bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of dysregulated long noncoding RNA and associated mechanism in gastric cancer
Authors: Shao Liang , Ming Yanan , Zhou Zhaoming
Published: November 2020

BackgroundsGastric cancer (GC) is one of the most malignant epithelial tumors. The incidence of GC varies worldwide, and nearly half of the cases occur in Asian countries, especially in Japan and China. GC is the 3rd leading cause of cancer-related deaths in the world, and current prognosis of advanced GC remains dismal despite improvements in diagnosis and therapy. Our current study aimed to identify significant long noncoding RNAs with the prognostic potential and preliminarily to investigate the underlying mechanisms the identified long noncoding RNAs.MethodsWe retrieved articles reporting human LncRNA microarray in GC patients and pooled eligible studies for meta-analysis. GEO2R and Qigen’s IPA analysis was utilized for searching potential interacted molecules with differentially expressed LncRNA in GC. The expression of eligible LncRNA and molecules in GC were validated in public GC dataset by GEPIA website. And Kaplan Meier plots was employed to analyze the correlation between target molecules and prognosis of GC.ResultsThis study identified a variety of reports to investigate the expression of lncRNAs in GC development using high-throughput lncRNA detection. Eight of them were further verified with significant expression in GC tissues by using Gene Expression Profiling Interactive Analysis (GEPIA). Next, the molecular interactions with eight lncRNAs were further identified by using Qiagen’s IPA system. Simultaneously, differentially expressed genes (DEGs) of GC were also identified via the GEO2R online tool and datasets (GSE54129, GSE19826, and GSE79973). Finally, through Venn diagram analysis, our study found that IGF2BP3 and FOLR1 have strong relationship with lncRNAs H19 and PVT1 respectively in the background of stomach cancer. The expression of IGF2BP3 and FOLR1 in GC was further revealed to be correlate to a worsening prognosis for GC patients by Kaplan Meier plots. IGF2BP3 promotes the expression of H19 and PEG10, the down-regulation of which might improve the GC prognosis. FOLR1 is a crucial component of cell metabolism and DNA synthesis/repair required for cancer cell division. Currently, there is no evidence to report IGF2BP3 and FOLR1 to correlate to GC prognosis.ConclusionIn summary, using an integrated bioinformatic approach we identified eight lncRNAs with prognostic potential in GC patients and further revealed two axes - H19-IGF2BP3 and PVT1-FOLR1 – that might interpret the underlying mechanism involving in prognosis of GC and provide new insights into the etiology and management of GC patients.
Screening of Graves' Disease Susceptibility Genes by Whole Exome Sequencing in a Three-generation Family
Authors: Hu Zhuoqing , Li Wei , Li Miaosheng , Wei Hao , Hu Zhihui , Chen Yanting , Luo Ai , Li Wangen
Published: November 2020

Background: Graves’ disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. However, little is known about susceptibility genes for GD in the three-generation family.Methods: DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. The Whole Exome Sequencing (WES) was utilized to screen the genome for SNVs associated with GD and the Sanger Sequencing was used to confirm the potential disease-causing genes.Results: In the case study, there were five patients with Graves’ disease(GD) from a three-generation family. The SNVs of MAP7D2(c. 452C>T: p. A151V), SLC1A7(c. 1204C>T: p. R402C), TRAF3IP3(c. 209A>T: p. N70I), PTPRB(c. 3472A>G: p. S1158G), PIK3R3(c. 121C>T: p. P41S), DISC1(c. 1591G>C: p. G531R) were found to be associated with the familial GD and the Sanger sequencing had confirmed these variations. Furthermore, PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions.Conclusion: The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.
High Anemia Prevalence in Korean Older Adults, an Advent Healthcare Problem: 2007-2016 KNHANES
Authors: Chueh Hee won , Jung Hye Lim , Shim Ye Jee , Choi Hyoung Soo , Han Jin Yeong
Published: November 2020

BACKGROUND: Anemia is associated with high morbidity and mortality in older people. However, the prevalence and characteristics of anemia in older individuals are not fully understood, and national data on these aspects in older Korean adults are lacking. This study aimed to evaluate the prevalence and characteristics of anemia in older adults using data from the Korea National Health and Nutrition Examination Survey (KNHANES), which is a nationwide cross-sectional epidemiological study conducted by the Korean Ministry of Health and Welfare.METHODS: Data from a total of 62,825 participants of the 2007-2016 KNHANES were compiled and analyzed to investigate differences in participant characteristics and potential risk factors for anemia. Differences in clinical characteristics of participants were compared across subgroups using the chi-square test for categorical variables and independent t-test for continuous variables. Univariate and multivariate analyses using logistic regression were performed to identify related clinical factors.RESULTS: The prevalence of anemia was higher in the population aged ≥ 65 years than in the younger population. Anemia was also more prevalent among females than among males, but this difference was not significant in people aged >85 years. Being underweight, receiving a social allowance, living alone, and having comorbidities such as hypertension, rheumatoid arthritis, diabetes mellitus (DM), cancer, and chronic renal failure (CRF) were more common among older adults with anemia than among the population without anemia. In univariate and multivariate analyses, older age, female sex, underweight, and presence of comorbidities including rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia. CONCLUSIONS: This study revealed that age, female sex, underweight, and the presence of comorbidities such as rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia in older Korean adults. Further study on causal relationships between anemia and other variables in the older population is necessary.
Mild behavioral impairment is related to frailty in non-dementia older adults: a cross-sectional study
Authors: Fan Shaoyi , Liang Ximin , Yun Tianchan , Pei Zhong , Hu Bin , Ismail Zahinoor , Yang Zhimin , Xu Fuping
Published: November 2020

Background: Frailty and cognitive decline are highly prevalent among older adults. However, the relationship between frailty and mild behavioral impairment (MBI), a dementia risk syndrome characterized by later-life emergence of persistent neuropsychiatric symptoms, has yet to be elucidated. We aimed to evaluate the associations between MBI and frailty in older adults without dementia.Methods: In this cross-sectional study, a consecutive series of 137 older adults without dementia in the Anti-Aging Study, recruited from primary care clinics, were enrolled. Frailty was estimated using the Fried phenotype. MBI was evaluated by the Mild Behavioral Impairment Checklist (MBI-C) at a cut-off point of >8. Cognition was assessed with the Chinese versions of the Montreal Cognitive Assessment (MoCA-BC) and Mini-mental State Examination (MMSE). Multivariable logistic regression was performed to estimate the relationship between MBI and objective cognition with frailty status.Results: At baseline, 30.7% of the older adults had frailty and 18.2% had MBI (MBI+ status). Multivariable logistic regression analysis demonstrated that compared to those without MBI (MBI- status), MBI+ was more likely to have frailty (odds ratio [OR] = 7.44, 95% CI = 1.49-37.21, p = 0.02). Frailty and MBI were both significantly associated with both MMSE and MoCA-BC score (p<0.05).Conclusions: Both frailty and MBI status were associated with higher odds of cognitive impairment. MBI was significantly associated with an increased risk of having frailty in the absence of dementia. This association merits further study to identify potential strategies for the early detection, prevention and therapeutic intervention of frailty.
Variations in haematological and biochemical parameters in healthy ponies
Authors: Olga Witkowska-Piłaszewicz , Cywinska Anna , Katarzyna Michlik-Połczyńska , Michal Czopowicz , Katarzyna Strzelec , Anna Biazik , Marta Parzeniecka-Jaworska , Mark Crisman , Lucjan Witkowski
Published: November 2020

Background: Breed specific reference ranges for selected blood parameters are recommended for proper interpretation of blood tests, but there are only few reports dealing with ponies. The purpose of this study was to investigate if blood parameters differ among ponies’ classes and to check if general normal values for equine species are applicable to ponies.Results: All, except total protein concentration, biochemical parameter significantly (p<0.05) differed among ponies’ classes. The most pronounced difference was noted in blood lactate concentrations, higher (p<0.001) in the smallest ponies (class A). In all groups of ponies muscle enzymes (aspartate aminotransferase and creatine kinase) and urea were high when compared to normal values for equine species, but triglycerides and creatinine were low. Blood lactate concentration was high in comparison with normal values for horses only in class A ponies’.Conclusions: In healthy ponies, blood lactate concentration significantly differs between height classes. Normal values for equine species should not be directly applied to interpret the lactate, triglycerides, aspartate aminotransferase and creatine kinase values in ponies.
Noise-Robust Range Alignment Method for Inverse Synthetic Aperture Radar Based on Aperture Segmentation and Average Range Profile Correlation
Authors: Lu Yue , Yang Jian , Zhang Yue , Xu Shiyou
Published: November 2020

Range alignment is an essential procedure in the translation motion compensation of inverse synthetic aperture radar imaging. Global optimization or maximum-correlation-based algorithms have been used to realize range alignment. However, it is still challenging to achieve range alignment in low signal-to-noise ratio scenarios, which are common in inverse synthetic aperture radar imaging. In this paper, a novelanti-noise range alignment approach is proposed. In this new method, the target motion is modelled as a uniformly accelerated motion during a short sub-aperture time. Minimum entropy optimization is implemented to estimate the motion parameters in each sub-aperture. These estimated parameters can be used to align the profiles of the current sub-aperture. Once the range profiles of eachsub-aperture are aligned, the non-coherent accumulation gain is obtained by averaging all profiles in each sub-aperture, which can be used as valuable information. The accumulation and correlation method is applied to align the average range profiles of each sub-aperture because the former step focuses mainly on alignment within the sub-apertures. Experimental results based on simulated and real measured data demonstrate the effectiveness of the proposed algorithm in low signal-to-noise ratio scenarios.
Anti-tumor effect of miR-1291 in colorectal cancer
Authors: Wang Jiaqi , Hirose Haruka , Yokoyama Yuhki , Shimomura Yuki , Ikeshima Ryo , Tsujimura Naoto , Bonkobara Saki , Takeda Koki , Hata Tsuyoshi , Inoue Akira , Hiraki Masayuki , Ohtsuka Masahisa , Nishida Naohiro , Takahashi Hidekazu , Haraguchi Naotsugu , Tanaka Shinji , Wu Xin , Tanaka Susumu , Mori Masaki , Yamamoto Hirofumi
Published: November 2020

Background: MiR-1291 has an anti-tumor effect in carcinoma of kidney, esophagus, pancreas, and prostate. However, it’s role in colorectal cancer (CRC) has not been elucidated.Methods: In this study, we explored the effect of miR-1291 in CRC cells (HCT116, DLD-1, and HT29) in vitro, and performed a tumor growth inhibitory assay in a mouse therapeutic model using DLD-1 cells. Flow cytometric analysis and Western blotting were performed to examine a role of miR-1291 in cell cycle regulation. We performed luciferase reporter assay to verify the interaction between DCLK1 and miR-1291 in HCT116 cells. Cancer stemness was evaluated by identifying the expression of BMI1 and CD133, as well as performing sphere formation assay. Results: We found that miR-1291 significantly suppressed the proliferation, invasion, cell mobility, and colony formation capability of CRC cell lines. MiR-1291 caused altered expression of the cell cycle-regulatory proteins, representatively CDK inhibitors p21WAF1/CIP1 and p27KIP1 or CDK4. Moreover, intravenous administration of miR-1291 loaded on the super carbonate apatite delivery system significantly inhibited a tumor growth in the DLD-1 xenograft mouse model. A luciferase reporter assay showed that miR-1291 directly bound the 3’ UTR sequence of DCLK1 and suppressed its expression at both the mRNA and protein levels in HCT116 expressing the DCLK1 protein. In addition, miR-1291 suppressed cancer stem cell (CSC) markers BMI1 and CD133 as well as sphere formation ability in HCT116 cells. Conclusions: Taken together, these findings indicate that miR-1291 has an anti-tumor effect by modulating multiple functions, including cell cycle, invasiveness, and cancer stemness. Our data suggest that miR-1291 could be a promising nucleic acid medicine against CRC.
How to improve participant compliance and retention in clinical trials：A Scoping Review
Authors: Yu Mingkun , Lin Ziyi , Liang Changhao , Li Chengze , Zhang Zhijia , Liu Kexin , Li Xun , Liu Jianping , Fei Yutong
Published: November 2020

Background: The reliability of results can be compromised when subsets of participants who remain on a study differ from those who drop out. Although recent studies have investigated strategies for improving compliance and retention , there has been very little investigation of process factors, regardless of the type of literature and the publication date. factors that may influence how and why compliance and retention may be successful (or not).Aim: To identify process factors that may influence participant compliance and retention in clinical trials, and potential strategies to improve the compliance and retention, from published studies, grey literature, and the reference lists of included articles to facilitate future design and implementation of trials.Methods : Six databases and two clinical trial registries were searched on November 29, 2019. Surveys, interviews, retrospective data analyses, theoretical research, reviews and clinical studies aiming at investigating factors and potential strategies were included. Data synthesis followed an iterative process to develop a list of process factors and potential retention strategies.Results were presented mainly as texts, including visualization using word cloud, and descriptive data.Results: 182 publications were included in this review, composed of 58 retrospective reflection of RCTs based on 1,132 clinical trials with 177804 participants, 27 implementation researches, 22 theoretical researches, 20 interviews, 18 surveys, 17 randomized controlled trials, 8 literature reviews, 5 systematic review and meta analysis, 3 mixed methods researches, 2 case report, 1 meta-ethnographic synthesis and 1 cohort study. We identified 70 process factors that may affect the compliance and retention . The most commonly addressed factors were age, education, economy, trust in clinical trials, supporting from surrounding people, safety concerns and effectiveness. We found 42 potential strategies to improve compliance and retention. Strategies reported most frequently were that researchers should pay attention to the changes on participants' psychological condition, try their best to build good relationships, provide some compensation and educate the participants about compliance and retention . Conclusion：These factors that may affect the compliance and retention can help researchers predict participants who are less likely to adhere and develop screening tools to find efficiently their suitable participants. These potential strategies that may improve the compliance and retention.
WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019).
Authors: Sheppard-Olivares Sabina , Bello Nora , Johannes Chad M , Hocker Samuel , Billler Barbara , McKee Talon , McMillan Mattison , Husbands Brian , Wood Elizabeth , Wouda Raelene M
Published: November 2020

BACKGROUND: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These are malignant tumours with a high metastatic rate and limited efficacious chemotherapeutic options available. Recent literature supports the use of the multi-receptor tyrosine kinase inhibitor sunitinib malate for treatment of metastatic insulinoma in people. Toceranib phosphate is a veterinary targeted therapy that may provide benefit in treatment of canine insulinomas. The primary objectives of this study were to describe the duration of clinical benefit, defined as absence of clinical signs associated with hypoglycemia and/or measurable response according to the response evaluation criteria for solid tumours in dogs (cRECIST), and measures of outcome, namely progression free interval (PFI) and overall survival time (OST) in dogs diagnosed with insulinoma treated with toceranib. A secondary objective was to describe the adverse effects of toceranib in dogs with insulinoma.RESULTS: A medical record search identified 30 dogs diagnosed with insulinoma and treated with toceranib at five university hospitals and eight veterinary specialty referral hospitals. A majority (66.7%) of dogs with measurable disease experienced either complete response (CR), partial response (PR), or stable disease (SD) with toceranib therapy. The overall median progression free interval (PFI) was 561 days (95% confidence interval: [246, 727 days]). The overall median survival time (OST) was 656 days [310, 1045 days]. Larger dogs were at increased risk for disease progression (P = 0.0310) and death (P = 0.0064), with every 1 kg increase in body weight resulting in hazard ratios (HRs) of 1.045 [1.003, 1.084] and 1.05 [1.012, 1.090], respectively. In addition, time to disease progression was associated with use of therapies prior to toceranib (P = 0.0050) and type of veterinary practice (P = 0.0025). The most common adverse events with toceranib therapy were grade 1 or 2 gastrointestinal toxicities.CONCLUSIONS: Clinical benefit was reported in the majority of dogs diagnosed with insulinoma treated with toceranib, but randomized, prospective studies are needed to assess and quantify the effect of this therapy. The most commonly observed adverse events (AEs) were gastrointestinal AEs.
Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer
Authors: Qiu Yier , Lu Guowen , Wu Yingjie
Published: November 2020

Background: Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer.Method: Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set.Results: We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group.Conclusion: Our research demonstrated that high CDKN2A mRNA expression may be an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.
Moderately Reduced Estimated Glomerular Filtration Rate (eGFR) among Community - Dwelling Older People Associated with Increased Long Term Mortality: A Study from Low to Middle Income Country in Asia.
Authors: Skulratanasak Peenida , Chalermsri Chalobol , Aekplakorn Wichai , Srinonpras Varalak
Published: November 2020

Background: Reduced glomerular filtration rate (GFR) is regarded as a component of renal senescence; however, the full impact of chronic kidney disease (CKD) among older people is still not fully understood. This study aimed to investigate the effect of reduced GFR on all-cause mortality, and the combined effect of socioeconomic status and CKD on mortality among older Thai population. Methods: A retrospective cohort of Thai population aged >60 years was enrolled from the Fourth National Health Examination Survey, and estimated GFR (eGFR) and comorbid disease data were collected. Mortality information was gathered from the National Civil Registration and Vital Statistics System. Factors associated with all-cause mortality were determined using Cox proportional hazards model. Results: A total of 9,080 participants (mean age: 69.5 years) were included. Prevalence of CKD stage 3-5 was 53.3%. During the 2008-2015 period, the overall mortality rate among CKD was 28.9 per 1,000 person-years. The stages of CKD significantly associated with increased mortality were stages 3b, 4, and 5, as follows: HR: 1.4 (95% CI: 1.2-1.63), 2.2 (95% CI: 1.78-2.71), and HR: 5.9 (95% CI: 4.26-8.15), respectively. People with higher socioeconomic status and moderate-stage CKD had lower mortality than lower socioeconomic status moderate-stage CKD. Conclusion: Moderate decline in eGFR was found to be independently associated with all-cause mortality in Thai elderly population. Socioeconomic disparities were also observed among older CKD. Implementation of a mass screening program to identify asymptomatic individuals would accelerate diagnosis and treatment, and this would reduce the costs of care associated with advanced-stage disease.
Changing Rainfall Patterns in India: A Spatiotemporal Analysis of Trends & Impacts
Authors: Patel Praharsh , Khan Adeel
Published: November 2020

The hydrological cycle that starts with rainfall has been under major threat from the global temperature rise and climatic changes. In India, rainfall changes not only jeopardize water security but also have a major set-back for socio-economic stability. There have been attempts to decode the changing rainfall patterns in India but most of them conducted at wider spatial resolution (such as national, state, or sub-divisional level) fail to capture the essence of spatial variation in rainfall characteristics. To get a clearer understanding of change in key rainfall parameters, this paper analyses more than 197 million 0.25˚ x 0.25˚ gridded rainfall data points. The fine resolution 117 years (1901-2017) of daily rainfall data is utilized to test significant spatiotemporal trends in the quantum of rainfall and other key rainfall parameters such as rainy days, monsoon onset and withdrawal dates, occurrences of extreme rainfall events, and frequency of drought and high rainfall years. With an emphasis on changing climatic patterns since perceived climate change onset in the 1970s, the study identifies the regions with significant changes in rainfall patterns by comparing key parameters pre- & post- 1970s. The paper also highlights the major repercussions and challenges for the identified regions with significant changing rainfall patterns.
Model study of the influence of multi-joint muscles on the frequency characteristics of the human body
Authors:   St. Petersburg State University, Tregubov Vladimir P. , Egorova Nadezhda K. ,   St. Petersburg State University
Published: November 2020

It is noted that the Kelvin—Voigt model is unsuitable for describing some polymers and biological tissues. In these cases, a three-component combination of elements, which consists of a spring and damper, connected in parallel and a spring sequentially attached to them, is used. The force characteristic of such a combination includes not only the strain, strain rate, and force, but also the rate of force change. Examples of such systems are the blood vessel wall and the intervertebral disc, which have been given special attention. Since the motion of such systems is described by an ordinary third-order differential equation, they are classified as systems with a non-integer number of degrees of freedom. For a single-mass oscillating system with one and a half degrees of freedom, a transfer function was constructed using the Laplace transform. In addition, the amplitude-frequency response (AFR) was also constructed. Analysis of this characteristic showed that increasing the damping coefficient from zero to infinity first leads to a decrease in its maximum to a certain non-zero value, and then to an increase and reaching infinity with an infinite value of the damping coefficient. The same feature is demonstrated on a two-mass system of chain structure, each link of which has one and a half degrees of freedom. A sequential combination of seven such links was used to model the lumbar spine in the structure of a General body model of a sitting person subject to vertical vibration. Multi-link elastic-viscous joints were used to model the multi-articular muscles of the lumbar spine. Additional experimental studies are needed to determine the numerical values of the parameters of the proposed model.
Case report: Diabetic mastopathy
Authors:   V. F. Snegiryov Maternity Hospital No. 6, Musina Ekaterina
Published: November 2020

Diabetic mastopathy (DMP) is a rare fibrotic disease of the mammary gland (less than 1 % among benign diseases). It was first described in 1984 by Soler & Khardori in women who have suffered from type 1 diabetes mellitus for a long time. Clinically, DMP can manifest as single or double-sided, palpable, movable, painless seals. Often, DMP is a random finding in a mammographic examination of asymptomatic patients. At the same time, radiological signs are more often non-specific. When ultrasound examination of the mammary gland with DMP can be visualized hypoechoic formations with fuzzy, uneven contours, heterogeneous structure. Clinical, ultrasound and radiological manifestations of DMP are often associated by specialists with malignancy, which leads to unnecessary invasive procedures. In this regard, of interest is the clinical case of DMP in a woman of reproductive age with type 1 diabetes, repeated trepanobiopsy of the breast. The described clinical observation represents the case of repeated invasive intervention, which proves the connection between the long-term decompensation of type 1 diabetes that occurred in the juvenile age and the progression of the pathological process in the mammary glands under hyperglycemia.
The human placenta and aneuploidy — trisomies 21, 18, 13
Authors:   St. Petersburg State University, Kolobov Andrey , Lychyova Anna ,   St. Petersburg State University, Karev Vadim ,   Pediatric Research and Clinical Center for Infectious Diseases, Kolobova Oksana ,   St. Petersburg State University
Published: November 2020

The purpose of this research was to investigation the morphological features of human placenta with karyotyped trisomy 21, 18 and 13 chromosomes. The study included 50 placenta of fetuses in miscarriages pregnancy at 19–20 weeks, among them 10 placentas obtained as a result of induced abortions due to karyotyped trisomy 21 of the fetuses; 10 placentas obtained as a result of induced abortions due to karyotyped trisomy 18 of the fetuses; 10 placentas obtained as a result of induced abortions due to karyotyped trisomy 13 in the fetuses; 20 placentas obtained as a result of spontaneous miscarriages without any congenital defects and abnormal karyotype of the fetuses. As a result of the investigation, in placentas with karyotyped trisomies, a violation of villi branching was noted. With karyotyped trisomy 21, inhibition of angiogenesis and sclerosis of villi with proliferation of fibroblasts were revealed. In cells of chorionic villi with karyotyped trisomy 18, increased apoptosis was noted. In placentas with karyotyped trisomy 13 hydropic changes in villus stroma and inhibition of angiogenesis were noted. As a result of the study, in placentas with karyotyped trisomies, a violation of villi branching was noted. With karyotyped trisomy 21, inhibition of angiogenesis and sclerosis of villi with proliferation of fibroblasts were revealed. In cells of chorionic villi with karyotyped trisomy 18, increased apoptosis was noted. In placentas with karyotyped trisomy 13 hydropic changes in villus stroma and inhibition of angiogenesis were noted.
Behavioral audit of safety as a tool for decreasing occupational health and safety risk of healthcare providers
Authors:   St. Petersburg State University, Kopytenkova Olga , Shilova Еkaterina ,   Emperor Alexander I St. Petersburg State Transport University
Published: November 2020

The causes of the high infection rate of health workers in case of unfavorable epidemic situation,as well as occupational risks of health workers related to work conditions characterized by the presence of a complex of unfavorable factors of production environment; noted the combined effects of behavioural risk factors for health of health workers with professional risk, enhancing the cumulative negative impacts in professional deformation of the part of health workers, neglecting the requirements of safe labour; stressed the need for preventive work based on continuous and effective monitoring and evaluation of improvement actions, improvement and development of the management system of occupational health and safety is regulated by the system of standards for labor safety, a significant lack of which in healthcare institutions is the lack of such an effective interactive tool for enhancing motivation.
Eco-Friendly Synthesis of Peptides Using Fmoc-Amino Acid Chlorides as Coupling Agent Under Biphasic Condition
Authors: Khatavi Santosh Y. , Kantharaju Kamanna
Published: November 2020

Background:

Agro-waste derived solvent media act as a greener process for the peptide
bond formation using Nα-Fmoc-amino acid chloride and amino acid ester salt with in situ neutralization
and coupling under biphasic condition. The Fmoc-amino acid chlorides are prepared by the
reported procedure of freshly distilled SOCl2 with dry CH2Cl2. The protocol found many added advantages
such as neutralization of amino acid ester salt and not required additional base for the neutralization,
and directly coupling take place with Fmoc-amino acid chloride gave final product
dipeptide ester in good to excellent yields. The protocol occurs with complete stereo chemical integrity
of the configuration of substrates. Here, we revisited Schotten-Baumann condition, instead
of using inorganic base.

Objective:

To develop green protocol for the synthesis of peptide bond using Fmoc-amino acid
chloride with amino acid esters salt.

Methods:

The final product isolated is analyzed in several spectroscopic and analytical techniques
such as FT-IR, 1H-, 13C-NMR, Mass spectrometry and RP-HPLC to check stereo integrity and purity
of the product.

Conclusion:

The present method developed greener using natural agro-waste (lemon fruit shell
ash) derived solvent medium for the reaction and not required chemical entity.
Sex Differences and Emerging New Risk Factors for Atherosclerosis and Its Thrombotic Complications
Authors: Padro Teresa , Muñoz-Garcia Natalia , Peña Esther , Badimon Lina
Published: November 2020

Cardiovascular diseases (CVD) remain the world's leading cause of death and disability in both men
and women, but with different prognostics and outcomes between sexes. Although the burden of CVD is generally
related to the conventional risk factors, the relevance of non-traditional risk factors is increasingly being
recognized to explain the so-called “residual risk”. Men and women share many similarities regarding classical
cardiovascular risk factors but have different disease pathophysiology, clinical presentations, prevalence, and
outcomes of CVDs. How sex-specificities regarding the effects of non-traditional risk factors may contribute to
the evolution of atherosclerosis and its clinical manifestations in males and females remain largely underanalyzed.
The present review summarizes the current knowledge for sex differences in atherosclerotic plaque
composition and clinical evolution in association with risk factors, such as inflammation, lipoprotein(a), hemostasis,
intraplaque calcification, and depression. We further discuss the potential sex-differential impact of
chronic infectious diseases, gut microbiome and, epigenetic gene expression regulation for atherosclerosis and
the effect of female-specific disorders in CVD.
Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19
Authors: Rehman Md. Tabish , AlAjmi Mohamed F. , Hussain Afzal
Published: November 2020

Background:

The emergence and dissemination of SARS-CoV-2 has caused high mortality and
enormous economic loss. Rapid development of new drug molecules is the need of hour to fight COVID-19.
However, the conventional approaches of drug development are time consuming and expensive. Here, we have
adopted a computational approach to identify lead molecules from nature. Ligands from natural compounds library
available at Selleck Inc (L1400) have been screened for their ability to bind and inhibit the main protease
(3CLpro) of SARS-CoV-2.

Methods:

The natural compounds library of Selleck Inc. (Catalog No. L1400) were retrieved from
www.selleckchem.com. It contains 2230 compounds in sdf format, curated from natural sources. Prior to molecular
docking, all the ligands were prepared by adding hydrogen atoms and merging them with non-polar hydrogen
atoms. Gasteiger partial charges were added, rotatable bonds were defined, and the energies were minimized
using MMFF94 forcefield (11,12). The three-dimensional coordinates of the main protease (Mpro), also
known as 3C-like protein (3CLpro), was downloaded from the protein databank available at
https://www.rcsb.org/structure/6LU7. The structure was solved to a resolution of 2.16 Å and is bound with a
peptide-like inhibitor (N3)(8). The structure of target was prepared for molecular docking by adding hydrogen
atoms, Kollman united atom type charges and solvation parameters using AutoDock Tool (ADT) (13).

Results:

We found that Kaempferol, Quercetin, and Rutin were bound at the substrate binding pocket of
3CLpro with high affinity (105-106 M-1) and interact with the active site residues such as His41 and Cys145
through hydrogen bonding and hydrophobic interactions. In fact, the binding affinity of Rutin (~106 M-1) was
much higher than Chloroquine (~103 M-1) and Hydroxychloroquine (~104 M-1), and the reference drug
Remdesivir (~105 M-1).

Conclusion:

The results suggest that natural compounds such as flavonoids have the potential to be developed
as novel inhibitors of SARS-CoV-2 with a comparable/higher potency as that of Remdesivir. However, their
clinical usage on COVID-19 patients is a subject of further investigations and clinical trials.
Applications and Functions of γ-Poly-Glutamic Acid and its Derivatives in Medicine
Authors: Wang Guoliang , Liu Qing , Yang Young M. , Lee Soo-Ung , Han Jee-Soo , Jang Kyoung-Jin , Kang Dong Y. , Sp Nipin , Li Zhandong , Tong Tao
Published: November 2020

Background:

γ-Poly-Glutamic Acid (γ-PGA) is a naturally occurring homo-polyamide produced
by various strains of Bacillus. It is made from repeating units of L-glutamic acid, D-glutamic acid,
or both connected through amide linkages between α-amino and γ-carboxylic acid groups. As a biopolymer
substance, the attractive properties of γ-PGA are that it is water-soluble, biodegradable, biocompatible,
non-toxic, non-immunogenic, and edible. Therefore, it can be used as a green and environmentally
friendly biological material.

Methods:

The review concentrates on the reports revealing the functions and potential use of γ-PGA
and its derivatives in medicine.

Results & Discussion:

γ-PGA is described to possess several properties that may be exploited in medicine.
The biopolymer reportedly has been successfully applied not only as a metal chelator, drug carrier/
deliverer, and gene vector, but also used safely as a vaccine adjuvant, tissue engineering material, and
contrast agent.

Conclusion:

γ-PGA could be potentially considered as a potential biomedical material in the field of
medicine.
An Overview of Computer-aided Drug Design Tools and Recent Applications in Designing of Anti-diabetic Agents
Authors: Kaur Paranjeet , Khatik Gopal
Published: November 2020

Background:

In this fast-growing era, high throughput data is now being easily accessed by getting transformed into datasets which store the information. Such information is valuable to optimize the hypothesis and drug design via computer-aided drug design (CADD). Nowadays, we can explore the role of CADD in various disciplines like Nanotechnology, Biochemistry, Medical Sciences, Molecular Biology, etc.

Methods:

We searched the valuable literature using a pertinent database with given keywords like computer-aided drug design, anti-diabetic, drug design, etc. We retrieved all valuable articles which are recent and discussing the role of computation in the designing of anti-diabetic agents.

Results:

To facilitate the drug discovery process, the computational approach has set landmarks in the whole pipeline for drug discovery from target identification and mechanism of action to the identification of leads and drug candidates. Along with this, there is a determined endeavor to describe the significance of in-silico studies in predicting the absorption, distribution, metabolism, excretion, and toxicity profile. Thus, globally, CADD is accepted with a variety of tools for studying QSAR, virtual screening, protein structure prediction, quantum chemistry, material design, physical and biological property prediction.

Conclusion:

Computer-assisted tools are used as the drug discovery tool in the area of different diseases, and here we reviewed the collaborative aspects of information technologies and chemoinformatic tools in the discovery of anti-diabetic agents, keeping in view the growing importance for treating diabetes.
Application of Ultrasound Elastography for Assessing Intestinal Fibrosis in Inflammatory Bowel Disease: Fiction or Reality?
Authors: Gabbiadini Roberto , Zacharopoulou Eirini , Furfaro Federica , Craviotto Vincenzo , Zilli Alessandra , Gilardi Daniela , Roda Giulia , Loy Laura , Fiorino Gionata , Peyrin-Biroulet Laurent , Danese Silvio , Allocca Mariangela
Published: November 2020

Background:

Intestinal fibrosis and subsequent strictures represent an important burden
in inflammatory bowel disease (IBD). Both the detection and evaluation of the degree of fibrosis in
stricturing Crohn’s disease (CD) are important when deciding the best therapeutic strategy (medical
anti-inflammatory therapy, endoscopic dilation, surgery). Ultrasound elastography (USE) is a
non-invasive technique that has been proposed in the field of IBD for evaluating intestinal stiffness
as a biomarker of intestinal fibrosis.

Objective:

The aim of this review is to discuss the ability and
current role of ultrasound elastography in the assessment of intestinal fibrosis. Results and Conclusion:
Data on USE in IBD are provided by pilot and proof-of-concept studies with small sample
size. The first type of USE investigated was strain elastography, while shear wave elastography has
been introduced recently. Despite the heterogeneity of the methods of the studies, USE has been
proven to be able to assess intestinal fibrosis in patients with stricturing CD. However, before introducing
this technique in current practice, further studies with larger sample sizes are needed. In addition,
the use of homogeneous parameters, the assessment of reproducibility, and the identification
of validated cut-off values are essential.
Novel Mitochondria-targeted Drugs for Cancer Therapy
Authors: Fialova Jindriska Leischner , Raudenska Martina , Jakubek Milan , Kejik Zdenek , Martasek Pavel , Babula Petr , Matkowski Adam , Filipensky Petr , Masarik Michal
Published: November 2020

The search for mitochondria-targeted drugs has dramatically risen over the last decade. Mitochondria
are essential organelles serving not only as a powerhouse of the cell but also as a key player
in cell proliferation and cell death. Their central role in the energetic metabolism, calcium homeostasis
and apoptosis makes them an intriguing field of interest for cancer pharmacology. In cancer
cells, many mitochondrial signaling and metabolic pathways are altered. These changes contribute to
cancer development and progression. Due to changes in mitochondrial metabolism and changes in
membrane potential, cancer cells are more susceptible to mitochondria-targeted therapy. The loss of
functional mitochondria leads to the arrest of cancer progression and/or a cancer cell death. Identification
of mitochondrial changes specific for tumor growth and progression, rational development of new
mitochondria-targeted drugs and research on delivery agents led to the advance of this promising area.
This review will highlight the current findings in mitochondrial biology, which are important for cancer
initiation, progression and resistance, and discuss approaches of cancer pharmacology with a special
focus on the anti-cancer drugs referred to as ‘mitocans’.
Comparative Evaluation of the Transdermal Permeation Effectiveness of Fu’s Cupping Therapy on Eight Different Types of Model Drugs
Authors: Miao Yanyan , Xu Jian , Liu Yao , Yang Fangfang , Zheng Xiaoxia , Xie Weijie , Zhang Yongping
Published: November 2020

Background::

Overcoming the skin barrier to achieve the transdermal penetration of
drugs across the Stratum Corneum (SC) remains a significant challenge. Our previous study
showed that Fu’s Cupping Therapy (FCT) contributes to the transdermal enhancement and percutaneous
absorption rate of representative drugs and improves their clinical effects. This work evaluated
the transdermal enhancement effect of FCT on drugs with different Molecular Weights (MW).

Methods::

We investigated the enhancements in the transdermal penetration of eight types of model
drugs through the skin of BALB/c-nu mice and Sprague Dawley rats using Franz diffusion devices.
In addition, 3% azone, 5% azone, 3% peppermint oil, and 5% peppermint oil were used as penetration
enhancers to study the transdermal behaviour of these drugs.

Results::

Our results showed that the BALB/c-nu mouse skin was the best transdermal media, and
the optimal time for FCT was 10 min. Compared with other penetration enhancers, FCT exerted a
significantly improved effect on enhancing the percutaneous penetration of the selected log(P)-
model drugs in addition to the two large MW drugs (ginsenoside Rg1 and notoginsenoside R1). Statistical
analysis revealed that the relationship between the log(P) of various model drugs and the
permeability coefficient [log(Pcm)] of the FCT group was log(Pcm)=0.080(log(P))2-0.136
(log(P))-0.282.

Conclusion::

FCT may be used as a novel method for enhancing physical penetration and thus effectively
promoting the transdermal absorption of drugs and might lay a foundation for future research
on drug transdermal technology.
Cutaneous Autoimmune Phenomena of the Anti-TNFa Biosimilars. Casebased Review
Authors: Pelechas Eleftherios , Papoudou-Bai Alexandra , Voulgari Paraskevi V. , Drosos Alexandros A.
Published: November 2020

Background:

Psoriasis (Pso) is a common chronic inflammatory disease affecting the
skin, both sexes, and all ages. It can be associated with other chronic inflammatory musculoskeletal
disorders and certain drugs, including tumor necrosis factor α (TNFα) antagonists.

Case Presentation:

A 64-year-old man with seronegative rheumatoid arthritis (RA) refractory to leflunomide
and prednisone was treated with SB-4 (Benepali), an etanercept biosimilar 50mg/week
subcutaneously. He responded well to the treatment, but a year later, he developed erythematous
skin eruptions affecting mainly in the palms of both hands. Skin biopsy showed a picture compatible
with Pso. SB-4 was discontinued, and the skin lesions disappeared with the addition of topical
steroid therapy. This is the only case of psoriatic skin lesions associated with SB-4 treatment.

Conclusion:

Thus, we review and discuss the relevant literature of Pso cases related to SB-4 and
other anti-TNFα biosimilars. Rheumatologists dealing with patients on anti-TNFα biosimilars
should be aware of and recognize these complications.
Heat Transfer Modeling in Bone Tumour Hyperthermia Induced by Hydroxyapatite Magnetic Thermo-Seeds
Authors: Fanari Fabio , Mariani Lorena , Desogus Francesco
Published: November 2020

Background:

Hyperthermia is an adjuvant oncologic thermal therapy. In the case of deep-seated bone cancers, the interstitial hyperthermia treatment can be performed using thermo-seeds, implanted biomaterial components that are able to convert external electromagnetic power into thermal one. Several magnetic biomaterials have been synthesized for thermal treatments of cancer. However, less attention has been paid to the modeling description of the therapy, especially when the bio-heat transfer process is coupled to the electromagnetic heating.

Objective:

In this work, a comparison between the available analytical and numerical models is presented.

Methods:

A non-linear multiphysics model is used to study and describe the performance of cylindrical magnetic hydroxyapatite thermo-seeds to treat residual cancer cells of bone tumours.

Results:

The thermal dynamics and treatment outcome are carefully evaluated. Under the exposure of a magnetic field of 30 mT, working at 300 kHz, it was found that magnetic hydroxyapatite implants with a size of 10 mm × 10 mm could increase the temperature above 42 °C for 60 min.

Conclusion:

The proposed model overcomes the limitations of the available theoretical frameworks, and the results reveal the relevancy of the implant geometry to the effectiveness of the hyperthermia treatment.
Research on climate change adaption in cities, funded by ERCA
Authors: Inatsu Masaru
Published: November 2020

There is growing global concern over climate change and research is being conducted to investigate the impact this phenomenon will have on the world. To support this research the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) has developed the d4PDF,
the world's largest collection of simulation data about climate change. Professor Masaru Inatsu, from Department of Earth and Planetary Science at Hokkaido University, is working alongside Associate Professor Tetsuya Takemi, from Kyoto University, and Professor Hiroyuki Kusaka, from University
of Tsukuba, in collaboration with a number of research partners from other leading research groups, to use this data to enable a better understanding of the impact of extreme weather on major cities in Japan.