bluuebunny/crossref_metadata_2025 huggingface dataset:
Hitit Savaş Dönemlerinde Dinin Kullanımı
Authors: TURGUT Murat
Published: August 2022

Antik Çağ’dan günümüze kadarki toplumların çoğu dinin günlük hayatta olduğu gibi savaşlar üzerinde de önemli etkisinin olduğuna inanmışlardır. Çağdaşı diğer toplumlar gibi Hititlerde de din neredeyse her alanda etkili olmuştur. Bu alanlardan birisi de savaştır.
Din Hitit savaşlarında önemli rol oynamıştır. Savaşa çıkmadan önce savaşın sonucunu kehanet yolu ile öğrenmeye çalışmışlardır. Savaşın sonucunu etkileyebilsinler diye tanrılara sunular gerçekleştirmişlerdir. Ayrıca savaş sırasında gerçekleştirdikleri arınma ritüelleri ile orduyu arındırmışlardır.
Bu makalede arkeolojik ve yazılı belgelerin ışığında savaş öncesi, savaş dönemi ve savaştan sonraki dönemlerinin din ile nasıl ilişkili olduğu incelenmiştir.
Revealing the rhetorical moves and linguistic patterns in discipline-related undergraduate thesis
Authors: Simanjuntak Risa Rumentha
Published: August 2022

Previous studies have provided exciting findings for language variations in theses and dissertations. However, not many studies have revealed the rhetorical analysis of the undergraduate abstracts. This study investigated the rhetorical structure of undergraduate thesis abstracts to reveal the constructions of the genre by novice writers. It further explored the variations between two groups of writers, students with the native language of English and Indonesian students writing in English. The aim was to present the commonalities and differences within the genre and finally conclude the genre’s conventions. The corpus for this study consisted of 180 undergraduate thesis abstracts from 12 universities in the United States, New Zealand, and Indonesia from Computer Science. The findings of this study revealed certain conventions consisting of rhetorical moves and rhetorical strategies used to perform the rhetorical moves. Differences between native writers of English and non-native writers of English included the use of lexical items and lexico-grammatical constructions in presenting arguments and evidence. The study concluded that socio-cultural factors, such as institutional guidelines for thesis writing and students’ first language, may contribute to the genre's variations.
Study on the Modulation of MDA and Lipid Profile Status of Some Women during Menstrual Cycle
Authors: Simeon George Gborienemi , Eroh Amos , Halliday Onuoha
Published: August 2022

Study was carried out to evaluate levels of Malondialdehyde and lipid profile parameters of some women in different phases of menstrual cycle. All subjects were premenopausal within childbearing age between 18 years to 50 years who had normal 28 days cycle. Blood samples were collected at follicular, ovulatory and luteal phase and their lipid profile and Malondialdehyde levels were determined spectrophotometrically. Applying analysis of variance with P value at (P<0.05) cholesterol and low-density lipoprotein showed significant difference at follicular and luteal phases. Marked variation was observed in all three phases for malondialdehyde with a peak at ovulatory phase. Pattern of result could be used to explain the interplay of lipids and hormonal behavior in menstruation.
Research Center for Psychotechnics Cognitive Impairments in Patients with Epilepsy
Authors: Stepanenko V
Published: August 2022

Cognitive impairment in epilepsy is an important problem. The understanding of the pathogenesis of disorders of higher nervous functions is based on the interaction of several factors, which include the form and duration of the disease, gender differences.
Viscoelastic Or Viscoplastic Glucose Theory (vgt #64): Estimated Risk Probability Percentages of Prostate Cancer and its Moving Trend over 12+ years from 1/1/2010 to 4/18/2022 using Metabolism index, Obesity, Diet, and Exercise as the 4 Influential Factors for Prostate Cancer Risk % based on GH-Meth
Authors: Hsu Gerald C
Published: August 2022

Recently, a friend of the author died from prostate cancer and leukemia. This news caused the author to read a few published medical articles regarding prostate cancer. He then outlines some key information in the Introduction section. The selected information sources have been referenced within this section and will not be listed in the Reference section.
Abordaje fenomenográfico sobre la interculturalidad en docentes aimarahablantes de educación básica de Lima Metropolitana
Authors: Escobar-Maquera Edi , Carcausto-Calla Wilfredo
Published: August 2022

La presente investigación muestra las formas cualitativamente diferentes en que los docentes aimarahablantes de Educación Básica experimentan la interculturalidad en un contexto urbano de Lima Metropolitana, la cual concentra la mayor cantidad de hablantes de lenguas indígenas en el Perú. El objetivo del estudio es analizar las percepciones de los docentes aimarahablantes acerca de la interculturalidad. Se trata de una investigación cualitativa basada en la fenomenografía, donde se aplicó una entrevista semiestructurada en profundidad a 10 participantes seleccionados intencionalmente por conveniencia bajo el criterio de saturación. Del análisis inductivo del corpus emergieron 6 categorías: interculturalidad como valorar nuestra lengua, interculturalidad como hablar nuestra lengua, interculturalidad como diálogo para la convivencia, interculturalidad como inclusión de la diversidad, interculturalidad como diálogo de saberes e interculturalidad como práctica de tolerancia.
Turismo místico: revisión de la literatura científica
Authors: Cayo-Velásquez Noemi E. , Arcaya-Chambilla Luz E. , Apaza-Tarqui Alejandro
Published: August 2022

En el Perú el turismo es una de las actividades económicas más importantes, debido a su contribución en el ámbito de las inversiones, como por su participación en la generación de empleos, sobre todo por su contribución de divisas, por consiguiente, en los últimos años ha provocado el surgimiento de nuevas alternativas y oportunidades para las comunidades locales; en tal sentido el propósito de esta investigación fue analizar la producción científica sobre la gestión del desarrollo del turismo místico en los trabajos de tesis doctorales y artículos de investigación; con la finalidad de conocer los últimos aportes científicos en los estudios realizados hasta la fecha; el enfoque de la investigación es mixto, para la obtención de datos se utilizó la herramienta Google Académico, las bases de datos Science Direct, Redalyc y Dialnet, se logró acceder a 32 publicaciones, de las cuales se escogieron aquellas que, según el contenido de su introducción y conclusiones investigan la relación turismo-misticismo; de los cuales se eligió 15 investigaciones los mismos, abordan un soporte metodológico para clarificar el concepto de turismo místico y establecen las peculiaridades básicas que resalten la importancia del mismo para el desarrollo del turismo.
Expandir la clase y transformar el compromiso agente de futuros formadores
Authors: Rigo Daiana Y. , Llanes Lucía , Rovere Romina
Published: August 2022

El estudio que se presenta tiene como objetivo promover y comprender el compromiso agente de estudiantes, futuros formadores, en educación inicial a través de una experiencia educativa expandida con la finalidad de repensar proactivamente su rol profesional. Participaron 41 estudiantes del Profesorado y la Licenciatura en Educación Inicial, que estaban cursando el tercer año de la carrera en la Universidad Nacional de Río Cuarto, Argentina. Bajo un diseño cualitativo interpretativo, se diseñó una experiencia educativa expansiva para que los estudiantes pudieran repensar proactivamente desde sus agencias su rol profesional, a partir de una actividad que proponía ir al territorio, específicamente, caminar la ciudad, en busca de arte para enseñar. Se recolectaron datos en tres momentos, durante, casi finalizada la investigación y ya concluida. Los resultados muestran que los estudiantes desarrollan acciones y emociones proactivas que motivan re pensar el rol docente, así como nuevas perspectivas docentes en transformación a partir del reconocimiento y construcción educativa de nuevos territorios y miradas del ser docente. Lo hallado muestra la importancia de re pensar la formación docente inicial en pos de promover instancias formativas orientadas a propiciar el compromiso agente, la participación activa y la iniciativa a innovar la práctica profesional.
The Methods for Emergency Robot Self-Оrganization Control
Authors:   Plekhanov Russian University of Economics, Moscow, Russia, Ross Gennady , Konyavsky Valery
Published: August 2022

The chapter demonstrates that the efficiency of self-organization of multi-agent systems (MAS) for controlling robots in emergency situations can be significantly increased if robots are provided with the ability to plan their behavior. The principles, requirements and tasks of the robot self-organization control are described. A concept for the development of evolutionary simulation methods (market models), which include a set of interlinked simulation models for swarm robot self-organization control, is proposed. The example of an algorithm for MAS robotic emergency control is given.
Fabrication of multifunctional alginate microspheres containing hydroxyapatite powder for simultaneous cell and drug delivery
Authors: Kim Jueun , Choi Yeong-Jin , Park Honghyun , Yun Hui-suk
Published: August 2022

Novel alginate-hydroxyapatite hybrid microspheres were developed for simultaneous delivery of drugs and cells as a multifunctional bone substitute for osteoporotic bone tissue regeneration. The microspheres were used to enhance osteogenesis and to carry and deliver quercetin, a representative phytoestrogen that controls bone tissue regeneration metabolism in osteoporosis patients, through sustained release over a long period. To overcome quercetin’s hydrophobicity and low solubility in aqueous environments, we added it to the surface of hydroxyapatite (HAp) nanoparticles before mixing them with an alginate solution. The homogeneous distribution of the HAp nanoparticles in the alginate solution was essential for preventing nozzle clogging and achieving successfully fabricated hybrid microspheres. To this end, a 3D ultrasonic treatment was applied. Electrostatic microencapsulation was then used to fabricate hybrid alginate-HAp microspheres containing quercetin and cells. The microspheres were approximately 290.7 ± 42.5 μm (aspect ratio of 1). The sustained release of quercetin was confirmed during a test period of 20 weeks. The cells in the hybrid microspheres maintained good cell viability during the entire testing period, and their osteogenic differentiation behavior was boosted by the presence of HAp. Thus, osteogenic differentiation could be greatly improved by adding quercetin. These novel multi-biofunctional hybrid microspheres have great potential for the regeneration of osteoporotic bone tissue at indeterminate defect sites.
Application of bioreactor technology for cell culture-based viral vaccine production: Present status and future prospects
Authors: Fang Zhongbiao , Lyu Jingting , Li Jianhua , Li Chaonan , Zhang Yuxuan , Guo Yikai , Wang Ying , Zhang Yanjun , Chen Keda
Published: August 2022

Bioreactors are widely used in cell culture-based viral vaccine production, especially during the coronavirus disease 2019 (COVID-19) pandemic. In this context, the development and application of bioreactors can provide more efficient and cost-effective vaccine production to meet the global vaccine demand. The production of viral vaccines is inseparable from the development of upstream biological processes. In particular, exploration at the laboratory-scale is urgently required for further development. Therefore, it is necessary to evaluate the existing upstream biological processes, to enable the selection of pilot-scale conditions for academic and industrial scientists to maximize the yield and quality of vaccine development and production. Reviewing methods for optimizing the upstream process of virus vaccine production, this review discusses the bioreactor concepts, significant parameters and operational strategies related to large-scale amplification of virus. On this basis, a comprehensive analysis and evaluation of the various process optimization methods for the production of various viruses (SARS-CoV-2, Influenza virus, Tropical virus, Enterovirus, Rabies virus) in bioreactors is presented. Meanwhile, the types of viral vaccines are briefly introduced, and the established animal cell lines for vaccine production are described. In addition, it is emphasized that the co-development of bioreactor and computational biology is urgently needed to meet the challenges posed by the differences in upstream production scales between the laboratory and industry.
Assessment of Serum Free Light Chains as a Marker of Diabetic Nephropathy; A Cross-Sectional Study in the Kumasi Metropolis
Authors: Sorvor Elizabeth , Owiredu William K. B. A. , Okyere Perditer , Annani-Akollor Max Efui , Donkor Sampson , Bannor Richard , Sorvor Felix B.K. , Ephraim Richard K.D.
Published: August 2022

Aims

Although traditional tests such as serum urea, creatinine, and microalbuminuria have been widely employed in the diagnosis of diabetic nephropathy, their sensitivity and accuracy are limited because kidney damage precedes the excretion of these biomarkers. This study investigated the role of serum free light chains in the disease manifestation of diabetic nephropathy.

Materials and Methods

Using a cross-sectional design we recruited 107 diabetes mellitus out-patients who visited the Diabetes and Renal Disease Clinics at the Komfo Anokye Teaching Hospital, Manhyia District Hospital, and Suntreso Government Hospital all in Ghana from November 2019 to February 2020. Five (5) mls of blood was collected from each participant and analyzed for fasting blood glucose (FBG) urea, creatinine, immunoglobulin free light chains. Urine samples were obtained and analyzed for albumin. Anthropometric characteristics were also measured. Data were analyzed using descriptive analysis, analysis of variance (ANOVA) test, Tukey HSD post hoc, and Kruskal Wallis test. Chi-squared test was used to examine if there are significant associations with the indicators of interest. In addition, Spearman’s correlation was used to test for associations between appropriate variables. Receiver operating characteristic analysis (ROC) was also performed to assess the diagnostic performance of free light chains.

Results

The mean age of studied participants was 58.2 years (SD: ± 11.1), 63.2% were females and most of the participants were married (63.0%). The mean FBG of the studied participants was 8.0mmol/L (SD: ± 5.86), and the average duration of diabetes mellitus (DM) was 11.88 years (SD: ± 7.96). The median serum Kappa, Lambda, and Kappa: Lambda ratios for the studied participants were 18.51 (15.63-24.18), 12.19(10.84-14.48), and 1.50(1.23-1.86) respectively. A positive correlation was observed between albuminuria and; Kappa (rs=0.132; p=0.209), and Lambda (rs=0.076; p=0.469). However, a negative correlation was observed between albuminuria and K: L ratio (rs=-0.006; p=0.956).

Conclusions

The current study observed an increasing trend in the levels of free light chains and degree of diabetic nephropathy, although not statistically significant. The exploration of serum free light chains as a better marker of diabetic nephropathy showed very promising results but further studies are required to elucidate its predictive value as a diagnostic tool for diabetic nephropathy.
Connexin 30 deletion exacerbates cochlear senescence and age-related hearing loss
Authors: Paciello Fabiola , Zorzi Veronica , Raspa Marcello , Scavizzi Ferdinando , Grassi Claudio , Mammano Fabio , Fetoni Anna Rita
Published: August 2022

Pathogenic mutations in the Gjb2 and Gjb6 genes, encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, have been linked to the most frequent monogenic hearing impairment, nonsyndromic hearing loss, and deafness DFNB1. It is known that Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that partial deletion of Cx26 can accelerate age-related hearing loss (ARHL), a multifactorial complex disorder, with both environmental and genetic factors contributing to the etiology of the disease. Here, we investigated the role of Cx30 in cochlear-aging processes using a transgenic mouse model with total deletion of Cx30 (Cx30 ΔΔ mice), in which Cx30 was removed without perturbing the surrounding sequences. We show that these mice are affected by exacerbated ARHL, with increased morphological cochlear damage, oxidative stress, inflammation, and vascular dysfunctions. Overall, our data demonstrate that Cx30 deletion can be considered a genetic risk factor for ARHL, making cochlear structures more susceptible to aging processes.
Structure–function analysis of the ER-peroxisome contact site protein Pex32
Authors: Wu Fei , van der Klei Ida J.
Published: August 2022

In the yeast Hansenula polymorpha, the ER protein Pex32 is required for associating peroxisomes to the ER. Here, we report on a structure–function analysis of Pex32. Localization studies of various Pex32 truncations showed that the N-terminal transmembrane domain of Pex32 is responsible for sorting. Moreover, this part of the protein is sufficient for the function of Pex32 in peroxisome biogenesis. The C-terminal DysF domain is required for concentrating Pex32 at ER-peroxisome contact sites and has the ability to bind to peroxisomes. In order to better understand the role of Pex32 in peroxisome biogenesis, we analyzed various peroxisomal proteins in pex32 cells. This revealed that Pex11 levels are strongly reduced in pex32 cells. This may explain the strong reduction in peroxisome numbers in pex32 cells, which also occurs in cells lacking Pex11.
Study on the potential mechanism of the active components in YiYiFuZi powder in homotherapy for hetropathy of coronary heart disease and rheumatoid arthritis
Authors: Wang Yuming , Li Xiaokai , Gu Kun , Gou Jing , Li Xue , Dong Yaqian , Li Rui , Wei Jinxia , Dou Zhiying , Li Yubo
Published: August 2022

In recent years, the incidence of coronary heart disease and rheumatoid arthritis has been increasing, which has become a common public health problem worldwide. YiYiFuZi (YYFZ ) powder is a classical traditional Chinese prescription, which is commonly used to treat metabolic diseases such as rheumatoid arthritis, with an ideal curative effect, but the therapeutic mechanism is still unclear. In this study, from the perspective of clinical metabolomics, combined with network pharmacology, we sought the comorbidity mechanism and key targets of coronary heart disease and rheumatoid arthritis and the mechanism by which YYFZ powder exerts therapeutic effects, combined with molecular docking and atomic force microscopy to determine the effective components, and found that the higenamine and steroid components in YYFZ powder can bind acid sphingomyelinase enzymes to affect the sphingolipid pathway to produce therapeutic effects, which can bind to sugars existing as a glycoside.
Intravascular imaging in coronary stent restenosis: Prevention, characterization, and management
Authors: Abouelnour Amr , Gori Tommaso
Published: August 2022

Despite the introduction of drug-eluting stents to combat the neointimal hyperplasia that occurred after BMS implantation, in-stent restenosis is still encountered in a significant number of patients, particularly as increasingly complex lesions are tackled by percutaneous coronary intervention. Many biological and mechanical factors interplay to produce restenosis, some of which are avoidable. Intravascular imaging provided unique insights into various forms of stent-related mechanical issues that contribute to this phenomenon. From a practical perspective, intravascular imaging can therefore help to optimize the stenting procedure to avert these issues. Moreover, once the problem of restenosis eventuates, imaging can guide the management by tackling the underlying identified mechanism. Finally, it can be used to evaluate the re-intervention results. Nevertheless, with the emergence of different treatment options, more evidence is needed to define patient/lesion-specific characteristics that may help to tailor treatment selection in a way that improves clinical outcomes.
Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques
Authors: Ren Jinrui , Lv Yanze , Wu Lianglin , Chen Siliang , Lei Chuxiang , Yang Dan , Li Fangda , Liu Changzheng , Zheng Yuehong
Published: August 2022

Objectives

Abdominal aortic aneurysm (AAA) is a cardiovascular disease with high mortality and pathogenesis closely related to various cell death types, e.g., autophagy, apoptosis and pyroptosis. However, the association between AAA and ferroptosis is unknown.

Methods

GSE57691 and GSE98278 dataset were obtained from the Gene Expression Omnibus database, and a ferroptosis-related gene (FRG) set was downloaded from the FerrDb database. These data were normalized, and ferroptosis-related differentially expressed genes (FDEGs, AAA vs. normal samples) were identified using the limma package in R. FRGs expression was analyzed by Gene Set Expression Analysis (GSEA), and FDEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses using the clusterProfiler package in R and ClueGO in Cytoscape. Protein–protein interaction networks were assembled using Cytoscape, and crucial FDEGs were identified using CytoHubba. Critical FDEG transcription factors (TFs) were predicted with iRegulon. FDEGs were verified in GSE98278 set, and key FDEGs in AAA (compared with normal samples) and ruptured AAA (RAAA; compared with AAA samples) were identified. Ferroptosis-related immune cell infiltration and correlations with key genes were analyzed by CIBERSORT. Key FEDGs were reverified in Ang II-induced AAA models of ApoE–/– and CD57B/6J mice by immunofluorescence assay.

Results

In AAA and normal samples, 40 FDEGs were identified, and the expression of suppressive FRGs was significantly downregulated with GSEA. For FDEGs, the GO terms were response to oxidative stress and cellular response to external stimulus, and the KEGG pathways were the TNF and NOD-like receptor signaling pathways. IL6, ALB, CAV1, PTGS2, NOX4, PRDX6, GPX4, HSPA5, HSPB1, and NCF2 were the most enriched genes in the crucial gene cluster. CEBPG, NFAT5, SOX10, GTF2IRD1, STAT1, and RELA were potential TFs affecting these crucial genes. Ferroptosis-related immune cells involved in AAA formation were CD8+ T, naive CD4+ T, and regulatory T cells (Tregs); M0 and M2 macrophages; and eosinophils. Tregs were also involved in RAAA. GPX4, SLC2A1, and PEBP1 expression was downregulated in both the RAAA and AAA samples. GPX4 and PEBP1 were more important in AAA because they influenced ferroptosis-related immune cell infiltration, and SLC2A1 was more important in RAAA.

Conclusions

This is the first study to show that ferroptosis is crucial to AAA/RAAA formation. The TNF and NOD-like signaling pathways and ferroptosis-related immune cell infiltration play key roles in AAA/RAAA. GPX4 is a key ferroptosis-related gene in AAA. Ferroptosis and related genes might be promising targets in the treatment of AAA/RAAA.
Coronary computed tomography angiography as a screening tool for moderate-high risk asymptomatic type 2 diabetes mellitus patients
Authors: Liu Qiaolu , Qiu Jianfeng , Sun Shuxin , Wang Xiaoqiang , Sun Zhanguo , Zhao Huihui
Published: August 2022

Background

There are few data on the clinical significance of coronary computed tomography angiography (CCTA) in asymptomatic type 2 diabetes mellitus (T2DM) patients. We performed a retrospective study to evaluate coronary heart disease (CHD) screening in asymptomatic patients with T2DM using CCTA and CHD risk stratification prediction.

Materials and methods

Data from 141 T2DM patients (58 ± 8 years, 57% males) without known symptoms suggestive of CHD who underwent CCTA were retrospectively analyzed. The patients were classified into three subgroups based on United Kingdom prospective diabetes study (UKPDS) CHD risk stratification prediction. Seventy-four patients without diabetes mellitus and CHD who underwent CCTA successively were chosen as the control group. The segment involvement score (SIS), segment stenosis score (SSS), stenosis coefficient (SC), severe proximal plaque (SPP) positive ratio and CCTA-adapted Leaman score (CT-LeSc) based on CCTA data were evaluated and compared among the groups.

Results

Compared with the patients in the control group, patients in the moderate-high risk DM groups had higher scores on the SIS, SSS, SC, CT-LeSc, and a higher SPP positive ratio (all p-values < 0.001), and no difference was observed between the low-risk group and the control group (p = 0.136, p = 0.088, p = 0.0.067, p = 0.225, p = 1.000, respectively). Compared with patients in the control group, the patients in the moderate-high risk DM groups had increased odds of SIS > 3 [odds ratio (OR) = 6.557, p < 0.001; OR = 4.455, p < 0.001, respectively], SSS > 5 (OR = 5.727, p < 0.001; OR = 5.144, p < 0.001, respectively), CT-LeSc > 8.7 (OR = 3.780, p = 0.001; OR = 2.804, p = 0.007, respectively), and obstructive stenosis (OR = 7.233, p < 0.001; OR = 5.787, p < 0.001, respectively).

Conclusion

The moderate-high CHD risk patients had increased odds of obstructive coronary artery stenosis, and the distribution of coronary artery stenosis was more extensive and more severe in that group compared to the patients without diabetes mellitus and CHD. CHD can be effectively screened in moderate-high risk asymptomatic T2DM patients using CCTA.
Exploring the role of uterine fibroids in promotion of cardiovascular diseases by diabetes exposure: Findings from national health and nutrition examination survey 1999–2006
Authors: Li Bin , Yuan Zhen , Zhang Yizhi , Li Feng , Huang Lin , Yang Zhihui , Liu Haiyue , Liu Zuheng
Published: August 2022

Objective

The relationship between uterine fibroids (UF) and cardiovascular diseases (CVDs) in the diabetes population seemed to remain undetermined in previous studies. This study aims to explore the association between UF and CVDs by using the database from the National Health and Nutrition Examination Survey (NHANES). To further evaluate the connection between UF and CVDs we also tested the potential differences due to diabetes exposure.

Materials and methods

National Health and Nutrition Examination Survey data (1999–2006) were collected and used in this study. A total of 5,509 individuals were included and analyzed. The student’s t-test and the chi-squared test were used to explore the demographic characteristic between UF and non-UF groups. Logistic regression analysis was performed to determine the odds ratios of UF and covariates.

Results

Female participants were divided into UF (n = 694, 12.60%) and non-UF (n = 4,815, 87.40%) groups. The incidence of CVDs in UF patients (n = 245, 35.30%) were higher than non-UF individuals (n = 776, 16.12%) (p < 0.001). In addition, each subtype of CVDs were also different, which contains hypertension (33.29 vs. 15.31%, p < 0.001), heart failure (1.59 vs. 0.52%, p < 0.01), angina (2.59 vs. 0.62%, p < 0.001), heart attack (1.73 vs. 0.58%, p < 0.01) and coronary heart disease (1.44 vs. 0.54%, p < 0.01). The odds ratios of CVDs according to logistic regression were 2.840 (95% CI: 2.387–3.379) for UF patients (p < 0.001), while the odds ratios (ORs) were 1.438 (95% CI: 1.175–1.760) after taking account for the age, body mass index (BMI), diabetes, race, education, and annual family income (p < 0.001). In addition, secondary analysis indicated more adverse effects in by UF exposure on CVDs risk among non-diabetes individuals (OR = 1.389, 95% CI = 1.124–1.718, p < 0.01) than diabetes patients (p = 0.063).

Conclusion

Overall, UFs were positively associated with CVDs, and this effect seems blunted by diabetes exposure.
Transenteric delivery of antibodies via an orally ingestible robotic pill yields high bioavailability comparable to parenteral administration in awake canines
Authors: Yamaguchi Alyson , Van Dam Jacques , Dhalla Arvinder K. , Horlen Kyle , Imran Mir , Vo April T. , Hashim Mir A.
Published: August 2022

Biotherapeutics such as peptides and antibodies are highly efficacious clinically but, unlike conventional medications, cannot be administered orally as they get digested and inactivated. Thus, biotherapeutics require parenteral routes for delivery, such as intravenous, intramuscular or subcutaneous administration. However, these delivery methods have limitations such as poor patient compliance or may require clinical supervision compared to oral therapies. We explored whether a novel, orally administered transenteric delivery system (Robotic Pill) could provide equivalent bioavailability to parenterally administered drugs. Utilizing an awake canine model, we demonstrated that orally administered Robotic Pills containing either human IgG or an anti-cytokine monoclonal antibody directed against either TNFα or interleukin-17A yielded bioavailability equivalent to parenterally administered controls. The ability to achieve clinically relevant blood levels of biotherapeutics via any orally administered preparation represents an important advance in drug delivery.
Deciphering the Properties of Different Arctic Ice Types During the Growth Phase of MOSAiC: Implications for Future Studies on Gas Pathways
Authors: Angelopoulos Michael , Damm Ellen , Simões Pereira Patric , Abrahamsson Katarina , Bauch Dorothea , Bowman Jeff , Castellani Giulia , Creamean Jessie , Divine Dmitry V. , Dumitrascu Adela , Fons Steven W. , Granskog Mats A. , Kolabutin Nikolai , Krumpen Thomas , Marsay Chris , Nicolaus Marcel , Oggier Marc , Rinke Annette , Sachs Torsten , Shimanchuk Egor , Stefels Jacqueline , Stephens Mark , Ulfsbo Adam , Verdugo Josefa , Wang Lei , Zhan Liyang , Haas Christian
Published: August 2022

The increased fraction of first year ice (FYI) at the expense of old ice (second-year ice (SYI) and multi-year ice (MYI)) likely affects the permeability of the Arctic ice cover. This in turn influences the pathways of gases circulating therein and the exchange at interfaces with the atmosphere and ocean. We present sea ice temperature and salinity time series from different ice types relevant to temporal development of sea ice permeability and brine drainage efficiency from freeze-up in October to the onset of spring warming in May. Our study is based on a dataset collected during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 and 2020. These physical properties were used to derive sea ice permeability and Rayleigh numbers. The main sites included FYI and SYI. The latter was composed of an upper layer of residual ice that had desalinated but survived the previous summer melt and became SYI. Below this ice a layer of new first-year ice formed. As the layer of new first-year ice has no direct contact with the atmosphere, we call it insulated first-year ice (IFYI). The residual/SYI-layer also contained refrozen melt ponds in some areas. During the freezing season, the residual/SYI-layer was consistently impermeable, acting as barrier for gas exchange between the atmosphere and ocean. While both FYI and SYI temperatures responded similarly to atmospheric warming events, SYI was more resilient to brine volume fraction changes because of its low salinity (<2). Furthermore, later bottom ice growth during spring warming was observed for SYI in comparison to FYI. The projected increase in the fraction of more permeable FYI in autumn and spring in the coming decades may favor gas exchange at the atmosphere-ice interface when sea ice acts as a source relative to the atmosphere. While the areal extent of old ice is decreasing, so is its thickness at the onset of freeze-up. Our study sets the foundation for studies on gas dynamics within the ice column and the gas exchange at both ice interfaces, i.e. with the atmosphere and the ocean.
Mechanical properties and instability analysis of concrete specimens with horizontal holes of different diameters
Authors: Fang Juejing , Yang Ke , Lyu Xin , Tang Jinzhou , Zhang Jiqiang
Published: August 2022

Uniaxial compression tests were carried on 12 concrete specimens with six different diameter holes using a rigid test machine, and the stress–strain relationship was analyzed in different hole diameter specimens. The effects of different hole diameters on specimen compression strength, elastic modulus, and Poisson’s ratio were studied, and the failure form and instability mode of concrete specimens with holes of different diameters were evaluated. The results show that the larger the compression strength of the specimen, the larger the axial and horizontal strains. As the hole diameter increased from 0 to 50 mm, the compression strength and elastic modulus reduced. The decreasing trend slowed down, and the relationships between the hole diameter and compression strength, and elastic modulus could be represented by negative liner functions. The Poisson ratio of the specimen increased in waves with the increase in hole diameter from 0 to 50 mm. A crack in the concrete specimen with 0–20 mm diameter hole started at the upper and lower diagonal angles of the hole wall; a crack in the concrete specimen with 30–50 mm diameter hole started at the left and right parts of the hole wall. The instability mode of concrete specimens with horizontal holes of different diameters was divided into shear dislocation instability and planar splitting instability.
Effects of Bu Shen Hua Zhuo formula on the LPS/TLR4 pathway and gut microbiota in rats with letrozole-induced polycystic ovary syndrome
Authors: Wang Yang , Xiao Hui , Liu Yanxia , Tong Qing , Yu Yanyan , Qi Bing , Bu Xiaoling , Pan Tianyuan , Xing Yu
Published: August 2022

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in gynecology. Traditional Chinese medicine (TCM) is widely used for the treatment of PCOS in China. The Bu Shen Hua Zhuo formula (BSHZF), a TCM decoction, has shown great therapeutic efficacy in clinical practice. However, the mechanism underlying the BSHZF function in PCOS remains unclear. This study aimed to identify the potential mechanisms of action of BSHZF in the treatment of PCOS. PCOS-model rats treated with letrozole were administered different doses of BSHZF, metformin, and 1% carboxymethylcellulose. Serum sex hormones, fasting blood glucose, and fasting insulin levels were measured, and the morphology of the ovaries was observed in each group, including the normal group. The structure and abundance of the gut microbiota in rats were measured using 16S ribosomal RNA gene sequencing. Toll-like receptor 4 (TLR4) and phospho-NF-κB p65 levels in the ovarian tissue of the rats were detected using Western blotting. Furthermore, the levels of lipopolysaccharide (LPS) and inflammatory cytokines TNF-α, IL-6, and IL-8 in the serum of rats were detected by ELISA. The results showed that BSHZF administration was associated with a decrease in body weight, fasting blood glucose, fasting insulin, and testosterone and changes in ovarian morphology in PCOS-model rats. Moreover, BSHZF was associated with an increase in the α-diversity of gut microbiota, decrease in the relative abundance of Firmicutes, and increase in Lactobacillus and short chain fatty acid–producing bacteria (Allobaculum, Bacteroides, Ruminococcaceae_UCG-014). Furthermore, BSHZF may promote carbohydrate and protein metabolism. In addition, BSHZF was associated with a decrease in the serum level of LPS and TLR4 expression, thereby inhibiting the activation of the NF-κB signaling–mediated inflammatory response in ovarian tissue. Therefore, the beneficial effects of BSHZF on PCOS pathogenesis are associated with its ability to normalize gut microbiota function and inhibit PCOS-related inflammation.
Increased plasma ANGPTL7 levels with increased obstructive sleep apnea severity
Authors: Leentjens M. , Alterki Abdulmohsen , Abu-Farha Mohamed , Bosschieter P. F. N. , de Raaff CAL. , de Vries CEE. , Al Shawaf Eman , Thanaraj Thangavel Alphonse , Al-Khairi Irina , Cherian Preethi , Channanath Arshad , Kavalakatt Sina , van Wagensveld B. A. , de Vries N. , Abubaker Jehad
Published: August 2022

Background

Weight-loss surgery is one of the recommended methods for treating obstructive sleep apnea (OSA) in obese patients. While weight reduction is critical to relieve symptoms of OSA, the biochemical factors involved in post-surgery improvement are still unknown. We aimed to explore the link between ANGPTL7 and OSA in patients with different OSA severity. Furthermore, we examined the effect of treating OSA with bariatric surgery on ANGPTL7 level.

Methods

We quantified levels of circulating ANGPTL7 in fasting plasma and adipose tissue samples of 88 participants before and after bariatric surgery. Confocal microscopy analyses were also performed to assess the ANGPTL7 expression in subcutaneous white adipose tissue biopsies obtained from people with moderate-to-severe OSA compared to those with none or mild OSA. The study involved 57 individuals with none or mild OSA and 31 patients with moderate-to-severe OSA.

Results

Levels of circulating ANGPTL7 were significantly higher in people with moderate-to-severe OSA (1440 ± 1310 pg/ml) compared to the none or mild OSA group (734 ± 904 pg/ml, p = 0.01). The increase in ANGPTL7 correlated significantly and positively with the apnea-hypopnea index (AHI, r = .226, p = .037), and AHI-supine (r = .266, p = .019) in participants with moderate-to-severe OSA. Multivariate logistic regression analysis demonstrated an association between ANGPTL7 and OSA severity (log2 ANGPTL7; OR =1.24, p = 0.024). ANGPTL7 levels exhibited significant positive correlations with the levels of TG and oxLDL (p-value = 0.002 and 0.01 respectively). Bariatric surgery reduced the levels of both ANGPTL7 and AHI significantly.

Conclusion

Here we report significantly increased levels of ANGPTL7 both in the circulation and in adipose tissue of patients with OSA, which concurred with increased inflammation and OSA severity. Levels of ANGPTL7 decreased significantly as OSA showed a significant improvement post-surgery supporting a potential role for ANGPTL7 in either OSA progression or a role in an OSA-related mechanism.
Influence of dipeptidyl peptidase-4 inhibitors on glycemic variability in patients with type 2 diabetes: A meta-analysis of randomized controlled trials
Authors: Chai Shangyu , Zhang Ruya , Zhang Ye , Carr Richard David , Zheng Yiman , Rajpathak Swapnil , Yu Miao
Published: August 2022

Objective

The influence of dipeptidyl peptidase-4 (DPP4) inhibitors on glycemic variability compared to other oral antidiabetic drugs (OADs), measured based on the mean amplitude of glycemic excursions (MAGE), has not been comprehensively analyzed. The aim of the study was to perform a meta-analysis to compare the effects of DPP4 inhibitors on MAGE with other OADs in type 2 diabetes mellitus (T2DM) patients without concurrent insulin treatments.

Methods

The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant randomized controlled trials (RCTs). Study characteristics and outcome data were independently extracted by two authors. A random-effect model was used to combine the results.

Results

Fourteen studies with 855 patients were included. Compared to other OADs, DPP4 inhibitors significantly reduced MAGE (mean difference [MD]: -0.69 mmol/L, 95% confidence interval [CI]: -0.95 to -0.43, P<0.001) with mild heterogeneity (I2 = 28%). Predefined subgroup analyses suggested that DPP4 inhibitors were more effective in reducing MAGE compared to insulin secretagogues (MD: -0.92 mmol/L, P<0.001) and non-secretagogues (MD: -0.43 mmol/L, P=0.02), as well as compared to sulfonylureas (MD: -0.91 mmol/L, P<0.001) and sodium glucose cotransporter 2 inhibitors (MD: -0.67 mmol/L, P=0.03).

Conclusions

DPP4 inhibitors may significantly reduce glycemic variability compared to other oral anti-diabetic drugs, as evidenced by MAGE in T2DM patients with no concurrent insulin treatment.

Systematic review registration

INPLASY, registration number: INPLASY2021120113.
Codon Usage is Influenced by Compositional Constraints in Genes Associated with Dementia
Authors: Alqahtani Taha , Khandia Rekha , Puranik Nidhi , Alqahtani Ali M. , Alghazwani Yahia , Alshehri Saad Ali , Chidambaram Kumarappan , Kamal Mohammad Amjad
Published: August 2022

Dementia is a clinical syndrome characterized by progressive cognitive decline, and the symptoms could be gradual, persistent, and progressive. In the present study, we investigated 47 genes that have been linked to dementia. Compositional, selectional, and mutational forces were seen to be involved. Nucleotide components that influenced A- and GC-affected codon usages bias at all three codon positions. The influence of these two compositional constraints on codon usage bias (CUB) was positive for nucleotide A and negative for GC. Nucleotide A also experienced the highest mutational force, and GC-ending codons were preferred over AT-ending codons. A high bias toward GC-ending codons enhances the gene expression level, evidenced by the positive association between CAI- and GC-ending codons. Unusual behavior of the TTG codon showing an inverse relationship with the GC-ending codon and negative influence of gene expression, behavior contrary to all other GC-ending codons, shows an operative selectional force. Furthermore, parity analysis, higher translational selection value, preference of GC-ending codons over AT-ending codons, and association of gene length with gene expression refer to the dominant role of selection pressure with compositional constraint and mutational force-shaping codon usage.
The Emergence of Rod-Cone Cellular Interaction
Authors: Aït-Ali Najate , Léveillard Thierry
Published: August 2022

We studied the origin of rod-derived cone viability factor (RdCVF) during evolution. In mammals, the nucleoredoxin-like 1 gene (NXNL1) produces a truncated thioredoxin-like protein, RdCVF, by intron retention in rod photoreceptors of the retina. This protein prevents the secondary cone degeneration in animal models of rod-cone degeneration. Extracellular RdCVF binds to a complex at the surface of the cones, composed of the basigin-1, a photoreceptor specific alternative splicing product of the basigin gene, and GLUT1, the glucose transporter. RdCVF accelerates glucose uptake allosterically. Glucose is either metabolized by aerobic glycolysis to sustain cone outer segment renewal or by the pentose phosphate pathway to support redox power to the thioredoxin RdCVFL. RdCVF signaling predates the appearance of the eye and evolved through two alternative splicing events. RdCVF signaling is observed first in hydra where it regulates an unknown signaling. A scallop RdCVF protein is produced by ciliated photoreceptors of the retina and binds its receptor, BSG1, the first occurrence of RdCVF/BSG1 signaling. In the lamprey, RdCVF metabolic signaling between rod and cones is fully operational. In the mouse, the production of BSG1 is regulated through alternative splicing. This signaling was extended to other regions of the brain, via its paralogue NXNL2.
YT521-B homology domain family proteins as N6-methyladenosine readers in tumors
Authors: Yang Heng , Chiang Chengyao , Luo Qinhong , Chen Chunlan , Huang Junrong , Zhu Lizhi , Zheng Duo
Published: August 2022

N6-methyladenosine (m6A) is the most abundant internal chemical modification of eukaryotic mRNA and plays diverse roles in gene regulation. The m6A modification plays a significant role in numerous cancer types, including kidney, stomach, lung, bladder tumors, and melanoma, through varied mechanisms. As direct m6A readers, the YT521-B homology domain family proteins (YTHDFs) play a key role in tumor transcription, translation, protein synthesis, tumor stemness, epithelial–mesenchymal transition (EMT), immune escape, and chemotherapy resistance. An in-depth understanding of the molecular mechanism of YTHDFs is expected to provide new strategies for tumor treatment. In this review, we provide a systematic description of YTHDF protein structure and its function in tumor progression.
3D structures inferred from cDNA clones identify the CD1D-Restricted γδ T cell receptor in dromedaries
Authors: Linguiti Giovanna , Tragni Vincenzo , Pierri Ciro Leonardo , Massari Serafina , Lefranc Marie-Paule , Antonacci Rachele , Ciccarese Salvatrice
Published: August 2022

The Camelidae species occupy an important immunological niche within the humoral as well as cell mediated immune response. Although recent studies have highlighted that the somatic hypermutation (SHM) shapes the T cell receptor gamma (TRG) and delta (TRD) repertoire in Camelus dromedarius, it is still unclear how γδ T cells use the TRG/TRD receptors and their respective variable V-GAMMA and V-DELTA domains to recognize antigen in an antibody-like fashion. Here we report about 3D structural analyses of the human and dromedary γδ T cell receptor. First, we have estimated the interaction energies at the interface within the human crystallized paired TRG/TRD chains and quantified interaction energies within the same human TRG/TRD chains in complex with the CD1D, an RPI-MH1-LIKE antigen presenting glycoprotein. Then, we used the human TRG/TRD-CD1D complex as template for the 3D structure of the dromedary TRG/TRD-CD1D complex and for guiding the 3D human/dromedary comparative analysis. The choice of mutated TRG alternatively combined with mutated TRD cDNA clones originating from the spleen of one single dromedary was crucial to quantify the strength of the interactions at the protein-protein interface between the paired C. dromedarius TRG and TRD V-domains and between the C. dromedarius TRG/TRD V-domains and CD1D G-domains. Interacting amino acids located in the V-domain Complementarity Determining Regions (CDR) and Framework Regions (FR) according to the IMGT unique numbering for V-domains were identified. The resulting 3D dromedary TRG V-GAMMA combined with TRD V-DELTA protein complexes allowed to deduce the most stable gamma/delta chains pairings and to propose a candidate CD1D-restricted γδ T cell receptor complex.
Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis
Authors: Kokubo Kota , Onodera Atsushi , Kiuchi Masahiro , Tsuji Kaori , Hirahara Kiyoshi , Nakayama Toshinori
Published: August 2022

Type 2 helper T (Th2) cells, a subset of CD4+T cells, play an important role in the host defense against pathogens and allergens by producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, to trigger inflammatory responses. Emerging evidence reveals that Th2 cells also contribute to the repair of injured tissues after inflammatory reactions. However, when the tissue repair process becomes chronic, excessive, or uncontrolled, pathological fibrosis is induced, leading to organ failure and death. Thus, proper control of Th2 cells is needed for complete tissue repair without the induction of fibrosis. Recently, the existence of pathogenic Th2 (Tpath2) cells has been revealed. Tpath2 cells produce large amounts of Th2 cytokines and induce type 2 inflammation when activated by antigen exposure or tissue injury. In recent studies, Tpath2 cells are suggested to play a central role in the induction of type 2 inflammation whereas the role of Tpath2 cells in tissue repair and fibrosis has been less reported in comparison to conventional Th2 cells. In this review, we discuss the roles of conventional Th2 cells and pathogenic Th2 cells in the sequence of tissue inflammation, repair, and fibrosis.