bluuebunny/crossref_metadata_2025 huggingface dataset:
Denegiy Sanal Deneme Uygulamasının Müşterilerin Eşarp Alışverişlerine Etkisinin Teknoloji Kabul Modeli İle İncelenmesi
Authors: ÇAKMAK Ali Çağlar , PEMBE Nejla
Published: October 2022

Gelişen ve değişen dünya koşullarında tüketicilerin satın alma tercih ve davranışlarının incelenmesi işletmeler açısından kaçınılmaz hale gelmiştir. Son yıllarda pazarlama dünyasında kadın tüketicilerin satın alma davranışları oldukça önemli bir hal almıştır. Bu noktada işletmeler kadın tüketicilerin talep ve ihtiyaçları doğrultusunda stratejiler geliştirmeli, hangi ürünü neden ve nereden satın aldıklarını tespit etmeye yönelik çalışmalar yürütmelidir. Tüketici davranışlarının incelenmesinde Teknoloji Kabul Modeli (TAM) önemli bir yere sahiptir. Model ilk olarak 1986 yılında Fred Davis tarafından önerilmiş ve 1989 yılında geliştirilmiştir. Bu çalışmada kadın tüketicilerin giyim ürünleri ile ilgili satın alma davranışlarının Teknoloji Kabul Modeli ile incelenmesi amaçlanmıştır. Bu anlamda Kahramanmaraş ilinde bir mağazadan alışveriş yapan kadın tüketicilere yönelik deney ve anket çalışması yapılmış ve elde edilen sonuçlar SPSS 20 programı ile analiz edilmiştir.
Right Treatment to the Right Patient in Moderate-to-Severe Psoriasis: Discussion on Difference
Authors: Woods Kathryn
Published: October 2022

The main objectives of the symposium were to define the need for ambitious goals in the treatment of psoriasis, including the importance of clear skin, from the patients’ perspective and to discuss the considerations that make a difference in ensuring that the right treatment reaches the right patient. The final aim was to consider what else dermatologists can be doing to help patients beyond the prescribed medication. Prof Kirby started the symposium by introducing a thought-provoking video of a patient describing his psoriasis journey and the challenges he faced in finding the right treatment. Prof Kirby went on to encourage the panel and audience to provide their views on the critical questions that tell us how we should be managing patients with moderate-to-severe psoriasis. Prof Mrowietz then involved the audience in a discussion of which drug features they consider to be the most important when finding the optimum treatment for patients, particularly now that more treatment options are available. Prof Mrowietz highlighted the importance of a patient-centric approach in treatment selection and the impact that psoriasis has beyond the skin. Prof Iversen presented on the need for ambitious treatment goals in moderate-to-severe psoriasis, beyond Psoriasis Area Severity Index (PASI) 90 and towards absolute PASI values, and presented the evidence linking higher PASI goals with improved quality of life. Prof Iversen concluded the symposium with a discussion on the management of comorbidity and risk factors in moderate-to-severe psoriasis.
Navigating the Road to Psoriasis Control in Women: Strategies to Optimise the Reproductive Journey
Authors: Tonarelli Lorena
Published: October 2022

The importance of discussions around the management of women of childbearing age with psoriasis, an issue that has been largely neglected for many years, was introduced and emphasised by Prof Ryan as the topic for this symposium. The changing needs and hurdles faced by this patient population due to the different hormonal phases throughout a woman’s reproductive life can reduce quality of life (QoL), aggravate disease burden, and complicate treatment decisions. This was exemplified by Dr Kleyn using three case studies for which delegates provided useful insights on management options. It was noted that fears and misconceptions often result in women of childbearing age delaying the decision to start a family and that improved doctor–patient interactions are key to helping women overcome concerns surrounding conception and pregnancy.

Prof Augustin discussed the significant impact of psoriasis on physical and psychological comorbidities and stigmatisation using the concept of cumulative life-course impairment (CLCI) as a measure. He then presented clinical trial data on anti-TNF biologic therapy during pregnancy, with a particular focus on results relating to placental transfer and transfer into breast milk. The delegates’ opinions on family planning and postpartum flares were then sought for three relevant clinical scenarios illustrated by Prof Ryan. The use of anti-TNF agents in women who are actively trying to conceive, are pregnant, or are breastfeeding was discussed, with the majority of delegates indicating that they would recommend anti-TNF treatment to patients where appropriate. The lack of practical guidance in dermatology the management of women of childbearing age with psoriasis was highlighted, and the symposium concluded with an overview of current recommendations by the European League Against Rheumatism (EULAR) for patients with rheumatological conditions. These emphasise the importance of discussing family planning with female patients and directly involving them in treatment decisions to optimise their reproductive journey.
PENGARUH AKTIVITAS INTEGRATED MARKETING COMMUNICATION DAN BRAND IMAGE TERHADAP KEPUTUSAN MENGGUNAKAN INDIHOME (SURVEY PADA PELANGGAN INDIHOME DI FACEBOOK INFO PASANG WIFI INDIHOME)
Authors: Situmeang Ilona Vicenovie Oisina
Published: October 2022

Indihome dalam memasarkan produknya menggunakan berbagai aktifitas Integreted Marketing Communication, hal ini dilakukan agar mnyebarkan informasi tentang produk Indihome kepada seluruh masyarakat. Namun karena Brand Image Indihome dimasyarakat tercipta positif mendukung Indihome dalam memasarkan produknya agar dapat menciptakan daya Tarik masyarakat untuk menggunakan Indihome. Teori yang digunakan Elaborations Likehood Model. Metodologi penelitian menggunakan paradigma positivism, pendekatan kuantitatif, sifat eksplanatif dan metode survey. Populasi penelitian ini merupakan pengikut dari akun Facebook Info Pasang Wifi Indihome dan yang menjadi sampel dengan menggunakan rumus Slovin diperoleh 100 orang responden dengan Teknik purposive sampling. Hasil yang diperoleh terdapat pengaruh yang kuat dan positif antara Aktifitas Integreted Marketing Communications dan brand image terhadap keputusan menggunakan Indihome.
Investigação sobre as percepções dos professores em relação ao processo de ensino mais inclusivo no contexto escolar
Authors: de Fatima Franzin Rozelaine , Vanderlei dos Santos Antonio , Caetano Zandona Alioha
Published: October 2022

O presente estudo justifica-se pelas inquietações dos pesquisadores perante ao ensino de alunos surdos, pois tem-se resultados de estudos de outros autores, que muitas vezes os professores não têm qualificação adequada para atender a demanda de alunos com algum tipo de deficiência. Assim as perguntas que envolvem essa pesquisa estão centradas em: como está a qualificação docente perante questões inclusivas? A prática pedagógica está centrada em metodologias inclusivas? Nesse sentido, o objetivo principal é investigar de que forma o professor está atuando no contexto inclusivo a fim de contribuir com o processo de ensino aprendizagem de alunos surdos, que convivem num contexto escolar regular com diversas realidades. A metodologia está baseada na análise das informações supracitadas, que foram organizadas por meio da realização de um questionário e os resultados demonstraram que a maioria dos professores já tiveram ou tem alunos com alguma deficiência e que na sua maioria, não usam metodologias diferenciadas para ensino, mas se mostraram preocupados em querer se qualificar e melhorar o processo de ensino aprendizagem dos alunos com deficiência auditiva. Conclui-se que existe diversas metodologias que podem ser utilizadas pelos professores em sala de aula para trabalhar com alunos surdos e que possibilita a construção do conhecimento e melhoria no processo de ensino, além de disponibilizar aos professores novas formas de organizar sua prática pedagógica.
O atletismo em pauta: uma revisão dos TCCs defendidos no Departamento de Educação Física da UEM
Authors: Tymoniuk Zanelli Daniel , Melleiro Malagutti João Paulo , Vasconcellos Ribeiro Carlos Henrique , Roberto Rojo Jeferson
Published: October 2022

O atletismo possui várias provas e formas de ser trabalhado na Educação Física, portanto, o presente estudo objetivou analisar a produção científica em formato de TCC produzida no Departamento de Educação Física da UEM, para isso foi utilizado os arquivos de TCC disponíveis no site do DEF/UEM, somando 34 trabalhos que falavam sobre o tema, de 1904 TCCs produzidos no departamento de 1993 a 2020. Os resultados mostraram que no DEF/UEM prevalece o estudo do atletismo com a perspectiva biodinâmica, com predominância da motivação dos atletas a praticarem o atletismo e aponta que o cenário apresentado nas pesquisas sobre TCC do DEF/UEM não tem relações diretas com a orientação, já que os orientadores mais procurados não têm vínculo à disciplina de psicologia do esporte.
Modification of phosphoinositides by the Shigella effector IpgD during host cell infection
Authors: Tran Van Nhieu Guy , Latour-Lambert Patricia , Enninga Jost
Published: October 2022

Shigella, the causative agent of bacillary dysentery, subvert cytoskeletal and trafficking processes to invade and replicate in epithelial cells using an arsenal of bacterial effectors translocated through a type III secretion system. Here, we review the various roles of the type III effector IpgD, initially characterized as phosphatidylinositol 4,5 bisphosphate (PI4,5P2) 4-phosphatase. By decreasing PI4,5P2 levels, IpgD triggers the disassembly of cortical actin filaments required for bacterial invasion and cell migration. PI5P produced by IpgD further stimulates signaling pathways regulating cell survival, macropinosome formation, endosomal trafficking and dampening of immune responses. Recently, IpgD was also found to exhibit phosphotransferase activity leading to PI3,4P2 synthesis adding a new flavor to this multipotent bacterial enzyme. The substrate of IpgD, PI4,5P2 is also the main substrate hydrolyzed by endogenous phospholipases C to produce inositoltriphosphate (InsP3), a major Ca2+ second messenger. Hence, beyond the repertoire of effects associated with the direct diversion of phoshoinositides, IpgD indirectly down-regulates InsP3-mediated Ca2+ release by limiting InsP3 production. Furthermore, IpgD controls the intracellular lifestyle of Shigella promoting Rab8/11 -dependent recruitment of the exocyst at macropinosomes to remove damaged vacuolar membrane remnants and promote bacterial cytosolic escape. IpgD thus emerges as a key bacterial effector for the remodeling of host cell membranes.
The synthesis of extracellular vesicles by the protistan parasite Blastocystis
Authors: Leonardi Steven Santino , Koh Eileen Yiling , Deng Lei , Huang Chenyuan , Tong Lingjun , Wang Jiong-Wei , Tan Kevin Shyong-Wei
Published: October 2022

Blastocystis is a genus of single-celled protist belonging to the stramenopile group. Prior studies have shown that isolates of Blastocystis subtype 7 (ST7) induced higher levels of intestinal epithelial cell damage and gut microbiota dysbiosis in comparison to other subtypes in in vivo and in vitro settings. Prior research has shown a link between gut dysbiosis and exposure to extracellular vesicles (EVs) produced by pathogenic microorganisms. This study demonstrates a protocol for the isolation of EVs from Blastocystis ST7 via ultracentrifugation. Nanoparticle tracking analysis and transmission electron microscopy were used to assess EV size and morphology. The protein content of isolated EVs was assessed by mass spectrophotometry and the presence of EV markers were evaluated by Western blotting. Finally, the EVs were cocultured with prominent human gut microbiome species to observe their effect on prokaryote growth. Our data shows that Blastocystis ST7 secretes EVs that are similar in morphology to previously characterized EVs from other organisms and that these EVs contain a limited yet unique protein cargo with functions in host-parasite intercellular communication and cell viability. This cargo may be involved in mediating the effects of Blastocystis on its surrounding environment.
A sandwich-like configuration with a signal amplification strategy using a methylene blue/aptamer complex on a heterojunction 2D MoSe2/2D WSe2 electrode: Toward a portable and sensitive electrochemical alpha-fetoprotein immunoassay
Authors: Chanarsa Supakeit , Jakmunee Jaroon , Ounnunkad Kontad
Published: October 2022

Liver cancer is one of the most common global health problems that features a high mortality rate. Alpha-fetoprotein (AFP) is a potential liver cancer biomarker for the diagnosis of liver cancer. The quantitative detection of AFP at an ultratrace level has important medical significance. Using the reaction of the antibody–antigen pair in an immunosensor enables the sensitive and selective AFP assay. Finding a strategy in signal generation and amplification is challenging to fabricate new sensitive electrochemical immunosensors for AFP detection. This study demonstrates the construction of a simple, reliable, and label-free immunosensor for the detection of AFP on a smart phone. Exfoliated two-dimensional (2D) molybdenum diselenide (MoSe2) and 2D tungsten diselenide (WSe2) were employed to modify the disposable screen-printed carbon electrode (SPCE) to use as the electrochemical platform, which is affixed to a small potentiostat connected to a smart phone. The modified electrode offers antibody immobilization and allows detection of AFP via an immunocomplex forming a sandwich-like configuration with the AFP-corresponding aptamer. A heterojunction 2D MoSe2/2D WSe2 composite improves the SPCE’s reactivity and provides a large surface area and good adsorption capacity for the immobilizing antibodies. The signal generation for the immunosensor is from the electrochemical response of methylene blue (MB) intercalating into the aptamer bound on the electrode. The response for the proposed sandwich-like immunosensor is proportional to the AFP concentration (1.0–50,000 pg ml-1). The biosensor has potential for the development of a simple and robust point-of-care diagnostic platform for the clinical diagnosis of liver cancer, achieving a low limit of detection (0.85 pg ml-1), high sensitivity, high selectivity, good stability, and excellent reproducibility.
The interactive feedback mechanisms between terrestrial water storage and vegetation in the Tibetan Plateau
Authors: Deng Haijun , Chen Yaning , Chen Xingwei , Li Yang , Ren Zhiguo , Zhang Zhiwei , Zheng Zhouyao , Hong Sheng
Published: October 2022

A component of terrestrial water storage, vegetation is also an influential driver of changes in terrestrial water storage. In the context of warming on the Tibetan Plateau, it is essential to explore the relationship between changes in terrestrial water storage and vegetation in this region to understand further the role of vegetation in the changes of water systems in alpine mountains. Our study combines terrestrial water storage anomalies data and vegetation indices to determine how their interact. The results indicate a warming rate of 0.44°C/decade (p<0.01) over the Tibetan Plateau from 1980–2020, while evapotranspiration trended upward (12.9 mm/decade, p<0.01), which is slower than precipitation (15 mm/decade, p<0.01). On the Tibetan Plateau, spatial-temporal differences in temperature, precipitation, and evapotranspiration dominate the variations in terrestrial water storage. The change in terrestrial water storage was relatively stable from 2003 to 2011, but decreased from 2012 to 2016. Terrestrial water storage increased in endorheic basins while decreasing in exorheic basins. Partial correlation analysis indicates a negative correlation between the terrestrial water storage anomaly and the temperature. It is found that terrestrial water storage and net precipitation are positively correlated in the Yangtze River Basin and the northeast of the endorheic basins. However, the Qaidam Basin and the north part of the Yellow River Basin are negatively correlated. Under the current climate change state (the increased rate of precipitation is faster than actual evapotranspiration), vegetation change has an insignificant impact on the changes in terrestrial water storage. In contrast, changes in terrestrial water storage (surplus/deficit) significantly affect vegetation changes (greening/browning) in parts of the Tibetan Plateau. The study contributes to a deeper understanding of the relationship between water system changes and vegetation on the Tibetan Plateau.
Effect of warming on the carbon flux of the alpine wetland on the Qinghai–Tibet Plateau
Authors: Yasin Adile , Niu Bin , Chen Zhengan , Hu Yilun , Yang Xiaoqin , Li Yue , Zhang Gengxin , Li Fengjie , Hou Weiguo
Published: October 2022

Under the scenario of global warming, the response of greenhouse gas emissions from alpine wetlands remains unclear. In this study, fluxes of CO2 and CH4 were measured during daytime for the microtopographic features of hollows and hummocks in a wetland in the Tibetan Plateau under two elevated temperatures, increments of ∼1°C (T1 treatment) and ∼2°C (T2 treatment), during the growing season in 2019. The results showed that warming significantly increased the cumulative net ecosystem CO2 exchanges (NEE) for both microtopographic features in the wetland compared to the control due to a combination of the increased gross primary production (GPP) with an increase in ecosystem respiration (ER). Similarly, warming also increased cumulative CH4 emission significantly. The effect was stronger for T2 than that for T1 for all component fluxes (GPP, ER, NEE, and CH4). Generally, NEE and CH4 fluxes both rose at first and then decreased. NEE peaked at the end of July for both hollows and hummocks, while CH4 emissions peaked in the middle of August. The cumulative CH4 emissions from the hummocks were significantly higher than those of the hollows, and CH4 emissions under illumination were significantly higher than those in darkness, which may be caused by the irradiation-sensitive vegetable internal convective gas transport system which diffuses CH4 from the pedosphere. This study revealed that warming strengthened the function of the CO2 sink but also increased CH4 emissions from the alpine wetlands on the Qinghai–Tibet Plateau.
Differences in spine volumetric bone mineral density between grade 1 vertebral fracture and non-fractured participants in the China action on spine and hip status study
Authors: Liu Yandong , Yu Aihong , Li Kai , Wang Ling , Huang Pengju , Geng Jian , Zhang Yong , Duanmu Yang-yang , Blake Glen M. , Cheng Xiaoguang
Published: October 2022

Purpose

This study evaluated the prevalence of vertebral fractures (VF) in middle-aged and elderly Chinese men and women and explored the differences in lumbar spine volumetric bone mineral density (vBMD) derived from quantitative CT (QCT) between those with a grade 1 vertebral fracture and non-fractured individuals.

Materials and methods

3,457 participants were enrolled in the China Action on Spine and Hip Status (CASH) study and had upper abdominal CT examinations. Vertebral fractures were identified by Genant’s semi-quantitative method from lateral CT scout views or CT sagittal views. L1-3 vBMD was measured by Mindways QCT Pro v5.0 software. The characteristics of different fracture severity groups were compared using one-way ANOVA, independent-samples t-tests, and Kruskal-Wallis H-tests.

Results

1267 males (aged 62.77 ± 9.20 years) and 2170 females (aged 61.41 ± 9.01 years) were included in the analysis. In men, the prevalence of VF increased from 14.7% at age<50 years to 23.2% at age ≥70 years, and in women from 5.1% at age<50 years to 33.0% at age ≥70 years. Differences in mean age and vBMD were found between the different fracture grade groups. After age stratification, vBMD differences in men aged < 50 years old disappeared (p = 0.162) but remained in the older age bands. There was no significant difference in mean vBMD between those with multiple mild fractures and those with a single mild fracture.

Conclusion

In women, the prevalence of VF increased rapidly after age 50, while it grew more slowly in men. In general, with the exception of men <50 years old, participants with a grade 1 VF had lower vBMD than non-fractured individuals. The majority of women younger than 50 with a grade 1 VF had normal bone mass. We recommend that a vertebral height reduction ratio of <25% be diagnosed as a deformity rather than a fracture in people under the age of 50. The presence of multiple mild fractured vertebrae does not imply lower BMD.
Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy
Authors: Du Xiaohui , Yang Le , Kong Ling , Sun Ye , Shen Kunshuang , Cai Ying , Sun Hui , Zhang Bo , Guo Sifan , Zhang Aihua , Wang Xijun
Published: October 2022

Diabetic retinopathy (DR) is a universal microvascular complication of diabetes mellitus (DM), which is the main reason for global sight damage/loss in middle-aged and/or older people. Current clinical analyses, like hemoglobin A1c, possess some importance as prognostic indicators for DR severity, but no effective circulating biomarkers are used for DR in the clinic currently, and studies on the latent pathophysiology remain lacking. Recent developments in omics, especially metabolomics, continue to disclose novel potential biomarkers in several fields, including but not limited to DR. Therefore, based on the overview of metabolomics, we reviewed progress in analytical technology of metabolomics, the prominent roles and the current status of biomarkers in DR, and the update of potential biomarkers in various DR-related samples via metabolomics, including tear as well as vitreous humor, aqueous humor, retina, plasma, serum, cerebrospinal fluid, urine, and feces. In this review, we underscored the in-depth analysis and elucidation of the common biomarkers in different biological samples based on integrated results, namely, alanine, lactate, and glutamine. Alanine may participate in and regulate glucose metabolism through stimulating N-methyl-D-aspartate receptors and subsequently suppressing insulin secretion, which is the potential pathogenesis of DR. Abnormal lactate could cause extensive oxidative stress and neuroinflammation, eventually leading to retinal hypoxia and metabolic dysfunction; on the other hand, high-level lactate may damage the structure and function of the retinal endothelial cell barrier via the G protein-coupled receptor 81. Abnormal glutamine indicates a disturbance of glutamate recycling, which may affect the activation of Müller cells and proliferation via the PPP1CA–YAP–GS–Gln–mTORC1 pathway.
The present status of metformin in fertility-preserving treatment in atypical endometrial hyperplasia and endometrioid endometrial cancer
Authors: Guan Jun , Chen Xiao-Jun
Published: October 2022

Progestin therapy is the main fertility-sparing treatment for women with endometrial cancer (EC) and atypical endometrial hyperplasia (AEH). However, still 15-25% of these women failed to achieve complete response (CR) and then lost their fertility after definitive surgery. Metformin has been demonstrated to play an anti-cancer role in multiple cancers including EC. Several studies also suggested metformin had potential benefit in improving the therapeutic outcome of fertility-preserving treatment alongside with progestin. This review has discussed existed evidence regarding the effect of metformin combined with progestin for women with AEH and EC who desire childbearing. Nevertheless, the therapeutic effect of metformin varied in different studies due to the high heterogeneity in the patient’s characteristics, the inconsistency in dose and treatment duration of metformin, the combined use of hysteroscopy, the insufficient sample size and underpowered study-design. Therefore, care should be taken when interpreting the current results on this issue. Till now, there is still no strong evidence supporting the use of metformin in fertility-preserving treatment in AEH and EEC patients. Further research is needed to provide high-quality data to validate the role of metformin as adjunctive therapy alongside with progestin to preserve fertility for AEH and EEC patients.
Therapeutic effect and safety of curcumin in women with PCOS: A systematic review and meta-analysis
Authors: Shen Wenjuan , Qu Yangfan , Jiang Huan , Wang Hongwei , Pan Yujia , Zhang Yuehui , Wu Xiaoke , Han Yanhua , Zhang Yang
Published: October 2022

Background

Polycystic ovary syndrome (PCOS) is a multi-factorial heterogeneous syndrome that has both adverse reproductive and metabolic implications for affected women and its management is a challenging clinical problem. Curcumin, as a phenolic compound with potent anti-inflammatory and antioxidant properties exerting positive effects on the lipid profile and insulin resistance, appears to be a valuable treatment regimen for patients with PCOS.

Objective

This study aimed to evaluate the efficacy and safety of curcumin in the treatment of PCOS.

Methods

Chinese databases (Chinese National Knowledge Infrastructure, China Biology Medicine Databases, VIP database, Wanfang Database, and Chinese Clinical Trial Registry) and English databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus and Clinical trials) were thoroughly investigated through screening randomized controlled trials on curcumin in PCOS published from the date of inception to May 2022. Standardized data search and abstraction were conducted following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Quantitative and qualitative analyses were performed. Heterogeneity was assessed using I2 statistics.

Results

A total of 447 patients from seven randomized controlled trials were included in the meta‐analysis. Results showed that the ingestion of curcumin decreased body mass index (WMD -0.267, 95% CI -0.450 to -0.084, P = 0.004, I2 = 0.0%), fasting plasma glucose (WMD -3.618, 95% CI -5.165 to -2.071, P < 0.001, I2 = 20.4%), insulin (WMD -1.834, 95% CI -2.701 to -0.968, P < 0.001, I2 = 8.4%), homeostatic model assessment for insulin resistance (WMD -0.565, 95% CI -0.779 to -0.351, P < 0.001, I2 = 0.0%), total cholesterol (WMD -15.591, 95% CI -27.908 to -3.273, P = 0.013, I2 = 68.9%), C-reactive protein (WMD -0.785, 95% CI -1.553 to -0.017, P = 0.045, I2 = 23.9%), and increased the quantitative insulin sensitivity check index (WMD 0.011, 95% CI 0.005 to 0.017, P = 0.001, I2 = 39.6%). As for safety, the treatment group did not cause significant adverse reactions than that in the control group.

Conclusion

In light of presented findings, curcumin has beneficial effects on serum markers of inflammation, weight loss and glucose and lipid metabolism in patients with PCOS. The incidence of adverse reactions does not increase with the application of curcumin. However, a larger, more definitive study is needed to further investigate these results.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022332394.
The association between normal serum sodium levels and bone turnover in patients with type 2 diabetes
Authors: Huang Hai-yan , Huang Zhi-qi , Hua Ling-yan , Liu Wang-shu , Xu Feng , Ge Xiao-qin , Lu Chun-feng , Su Jian-bin , Wang Xue-qin
Published: October 2022

Background

Sodium is a critically important component of bones, and hyponatremia has firmly been established as a risk factor associated with the incidence of fragility fractures. However, researches have also revealed that lower serum sodium are linked to reductions in muscle mass and a higher risk of cardiovascular disease even when these levels are within the normal range. Accordingly, this study was developed to examine the relationships between normal serum sodium concentrations and bone turnover in patients with type 2 diabetes (T2D).

Methods

Patients with T2D were enrolled in the present study from January 2021 to April 2022. All patients underwent analyses of serum sodium levels, oral glucose tolerance testing (OGTT), bone turnover markers (BTMs), and dual-energy X-ray absorptiometry (DXA) scanning. BTMs included bone formation markers osteocalcin (OC) and N-terminal propeptide of type-I procollagen (PINP), and bone resorption marker C-terminal telopeptide (CTx). Patients were stratified into three subgroups based on the tertiles of their serum sodium concentrations.

Results

In total, 372 patients with T2D and sodium levels in the normal range were enrolled in this study. Serum OC and PINP levels were increased from subgroup with the low sodium tertile to that with the high sodium tertile (p for trend < 0.05), whereas CTx level was comparable among the subgroups. A positive correlation was detected between serum sodium levels and both lnOC (r = 0.210, p < 0.001) and lnPINP (r = 0.196, p < 0.001), with these relationships remaining significant even following adjustment for age, sex, body mass index (BMI), and HbA1c. Only after adjusting for these four factors a positive correlation was detected between serum sodium levels and CTx levels (r = 0.108, p < 0.05). Linear regression analyses revealed that following adjustment for potential covariates, serum sodium level was and positively significantly associated with lnOC level (β = 0.134, t = 2.281, p < 0.05) and PINP level (β = 0.179, t = 3.023, p < 0.01).

Conclusion

These results highlight a significant association between low-normal serum sodium levels and low bone turnover.
Association of estimated glomerular filtration rate and incident pre-diabetes: A secondary 5-year longitudinal cohort study in Chinese people
Authors: Wang Xiaoyu , Huang Cheng , Liu Yufei , Han Yong , Hu Haofei
Published: October 2022

Objective

There is still limited evidence regarding the relationship between the estimated glomerular filtration rate (eGFR) and pre-diabetes. For that reason, our research aims to survey the association of eGFR with pre-diabetes.

Methods

This study was a retrospective cohort study, which consecutively and non-selectively collected a total of 173301 participants from Rich Healthcare Group in China from January 2010 to 2016. We then used the Cox proportional-hazards regression model to explore the relationship between baseline eGFR and pre-diabetes risk. Using a Cox proportional hazards regression with cubic spline function and smooth curve fitting (cubical spline smoothing), we were able to determine the non-linear relationship between eGFR and pre-diabetes. Additionally, we also conducted a series of sensitivity analyses and subgroup analyses. The DATADRYAD website was updated with data.

Results

The mean age of the included individuals was 40.95 ± 11.94 years old, and 92318 (53.27%) were male. The mean baseline eGFR was 111.40 ± 14.77 ml/min per 1.73 m2. During a median follow-up time of 3.0 years, 18333 (10.58%) people experienced pre-diabetes. As a result of adjusting for covariates, eGFR had a negative association with incident pre-diabetes (HR=0.993, 95%CI: 0.992-0.995). There was also a U-shaped curve relationship between eGFR and pre-diabetes, and the inflection point of eGFR was 129.793 ml/min per 1.73 m2. HRs on the left and right sides of the inflection point were respectively 0.993 (0.991-0.994) and 1.023 (1.010- 1.037). Our results were robust in the sensitivity analysis. Subgroup analyses indicated that eGFR was strongly associated with the risk of pre-diabetes among participants who were younger than 30 years and 40-70 years, as well as among those who had never smoked. In contrast, the association of eGFR with the risk of pre-diabetes was attenuated among participants who were 30-40 years of age and 70 years of age or older, and among those who currently smoked.

Conclusion

This study demonstrates a negative and U-shaped curve association between eGFR and the risk of pre-diabetes among the general Chinese population. Either reduced renal function or glomerular hyperperfusion status may be associated with an increased risk of prediabetes.
Associations between urea nitrogen and risk of depression among subjects with and without type 2 diabetes: A nationwide population-based study
Authors: Mao Yafei , Li Xinyuan , Zhu Shumin , Ma Jin , Geng Yulan , Zhao Yuanyuan
Published: October 2022

Background

Depression and type 2 diabetes (T2D) are serious public health problems with irreversible health consequences and a significant economic burden on the healthcare system. Previous studies have suggested that blood urea nitrogen (BUN) was inversely longitudinally associated with incidence of diabetes and depression in adults, but few well-designed studies have examined the effects of status of T2D on the full range of relationship between BUN and depression.

Methods

The analysis sample consisted of adults aged≥20 years from the 2007-2014 National Health and Nutrition Examination Survey (NHANES) who completed the Patient Health Questionnaire-9 (PHQ–9), involving 19,005 participants. By stratifying participants according to T2D status, we further assessed the difference between BUN and risk of depression in participants with and without T2D using multivariate logistic regression (interaction test).

Results

In this cross-sectional study, the association between BUN and depression prevalence appeared to differ between the T2D and non-T2D groups (OR: 1.00, 95% Cl: 0.95-1.05 vs. OR: 0.89, 95% Cl: 0.85-0.93). In addition, there was evidence of an interaction between BUN levels and T2D status in reducing the risk of depression (P value for interaction = 0.032.) The relationship between BUN and depressive symptoms was significant in non-T2D subjects (P < 0.001), but not in T2D (P = 0.940).

Conclusions

Our findings suggest that there is a significant relationship between BUN and depression, and T2D status may influence the association between BUN and the risk of depression. Such findings require further prospective studies to provide more evidence.
rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis
Authors: Shen Weiran , Liu Shengjiang , Ou Li
Published: October 2022

Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in clinical settings, a meta-analysis of 255 clinical trials was performed. A total of 7,289 patients are planned to be dosed. AAV2 was the most dominantly used serotype (29.8%, n=72), and 8.3% (n=20) of trials used engineered capsids. 38.7% (n=91) of trials employed neutralizing antibody assays for patient enrollment, while 15.3% (n=36) used ELISA-based total antibody assays. However, there was high variability in the eligibility criteria with cut-off tiers ranging from 1:1 to 1:1,600. To address potential immunogenicity, 46.3% (n=118) of trials applied immunosuppressants (prophylactic or reactive), while 32.7% (n=18) of CNS and 37.5% (n=24) of ocular-directed trials employed immunosuppressants, possibly due to the immune-privileged status of CNS and retina. There were a total of 11 patient deaths across 8 trials, and 18 out of 30 clinical holds were due to toxicity findings in clinical studies. 30.6% (n=78) of trials had treatment-emergent serious adverse events (TESAEs), with hepatotoxicity and thrombotic microangiopathy (systemic delivery) and neurotoxicity (CNS delivery) being the most prominent. Additionally, the durability of gene therapy may be impacted by two distinct decline mechanisms: 1) rapid decline presumably due to immune responses; or 2) gradual decline due to vector dilution. The durability varied significantly depending on disease indication, dose, serotypes, and patient individuals. Most CNS (90.0%) and muscle trials (73.3%) achieved durable transgene expression, while only 43.6% of ocular trials had sustained clinical outcomes. The rAAV production system can affect rAAV quality and thus immunogenicity and toxicity. Out of 186 trials that have disclosed production system information, 63.0% (n=126) of trials used the transient transfection of the HEK293/HEK293T system, while 18.0% (n=36) applied the baculovirus/Sf9 (rBac/Sf9) system. There were no significant differences in TESAEs and durability between AAV generated by rBac/Sf9 and HEK293/HEK293T systems. In summary, rAAV immunogenicity and toxicity poses significant challenges for clinical development of rAAV gene therapies, and it warrants collaborative efforts to standardize monitoring/measurement methods, design novel strategies to overcome immune responses, and openly share relevant information.
Effects of extracellular adhesion molecules on immune cell mediated solid tumor cell killing
Authors: Kim Seong-Eun , Yun Suji , Doh Junsang
Published: October 2022

Adoptive cell therapy (ACT) using ex vivo engineered/expanded immune cells demonstrated poor efficacy against solid tumors, despite its great success in treating various hematopoietic malignancies. To improve ACT for solid tumors, it is crucial to comprehend how the numerous components of the tumor microenvironment (TME) surrounding solid tumor cells influence killing ability of immune cells. In this study, we sought to determine the effects of extracellular adhesion provided by extracellular matrix (ECM) of TME on immune cell cytotoxicity by devising microwell arrays coated with proteins either preventing or promoting cell adhesion. Solid tumor cells in bovine serum albumin (BSA)-coated microwells did not attach to the surfaces and exhibited a round morphology, but solid tumor cells in fibronectin (FN)-coated microwells adhered firmed to the substrates with a flat shape. The seeding densities of solid tumor cells and immune cells were tuned to maximize one-to-one pairing within a single microwell, and live cell imaging was performed to examine dynamic cell-cell interactions and immune cell cytotoxicity at a single cell level. Both natural killer (NK) cells and T cells showed higher cytotoxicity against round tumor cells in BSA-coated microwells compared to flat tumor cells in FN-coated microwells, suggesting that extracellular adhesion-mediated firm adhesion of tumor cells made them more resistant to immune cell-mediated killing. Additionally, NK cells and T cells in FN-coated microwells exhibited divergent dynamic behaviors, indicating that two distinct subsets of cytotoxic lymphocytes respond differentially to extracellular adhesion cues during target cell recognition.
Adaptation of African swine fever virus to porcine kidney cells stably expressing CD163 and Siglec1
Authors: Gao Qi , Yang Yunlong , Luo Yizhuo , Zheng Jiachen , Gong Lang , Wang Heng , Feng Yongzhi , Gong Ting , Wu Dongdong , Wu Ruixia , Zheng Xiaoyu , Zheng Zezhong , Zhang Guihong
Published: October 2022

African swine fever virus (ASFV) is a complex large DNA enveloped virus that causes African swine fever (ASF) with a fatality rate of up to 100%, seriously threatening the global swine industry. Due to the strict cell tropism of ASFV, there is no effective in vitro cell line, which hinders its prevention and control. Herein, we analyzed genome-wide transcriptional profiles of ASFV-susceptible porcine alveolar macrophages (PAMs) and non-susceptible cell lines PK15 and 3D4-21, an found that PAM surface pattern recognition receptors (PRRs) were significantly higher and common differential genes were significantly enriched in phagocytosis compared with that observed in PK15 and 3D4-21 cell lines. Therefore, endocytosis functions of host cell surface PRRs may play key roles in ASFV infection in vitro. ASFV was found to be infective to PK15 and 3D4-21 cell lines overexpressing CD163 and Siglec1, and to the PK15S1-CD163 cell line stably expressing CD163 and Siglec1. However, the PK15 and 3D4-21 cell lines overexpressing CD163 or Siglec1 alone were not infectious. Simultaneous interference of CD163 and Siglec1 in PAMs with small interfering RNA (siRNA) significantly reduced the infectivity of ASFV. However, siRNA interference of CD163 and Siglec1 respectively did not affect ASFV infectivity. ASFV significantly inhibited IFN expression levels in PAMs and PK15S1-CD163 cells, but had no effect on PK15 and 3D4-21 cell lines. These results indicate that CD163 and Siglec1 are key receptors for ASFV-infected host cells, and both play a synergistic role in the process of ASFV infection. ASFV inhibits IFN expression in susceptible cells, thereby downregulating the host immune response and evading the immune mechanism. The discovery of the ASFV receptor provides novel ideas to study ASFV and host cell interactions, pathogenic mechanisms, development of receptor blockers, vaccine design, and disease resistance breeding.
MicroRNAs as immune regulators and biomarkers in tuberculosis
Authors: Wang Lulu , Xiong Yan , Fu Beibei , Guo Dong , Zaky Mohamed Y. , Lin Xiaoyuan , Wu Haibo
Published: October 2022

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), is one of the most lethal infectious disease worldwide, and it greatly affects human health. Some diagnostic and therapeutic methods are available to effectively prevent and treat TB; however, only a few systematic studies have described the roles of microRNAs (miRNAs) in TB. Combining multiple clinical datasets and previous studies on Mtb and miRNAs, we state that pathogens can exploit interactions between miRNAs and other biomolecules to avoid host mechanisms of immune-mediated clearance and survive in host cells for a long time. During the interaction between Mtb and host cells, miRNA expression levels are altered, resulting in the changes in the miRNA-mediated regulation of host cell metabolism, inflammatory responses, apoptosis, and autophagy. In addition, differential miRNA expression can be used to distinguish healthy individuals, patients with TB, and patients with latent TB. This review summarizes the roles of miRNAs in immune regulation and their application as biomarkers in TB. These findings could provide new opportunities for the diagnosis and treatment of TB.
Exposure to ambient gaseous pollutant and daily hospitalizations for Sjögren’s syndrome in Hefei: A time-series study
Authors: Zhang Tian-Ping , Wang Li-Jun , Wang Shan , Wang Ping , Zhou Xiao-Hui , Wang Li , Yang Chun-Mei , Li Xiao-Mei
Published: October 2022

Objective

Increasing evidence suggested that gaseous pollutants were associated with the development of autoimmune diseases, while there were few studies on the association between gaseous pollutants and Sjögren’s syndrome (SS). This study sought to assess the relationship between exposure to several gaseous pollutants and the hospitalizations for SS.

Methods

The data regarding SS hospitalizations, gaseous pollutants, and meteorological factors in Hefei from 2016 to 2021 were collected. A distributed lag non-linear model combined with a generalized linear model were adopted to analyze the association between gaseous pollutants and SS hospitalizations, and stratified analyses were also conducted.

Results

We detected significant associations between gaseous pollutants (NO2, SO2, O3, CO) and SS hospitalizations. Exposure to NO2 was linked with the elevated risk of hospitalizations for SS (RR=1.026, lag1 day). A positive correlation between CO exposure and hospitalizations for SS was found (RR=1.144, lag2 day). In contrast, exposure to SO2, O3 was respectively related to the decreased risk of hospitalizations for SS (SO2: RR=0.897, lag14 day; O3: RR=0.992, lag9 day). Stratified analyses found that female patients were more vulnerable to these gaseous pollutants. SS patients ≥ 65 years were more susceptible to NO2, CO exposure, and younger patients were more vulnerable to O3 exposure. In addition, exposure to O3, CO in cold season were more likely to affect hospitalizations for SS.

Conclusion

Our results demonstrated a significant association between exposure to NO2, CO and elevated risk of hospitalizations for SS, and SO2, O3 exposure might be linked to reduced risk of SS hospitalizations.
The current landscape of predictive and prognostic biomarkers for immune checkpoint blockade in ovarian cancer
Authors: Xu Yufei , Zuo Fengli , Wang Huiling , Jing Jing , He Xiujing
Published: October 2022

Immune checkpoint blockade (ICB) therapy has evoked a prominent shift in anticancer therapy. Durable clinical antitumor activity to ICB has been observed in patients with ovarian cancer (OC). However, only a subset of patients derive clinical benefit, and immune-related adverse events (irAEs) caused by ICB therapy can lead to permanent tissue damage and even fatal consequences. It is thus urgent to develop predictive biomarkers to optimize patient outcomes and minimize toxicity risk. Herein, we review current predictive and prognostic biomarkers for checkpoint immunotherapy in OC and highlight emerging biomarkers to guide treatment with ICB. The prevalent biomarkers, such as PD-L1 expression status, tumor-infiltrating lymphocytes, mutational burden, and immune gene signatures, are further discussed. We provide a state-of-the-art survey on prognostic and predictive biomarkers for checkpoint immunotherapy and offer valuable information for guiding precision immunotherapy
CD8+ T-cell immune escape by SARS-CoV-2 variants of concern
Authors: Kombe Kombe Arnaud John , Biteghe Fleury Augustin Nsole , Ndoutoume Zélia Nelly , Jin Tengchuan
Published: October 2022

Despite the efficacy of antiviral drug repositioning, convalescent plasma (CP), and the currently available vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the worldwide coronavirus disease 2019 (COVID-19) pandemic is still challenging because of the ongoing emergence of certain new SARS-CoV-2 strains known as variants of concern (VOCs). Mutations occurring within the viral genome, characterized by these new emerging VOCs, confer on them the ability to efficiently resist and escape natural and vaccine-induced humoral and cellular immune responses. Consequently, these VOCs have enhanced infectivity, increasing their stable spread in a given population with an important fatality rate. While the humoral immune escape process is well documented, the evasion mechanisms of VOCs from cellular immunity are not well elaborated. In this review, we discussed how SARS-CoV-2 VOCs adapt inside host cells and escape anti-COVID-19 cellular immunity, focusing on the effect of specific SARS-CoV-2 mutations in hampering the activation of CD8+T-cell immunity.
Controlling factors of the climatological annual cycle of the surface mixed layer oxygen content: A global view
Authors: Wang Zhankun , Garcia Hernan E. , Boyer Tim P. , Reagan James , Cebrian Just
Published: October 2022

The annual cycle of global dissolved oxygen content (O2C) and mean oxygen concentration in the surface mixed layer are estimated using monthly climatological oxygen fields from the World Ocean Atlas 2018 (WOA18). The largest seasonal variability in the mixed layer O2C occurs in the extra-tropics between 30° and 70° latitude of each hemisphere. A global view of the role of entrainment, air-sea flux, and biological activity in controlling the oxygen content/concentration annual cycle in the mixed layer is determined using an oxygen mass balance model. Based on the relative percentage from the mass balance model, entrainment is only a significant driver (contributing to 20-40% of the total changes) from mid-fall to early spring when the mixed layer deepens and transfers oxygen to deeper waters. Both the air-sea oxygen flux and biological activity show strong annual cycles and play critical roles in the annual cycle of O2C in the mixed layer. Air-sea oxygen flux is ingassing from late fall to early spring and outgassing between late spring and early fall. It is a substantial factor throughout the year and controls 40-60% of the oxygen changes in most months. Biological activity is a net source (production) in the spring and summer and a net sink (consumption) in the late fall and winter for the mixed layer oxygen content. Biological activity plays a more important role during spring/summer (40-60%) than that during fall/winter (10-30%) in controlling the overall oxygen change in each month. The model estimates a mean value (±SD) of 3.06±1.61 mol C m-2 yr-1 and a total of 863.7±73.8 Tmol C yr-1 for the global annual net ocean community production (ANCP) between 60°S and 60°N latitude, which are in fairly good agreement with previous studies.