bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the clinical effect of empagliflozin on glycemic and non-glycemic parameters in Japanese patients with type 2 diabetes and cardiovascular disease treated with or without baseline metformin
Authors: Tanaka Atsushi , Shimabukuro Michio , Teragawa Hiroki , Okada Yosuke , Takamura Toshinari , Taguchi Isao , Toyoda Shigeru , Tomiyama Hirofumi , Ueda Shinichiro , Higashi Yukihito , Node Koichi ,   the EMBLEM Investigators
Published: July 2021

Background

The most recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors should be considered preferentially in patients with T2D with either a high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of conventional metformin therapy. Whether the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin therapy however remains unclear.

Methods

The study was a post hoc analysis of the EMBLEM trial (UMIN000024502). All participants (n = 105; women 31.4%; mean age 64.8 years) had both T2D and CVD and were randomized to either 24 weeks of empagliflozin 10 mg daily or placebo. Analysis of the data assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin.

Results

Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the decrease in systolic blood pressure from baseline levels was greater in patients receiving metformin, compared to that observed in metformin-naïve patients (group difference − 8.5 [95% confidence interval (CI) − 17.7 to 0.6 mmHg], p = 0.066). Reduction in body mass index (BMI) was significantly greater in patients receiving baseline metformin, relative to nonusers (− 0.54 [95% CI − 1.07 to − 0.01] kg/m2, p = 0.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I (hs-TnI) was 0.74 (95% CI 0.59 to 0.92, p = 0.009). No obvious differences were observed in glycemic parameters (fasting plasma glucose, glycohemoglobin, and glycoalbumin) between the baseline metformin users and nonusers.

Conclusion

Our findings suggest 24 weeks of empagliflozin treatment was associated with an improvement in glycemic control, irrespective of the baseline use of metformin therapy. The effects of empagliflozin on reductions in BMI and hs-TnI were more apparent in patients who received baseline metformin therapy, compared to that observed in metformin-naïve patients.

Trial registration University Medical Information Network Clinical Trial Registry, number 000024502
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

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

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

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

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

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

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

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

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

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

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

Background

A 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.

Methods

Candidate 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.

Results

Fifteen 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.

Conclusions

Our 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

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.
Chronotype: what role in the context of gastroenteropancreatic neuroendocrine tumors?
Authors: Barrea Luigi , Muscogiuri Giovanna , Pugliese Gabriella , Modica Roberta , Laudisio Daniela , Aprano Sara , Faggiano Antongiulio , Colao Annamaria , Savastano Silvia
Published: July 2021

Background

Chronotype is defined as a trait determining the subject circadian preference in behavioral and biological rhythms relative to external light–dark cycle. Although individual differences in chronotype have been associated with an increased risk of developing some types of cancer, no studies have been carried out in gastroenteropancreatic neuroendocrine tumors (GEP-NET).

Materials

We investigate the differences in chronotype between 109 GEP-NET and 109 healthy subjects, gender-, age-, and BMI-matched; and its correlation with tumor aggressiveness.

Results

GEP-NET patients have a lower chronotype score (p = 0.035) and a higher percentage of evening chronotype (p = 0.003) than controls. GEP-NET patients with morning chronotype had lower BMI, waist circumference, and higher percentage of MetS (p < 0.001) than evening type. Interestingly, considering the clinical pathological characteristics, patients with the presence of metastasis, grading G2, and in progressive disease presented the lower chronotype score (p = 0.004, p < 0.001, and p = 0.002; respectively) compared to other categories. Chronotype score was negatively associated with anthropometric measurements, metabolic profile, percentage of MetS, and Ki67 index (p < 0.001 for all).

Conclusions

GEP-NET patients have an unhealthy metabolic profile and present more commonly an evening chronotype. These results support the importance of including the assessment of chronotype in an adjunctive tool for the prevention of metabolic alterations and tumor aggressiveness of GEP-NET.
Willingness to use HIV pre-exposure prophylaxis and associated factors among men who have sex with men in Liuzhou, China
Authors: Fu Yuansheng , Ashuro Akililu Alemu , Feng Xianxiang , Wang Ting , Zhang Sichen , Ye Dongqing , Fan Yinguang
Published: July 2021

Background

HIV pre-exposure prophylaxis (PrEP) is a key component of HIV combination prevention strategies and has the potential to decrease the incidence of HIV in men who have sex with men (MSM). This study aimed to evaluate levels of PrEP acceptability and explore factors associated with willingness to use PrEP among MSM in Liuzhou, China.

Methods

Between November 2017 and May 2019, a cross-sectional survey was conducted among 829 MSM. The study participants were recruited through a nonprobability sampling method. The participants’ demographics, HIV/AIDS knowledge, sexual behaviors, drug use and HIV test history were collected. Multivariate logistic regression was performed to identify factors associated with willingness to use PrEP.

Results

A total of 829 MSM completed the survey, and 30.28% (95% CI 27.3–33.4) were willing to use PrEP. In multivariate logistic regression, factors associated with a higher willingness to use PrEP included Zhuang or Han ethnic origin, recruitment through peer introduction or gay venues, pursuit of a higher education level, previous HIV testing and oral sex with a man. Conversely, having casual sex in the past 6 months was associated with a lower willingness to use PrEP.

Conclusions

MSM in Liuzhou reported a relatively low level of willingness to use PrEP. The results indicate the need for effective education, targeted intervention, and implementation strategies to promote PrEP acceptance among MSM.
Dynamic balancing responses in unilateral transtibial amputees following outward-directed perturbations during slow treadmill walking differ considerably for amputated and non-amputated side
Authors: Olenšek Andrej , Zadravec Matjaž , Burger Helena , Matjačić Zlatko
Published: July 2021

Background

Due to disrupted motor and proprioceptive function, lower limb amputation imposes considerable challenges associated with balance and greatly increases risk of falling in presence of perturbations during walking. The aim of this study was to investigate dynamic balancing responses in unilateral transtibial amputees when they were subjected to perturbing pushes to the pelvis in outward direction at the time of foot strike on their non-amputated and amputated side during slow walking.

Methods

Fourteen subjects with unilateral transtibial amputation and nine control subjects participated in the study. They were subjected to perturbations that were delivered to the pelvis at the time of foot strike of either the left or right leg. We recorded trajectories of center of pressure and center of mass, durations of in-stance and stepping periods as well as ground reaction forces. Statistical analysis was performed to determine significant differences in dynamic balancing responses between control subjects and subjects with amputation when subjected to outward-directed perturbation upon entering stance phases on their non-amputated or amputated sides.

Results

When outward-directed perturbations were delivered at the time of foot strike of the non-amputated leg, subjects with amputation were able to modulate center of pressure and ground reaction force similarly as control subjects which indicates application of in-stance balancing strategies. On the other hand, there was a complete lack of in-stance response when perturbations were delivered when the amputated leg entered the stance phase. Subjects with amputations instead used the stepping strategy and adjusted placement of the non-amputated leg in the ensuing stance phase to make a cross-step. Such response resulted in significantly larger displacement of center of mass.

Conclusions

Results of this study suggest that due to the absence of the COP modulation mechanism, which is normally supplied by ankle motor function, people with unilateral transtibial amputation are compelled to choose the stepping strategy over in-stance strategy when they are subjected to outward-directed perturbation on the amputated side. However, the stepping response is less efficient than in-stance response.
Efficacy and safety of oncolytic viruses in advanced or metastatic cancer: a network meta-analysis
Authors: Xie Ruiyang , Bi Xingang , Shang Bingqing , Zhou Aiping , Shi Hongzhe , Shou Jianzhong
Published: July 2021

Background

Oncolytic viruses (OVs) have shown prospects in advanced and metastatic cancer, and many clinical trials have been carried out. To compare OV therapies comprehensively and provide a categorized profile and ranking of efficacy and safety, a network meta-analysis was conducted.

Methods

A total of 5948 studies were screened and 13 randomized controlled trials with 1939 patients, of whom 1106 patients received OV therapies, comparing four OVs (NTX-010, pexastimogene devacirepvec (Pexa-Vec), talimogene laherparepvec (T-VEC), and pelareorep) were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: objective response rate (ORR) and grade ≥ 3 adverse events.

Results

Compared to systemic treatments alone, talimogene laherparepvec (T-VEC) (OR 7.00, 95% CI 1.90–26.00) and T-VEC plus systemic treatment (2.90, 0.80–11.00) showed better objective response rates (ORRs), whereas Pexa-Vec 1 * 109 pfu plus systemic treatment (0.91, 0.26–3.00) and pelareorep plus systemic treatment (1.10, 0.61–2.00) were found to be comparable. The grade ≥ 3 adverse event ranking of the treatments from worst to best was as follows: T-VEC (ranking probability 24%), Pexa-Vec 1 * 109 pfu plus systemic treatment (21%), Pexa-Vec 1 * 109 pfu (17%), T-VEC plus systemic treatment (13%), pelareorep plus systemic treatment (13%), systemic treatments (18%), Pexa-Vec 1 * 108 pfu (12%), and NTX-010 (20%).

Conclusions

Compared with other oncolytic virus therapies for patients with advanced or metastatic cancer, T-VEC and T-VEC plus systemic treatment appear to provide the best ORR therapy in terms of monotherapy and combination respectively, but should be given with caution to grade ≥ 3 adverse events. Conversely, combining OVs with chemotherapy or target agents was demonstrated not to improve efficacy compared with chemotherapy or target agents alone. Combining OV therapies with immune-checkpoint inhibitors, instead of chemotherapy or target agents, tended to provide better ORRs without causing severe adverse events. This study will guide treatment choice and optimize future trial designs for investigations of advanced or metastatic cancer.
A retrospective study on incidence, diagnosis, and clinical outcome of gastric-type endocervical adenocarcinoma in a single institution
Authors: Radomska Anna , Lee Daniel , Neufeld Heather , Korte Nancy , Torlakovic Emina , Agrawal Anita , Chibbar Rajni
Published: July 2021

Background

Gastric-type endocervical adenocarcinoma is rare but the most common subtype of cervical adenocarcinoma not associated with human papillomavirus. It is more aggressive with a shorter five-year survival rate compared to human papillomavirus-associated usual type endocervical adenocarcinoma. The objectives of our study were to determine the incidence and clinical-pathological characteristics of Gastric-type endocervical adenocarcinoma in a single institution.

Methods

Twenty four cases of invasive cervical adenocarcinoma were identified between January 2000 and December 2015, from the Saskatoon Health Region pathology database using International Endocervical Adenocarcinoma Criteria and Classification to retrospectively classify endocervical adenocarcinoma. Immunohistochemistry was performed with antibodies for Gastric mucin-6 (MUC-6), p16INK4a, cyclin-dependent kinase inhibitor 2A (p16), p53 protein (p53), estrogen and progesterone receptors. Clinical and pathological data was retrieved from pathology reports and charts. Statistical analysis was performed using Mann-Whitney U test and Chi-Square test.

Results

Using the International Endocervical Adenocarcinoma Criteria and Classification criteria, 19 cases (79.2%) were classified as human papillomavirus-associated usual type endocervical adenocarcinoma, and five cases (20.8%) as Gastric-type endocervical adenocarcinoma. In our study 40% of Gastric-type endocervical adenocarcinoma cases presented at stage III compared to none of the usual type endocervical carcinoma cases. All the Gastric-type endocervical adenocarcinoma cases were positive for MUC-6, and negative for p16. 60% Gastric-type endocervical adenocarcinoma cases demonstrated mutant type p53 staining. In contrast, 84.2% of human papillomavirus-associated usual type endocervical adenocarcinoma cases showed block like nuclear and cytoplasmic positivity with p16 antibodies. The Gastric-type endocervical adenocarcinoma group had significantly shorter median survival time than human papillomavirus-associated usual type endocervical adenocarcinoma group, Gastric-type endocervical adenocarcinoma is 22 months compared to human papillomavirus-associated usual type endocervical adenocarcinoma at 118 months (p = 0.043).

Conclusions

In this study, Gastric-type endocervical adenocarcinoma accounted for 20.8% of all cervical adenocarcinoma with higher stage at presentation and shorter overall survival. Criteria proposed by International Endocervical Adenocarcinoma Criteria and Classification (IECC) are simple and reproducible in differentiating between, HPV- associated (HPVA) and non HPV associated (NHPVA) endocervical adenocarcinoma. Although none of the IHC assays is specific for GAS, but p16, MUC-6, ER, PR and p53 may further aid in confirming GAS and to differentiate it from benign and malignant mimics.
Comparison of the composition of lymphocyte subpopulations in non-relapse and relapse patients with squamous cell carcinoma of the head and neck before, during radiochemotherapy and in the follow-up period: a multicenter prospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)
Authors: Niu Minli , Combs Stephanie E. , Linge Annett , Krause Mechthild , Baumann Michael , Lohaus Fabian , Ebert Nadja , Tinhofer Ingeborg , Budach Volker , von der Grün Jens , Rödel Franz , Grosu Anca-Ligia , Multhoff Gabriele
Published: July 2021

Background

Radiochemotherapy (RCT) has been shown to induce changes in immune cell homeostasis which might affect antitumor immune responses. In the present study, we aimed to compare the composition and kinetics of major lymphocyte subsets in the periphery of patients with non-locoregional recurrent (n = 23) and locoregional recurrent (n = 9) squamous cell carcinoma of the head and neck (SCCHN) upon primary RCT.

Methods

EDTA-blood of non-locoregional recurrent SCCHN patients was collected before (t0), after application of 20–30 Gy (t1), in the follow-up period 3 (t2) and 6 months (t3) after RCT. In patients with locoregional recurrence blood samples were taken at t0, t1, t2 and at the time of recurrence (t5). EDTA-blood of age-related, healthy volunteers (n = 22) served as a control (Ctrl). Major lymphocyte subpopulations were phenotyped by multiparameter flow cytometry.

Results

Patients with non-recurrent SCCHN had significantly lower proportions of CD19+ B cells compared to healthy individuals before start of any therapy (t0) that dropped further until 3 months after RCT (t2), but reached initial levels 6 months after RCT (t3). The proportion of CD3+ T and CD3+/CD4+ T helper cells continuously decreased between t0 and t3, whereas that of CD8+ cytotoxic T cells and CD3+/CD56+ NK-like T cells (NKT) gradually increased in the same period of time in non-recurrent patients. The percentage of CD4+/CD25+/FoxP3+ regulatory T cells (Tregs) decreased directly after RCT, but increased above initial levels in the follow-up period 3 (t2) and 6 (t3) months after RCT. Patients with locoregional recurrence showed similar trends with respect to B, T cells and Tregs between t0 and t5. CD4+ T helper cells remained stably low between t0 and t5 in patients with locoregional recurrence compared to Ctrl. NKT/NK cell subsets (CD56+/CD69+, CD3−/CD56+, CD3−/CD94+, CD3−/NKG2D+, CD3−/NKp30+, CD3−/NKp46+) increased continuously up to 6 months after RCT (t0-t3) in patients without locoregional recurrence, whereas in patients with locoregional recurrence, these subsets remained stably low until time of recurrence (t5).

Conclusion

Monitoring the kinetics of lymphocyte subpopulations especially activatory NK cells before and after RCT might provide a clue with respect to the development of an early locoregional recurrence in patients with SCCHN. However, studies with larger patient cohorts are needed.

Trial registration

Observational Study on Biomarkers in Head and Neck Cancer (HNprädBio), NCT02059668. Registered on 11 February 2014, https://clinicaltrials.gov/ct2/show/NCT02059668.
Incidence and related risk factors of radiographic knee osteoarthritis: a population-based longitudinal study in China
Authors: Zhang Liyi , Lin Chutong , Liu Qiang , Gao Jiaxiang , Hou Yunfei , Lin Jianhao
Published: July 2021

Objective

To explore the incidence and risk factors for radiographic knee osteoarthritis (ROA) in a suburban area of China.

Methods

Shunyi Osteoarthritis Study was a population-based, longitudinal study of knee osteoarthritis in Shunyi, a suburban area of Beijing, China. A total of 1295 residents aged over 50 years were recruited with fully informed by randomized cluster sampling and were followed up 3 years later. At the time of baseline and follow-up visits, participants completed a home interview questionnaire and received a clinical examination including height, weight, range of motion (ROM), chair stand test, 50-foot walk test, and weight-bearing posterior-anterior semi-flexed view of radiographs at tibiofemoral joints. The incident ROA for a knee was defined if its KL grade was no more than grade 1 at baseline visit and no less than grade 2 at the follow-up visit. A patient without ROA in both knees at the baseline visit and with ROA in at least one knee at the follow-up visit was viewed as an incident case of ROA in patient level. Generalized linear model and generalized estimating equation were performed to examine the association between socio-demographic factors, physical function as well as baseline knee joint condition, and incident ROA in patient and knee level.

Results

A total of 1295 residents were recruited at baseline in 2014, and 962 (74.3%) residents were followed in 2017. The annual cumulative incidence of ROA was 3.6% at knee level and 5.7% at patient level. Older age (per year, adjusted odds ratio (OR) = 1.079; 95% confidence interval (CI), 1.042-1.117), overweight (adjusted OR = 2.086; 95% CI, 1.286-3.385), female (adjusted OR = 1.756; 95% CI, 1.074-2.877), less ROM (per degree, adjusted OR = 0.952; 95% CI, 0.923-0.983) and Kellgren and Lawrence (KL) grade 1 at baseline (adjusted OR = 8.527; 95% CI, 5.489-13.246) were risk factors for incident ROA.

Conclusion

The incidence of knee ROA in Chinese suburban area was high. Advanced age, female, overweight, less range of motion, and KL grade 1 at baseline were associated with an increased risk of incident ROA.
The influence of early thoracic fusion on the pulmonary function of patients with idiopathic scoliosis in the early period of the second growth peak with different Risser signs
Authors: Xu Xiaolin , Wang Shengru , Yang Yang , Du You , Lin Guanfeng , Zhang Jianguo
Published: July 2021

Background

Previous reports confirmed early spinal fusion may compromise pulmonary function and thoracic development in skeletal immature patients with scoliosis. However, the different effects in patients with various Risser signs remain unknown. This study aimed to compare the influence of early thoracic fusion on pulmonary function and thoracic growth in patients with idiopathic scoliosis (IS) with closed triangular cartilage (TRC) and different Risser signs.

Methods

Thirty-six patients with IS and a closed TRC were retrospectively selected and divided into the low Risser (LR, Risser sign ≤2, 22 patients) and high Risser (HR, 2<Risser sign≤4, 14 patients) groups. Patient age, Risser sign, main Cobb angle, thoracic kyphosis, and fusion levels were recorded. Perioperative and minimum of 2-year follow-up pulmonary function and thoracic diameters were compared between both groups.

Results

There were no differences in patients’ general characteristics between two groups. The preoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were 2.06±0.43 L and 2.50±0.49 L, respectively, in the LR group, and 2.31±0.49 L (p = 0.067) and 2.74±0.56 L (p = 0.122), respectively, in the HR group. While these values significantly increased postoperatively, to 2.62±0.46 L (p < 0.001) and 3.09±0.69 L (p < 0.001), in the LR group, they remained unchanged in the HR group [2.53±0.56 L (p = 0.093) and 2.70±0.98 L (p = 0.386), respectively]. The FEV1/FVC in both groups was >80% before and after surgery. The T1-T12 and anteroposterior thoracic diameter significantly increased after surgery in both groups, while the maximum inner chest diameter only increased in the LR group at the final follow-up. However, there were no significant differences in respiratory function and thoracic data between both groups.

Conclusion

For patients with IS, early fusion did not deteriorate pulmonary function or thoracic development in TRC-closed patients whose Risser sign was ≤2 compared with those with a Risser sign >2.