant, such as p63 and Srebp, bind. Overall, starting from clinically relevant data and progressing into experimental validation, our work suggests NUAK2 and RCan2 as novel candidate players of the p53 mutant pro-tumorigenic network whose prognostic and therapeutic interest might attract future studies.
Efficacy of low-load resistance training combined with blood flow restriction vs. high-load resistance training on sarcopenia among community-dwelling older Chinese people: study protocol for a 3-arm randomized controlled trial
Authors: Chen Nan , He Xiangfeng , Zhao Guoyun , Lu Linqian , Ainsworth Barbara E. , Liu Yu , Wu Xie 
Published: August 2021

AbstractBackgroundSarcopenia is accompanied by a decline in muscle mass, muscle strength, and muscle function. Resistance training is the most potential training method for the prevention and treatment of sarcopenia. However, the conventional high-load resistance training (CRT) recommended by the American College of Sports Medicine is a challenge for older people with sarcopenia. As a novel training method, low-load resistance training combined with blood flow restriction (LRT-BFR) may elicit similar muscle mass and muscle strength gains as CRT but with less effort. The objectives of this study are to assess and compare the efficacy and safety of 12-week LRT-BFR and CRT on muscle strength, muscle performance, body composition, pulmonary function, blood biomarkers, CVD risk factors, and quality of life in community-dwelling older Chinese people with sarcopenia.MethodThis is a 12-week, assessor-blinded, 3-arm randomized controlled trial with a non-exercise control group. Community-dwelling people over 65 years will be screened for sarcopenia according to the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS). Fifty-one subjects will be randomized into a LRT-BFR group (n= 17), a CRT group (n= 17), and a no-strength training control group (n= 17). The primary outcome is lower limb muscle strength. The secondary outcomes are body composition, upper limb muscle strength, pulmonary function, blood biomarkers, CVD risk factors, and quality of life. Post-intervention follow-up will be performed for 12 weeks. These indicators will be assessed at baseline (0 week), after the 12-week intervention (12 weeks), and at follow-up (24 weeks). The adverse events will also be reported. Data will be analyzed for all participants in an intent-to-treat plan.DiscussionThis study is the first RCT that will systematically measure and compare the efficacy and safety of LRT-BFR and CRT in older people with sarcopenia on muscle strength, body composition, pulmonary function, blood biomarkers (inflammatory biomarkers, hormone, and growth factors), CVD risk factors, and quality of life. This study can provide an efficient and safe method to prevent the progression of sarcopenia in older people.Trial registrationChinese Clinical Trial RegistryChiCTR2100042803. Registered on 28 January 2021.
Forecasting the carsharing service demand using uni and multivariable models
Authors: Alencar Victor Aquiles , Pessamilio Lucas Ribeiro , Rooke Felipe , Bernardino Heder Soares , Borges Vieira Alex 
Published: August 2021

AbstractCarsharing is ana lternative to urban mobility that has been widely adopted recently. This service presents three main business models: two of these models base their services on stations while the remainder, the free-floating service, is free of fixed stations. Despite the notable advantages of carsharing, this service is prone to several problems, such as fleet imbalance due to the variance of the daily demand in large urban centers. Forecasting the demand for the service is a key task to deal with this issue. In this sense, in this work, we analyze the use of well-known techniques to forecast a carsharing service demand. More in deep, we evaluate the use of the Long Short-Term Memory (LSTM) and Prophet techniques to predict the demand of three real carsharing services. Moreover, we also evaluate seven state-of-the-art forecasting models on a given free-floating carsharing service, highlighting the potentials of each technique. In addition to historical carsharing service data, we have also used climatic series to enhance the forecasting. Indeed, the results of our analysis have shown that the addition of meteorological data improved the models’ performance. In this case, the mean absolute error of LSTM may fall by half, when using the climate data. When considering the free-floating carsharing service, and prediction for the short-term (i.e., 12 hours), the boosting algorithms (e.g. XGBoost, Catboost, and LightGBM) present superior performance, with less than 20% of mean absolute error when compared to the next best-ranked model (Prophet). On the other hand, Prophet performed better for predictions conducted on long-term periods.