bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aggravation of functional mitral regurgitation on left ventricle stiffness in type 2 diabetes mellitus patients evaluated by CMR tissue tracking
Authors: Zhang Yi , Yan Wei-feng , Jiang Li , Shen Meng-ting , Li Yuan , Huang Shan , shi Ke , Yang Zhi-gang 
Published: July 2021

Abstract
Background
Functional mitral regurgitation (FMR) is one of the most common heart valve diseases in diabetes and may increase left ventricular (LV) preload and aggravate myocardial stiffness. This study aimed to investigate the aggravation of FMR on the deterioration of LV strain in type 2 diabetes mellitus (T2DM) patients and explore the independent indicators of LV peak strain (PS).

Materials and methods
In total, 157 T2DM patients (59 patients with and 98 without FMR) and 52 age- and sex-matched healthy control volunteers were included and underwent cardiac magnetic resonance examination. T2DM with FMR patients were divided into T2DM patients with mild (n = 21), moderate (n = 19) and severe (n = 19) regurgitation. LV function and global strain parameters were compared among groups. Multivariate analysis was used to identify the independent indicators of LV PS.

Results
The T2DM with FMR had lower LV strain parameters in radial, circumferential and longitudinal direction than both the normal and the T2DM without FMR (all P < 0.05). The mild had mainly decreased peak diastolic strain rate (PDSR) compared to the normal. The moderate had decreased peak systolic strain rate (PSSR) compared to the normal and PDSR compared to the mild and the normal. The severe FMR group had decreased PDSR and PSSR compared to the mild and the normal (all P < 0.05). Multiple linear regression showed that the regurgitation degree was independent associated with radial (β = − 0.272), circumferential (β = − 0.412) and longitudinal (β = − 0.347) PS; the months with diabetes was independently associated with radial (β = − 0.299) and longitudinal (β = − 0.347) PS in T2DM with FMR.

Conclusion
FMR may aggravate the deterioration of LV stiffness in T2DM patients, resulting in decline of LV strain and function. The regurgitation degree and months with diabetes were independently correlated with LV global PS in T2DM with FMR.
Lnc-STYK1-2 regulates bladder cancer cell proliferation, migration, and invasion by targeting miR-146b-5p expression and AKT/STAT3/NF-kB signaling
Authors: Dai Ranran , Jiang Qingping , Zhou You , Lin Ruifeng , Lin Hai , Zhang Yumin , Zhang Jinhu , Gao Xingcheng 
Published: July 2021

Abstract
Background
Epigenetic modulation by noncoding RNAs substantially contributes to human cancer development, but noncoding RNAs involvement in bladder cancer remains poorly understood. This study investigated the role of long noncoding RNA (lncRNA) lnc-STYK1-2 in tumorigenesis in cancerous bladder cells.

Methods
Differential lncRNA and mRNA profiles were characterized by high-throughput RNA sequencing combined with validation via quantitative PCR. Bladder cancer cell proliferation was assessed through MTS, and bladder cancer cell migration and invasion were assessed through a Transwell system. The in vivo tumorigenesis of bladder cancer cells was evaluated using the cancer cell line-based xenograft model. The dual-luciferase reporter assay verified the association of miR-146b-5p with lnc-STYK1-2 and the target gene. Protein abundances and phosphorylation were detected by Western blotting.

Results
Alterations in lncRNA profiles, including decreased lnc-STYK1-2 expression, were detected in bladder cancer tissues compared with adjacent noncancerous tissues. lnc-STYK1-2 silencing effectively promoted proliferation, migration, and invasion in two bladder cancer cell lines, 5637 and T24, and their tumorigenesis in nude mice. lnc-STYK1-2 siRNA promoted miR-146b-5p and reduced ITGA2 expression in bladder cancer cells. Moreover, miR-146b-5p suppressed ITGA2 expression in bladder cancer cells through direct association. Also, lnc-STYK1-2 directly associated with miR-146b-5p. Finally, miR-146b-5p inhibitors abrogated the alterations in bladder cell functions, ITGA2 expression, and phosphorylation of AKT, STAT3, and P65 proteins in 5637 and T24 cells induced by lnc-STYK1-2 silencing.

Conclusion
lnc-STYK1-2 inhibited bladder cancer cell proliferation, migration, and tumorigenesis by targeting miR-146b-5p to regulate ITGA2 expression and AKT/STAT3/NF-kB signaling.
Association between WNT-1-inducible signaling pathway protein-1 (WISP1) genetic polymorphisms and the risk of gastric cancer in Guangxi Chinese
Authors: Liu Yanqiong , Qin Weijuan , Zhang Fuyong , Wang Jian , Li Xi , Li Shan , Qin Xue , Lu Yuefeng 
Published: July 2021

Abstract
Background
WNT1-inducible signaling pathway protein 1 (WISP1) is a member of the CCN protein family and a downstream target of β-catenin. Aberrant WISP1 expression may be involved in carcinogenesis. To date, no studies have investigated the association between single-nucleotide polymorphisms (SNPs) of WISP1 and gastric cancer. Therefore, we conducted this study to explore their relationship.

Methods
Polymerase chain reaction-restriction fragment length polymorphism assay was used to analyze three SNPs of WISP1 in 204 gastric cancer patients and 227 controls.

Results
Overall, we could not identify a significant association between WISP1 SNPs and gastric cancer risk. However, the subgroup analysis demonstrated that the presence of the rs7843546 T allele was associated with a significantly decreased risk of gastric cancer in those of Han Chinese ethnicity (CT vs. CC: OR = 0.33, 95%CI 0.14–0.78; TT vs. CC: OR = 0.29, 95%CI 0.11–0.76; CT + TT vs. CC: OR = 0.32, 95%CI 0.14–0.74). In addition, patients with the rs7843546 TT genotype display a 0.34-fold lower risk of developing stage I/II gastric cancer than those with the CC genotype Furthermore, individuals ≥ 50 years old who carried the rs10956697 AC genotype had a significantly decreased risk of gastric cancer (OR = 0.58, 95%CI 0.35–0.98). Smokers with the rs10956697 AC and AC + AA genotypes exhibited a 0.28-fold lower and 0.32-fold lower risk of gastric cancer, respectively.

Conclusions
The WISP1 SNPs rs7843546 and rs10956697 were, for the first time, found to reduce susceptibility to gastric cancer in various subgroups of Guangxi Chinese.
Evaluation of direct costs associated with the management of clinical stage of malaria in children under five years old in Gabon
Authors: Moukoumbi Lipenguet Gaëtan , Ngoungou Edgard Brice , Ibinga Euloge , Engohang-Ndong Jean , Wittwer Jérôme 
Published: July 2021

Abstract
Background
Malaria is one of the leading causes of morbidity and mortality in African countries. It is one of the leading causes of hospital visits and hospitalization in pediatric wards for children under 5 years old. Interestingly however, the economic burden of this disease remains unknown in these endemic countries including Gabon. The purpose of this study is to assess the direct hospital cost for the management of malaria in children under 5 years old at the Libreville University Hospital Centre (CHUL, Centre Hospitalier Universitaire de Libreville) in Gabon.

Methods
This research work is a retrospective study using a comprehensive review of medical records of patients seen at the CHUL over a two-year period extending from January 2018 through December 2019. The study focused on children under 5 years old, admitted for malaria in the paediatric ward of the CHUL. The analysis targeted specifically direct hospital costs, which excluded salary and wages of health care workers. The monetary currency used in this study was the CFA francs, as that currency is the one used in Central Africa (as reference, 1 Euro = 656 CFA francs).

Results
For the set timeframe, 778 patient records matched the study criteria. Thus, out of 778 admitted patients, 58.4% were male while 41.5% were female. Overall, the average age was 13.2 months (± 13.8 months). The total cost incurred by the hospital for the management of these 778 malaria patients was 94,922,925 CFA francs (144,699.58 €), for an average expense per patient topping at 122,008 CFA francs (185.99 €). The highest expenditure items were hospitalizations (44,200,000 CFA francs, 67,378.1 €), followed by drugs (26,394,425 CFA francs, 40,235.4 €) and biomedical examinations (14,036,000 CFA francs, 21,396.34 €).

Conclusion
The financial burden for managing malaria in the paediatric ward seems to be very high, not only for the hospital, but also for families in spite of the government medical insurance coverage in some cases. These findings bring new insights as to the urgency to develop policies that foster preventive initiatives over curative approaches in the management of malaria in children in endemic countries.
A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery
Authors: Xiao Jianmin , Yan Miao , Zhou Ke , Chen Hui , Xu Zhaowei , Gan Yuehao , Hong Biao , Tian Geng , Qian Junchao , Zhang Guilong , Wu Zhengyan 
Published: July 2021

Abstract
The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.
Impact of tobacco and/or nicotine products on health and functioning: a scoping review and findings from the preparatory phase of the development of a new self-report measure
Authors: Afolalu Esther F. , Spies Erica , Bacso Agnes , Clerc Emilie , Abetz-Webb Linda , Gallot Sophie , Chrea Christelle 
Published: July 2021

Abstract
Background
Measuring self-reported experience of health and functioning is important for understanding the changes in the health status of individuals switching from cigarettes to less harmful tobacco and/or nicotine products (TNP) or reduced-risk products (RRP) and for supporting tobacco harm reduction strategies.

Methods
This paper presents insights from three research activities from the preparatory phase of the development of a new self-report health and functioning measure. A scoping literature review was conducted to identify the positive and negative impact of TNP use on health and functioning. Focus groups (n = 29) on risk perception and individual interviews (n = 40) on perceived dependence in people who use TNPs were reanalyzed in the context of health and functioning, and expert opinion was gathered from five key opinion leaders and five technical consultants.

Results
Triangulating the findings of the review of 97 articles, qualitative input from people who use TNPs, and expert feedback helped generate a preliminary conceptual framework including health and functioning and conceptually-related domains impacted by TNP use. Domains related to the future health and functioning measurement model include physical health signs and symptoms, general physical appearance, functioning (physical, sexual, cognitive, emotional, and social), and general health perceptions.

Conclusions
This preliminary conceptual framework can inform future research on development and validation of new measures for assessment of overall health and functioning impact of TNPs from the consumers’ perspective.
Adaptation and psychometric validation of Diabetes Health Profile (DHP-18) in patients with type 2 diabetes in Quito, Ecuador: a cross-sectional study
Authors: Benazizi Ikram , Bernal-Soriano Mari Carmen , Pardo Yolanda , Ribera Aida , Peralta-Chiriboga Andrés , Ferrer Montserrat , Alonso-Jaquete Alfonso , Alonso Jordi , Lumbreras Blanca , Parker Lucy Anne 
Published: July 2021

Abstract
Introduction
The Diabetes Health Profile (DHP‐18), structured in three dimensions (psychological distress (PD), barriers to activity (BA) and disinhibited eating (DE)), assesses the psychological and behavioural burden of living with type 2 diabetes. The objectives were to adapt the DHP‐18 linguistically and culturally for use with patients with type 2 DM in Ecuador, and to evaluate its psychometric properties.

Methods
Participants were recruited using purposive sampling through patient clubs at primary health centres in Quito, Ecuador. The DHP-18 validation consisted in the linguistic validation made by two Ecuadorian doctors and eight patient interviews. And in the psychometric validation, where participants provided clinical and sociodemographic data and responded to the SF-12v2 health survey and the linguistically and culturally adapted version of the DHP-18. The original measurement model was evaluated with confirmatory factor analysis (CFA). Reliability was assessed through internal consistency using Cronbach’s alpha and test–retest reproducibility by administering DHP-18 in a random subgroup of the participants two weeks after (n = 75) using intraclass correlation coefficient (ICC). Convergent validity was assessed by establishing previous hypotheses of the expected correlations with the SF12v2 using Spearman’s coefficient.

Results
Firstly, the DHP-18 was linguistically and culturally adapted. Secondly, in the psychometric validation, we included 146 participants, 58.2% female, the mean age was 56.8 and 31% had diabetes complications. The CFA indicated a good fit to the original three factor model (χ2 (132) = 162.738, p < 0.001; CFI = 0.990; TLI = 0.989; SRMR = 0.086 and RMSEA = 0.040. The BA dimension showed the lowest standardized factorial loads (λ) (ranging from 0.21 to 0.77), while λ ranged from 0.57 to 0.89 and from 0.46 to 0.73, for the PD and DE dimensions respectively. Cronbach’s alphas were 0.81, 0.63 and 0.74 and ICCs 0.70, 0.57 and 0.62 for PD, BA and DE, respectively. Regarding convergent validity, we observed weaker correlations than expected between DHP-18 dimensions and SF-12v2 dimensions (r > −0.40 in two of three hypotheses).

Conclusions
The original three factor model showed good fit to the data. Although reliability parameters were adequate for PD and DE dimensions, the BA presented lower internal consistency and future analysis should verify the applicability and cultural equivalence of some of the items of this dimension to Ecuador.
Effect and mechanism of downregulating the long-chain noncoding RNA TM4SF1-AS1 on the proliferation, apoptosis and invasion of gastric cancer cells
Authors: He Chengzhi , Qi Wenjing , Wang Zhihui 
Published: July 2021

Abstract
Background
To investigate long-chain noncoding TM4SF1-AS1 in gastric cancer (GC) tissues and cells.

Methods
TM4SF1-AS1 in 40 GC tissues and adjacent tissues was detected and compared using real-time fluorescence quantitative PCR (qRT-PCR). TM4SF1-AS1 in MKN28 and SGC7901 GC cells was downregulated using small interfering RNA (shRNA). The cells were grouped into an interference group (shTM4SF1-AS1 group) and a control group (shControl group). MTT and Transwell tests were applied to determine the proliferation and invasion of the cells in both groups, and flow cytometry was performed to assess the apoptosis rate in the two groups. Western blotting was performed to determine changes in key proteins in cells during the epithelial-to-mesenchymal transition (EMT) and in the TM4SF1 and PI3K-AKT signalling pathways in response to the downregulation of TM4SF1-AS1.

Results
The proliferation of MKN28 and SGC7901 in the shTM4SF1-AS1 group was significantly inhibited at 48 h and 72 h compared to that in the shControl group (all P < 0.05). In the shTM4SF1-AS1 group, the number of invaded MKN28 and SGC7901 cells was significantly lower than that in the shControl group (all P < 0.05). Apoptosis in the MKN28 and SGC7901 shTM4SF1-AS1 groups was significantly higher than that in the shControl group (all P < 0.05). Compared to those in the shControl group, levels of E-cadherin in EMT-related proteins were significantly elevated (P < 0.01), while levels of N-cadherin, Snail and Twist1 were significantly decreased (all P < 0.01). After silencing the expression of LncTM4SF1-AS1, the expression levels of TM4SF1 in the shTM4SF1-AS1 group were downregulated compared to those in the shControl group, and the p-PI3K and p-AKT proteins in the PI3K-AKT signalling pathway in the shTM4SF1-AS1 group were downregulated compared to those of the shControl group.

Conclusions
TM4SF1-AS1 is upregulated in gastric cancer tissues and cells. Interfering with and downregulating its expression inhibit cancer cell proliferation, invasion and the EMT and promote apoptosis. The underlying mechanism for these effects is related to silencing the TM4SF1 and PI3K-AKT signalling pathways. TM4SF1-AS1 may be a potential therapeutic target for gastric cancer.
Lemierre’s syndrome causing profound thrombocytopenia and respiratory failure: a case report
Authors: Below Samantha , Williams Elizabeth 
Published: July 2021

Abstract
Background
Lemierre’s syndrome is a rare oropharyngeal infection that can lead to metastatic septic emboli and thrombocytopenia. However, current literature does not report an effect on other cell lines, which we report for the first time in this case.

Case
A previously healthy young African American male presented with profound thrombocytopenia and leukopenia. He was tachypenic on presentation which progressed to respiratory failure requiring intubation. Blood cultures grew Fusobacterium necrophorum and imaging revealed internal jugular venous thrombosis. He was later diagnosed with Lemierre’s syndrome. The patient was treated with zosyn and fully recovered with no residual deficits in hemoglobin, white cell count, platelet level, or renal function.

Conclusion
Lemierre’s syndrome can cause severe disease in otherwise healthy patients via septicemia and widespread metastatic foci which can cause severe illness. While pulmonary complications are most common, there is little report of effects on other organ systems such as bone marrow and the kidneys. Clinicians should readily evaluate for Lemierre’s syndrome as the complications are severe and can lead to multiorgan failure.
Soluble P-selectin and correlation with Prothrombin Fragment 1 + 2 in myeloid malignancies in Cipto Mangunkusumo general hospital
Authors: Sukrisman Lugyanti 
Published: July 2021

Abstract
Background
Myeloid cells express microparticles that could increase the expression of adhesion molecules including P-selectin. We aimed to evaluate the level of soluble P-selectin (sP-selectin) and prothrombin fragment 1 + 2 (F1 + 2), and to determine correlation of sP-selectin with leukocyte count and F1 + 2 levels in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients.

Methods
Patients with newly diagnosed AML (n = 25), CML (n = 13), and controls (n = 17) were recruited in this study. The diagnosis of AML and CML is based on 2001 WHO and/or FAB criteria. Levels of sP-selectin and F1 + 2 were determined using enzyme-linked immunosorbent assay kits (Behring ELISA Processor-III® and Behring Enzygnost F1 + 2).

Results
sP-selectin was significantly elevated in CML patients compared to AML patients (p = 0.001). Levels of F1 + 2 in AML and CML patients were significantly increased in comparison to controls (p < 0.001 and p = 0.043). Levels of sP-selectin were significantly correlated to leukocyte count (r = 0.437; p = 0.029) and F1 + 2 (r = 0.436; p = 0.029) in AML patients.

Conclusions
AML and CML patients had an increased tendency to thrombosis. While CML patients had higher platelet and/or endothelial activation, hypercoagulable state are more pronounced in AML patients.
Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease
Authors: Tao Yiying , Wei Xing , Yue Yue , Wang Jiaxin , Li Jianzhong , Shen Lei , Lu Guoyuan , He Yang , Zhao Shidi , Zhao Fan , Weng Zhen , Shen Xiahong , Zhou Ling 
Published: July 2021

AbstractBackgroundA novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data.MethodsCandidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment.ResultsFifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls.ConclusionsOur results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.
Genetic alterations and functional networks of m6A RNA methylation regulators in pancreatic cancer based on data mining
Authors: Zeng Juan , Zhang Heying , Tan Yonggang , Wang Zhe , Li Yunwei , Yang Xianghong 
Published: July 2021

Abstract
Background
Pancreatic cancer is a fatal malignancy of the digestive system and the 5-year survival rate remains low. Therefore, new molecular therapeutic targets are required to improve treatments, prognosis, and the survival of patients. N6-methyladenosine (m6A) is the most prevalent reversible methylation in mammalian messenger RNA (mRNA) and has critical roles in the tumorigenesis and metastasis of various malignancies. However, the role of m6A in pancreatic cancer is still unclear. Exploring genetic alterations and functional networks of m6A regulators in pancreatic cancer may provide new strategies for its treatment.

Methods
In this study, we used data from the Cancer Genome Atlas (TCGA) database and other public databases through cBioPortal, LinkedOmics, UALCAN, GEPIA, STRING, and the database for annotation, visualization, and integrated discovery (DAVID) to systematically analyze the molecular alterations and functions of 20 main m6A regulators in pancreatic cancer.

Results
We found that m6A regulators had widespread genetic alterations, and that their expression levels were significantly correlated with pancreatic cancer malignancy. Moreover, m6A regulators were associated with the prognosis of pancreatic cancer patients.

Conclusions
m6A regulators play a crucial part in the occurrence and development of pancreatic cancer. Our study will guide further studies of m6A RNA modification in pancreatic cancer and could potentially provide new strategies for pancreatic cancer treatment.