bluuebunny/crossref_metadata_2025 huggingface dataset:
PANDEMİ DÖNEMİNDE ÜNİVERSİTE ÖĞRENCİLERİNİN ÇEVRİMİÇİ ÖĞRENMEYE HAZIRBULUNUŞLUKLARININ VE UZAKTAN EĞİTİME İLİŞKİN DENEYİMLERİNİN DEĞERLENDİRİLMESİ
Authors: ÜNAL Nursemin , ŞANLIER Nevin , ŞENGİL Ahmet
Published: January 2021

COVID-19 pandemisi, eğitim alanında teknolojinin kullanımını zorunlu hale getirmiş, uzaktan eğitim ve çevrimiçi öğrenme kavramlarını tekrar gündeme getirmiştir. Tanımlayıcı tipteki bu araştırmanın evrenini, bir vakıf üniversitesinin öğrencileri oluşturdu. Online anket ile öğrencilere veri toplama formları ulaştırıldı, katılmaya gönüllü olan ve formu eksiksiz dolduran 435 öğrencinin verileri ile çalışma tamamlandı. Veriler, Öğrenci Tanıtıcı Bilgi Formu ve Çevrimiçi Öğrenme Hazır Bulunuşluk Ölçeği (ÇÖHBÖ) kullanılarak toplandı. Öğrencilerin yarıya yakını cep telefonu ve bilgisayar sahibi olduğunu, ancak uzaktan eğitim sürecinde internet bağlantı sorunu yaşadıklarını belirtti. Öğrencilerin büyük kısmı (%67.40) uzaktan eğitimin tekrar etme olanağı sunduğunu belirtirken, çevrimiçi öğrenme hazırbulunuşluk düzeylerinin iyi olduğu (62.46±14.97 puan) değerlendirildi. Lisansüstü öğrencilerinin özgüdümlü öğrenme, öğrenen kontrolü ve motivasyonları alt boyutlarından yüksek puan aldığı tespit edildi. Ayrıca, tüm teknolojik aletlere ve sorunsuz internet bağlantısına sahip olanların çevrimiçi öğrenme hazırbulunuşluk ve alt boyut puanlarının daha yüksek olduğu saptandı. Uzaktan ve çevrimiçi öğrenmenin amacına ulaşabilmesi için, öğrencilerin hazırbulunuşluklarının değerlendirilmesi, öğrenci popülasyonu göz önünde bulundurularak eğitim planlaması yapılması gerekmektedir.
ADAPTATION OF THE DECISIONAL BALANCE AND SELF-EFFICACY SCALES FOR SEXUAL ABSTINENCE TO TURKISH: A VALIDITY AND RELIABILITY STUDY
Authors: KARATANA Özlem , ERGÜN Ayşe , BEYHAN Abdullah
Published: January 2021

The aim of this study is to make Turkish adaptation and psychometric analysis of the Decisional Balance Scale for Sexual Abstinence (DBSSA) and Self-Efficacy Scale for Sexual Abstinence (SESSA) developed in line with the Transtheoretical Model (TTM). DBSSA and SESSA were administered to total of 482 students, and 50 students were retested two weeks later. The validity of the scale was evaluated by; factor analysis, content and construct validity analysis while reliability was evaluated by internal consistency and test-retest. While content validity of scale was evaluated by receiving opinions from 12 experts, internal consistency, item analysis and test-retest results were evaluated via Cronbach alpha reliability coefficient and Pearson correlation analysis, respectively. The DBSSA content validity index was found as 0.97 and the SESSA content validity index was found as 1, and it was determined that there was a consensus among experts. Cronbach alpha reliability coefficient was found to be; 0,61 for pros/internal, 0.77 for pros/external, and 0.76 for cons among DBSSA subscales, while 0.88 for the SESSA. The test-retest reliability correlation was 0.70 for pros/internal, 0.70 for pros/external, and 0.80 for cons while 0.85 for SESSA. DBSSA and SESSA were found to be suitable, valid and reliable for Turkish culture.
59 YAŞ VE ÜZERİ KADINLARIN YAŞAM ŞEKİLLERİ İLE ÜRİNER İNKONTİNANS ARASINDAKİ İLİŞKİ
Authors: BAYIR Berna , SERCAN Aylin , YAMAN Esmahan , ÇELİK Gökçen , YILMAZ Sevim , BEŞYAPRAK Tuğba , KUTKAN Zeynep
Published: January 2021

Bu araştırmanın amacı 59 yaş ve üzeri kadınların yaşam şekilleri ile üriner inkontinans (Üİ) arasındaki ilişkiyi belirlemektir. Araştırma tanımlayıcı araştırma türlerinden kesitsel tipte bir araştırmadır. Veriler 59 yaş üzeri 240 kadın bireyden toplandı. Verilerin toplanmasında Sosyo-Demografik Özellikler formu ve İnkontinans Davranış Belirleme Formu kullanıldı. Veri analizi için IBM SPSS 20.0 paket programı kullanıldı. P< 0,05 olması istatistiksel olarak anlamlı kabul edildi. Araştırmaya katılan bireylerin çoğunlukla (%53,3) 59-64 yaş grubu aralığında olduğu görüldü. Üİ sorununu artıran faktörlere bakıldığında yaş ortalaması yüksek olan bireylerde, idrar yolu enfeksiyonu geçiren 89 bireyde ve jinekolojik bir ameliyat geçiren bireylerin tamamında inkontinans sorunuyla karşılaşıldığı görüldü. Bu sorunu yaşayan bireylerin %100’ünün kegel egzersizini hiç duymamış olduğu belirlendi. Araştırmaya göre Üİ ile bireysel ve jinekolojik özelikler karşılaştırıldığında, Üİ’nin; yaş, ilk adet yaşı, idrar söktürücü ilaç kullanma durumu, idrar yolu enfeksiyonunun varlığı ve jinekolojik ameliyat öyküsünün bulunması durumuyla ilişkili olduğu görülmüştür. Günlük alışkanlıklar göz önüne alındığında, gün içerisinde aşırı sıvı alımı ve kegel egzersizi yapma sıklığının, ayrıca gebeliğe yönelik özelliklerden ilk doğum yaşı, doğum sayısı, doğum şekli ve çoğul gebelik durumu gibi faktörlerin etkili olduğu belirlenmiştir. Buna yönelik yapılan uygulamaların yetersiz kaldığı, yeni eğitim planlarının oluşturulması gerektiği söylenebilir.
MORPHOMETRIC COMPARISON OF DIFFERENT RADIAL HEAD TYPES
Authors: ŞENOL Deniz , ÇAVUŞ Fatih , ÇEVİRGEN Furkan , ARPACI Muhammed Furkan , ÖZBAĞ Davut
Published: January 2021

The aim of this study is to determine morphometric measurements difference of radial head (RH) types. 49 dry radial bones were included in the study. After determining the types of radius, morphometric measurements were made with digital calliper. The parameters were determined as the length of radius, height of the radius, transverse diameter of RH, anterior-posterior diameter of RH, radial tuberosity transverse diameter and height, length and transverse diameter of ulnar notch. As the result of RH classification, it has been determined that; 20 bones had irregular, 15 bones had oval and 14 bones had round type. In order to on all group average; radius length of RH, the height of RH, transverse diameter of RH, anteroposterior diameter of RH were calculated as 207.99±21.97 mm, 9.45±1.68 mm, 19.94±3.15 mm, 20.20±3.09 mm respectively. In order to on all group aver-age; transverse diameter of radial tuberosity, height of radial tuberosity, the height of ulnar notch, transverse diameter of ulnar notch were 12.07±1.3 mm, 25.36±2.78 mm, 13.86±1.56 mm, 5.27±0.8 mm respectively. Ac-cording to the results of One Way Anova analysis, no statistically significant difference was found between RH types (p>0.05). No statistically significant difference was found between RH types in all parameters.
Loss Assessment of the Axial-Gap Size Effect in a Low-Pressure Turbine
Authors: Oettinger Marcel , Mimic Dajan , Henke Michael , Schmunk Oleg , Seume Jorg
Published: January 2021

The aim of this work is the decomposition, quantification, and analysis of losses related to the axial-gap size effect. Both experimental data and unsteady RANS calculations are investigated for axial gaps equal to 20%, 50% and 80% of the stator axial chord. A framework for identifying sources of loss typical in turbomachinery is derived and utilized for the low-pressure turbine presented. The analysis focuses on the dependency of these losses on the axial-gap variation. It is found that two-dimensional profile losses increase for smaller gaps due to higher wake-mixing losses and unsteady wake-blade interaction. Losses in the end-wall regions, however, decrease for smaller gaps. The total system efficiency can be described by a superposition of individual loss contributions, the optimum of which is found for the smallest gap investigated.

It is concluded that these loss contributions are characteristic for the medium aspect-ratio airfoils and operating conditions investigated. This establishes a deeper physical understanding for future investigations into the axial-gap size effect and its interdependency with other design parameters.
Causal Analysis of Health Interventions and Environments for Influencing the Spread of COVID-19 in the United States of America
Authors: Li Zhouxuan , Xu Tao , Zhang Kai , Deng Hong-Wen , Boerwinkle Eric , Xiong Momiao
Published: January 2021

Given the lack of potential vaccines and effective medications, non-pharmaceutical interventions are the major option to curtail the spread of COVID-19. An accurate estimate of the potential impact of different non-pharmaceutical measures on containing, and identify risk factors influencing the spread of COVID-19 is crucial for planning the most effective interventions to curb the spread of COVID-19 and to reduce the deaths. Additive model-based bivariate causal discovery for scalar factors and multivariate Granger causality tests for time series factors are applied to the surveillance data of lab-confirmed Covid-19 cases in the US, University of Maryland Data (UMD) data, and Google mobility data from March 5, 2020 to August 25, 2020 in order to evaluate the contributions of social-biological factors, economics, the Google mobility indexes, and the rate of the virus test to the number of the new cases and number of deaths from COVID-19. We found that active cases/1,000 people, workplaces, tests done/1,000 people, imported COVID-19 cases, unemployment rate and unemployment claims/1,000 people, mobility trends for places of residence (residential), retail and test capacity were the popular significant risk factor for the new cases of COVID-19, and that active cases/1,000 people, workplaces, residential, unemployment rate, imported COVID cases, unemployment claims/1,000 people, transit stations, mobility trends (transit), tests done/1,000 people, grocery, testing capacity, retail, percentage of change in consumption, percentage of working from home were the popular significant risk factor for the deaths of COVID-19. We observed that no metrics showed significant evidence in mitigating the COVID-19 epidemic in FL and only a few metrics showed evidence in reducing the number of new cases of COVID-19 in AZ, NY and TX. Our results showed that the majority of non-pharmaceutical interventions had a large effect on slowing the transmission and reducing deaths, and that health interventions were still needed to contain COVID-19.
Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure
Authors: Filipović Nenad , Ušjak Dušan , Milenković Marina T. , Zheng Kai , Liverani Liliana , Boccaccini Aldo R. , Stevanović Magdalena M.
Published: January 2021

Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), and Kocuria rhizophila (ATCC 9341), as well as Escherichia coli (ATCC 8739), Salmonella Abony (NCTC 6017), Klebsiella pneumoniae (NCIMB 9111) and Pseudomonas aeruginosa (ATCC 9027), and the standard yeast strain Candida albicans (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70–300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.
Inducing Non-genetically Modified Induced Embryonic Sertoli Cells Derived From Embryonic Stem Cells With Recombinant Protein Factors
Authors: Xu Chenze , Mohsin Ali , Luo Yanxia , Xie Lili , Peng Yan , Wang Qizheng , Ahmed Waqas , Hang Haifeng , Zhuang Yingping , Guo Meijin
Published: January 2021

Embryonic Sertoli cells (eSCs) possess multiple supporting functions and research value in gonadal development and sex determination. However, the limitation of acquiring quality eSCs had hindered the further application. Herein, we successfully derived non-genetically modified (non-GM)-induced embryonic Sertoli-like cells (eSLCs) from mouse embryonic stem cells (ESCs) with a TM4 cell-derived conditioned medium containing recombinant endogenous protein factorsSry,Sox9,Sf1,Wt1,Gata4, andDmrt1. These eSLCs were determined through morphology; transcriptional expression levels of stage-specific, epithelial, and mesenchymal marker genes; flow cytometry, immunofluorescence; and immunocytochemistry and functionally determined by coculture with spermatogonia stem cells. Results indicated that these eSLCs performed similarly to eSCs in specific biomarkers and expression of marker genes and supported the maturation of spermatogonia. The study induced eSLCs from mouse ESCs by defined protein factors. However, the inducing efficiency of the non-GM method was still lower than that of the lentiviral transduction method. Thus, this work established a foundation for future production of non-GM eSLCs for clinical applications and fundamental theory research.
Deficiency of Rbpj Leads to Defective Stress-Induced Hematopoietic Stem Cell Functions and Hif Mediated Activation of Non-canonical Notch Signaling Pathways
Authors: Lakhan Ram , Rathinam Chozha V.
Published: January 2021

Deregulated notch signaling has been associated with human pathobiology. However, functions of notch pathways in hematopoiesis remain incompletely understood. Here, we ablated canonical notch pathways, through genetic deletion of Rbpj, in hematopoietic stem cells (HSCs). Our data identified that loss of canonical notch results in normal adult HSC pool, at steady state conditions. However, HSC maintenance and functions in response to radiation-, chemotherapy-, and cytokine- induced stress were compromised in the absence of canonical notch. Rbpj deficient HSCs exhibit decreased proliferation rates and elevated expression of p57Kip2. Surprisingly, loss of Rbpj resulted in upregulation of key notch target genes and augmented binding of Hes1 to p57 and Gata2 promoters. Further molecular analyses identified an increase in notch activity, elevated expression and nuclear translocation of Hif proteins, and augmented binding of Hif1α to Hes1 promoter in the absence of Rbpj. These studies, for the first time, identify a previously unknown role for non-canonical notch signaling and establish a functional link between Hif and Notch pathways in hematopoiesis.
Effect of Addition of Thyroxine in the Treatment of Graves’ Disease: A Systematic Review
Authors: Li Jun , Bai Litao , Wei Fan , Wei Maoying , Xiao Yao , Yan Weitian , Wei Junping
Published: January 2021

Graves’ disease is the most common cause of hyperthyroidism. Antithyroid drugs, radioiodine ablation, and surgery are the main treatments. Research has demonstrated that adding thyroxine to antithyroid therapy can improve the remission rate, and many similar studies have been conducted subsequently. The purpose of this systematic review was to investigate whether adding thyroxine to various treatments for Graves’ disease has a clinical benefit in remission/relapse rate, stable thyroid function, occurrence of Graves’ ophthalmopathy, etc. A total of 27 studies were included, and the risk of research bias was moderate to high. We discuss the role of thyroxine both in pharmacological and non-pharmacological therapeutic regimens. Overall, the available evidence does not support the indiscriminate addition of thyroxine to various treatments for Graves’ disease, especially in combination with oral antithyroid drugs. Further clinical studies are required to explore the indications of thyroxine addition in the treatment of Graves’ disease.
Biodiversity Patterns of Macroinvertebrate Assemblages in Natural and Artificial Lentic Waters on an Oceanic Island
Authors: Lamelas-López Lucas , Borges Paulo A. V. , Serrano Laura , Gonçalves Vitor , Florencio Margarita
Published: January 2021

The Azorean islands have been historically affected by human activities, mainly due to the combined effects of habitat degradation and fragmentation, and the introduction of exotic species. We here aim to analyze the role of environmental characteristics and spatial descriptors in supporting regional biodiversity of macroinvertebrates by considering natural ponds and artificial tanks. After the monthly variation of macroinvertebrate assemblages was assessed in three temporary and two permanent ponds in the Azorean island of Terceira during a complete inundation-desiccation annual cycle, the assemblage differences of 12 ponds (three temporary and nine permanent ponds) and 8 closely-located artificial tanks were analyzed across a range of landscape disturbances. Macroinvertebrate assemblages were found to differ according to hydroperiod and sampled months. Although the former explained the highest variance, macroinvertebrate differentiation by hydroperiod was also dependent on the study month. Our results also revealed a consistent monthly pattern of species replacement. However, the contribution of nestedness to the macroinvertebrate β-diversity was notable when temporary ponds were close to desiccation, probably indicating a deterministic loss of species due to the impoverished water conditions of the ponds facing desiccation. When the macroinvertebrate assemblages were analyzed in relation to physico-chemical variations and spatial descriptors, the artificial tanks were not clearly segregated from the natural ponds, and only differentiated by pH differences. In contrast, those natural ponds exhibiting high concentrations of total phosphorous (likely signs of anthropization) also discriminated the ordination of ponds in a distance-based redundancy analysis, and showed impoverished assemblages in comparison with well-preserved ponds. The macroinvertebrate assemblages of the natural ponds showed a significant spatial pattern, but this spatial influence was not significant when tanks and ponds were considered together. Our results suggest that tanks may act as possible reservoirs of biodiversity during the desiccation period of temporary ponds, but are unable to establish successful populations. These fishless permanent tanks can complement the conservation of a biodiversity that is largely maintained by the pristine high-altitude natural ponds. The establishment of a guideline for conservation management that also considers the artificial tanks is necessary to benefit the local and regional Azorean macroinvertebrate diversity.
Reduced Reproductive Success of Western Baltic Herring (Clupea harengus) as a Response to Warming Winters
Authors: Polte Patrick , Gröhsler Tomas , Kotterba Paul , von Nordheim Lena , Moll Dorothee , Santos Juan , Rodriguez-Tress Paco , Zablotski Yury , Zimmermann Christopher
Published: January 2021

Shallow estuaries, bays, and lagoons are generally considered hot spots of ocean productivity that often adjust rapidly to seasonal variations in atmospheric temperatures. During spring when biological reproductive processes begin in the temperate zones, regional climate variability can be immense and uncovering a non-linear biological response, such as fish recruitment to changing temperature regimes might be challenging. Using herring as a paradigm for a response of coastal spring productivity to regional climate drivers, we demonstrated how the annual timing of spawning periods can significantly affect the reproductive success of spring-spawning herring (Clupea harengus) in the western Baltic Sea. An investigation of spawning phenology in consecutive years indicated a temperature threshold range of 3.5–4.5°C triggering initial spawning in the coastal zone. Based on this finding, we analyzed the timing of larval hatching peaks, larval survival and recruitment to the adult population relative to multi-decadal time-series of seasonal sea-surface temperatures. The results revealed that the late seasonal onset of cold periods the corresponding elongation of the period where larvae hatch from the eggs and early larval hatching peaks significantly reduced larval production in a coastal nursery area and finally lead to a reduced abundance of juveniles in the entire distribution area. Using a combination of field research and time series analysis, we presented precedence for shifting regional winter regimes providing a present-day stressor to reproductive capacity of a central component of the coastal food web.
Antisynthetase Syndrome-Associated Interstitial Lung Disease: Monitoring of Immunosuppressive Treatment Effects by Chest Computed Tomography
Authors: Korsten Peter , Rademacher Jan-Gerd , Riedel Linn , Schnitzler Eva-Maria , Olgemöller Ulrike , Seitz Cornelia Sabine , Schmidt Jens , Larsen Jörg , Vasko Radovan
Published: January 2021

Background: Antisynthetase syndrome (ASyS) is a rare autoimmune disease characterized by inflammatory myopathy, arthritis, fever, and interstitial lung disease (ILD). Pulmonary involvement in ASyS significantly increases morbidity and mortality and, therefore, requires prompt and effective immunosuppressive treatment. Owing to the rarity of ASyS, limited data exists on progression and prognosis of ILD under immunosuppression.

Objectives: The objective of the study was to evaluate the radiological progression and outcome measures of ILD with immunosuppressive therapy in patients with ASyS.

Methods: Twelve patients with ASyS-associated ILD (ASyS-ILD) were included. Demographic and clinical data, including organ involvement, pulmonary function tests (PFT), laboratory parameters, imaging studies, and treatment regimens were retrospectively analyzed from routinely collected data. The extent of ground glass opacities, fibrotic changes and honeycombing was analyzed and scored using high-resolution chest computed tomography (HRCT) scans. HRCT findings were compared between baseline and follow-up examinations. In addition, patients were stratified depending on whether they had received rituximab (RTX) or not.

Results: Pulmonary function tests revealed stable lung function and follow-up HRCT scans showed an improvement of radiological alterations in the majority of ASyS patients under immunosuppressive therapy. We did not detect significant differences between the RTX- and non-RTX-treated groups, but the RTX-treated patients more frequently had myositis and relapsing disease.

Conclusions: Radiographic alterations in ASyS-associated ILD respond to immunosuppressive treatment. RTX is a feasible treatment option with similar clinical and radiographic outcomes in patients with relapsing disease and clinically apparent myositis.
Phenotypic Characterization and Whole-Genome Analysis of a Novel Bacteriophage HCF1 Infecting Citrobacter amalonaticus and C. freundii
Authors: Kumar Prince , Meghvansi Mukesh K. , Kamboj Dev V.
Published: January 2021

Citrobacterspecies often occur in sewage, food, soil, wastewater, and in the intestinal tract of animals and humans.Citrobacterspp. cause urinary tract infections (UTIs) and infantile meningitis in humans. Due to the presence of plasmid-encoded resistance genes,Citrobacterspp. are often resistant to many antibiotics. In this study,Citrobactervirus HCF1, a novel virulent bacteriophage capable of killingCitrobacter amalonaticusandCitrobacter freundii, was isolated from the sewage water. The isolated bacteriophage was characterized with respect to transmission electron microscopy, one-step growth curve, host range,in vitroefficacy, storage stability, and environmental stress tolerance. The one-step growth curve analysis revealed that the latent period of HCF1 was 30 min and the estimated burst size was 121 plaque-forming units (PFU) per bacterial cell. Host range testing indicated that the HCF1 was specific to theCitrobactergenus.In vitroefficacy assay in the effluent of an anaerobic biodigester showed that the HCF1 completely eliminated the host within 4 and 5 h at MOI:100 and MOI:10, respectively, thereby indicating its potential for combatingC. amalonaticusinfections. The isolated bacteriophage is considerably stable and tolerant to environmental stress. Furthermore, the complete genome of HCF1 was sequenced using Oxford Nanopore sequencing and the data were subjected to detailed bioinformatic analyses. NCBI-BLASTn analysis revealed that the HCF1 genome had a query coverage of 15–21% and a maximum similarity of 77.27–78.49% with 11 bacteriophages of theDrexlerviridaefamily. Detailed bioinformatic analysis of the genome profile suggests that HCF1 is a novelT1svirusbelonging to theTempevirinaesubfamily of theDrexlerviridaefamily.
A Revisit to the Research Updates of Drugs, Vaccines, and Bioinformatics Approaches in Combating COVID-19 Pandemic
Authors: Sumon Tofael Ahmed , Hussain Md. Ashraf , Hasan Md. Tawheed , Hasan Mahmudul , Jang Won Je , Bhuiya Eleus Hussain , Chowdhury Abdullah Al Mamun , Sharifuzzaman S. M. , Brown Christopher Lyon , Kwon Hyun-Ju , Lee Eun-Woo
Published: January 2021

A new strain of coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic was first detected in the city of Wuhan in Hubei province, China in late December 2019. To date, more than 1 million deaths and nearly 57 million confirmed cases have been recorded across 220 countries due to COVID-19, which is the greatest threat to global public health in our time. Although SARS-CoV-2 is genetically similar to other coronaviruses, i.e., SARS and Middle East respiratory syndrome coronavirus (MERS-CoV), no confirmed therapeutics are yet available against COVID-19, and governments, scientists, and pharmaceutical companies worldwide are working together in search for effective drugs and vaccines. Repurposing of relevant therapies, developing vaccines, and using bioinformatics to identify potential drug targets are strongly in focus to combat COVID-19. This review deals with the pathogenesis of COVID-19 and its clinical symptoms in humans including the most recent updates on candidate drugs and vaccines. Potential drugs (remdesivir, hydroxychloroquine, azithromycin, dexamethasone) and vaccines [mRNA-1273; measles, mumps and rubella (MMR), bacille Calmette-Guérin (BCG)] in human clinical trials are discussed with their composition, dosage, mode of action, and possible release dates according to the trial register of US National Library of Medicines (clinicaltrials.gov), European Union (clinicaltrialsregister.eu), and Chinese Clinical Trial Registry (chictr.org.cn) website. Moreover, recent reports on in silico approaches like molecular docking, molecular dynamics simulations, network-based identification, and homology modeling are included, toward repurposing strategies for the use of already approved drugs against newly emerged pathogens. Limitations of effectiveness, side effects, and safety issues of each approach are also highlighted. This review should be useful for the researchers working to find out an effective strategy for defeating SARS-CoV-2.
Fatty Acid Synthase Correlates With Prognosis-Related Abdominal Adipose Distribution and Metabolic Disorders of Clear Cell Renal Cell Carcinoma
Authors: Xu Wenhao , Hu Xiaoxin , Anwaier Aihetaimujiang , Wang Jun , Liu Wangrui , Tian Xi , Zhu Wenkai , Ma Chunguang , Wan Fangning , Shi Guohai , Qu Yuan-Yuan , Zhang Hailiang , Ye Dingwei
Published: January 2021

Purpose: Lipid metabolism reprogramming is a major pathway in tumor evolution. This study investigated fatty acid synthase (FASN) mRNA expression in anthropometric adipose tissue and elucidated the prognostic value and potential mechanism of clear cell renal cell carcinoma (ccRCC).

Materials and Methods: Transcription profiles were obtained from 533 ccRCC samples in The Cancer Genome Atlas (TCGA) cohorts. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry were performed to detect FASN expression in 380 paired ccRCC and normal tissues from the Fudan University Shanghai Cancer Center (FUSCC). Visceral adipose tissue (VAT) and subcutaneous adipose tissue were at the level of the umbilicus as measured by magnetic resonance imaging (MRI). Non-targeted metabolomics and in vitro experiments were used to reveal the biological functions of FASN.

Results: Increased FASN expression was significantly relevant to advanced T, N, and American Joint Committee on Cancer (AJCC) stages (p < 0.01) and significantly correlated to poor progression-free survival (PFS) and overall survival (OS) of 913 ccRCC patients in FUSCC and TCGA cohorts. Pearson's correlation coefficient indicated that FASN amplification was positively correlated to VAT% (r = 0.772, p < 0.001), which significantly correlated to poor PFS (HR = 2.066, p = 0.028) and OS (HR = 2.773, p = 0.023) in the FUSCC cohort. Transient inhibition or overexpression of FASN significantly regulated A498 and 786O cell proliferation and migration by regulating epithelial–mesenchymal transition. Inhibition of FASN led to a higher apoptotic rate and decreased lipid droplet formation compared with normal control in ccRCC cells. Non-targeted metabolomics showed that decreased de novo lipogenesis might be required to sustain an elevation of glycolytic activity in 786O cells by regulating galactinol, dl-lactate, N-acetylaspartylglutamate, and sucrose, thereby participating in carcinogenesis and progression of ccRCC.

Conclusion: This study demonstrated that FASN expression is positively related to aggressive cell proliferation, migration, apoptosis, and lipid droplet formation and regulates metabolic disorders of the ccRCC microenvironment. Additionally, elevated FASN mRNA expression is significantly correlated to the abdominal obesity distribution, especially VAT%, which is a significant predictor of a poor prognosis for ccRCC patients.
Human Dental Pulp Stem Cells Display a Potential for Modeling Alzheimer Disease-Related Tau Modifications
Authors: Gazarian Karlen , Ramirez-Garcia Luis , Tapía Orozco Luis , Luna-Muñoz José , Pacheco-Herrero Mar
Published: January 2021

We present here the first description of tau in human dental pulp stem cells (DPSCs) evidenced by RT-PCR data on expression of the gene MAPT and by immunocytochemical detection of epitopes by 12 anti-tau antibodies. The tau specificity of eight of these antibodies was confirmed by their affinity to neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) postmortem brain samples. We therefore used DPSCs and AD brain samples as a test system for determining the probability of the involvement of tau epitopes in the mechanisms converting tau into NFT in AD. Three antibodies to non-phosphorylated and seven antibodies to phosphorylated epitopes bound tau in both DPSCs and AD NFTs, thus suggesting that their function was not influenced by inducers of formation of NFTs in the AD brain. In contrast, AT100, which recognizes a hyperphosphorylated epitope, did not detect it in the cytoplasm of DPSCs but detected it in AD brain NFTs, demonstrating its AD diagnostic potential. This indicated that the phosphorylation/conformational events required for the creation of this epitope do not occur in normal cytoplasm and are a part of the mechanism (s) leading to NFT in AD brain. TG3 bound tau in the cytoplasm and in mitotic chromosomes but did not find it in nuclei. Collectively, these observations characterize DPSCs as a novel tau-harboring neuronal lineage long-term propagable in vitro cellular system for the normal conformational state of tau sites, detectable by antibodies, with their state in AD NFTs revealing those involved in the pathological processes converting tau into NFTs in the course of AD. With this information, one can model the interaction of tau with inducers and inhibitors of hyperphosphorylation toward NFT-like aggregates to search for drug candidates. Additionally, the clonogenicity of DPSCs provides the option for generation of cell lineages with CRISPR-mutagenized genes of familial AD modeling.
Risk and Prognosis of Secondary Bladder Cancer After Radiation Therapy for Rectal Cancer: A Large Population-Based Cohort Study
Authors: Guan Xu , Wei Ran , Yang Runkun , Lu Zhao , Liu Enrui , Zhao Zhixun , Chen Haipeng , Yang Ming , Liu Zheng , Jiang Zheng , Wang Xishan
Published: January 2021

Background

Although radiation therapy (RT) improves local control for rectal cancer (RC), the long-term risks from RT, including development of a secondary malignancy, are controversial. The risk and prognosis of secondary bladder cancer (SBC) in RC patients undergoing RT have not been adequately studied. Our goal is to investigate the impact of RT on the risk of developing SBC and assess their survival outcomes.

Methods

This large population-based study included RC patients as their initial primary cancer from nine registries of the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015. The cumulative incidence of SBC was assessed by using Fine and Gray’s competing risk regression. The standardized incidence ratio (SIR) was used to compare the incidence of SBC in RC survivors to the US general population. The Kaplan-Meier method was used to evaluate the 10-year overall survival (OS) and 10-year cancer specific survival (CSS) for patients with SBC.

Results

Of 74,646 RC patients, 24,522 patients were treated with surgery and RT and 50,124 patients were treated with surgery alone. The incidence of SBC was 1.85% among patients who received RT and 1.24% among patients who did not. The incidence of SBC in RC patients who received RT was higher than the US general population (SIR, 1.35; 95% CI, 1.19-1.53, P<0.05), and decreased with increasing age at diagnosis, and increased with time since diagnosis. In competing risk regression analysis, undergoing RT was associated with a higher risk of SBC (hazard ratio [HR], 1.443, 95% confidence interval [CI], 1.209-1.720; P<0.001). The results of the dynamic SIR for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency, and was significantly related to the variations of age at RC diagnosis and decreased with time progress. The 10-year OS and CSS among SBC patients after RT were comparable to SBC patients after NRT.

Conclusion

Radiation was associated with an increased risk of developing SBC in RC patients, and special attention should be paid to the surveillance of these patients.
PET/CT in Multiple Myeloma: Beyond FDG
Authors: Matteucci Federica , Paganelli Giovanni , Martinelli Giovanni , Cerchione Claudio
Published: January 2021

Recent advances in the diagnosis and treatment of multiple myeloma (MM) have highlighted the importance of imaging methods, not only in the localization and extent of the disease but also in prognostic stratification and assessment of response to therapy. In this context, PET/CT, combining both morphological and functional information, is particularly useful in this pathology. The tracer mostly used is 18F-FDG, a glucose analog, which provides extremely accurate information with a sensitivity ranging from 80 to 100%. However, this tracer has some limitations, mostly related to the physiological uptake of FDG in the bone marrow and brain, which reduce its effectiveness. For this reason, some studies in the literature have evaluated the effectiveness of other PET tracers, which provide information on protein metabolism or the synthesis of metabolic plasma membranes, such as choline and methionine, as well as innovative radiopharmaceuticals, directed against receptors expressed by cells of myeloma, including tracers directed to the chemokine receptor. This review analyzes the characteristics and accuracy of non-FDG tracers in the management of patients with multiple myeloma.
Overview of Monogenic Forms of Hypertension Combined With Hypokalemia
Authors: Lu Yi-Ting , Fan Peng , Zhang Di , Zhang Ying , Meng Xu , Zhang Qiong-Yu , Zhao Lin , Yang Kun-Qi , Zhou Xian-Liang
Published: January 2021

Hypertension is an important risk factor in many conditions and creates a heavy burden of disease and mortality globally. Polygenic hypertension is the most common form; however, it is increasingly recognized that monogenic hypertension is not rare, especially in patients with electrolyte disorders. Single genetic alterations are associated with plasma volume expansion and catecholamines/sympathetic excess with simultaneously increased potassium excretion in the urine and potassium intracellular shift. Early-onset refractory hypertension and profound hypokalemia are characteristics of monogenic hypertension. However, accumulated evidence shows the existence of phenotypic heterogeneity in monogenic hypertension meaning that, even for mild symptoms, clinicians cannot easily exclude the possibility of monogenic hypertension. Genetic, epigenetic and non-genetic factors are all possible mechanisms influencing phenotypic diversity. Genetic sequencing is a precise and efficient method that can broaden the mutant gene spectrum of the disease and is very helpful for understanding the pathophysiology of monogenic hypertension. Genetic sequencing, along with biochemical tests and imaging modalities, is essential for the early diagnosis and targeted management of monogenic hypertension to avoid long-term catastrophic complications.
Creatinine Trends to Detect Ibuprofen-Related Maturational Adverse Drug Events in Neonatal Life: A Simulation Study for the ELBW Newborn
Authors: van Donge Tamara , Allegaert Karel , Pfister Marc , Smits Anne , van den Anker John
Published: January 2021

Background:Recognizing a change in serum creatinine concentrations is useful to detect a renal adverse drug reaction signal. Assessing and characterizing the nephrotoxic side-effects of drugs in extremely low birth weight (ELBW, ≤1000 g) neonates remain challenging due to the high variability in creatinine in this population. This study aims to investigate and quantify the impact of ibuprofen treatment on kidney function, reflected by serum creatinine.

Method:A recently developed dynamical model for serum creatinine was used to simulate creatinine profiles for typical, reference ELBW neonates with varying gestational and postnatal ages whilst being exposed to ibuprofen treatment.

Results:The increase of serum creatinine concentrations due to ibuprofen treatment is most apparent during the first week of life. The difference in serum creatinine values between ibuprofen-exposed vs. non-exposed neonates decreases with increasing postnatal age, independent of gestational age.

Conclusion:The difference in serum creatinine concentrations between ibuprofen-exposed vs. non-exposed neonates decreases with postnatal age, indicating an increased clearing capacity and resulting in a weak ibuprofen-related adverse drug reaction signal beyond early neonatal life.
Application of Laser Microirradiation in the Investigations of Cellular Responses to DNA Damage
Authors: Kong Xiangduo , Wakida Nicole M. , Yokomori Kyoko
Published: January 2021

Since the laser has been invented it has been highly instrumental in ablating different parts of the cell to test their functionality. Through induction of damage in a defined sub-micron region in the cell nucleus, laser microirradiation technique is now established as a powerful real-time and high-resolution methodology to investigate mechanisms of DNA damage response and repair, the fundamental cellular processes for the maintenance of genomic integrity, in mammalian cells. However, irradiation conditions dictate the amounts, types and complexity of DNA damage, leading to different damage signaling responses. Thus, in order to properly interpret the results, it is important to understand the features of laser-induced DNA damage. In this review, we describe different types of DNA damage induced by the use of different laser systems and parameters, and discuss the mechanisms of DNA damage induction. We further summarize recent advances in the application of laser microirradiation to study spatiotemporal dynamics of cellular responses to DNA damage, including factor recruitment, chromatin modulation at damage sites as well as more global damage signaling. Finally, possible future application of laser microirradiation to gain further understanding of DNA damage response will be discussed.
Integrin, Exosome and Kidney Disease
Authors: Shen An-Ran , Zhong Xin , Tang Tao-Tao , Wang Cui , Jing Jing , Liu Bi-Cheng , Lv Lin-Li
Published: January 2021

Integrins are transmembrane receptors that function as noncovalent heterodimers that mediate cellular adhesion and migration, cell to cell communication, and intracellular signaling activation. In kidney, latency associated peptide-transforming growth factor β (TGF-β) and soluble urokinase plasminogen activator receptor (suPAR) were found as the novel ligands of integrins that contribute to renal interstitial fibrosis and focal segmental glomerular sclerosis glomerulosclerosis (FSGS). Interestingly, recent studies revealed that integrins are the compositional cargo of exosomes. Increasing evidence suggested that exosomal integrin played critical roles in diverse pathophysiologic conditions such as tumor metastasis, neurological disorders, immunology regulation, and other processes. This review will focus on the biology and function of exosomal integrin, emphasizing its potential role in kidney disease as well as its implications in developing novel therapeutic and diagnosis approaches for kidney disease.
Sample Size Requirements for Applying Diagnostic Classification Models
Authors: Sen Sedat , Cohen Allan S.
Published: January 2021

Results of a comprehensive simulation study are reported investigating the effects of sample size, test length, number of attributes and base rate of mastery on item parameter recovery and classification accuracy of four DCMs (i.e., C-RUM, DINA, DINO, and LCDMREDUCED). Effects were evaluated using bias and RMSE computed between true (i.e., generating) parameters and estimated parameters. Effects of simulated factors on attribute assignment were also evaluated using the percentage of classification accuracy. More precise estimates of item parameters were obtained with larger sample size and longer test length. Recovery of item parameters decreased as the number of attributes increased from three to five but base rate of mastery had a varying effect on the item recovery. Item parameter and classification accuracy were higher for DINA and DINO models.
The Effects of Responsible Gambling Pop-Up Messages on Gambling Behaviors and Cognitions: A Systematic Review and Meta-Analysis
Authors: Bjørseth Benjamin , Simensen Josefine Oudmayer , Bjørnethun Aina , Griffiths Mark D. , Erevik Eilin K. , Leino Tony , Pallesen Ståle
Published: January 2021

Pop-up messages utilized by gambling operators are normally presented to gamblers during gambling sessions in order to prevent excessive gambling and/or to help in the appraisal of maladaptive gambling cognitions. However, the effect of such messages on gambling behavior and gambling cognitions has not previously been synthesized quantitatively. Consequently, a meta-analysis estimating the efficacy of pop-up messages on gambling behavior and cognitions was conducted. A systematic literature search with no time constraints was performed on Web of Science, PsychInfo, Medline, PsychNET, and the Cochrane Library. Search terms included “gambling,” “pop-up,” “reminder,” “warning message,” and “dynamic message.” Studies based on randomized controlled trials, quasi-experimental designs and pre-post studies reporting both pre- and post-pop-up data were included. Two authors independently extracted data using pre-defined fields including quality assessment. A total of 18 studies were included and data were synthesized using a random effects model estimating Hedges' g. The effects of pop-ups were g = 0.413 for cognitive measures (95% CI = 0.115–0.707) and g = 0.505 for behavioral measures (95% CI = 0.256–0.746). For both outcomes there was significant between-study heterogeneity which could not be explained by setting (laboratory vs. naturalistic) or sample (gambler vs. non-gamblers). It is concluded that pop-up messages provide moderate effects on gambling behavior and cognitions in the short-term and that such messages play an important role in the gambling operators' portfolio of responsible gambling tools.
Inflammatory Activities in Type 2 Diabetes Patients With Co-morbid Angiopathies and Exploring Beneficial Interventions: A Systematic Review
Authors: Nwadiugwu Martin C.
Published: January 2021

Background: Diabetes is a long-term condition that can be treated and controlled but do not yet have a cure; it could be induced by inflammation and the goal of managing it is to prevent additional co-morbidities and reduce glycemic fluctuations. There is a need to examine inflammatory activities in diabetes-related angiopathies and explore interventions that could reduce the risk for future outcome or ameliorate its effects to provide insights for improved care and management strategies.

Method: The study was conducted in Embase (1946–2020), Ovid Medline (1950–2020), and PubMed databases (1960–2020) using the PICO framework. Primary studies (randomized controlled trials) on type 2 diabetes mellitus and inflammatory activities in diabetes-related angiopathies were included. Terms for the review were retrieved from the Cochrane library and from PROSPERO using its MeSH thesaurus qualifiers. Nine articles out of 454 total hits met the eligibility criteria. The quality assessment for the selected study was done using the Center for Evidence-Based Medicine Critical Appraisal Sheet.

Results: Data analysis showed that elevated CRP, TNF-α, and IL-6 were the most commonly found inflammatory indicator in diabetes-related angiopathies, while increased IL-10 and soluble RAGE was an indicator for better outcome. Use of drugs such as salsalate, pioglitazone, simvastatin, and fenofibrate but not glimepiride or benfotiamine reported a significant decrease in inflammatory events. Regular exercise and consumption of dietary supplements such as ginger, hesperidin which have anti-inflammatory properties, and those containing prebiotic fibers (e.g., raspberries) revealed a consistent significant (p < 0.05) reduction in inflammatory activities.

Conclusion: Inflammatory activities are implicated in diabetes-related angiopathies; regular exercise, the intake of healthy dietary supplements, and medications with anti-inflammatory properties could result in improved protective risk outcome for diabetes patients by suppressing inflammatory activities and elevating anti-inflammatory events.