bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotors and barriers to the implementation and adoption of assistive technology and telecare for people with dementia and their caregivers: a systematic review of the literature
Authors: Boyle Lydia D. , Husebo Bettina S. , Vislapuu Maarja 
Published: December 2022

Abstract
Background
One of the most pressing issues in our society is the provision of proper care and treatment for the growing global health challenge of ageing. Assistive Technology and Telecare (ATT) is a key component in facilitation of safer, longer, and independent living for people with dementia (PwD) and has the potential to extend valuable care and support for caregivers globally. The objective of this study was to identify promotors and barriers to implementation and adoption of ATT for PwD and their informal (family and friends) and formal (healthcare professionals) caregivers.

Methods
Five databases Medline (Ovid), CINAHL, Web of Science, APA PsycINFO and EMBASE were searched. PRISMA guidelines have been used to guide all processes and results. Retrieved studies were qualitative, mixed-method and quantitative, screened using Rayyan and overall quality assessed using Critical Appraisal Skills Programme (CASP) and Mixed Methods Assessment Tool (MMAT). Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria and assigned within categories of high, moderate, or low. NVivo was used for synthesis and analysis of article content. A narrative synthesis combines the study findings.

Results
Thirty studies (7 quantitative, 19 qualitative and 4 mixed methods) met the inclusion criteria. Identified primary promotors for the implementation and adoption of ATT were: personalized training and co-designed solutions, safety for the PwD, involvement of all relevant stakeholders, ease of use and support, and cultural relevance. Main barriers for the implementation and adoption of ATT included: unintended adverse consequences, timing and disease progress, technology anxiety, system failures, digital divide, and lack of access to or knowledge of available ATT.

Conclusion
The most crucial elements for the adoption of ATT in the future will be a focus on co-design, improved involvement of relevant stakeholders, and the adaptability (tailoring related to context) of ATT solutions over time (disease process).
Machine learning of plasma metabolome identifies biomarker panels for metabolic syndrome: findings from the China Suboptimal Health Cohort
Authors: Wang Hao , Wang Youxin , Li Xingang , Deng Xuan , Kong Yuanyuan , Wang Wei , Zhou Yong 
Published: December 2022

Abstract
Background
Metabolic syndrome (MetS) has been proposed as a clinically identifiable high-risk state for the prediction and prevention of cardiovascular diseases and type 2 diabetes mellitus. As a promising “omics” technology, metabolomics provides an innovative strategy to gain a deeper understanding of the pathophysiology of MetS. The study aimed to systematically investigate the metabolic alterations in MetS and identify biomarker panels for the identification of MetS using machine learning methods.

Methods
Nuclear magnetic resonance-based untargeted metabolomics analysis was performed on 1011 plasma samples (205 MetS patients and 806 healthy controls). Univariate and multivariate analyses were applied to identify metabolic biomarkers for MetS. Metabolic pathway enrichment analysis was performed to reveal the disturbed metabolic pathways related to MetS. Four machine learning algorithms, including support vector machine (SVM), random forest (RF), k-nearest neighbor (KNN), and logistic regression were used to build diagnostic models for MetS.

Results
Thirteen significantly differential metabolites were identified and pathway enrichment revealed that arginine, proline, and glutathione metabolism are disturbed metabolic pathways related to MetS. The protein-metabolite-disease interaction network identified 38 proteins and 23 diseases are associated with 10 MetS-related metabolites. The areas under the receiver operating characteristic curve of the SVM, RF, KNN, and logistic regression models based on metabolic biomarkers were 0.887, 0.993, 0.914, and 0.755, respectively.

Conclusions
The plasma metabolome provides a promising resource of biomarkers for the predictive diagnosis and targeted prevention of MetS. Alterations in amino acid metabolism play significant roles in the pathophysiology of MetS. The biomarker panels and metabolic pathways could be used as preventive targets in dealing with cardiometabolic diseases related to MetS.
The associations between changes in hepatic steatosis and heart failure and mortality: a nationwide cohort study
Authors: Park Jiyun , Kim Gyuri , Kim Hasung , Lee Jungkuk , Jin Sang-Man , Kim Jae Hyeon 
Published: December 2022

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is a well-known risk factor for cardiovascular (CV) disease (CVD) and mortality. However, whether the progression or regression of NAFLD can increase or decrease the risk of heart failure (HF) and mortality has not been fully evaluated. We investigated the association between changes in hepatic steatosis and the risks of incident HF (iHF), hospitalization for HF (hHF), and mortality including CV- or liver-related mortality.

Methods
Using a database from the National Health Insurance Service in Korea from January 2009 to December 2012, we analyzed 240,301 individuals who underwent health check-ups at least twice in two years. Hepatic steatosis was assessed using the fatty liver index (FLI), with an FLI ≥ 60 considered to indicate the presence of hepatic steatosis. According to FLI changes, participants were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models.

Results
Persistent hepatic steatosis increased the risk of iHF, hHF, and mortality including CV- and liver-related mortality compared with the group that never had steatosis (all P < 0.05). Incident hepatic steatosis was associated with increased risk for iHF and mortality including CV- or liver-related mortality (all P < 0.05). Compared with persistent steatosis, regression of hepatic steatosis was associated with decreased risk for iHF, hHF, and liver-related mortality (iHF, HR [95% CI], 0.800 [0.691–0.925]; hHF, 0.645 [0.514–0.810]; liver-related mortality, 0.434 [0.223–0.846]).

Conclusions
FLI changes were associated with increased or decreased risk of HF outcomes and mortality.
Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi
Authors: Mitchell Gabriel , Roma Guglielmo , Voorberg-van der Wel Annemarie , Beibel Martin , Zeeman Anne-Marie , Schuierer Sven , Torres Laura , Flannery Erika L. , Kocken Clemens H. M. , Mikolajczak Sebastian A. , Diagana Thierry T. 
Published: December 2022

Abstract
Background
The zoonotic simian parasite Plasmodium cynomolgi develops into replicating schizonts and dormant hypnozoites during the infection of hepatocytes and is used as a model organism to study relapsing malaria. The transcriptional profiling of P. cynomolgi liver stages was previously reported and revealed many important biological features of the parasite but left out the host response to malaria infection.

Methods
Previously published RNA sequencing data were used to quantify the expression of host genes in rhesus macaque hepatocytes infected with P. cynomolgi in comparison to either cells from uninfected samples or uninfected bystander cells.

Results
Although the dataset could not be used to resolve the transcriptional profile of hypnozoite-infected hepatocytes, it provided a snapshot of the host response to liver stage schizonts at 9–10 day post-infection and identified specific host pathways that are modulated during the exo-erythrocytic stage of P. cynomolgi.

Conclusions
This study constitutes a valuable resource characterizing the hepatocyte response to P. cynomolgi infection and provides a framework to build on future research that aims at understanding hepatocyte-parasite interactions during relapsing malaria infection.
Higher daytime systolic BP, prepregnancy BMI and an elevated sFlt-1/PlGF ratio predict the development of hypertension in normotensive pregnant women
Authors: Lara-Barea Almudena , Sánchez-Lechuga Begoña , Aguilar-Diosdado Manuel , López-Tinoco Cristina 
Published: December 2022

AbstractBackgroundThe risk of hypertensive disorders of pregnancy (HDP) varies in women with gestational diabetes mellitus (GDM), depending on the degree of insulin resistance and is also influenced by obesity. The aim of this study was to evaluate clinical features, blood pressure (BP) profiles and inflammatory markers, to identify patients with an elevated risk of developing HDP.MethodsA total of 146 normotensive pregnant women were studied. We analysed the relationships of BP profiles detected by ambulatory blood pressure monitoring (ABPM) with serum biomarkers and angiogenic factors and their association with the development of HDP.ResultsFourteen (9.6%) women developed HDP, of which 11 had GDM and 8 had obesity. Women with HDP had higher values of 24-h and daytime systolic/diastolic BP (113/69 vs. 104/64; 115/72 vs. 106/66 mmHg, respectively;p <  0.05). Higher levels of leptin (10.97 ± 0.82 vs. 10.2 ± 1.11;p = 0.018) andmonocyte chemoattractant protein-1 (MCP-1) (5.24 ± 0.60 vs. 4.9 ± 0.55;p = 0.044) and a higher soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio (4.37 ± 2.2 vs. 2.2 ± 1.43;p = 0.003) were also observed in the HDP patients. Multivariate analysis showed that a higher sFlt-1/PlGF ratio was associated with an increased risk of developing HDP [OR = 2.02; IC 95%: 1.35–3.05]. Furthermore, higher daytime systolic BP [OR = 1.27; IC 95% 1.00–1.26] and prepregnancy body mass index (BMI) [OR = 1.14; IC 95%: 1.01–1.30] significantly increased the risk of developing HDP.ConclusionsHigher daytime systolic BP values, prepregnancy BMI and the sFlt-1/PlGF ratio are useful for identifying normotensive pregnant women with an increased risk of developing HDP.
Strengthening research ethics governance and regulatory oversight in Central America and the Dominican Republic in response to the COVID-19 pandemic: a qualitative study
Authors: Canario Guzmán Julio Arturo , Orlich Jessie , Mendizábal-Cabrera Renata , Ying Argentina , Vergès Claude , Espinoza Eleonora , Soriano Mario , Cárcamo Elsy , Beltrán Briana , Mendoza Marrero Eddys Rafael , Sepulveda Reyna , Nieto Anderson Claudia , Feune de Colombi Nicole , Lescano Roxana , Pérez-Then Eddy , Lang Trudie , Alger Jackeline 
Published: December 2022

Abstract
Background
Good governance and regulatory supervision are required to conduct research in an international public health emergency context and to ensure compliance with ethical standards. The “Strengthening research ethics governance and regulatory oversight in Central America and the Dominican Republic in response to the COVID-19 pandemic” study is a regional effort in which research ethics stakeholders participated in addressing research ethics governance and preparedness response challenges to the COVID-19 pandemic in Central America and the Dominican Republic.

Methods
A qualitative action research study was conducted following a participatory approach. Research ethics stakeholders in Central America and the Dominican Republic were mapped; a regional webinar and three virtual workshops were conducted discussing research ethics governance, ethics review and collaborative research practice during the pandemic. A roundtable session presented results and obtained feedback on a draft of a policy to strengthen regional research ethics governance.

Results
Countries across Central America and the Dominican Republic are at different stages in their development of research ethics systems. Countries with more established systems before COVID-19 were better organized and prepared to respond. This finding argues against improvisation and supports further work on strengthening governance of research ethics systems. Community engagement in research ethics public policy-making is practically absent in the region. Research and research ethics collaboration schemes are lacking amongst the countries; however, there are incipient initiatives in the region, such as the Central America and Caribbean Network of Research Ethics Committees. A policy brief with recommendations on how to advance towards strengthening the governance of research ethics systems was prepared and submitted to the Central American Integration System for analysis and possible approval.

Conclusion
National research ethics systems in Central America and the Dominican Republic were unprepared to respond to the COVID-19 pandemic with respect to research oversight and effective collaboration. In most cases, national research ethics systems were found to be weak, and regional research collaboration was practically absent. To promote collaboration, a joint strategy needs to be developed with a regional vision towards sharing knowledge and best practices.
Role of miRNAs interference on ovarian functions and premature ovarian failure
Authors: Nouri Narjes , Shareghi-Oskoue Olduz , Aghebati-Maleki Leili , Danaii Shahla , Ahmadian Heris Javad , Soltani-Zangbar Mohammad Sadegh , Kamrani Amin , Yousefi Mehdi 
Published: December 2022

AbstractPremature ovarian failure is a to some extent unknown and intricate problem with diverse causes and clinical manifestations. The lack of ovarian sex hormones presumably is effective in the occurrence of ovarian failure. Our progress in this field has been very little despite undertaken scientific research endeavors; scholars still are trying to understand the explanation of this dilemmatic medical condition. In contrast, the practice of clinical medicine has made meaningful strides in providing assurance to the women with premature ovarian insufficiency that their quality of life as well as long-term health can be optimized through timely intervention. Very recently Scientists have investigated the regulating effects of small RNA molecules on steroidogenesis apoptosis, ovulation, gonadal, and corpus luteum development of ovaries. In this literature review, we tried to talk over the mechanisms of miRNAs in regulating gene expression after transcription in the ovary.
Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock
Authors: Endo Yusuke , Miyasho Taku , Endo Kanako , Kawamura Yoshio , Miyoshi Kenjiro , Takegawa Ryosuke , Tagami Takashi , Becker Lance B. , Hayashida Kei 
Published: December 2022

Abstract
Background
No direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model.

Methods
Thirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300–400), mild-to-moderate ARDS (100–300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers.

Results
Using CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98–1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS.

Conclusion
The pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.
Pharmaceutical targeting Th2-mediated immunity enhances immunotherapy response in breast cancer
Authors: Chen Yuru , Sun Jiazheng , Luo Yachan , Liu Jiazhou , Wang Xiaoyu , Feng Rui , Huang Jing , Du Huimin , Li Qin , Tan Jinxiang , Ren Guosheng , Wang Xiaoyi , Li Hongzhong 
Published: December 2022

Abstract
Background
Breast cancer is a complex disease with a highly immunosuppressive tumor microenvironment, and has limited clinical response to immune checkpoint blockade (ICB) therapy. T-helper 2 (Th2) cells, an important component of the tumor microenvironment (TME), play an essential role in regulation of tumor immunity. However, the deep relationship between Th2-mediated immunity and immune evasion in breast cancer remains enigmatic.

Methods
Here, we first used bioinformatics analysis to explore the correlation between Th2 infiltration and immune landscape in breast cancer. Suplatast tosilate (IPD-1151 T, IPD), an inhibitor of Th2 function, was then employed to investigate the biological effects of Th2 blockade on tumor growth and immune microenvironment in immunocompetent murine breast cancer models. The tumor microenvironment was analyzed by flow cytometry, mass cytometry, and immunofluorescence staining. Furthermore, we examined the efficacy of IPD combination with ICB treatment by evaluating TME, tumor growth and mice survival.

Results
Our bioinformatics analysis suggested that higher infiltration of Th2 cells indicates a tumor immunosuppressive microenvironment in breast cancer. In three murine breast cancer models (EO771, 4T1 and EMT6), IPD significantly inhibited the IL-4 secretion by Th2 cells, promoted Th2 to Th1 switching, remodeled the immune landscape and inhibited tumor growth. Remarkably, CD8+ T cell infiltration and the cytotoxic activity of cytotoxic T lymphocyte (CTL) in tumor tissues were evidently enhanced after IPD treatment. Furthermore, increased effector CD4+ T cells and decreased myeloid-derived suppressor cells and M2-like macrophages were also demonstrated in IPD-treated tumors. Importantly, we found IPD reinforced the therapeutic response of ICB without increasing potential adverse effects.

Conclusions
Our findings demonstrate that pharmaceutical inhibition of Th2 cell function improves ICB response via remodeling immune landscape of TME, which illustrates a promising combinatorial immunotherapy.
Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection
Authors: Li Xin , Li Ruoying , Ji Bingqing , Zhao Lili , Wang Junpeng , Yan Tianzhong 
Published: December 2022

Abstract
Background
Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structure at species level have not been identified. In the present study, we investigated the metagenomic and metabolic patterns of gut microbiota in AMR patients to provide a comprehensive and in-depth understanding of gut microbiota dysbiosis in AMR.

Methods
We enrolled 60 kidney transplantation recipients, 28 showed AMR and 32 were non-AMR controls with stable post-transplant renal functions. Shotgun sequencing and untargeted LC/MS metabolomic profiling of fecal samples were performed in kidney transplantation recipients with AMR and controls.

Results
Totally, we identified 311 down-regulated and 27 up-regulated gut microbial species associated with AMR after kidney transplantation, resulting in the altered expression levels of 437 genes enriched in 22 pathways, of which 13 were related to metabolism. Moreover, 32 differential fecal metabolites were found in recipients with AMR. Among them, alterations in 3b-hydroxy-5-cholenoic acid, l-pipecolic acid, taurocholate, and 6k-PGF1alpha-d4 directly correlated with changes in gut microbial species and functions. Specific differential fecal species and metabolites were strongly associated with clinical indexes (Cr, BUN, etc.), and could distinguish the recipients with AMR from controls as potential biomarkers.

Conclusions
Altogether, our findings provided a comprehensive and in-depth understanding of the correlation between AMR and gut microbiota, which is important for the etiological and diagnostic study of AMR after kidney transplantation.