bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 phobia in a boy with undiagnosed autism spectrum disorder: a case report
Authors: Sakamoto Shoko , Miyawaki Dai , Goto Ayako , Harima Yuji , Tokuhara Daisuke , Inoue Koki
Published: December 2020

BackgroundThe coronavirus disease (COVID-19) is affecting mental health profoundly. Previous studies have reported pandemic-related anxiety. Anxiety disorder and autism spectrum disorder (ASD) are relatively common comorbidities. However, thus far, there is no report of any patient with undiagnosed ASD who developed anxiety disorders caused by the COVID-19 pandemic.Case presentationIn this case report, we describe an 8-year-old Japanese boy with undiagnosed ASD who developed COVID-19 phobia, resulting in avoidant restrictive food intake disorder (ARFID). As COVID-19 was highly publicized in the mass media and the risk of droplet infection was emphasized upon, the patient began to fear viral contamination from food, culminating in a refusal to eat or even swallow his saliva. He was admitted to a pediatric medical center in Osaka with life-threatening dehydration and was then referred to our child psychiatry department for treatment. We clinically diagnosed the patient with COVID-19 phobia resulting in ARFID. We identified the characteristics of ASD from his present social communication skills and developmental history. We provided psychoeducation of ASD for the parents as well as administered supportive psychotherapy for the patient. Shortly after our intervention, which was designed to relieve his ASD-related anxiety, his dysphagia improved. Our findings suggest that children with undiagnosed ASD may develop COVID-19 phobia. In these cases, intervention for ASD, such as sharing information with parents and teachers to explain what autism is and how it is likely to affect the child’s development and function, and to make an individual education plan may be more appropriate than starting treatment for anxiety disorders as the first-line option.ConclusionCOVID-19 is the biggest pandemic in the recent past and more undiagnosed ASD patients who develop COVID-19 phobia may seek treatment. Clinicians should consider the underlying ASD in these patients and assess their developmental history, such as joint attention, as well as their present social communication skills.
Psychometric properties of the German Version of the Psychological Consequences of Screening Questionnaire (PCQ)
Authors: Fichtner Urs Alexander , Maun Andy , Farin-Glattacker Erik
Published: December 2020

Background:
This study aimed to translate the negative and positive items of the Psychological Consequences Questionnaire (PCQ) into German, to adapt this version to the context of screening for cirrhosis of the liver, and to test its psychometric properties.
Methods:
The three subscales (physical, emotional, and social) were translated into German using a forward-backward translation method. Furthermore, we adapted the wording to the context of liver diseases. We tested the acceptability, distribution properties, internal consistency, scale structure, and the convergent validity using an analysis sample of 443 patients who were screened for cirrhosis or fibrosis of the liver.
Results:
We found low non-response and non-unique answer rates on the PCQ items in general. However, positive items had higher non-response rates. All items showed strong floor effects. Cronbach’s alpha was high for both the negative (α = 0.95) and the positive PCQ scale (α = 0.90), as well as for the total PCQ scale (α = 0.90). Confirmatory factor analysis could reproduce the three dimensions that the PCQ intends to measure. However, it suggests not summing up a total PCQ score and instead treat the subscales separately. Convergent validity with the short form of the Spielberger State-Trait Anxiety Inventory (STAI-Y-6) was acceptable.
Conclusions:
Overall, our study results report a successful adaptation of the German PCQ with good performance in terms of acceptability, internal consistency, scale structure, and convergent validity. We could demonstrate that the German version of the PCQ is a useful and well-performing measurement for both negative and positive screening consequences, even in a non-cancer setting.
Tiredness of Life in Older Persons: An Evolutionary Concept Analysis
Authors: Humbeeck Liesbeth Van , Driedijk Femke , Mey Sarah De , Bock Reine De , Piers Ruth , Noortgate Nele Van Den
Published: December 2020

BackgroundOlder adults face accumulated vulnerabilities that can make day-to-day life a constant struggle. This may lead to the feeling that the story of their life has come to an end and a persistent death wish. In this context tiredness of life has become a widely used term, but remains a poorly understood concept in healthcare. This study seeks to review the health-related literature on tiredness of life and to identify attributes, antecedents and consequences of the concept. MethodsA concept analysis of the scientific literature in the health disciplines was performed using Rodgers’ evolutionary method. Four databases (Pubmed, Web of Science, CINAHL and EMBASE) were searched (January 2000-September 2019). ResultsThirty-three publications were included. Four defining attributes (being weary of life, motivational depletion, loss of meaning in life and an inability to connect to ones’ life), four antecedents (the experience of unpredictable circumstances, experienced age-related life struggles, the fear of dependency and social redundancy), and three consequences (euthanasia requests, voluntary refusal to eat and drink and suicide) were identified. Concepts such as ‘finished with life’, ‘suffering from life’ and ‘completed life’ were used interchangeably both in public debate as among health care providers and patients.ConclusionsInternational consensus definition on “tiredness of life” is currently lacking. Analysis of its defining attributes and antecedents provides important information related to its impact and potential risk factors. Clearly, more work is needed to grasp the experience of tiredness of life.
Prevalence and related risk factors of psychotic symptoms among inpatients infected with COVID-19 during the second wave pandemic
Authors: Zhang Zhiyang , Feng Yi , Song Rui , Yang Di , Duan Xuefei
Published: December 2020

Background
Possibility of psychotic symptoms and related risk factors among the normal person and infected patients during the outbreak of COVID-19 has been widely investigated in previous studies. With the arrival of the second wave of the epidemic in many countries around the word, the accordingly mental health outcomes were unclear yet, especially the mental health outcomes among infected patients. It aims to explore the prevalence of and related risk factors associated with psychotic symptoms in COVID-19 infected inpatients during the second wave.
Method:
A cross-sectional survey was conducted in five isolated wards of a designated hospital in Beijing, China, from 1 July to 15 July, 2020. The Mini-International Neuropsychiatric Interview (M.I.N.I) was conducted to assess the psychiatric disorders, and a serious of scales was used to measure self-reported psychotic symptoms and psychosomatic factors. Multivariate regression analysis was used to analyze the risk factors associated with psychotic symptoms.
Results
Among 199 infected participants, the prevalence of generalized anxiety symptoms is 51.3%, of depressive symptoms 41.2%, of PTSD symptoms 33.6%. Loneliness, hope, coping strategies, history of mental disorders were shared risk or protective factors across several psychotic symptoms. Perceived impact by COVID-19 is the specific risk factor associated with state anxiety symptoms.
Conclusions
The prevalence of symptoms of depression, anxiety and PTSS/PTSD is high among infected inpatients during the second wave of pandemic in Beijing. Clinical doctors must realize that infected inpatients during the second wave of pandemic are likely to suffer from depressive disorder, anxiety disorders and PTSS/PTSD, as well as some neuropsychiatric syndromes. Specific mental health care is urgently needed to help inpatients cope with the virus during the second wave of pandemic.
Predictors of illness severity in COVID-19 cases
Authors: AlDossary Reem A. , Alnimr Amani , Aljindan Reem , Alkharsah Khaled , Al-Qurayn Ahmed , Eltreifi Obeid , Alkuwaiti Feras , Almashouf Abdullah , Alshahlawi Ahmed , Alshammari Amal , Hudhaiah Dhoha , Alshahrani Mohammed , Bukhari Huda
Published: December 2020

Background

Multiple studies worldwide reported the clinical and epidemiological features of coronavirus disease 2019 (COVID-19) with limited reports form the Middle East area.
Methods

This is an observational study to describe the clinical and epidemiological features of 341 COVID-19 cases in the Eastern Province of Saudi Arabia over the first three months from reporting the first case in the country and identify factors associated with severity of the illness.
Results

The median age was 45 years and males were twice as affected as females (p value < 0.0001). The duration of viral shedding ranged from 9 to 36 days. The most common clinical presentations include fever, shortness of breath, cough, myalgia, sore throat, vomiting, and headache. Severe and critical cases were significantly higher in males compared to females (23% vs 8.7%), senior adults (> 65 years), Bengali ethnicity, and in patient with com-morbidities including diabetes, hypertension, and dyslipidemia (p-value = 0.001). Furthermore, case fatality rate was found to be 10% and was significantly higher in male gender compared to female (13.8%vs 2.6%), and in Asian ethnicity (17.9%) compared to Arabs (6%) and African counterparts (0) (p-value = 0.002). No association was found between viral load represented by the RT-PCR cycle threshold (Ct) values and severity of illness.
Conclusion

Age, gender and ethnicity are important predictors of COVID-19 severity while Cycle threshold (Ct) of SARS-CoV-2 RT-PCR test cannot be used as a predictor of criticality of illness.
Molecular characteristics of antibiotic resistance Escherichia coli and Klebsiella pneumoniae strains isolated from hospitalized patients in Tehran, Iran
Authors: Sharahi Javad Yasbolaghi , Hashemi Ali , Ardebili Abdollah , Davoudabadi Sara
Published: December 2020

Background

We evaluated the distribution of carbapenem and colistin resistance mechanisms of clinical E. coli and K. pneumoniae isolates from Iran.
Methods

Antibiotic susceptibility testing was performed by disc diffusion and microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The presence of extended spectrum β-lactamases (ESBLs) genes, carbapenemase genes, as well as fosfomycin resistance genes, and colistin resistance genes was also examined by PCR-sequencing. The ability of biofilm formation was assessed with crystal violet staining method. The expression colistin resistance genes were measured by quantitative reverse transcription-PCR (RT-qPCR) analysis to evaluate the association between gene upregulation and colistin resistance. Genotyping was performed using the multi-locus sequencing typing (MLST).
Results

From 2016 to 2018, a total of 165 clinical isolates of K. pneumoniae and E. coli were collected. Colistin and tigecycline were the most effective antimicrobial agents with 90.3% and 82.4% susceptibility. Notably, 16 (9.7%) isolates showed resistance to colistin. Overall, 33 (20%), 31 (18.8%), and 95 (57.6%) isolates were categorized as strong, moderate, and weak biofilm-producer, respectively. Additionally, blaTEM, blaSHV, blaCTX−M, blaNDM−1, and blaNDM−6 resistance genes were detected in 98 (59.4%), 54 (32.7%), 77 (46.7%), 3 (1.8%), and 3 (1.8%) isolates, respectively. Inactivation of mgrB gene due to nonsense mutations and insertion of IS elements was observed in 6 colistin resistant isolates. Colistin resistance was found to be linked to upregulation of pmrA-K, phoP, and phoQ genes. Three of blaNDM−1 and 3 of blaNDM−6 variants were found to be carried by IncL/M and IncF plasmid, respectively. MLST revealed that blaNDM positive isolates were clonally related and belonged to three distinct clonal complexes, including ST147, ST15 and ST3299.
Conclusions

The large-scale surveillance and effective infection control measures are also urgently needed to prevent the outbreak of diverse carbapenem- and colistin- resistant isolates in the future.
Impact of Surgery on Survival in Breast Cancer with Bone Metastases: a SEER database retrospective analysis
Authors: Peng pai , li yuan hong , chen yuan jiang , hu hua chao , chen xin , han tao yun , wang li jin
Published: December 2020

Purpose It was controversial to operate on the primary site of breast cancer with simple bone metastasis，we found that the surgery could improve survival in patients with breast cancer with bone metastases via a SEER database retrospective analysis.Method Totolly 2917 cases of breast cancer with bone metastasis, first diagnosed between 2010 and 2015 in the National Cancer Institute surveillance, Epidemiology, and Results Database (SEER).We assessed the effect of different surgical procedures on survival and prognosis by the correlation statistics.Results Compared with the non-surgical group , the prognosis of patients on the primary tumor surgical group shows the statistical significance (c2 = 146.023, P < 0.001), the survival benefit of the breast-conserving group was the highest for 70 months(c2=157.117,P<0.001). Compared with the non-surgery group, the median OS of primary surgery group was: HR=0.525, 95%CI=0.467-0.590,P<0.001. In the breast-conserving group, the median operative OS: HR=0.394, 95%CI=0.325-0.478,P<0.001. Conclusion: This study showed that primary surgery could improve the prognosis and overall survival of women with advanced breast cancer with bone metastasis alone. Under the condition of low tumor burden, breast conserving surgery was a better choice.
Study of Solving the Bottleneck Problem of the Estimation of Biological Dose in the Window of Time of Medical Emergency in Large-scale Nuclear Radiation Accidents
Authors: Liu Gang
Published: December 2020

Purpose

In order to achieve the goal of rapid response, effective disposal and protection of life of large-scale radiation events, how to establish the uniform standard curve of biological dose estimation for chromosome aberration analysis becomes an urgent need.
Methods

Chromosomal aberrations with different irradiation dose rates were used to analyze the biological dose curve and the share of the “dicentric + ring” caused by the dose rate at each dose point. The dose-rate effect of 60Co-rays on peripheral blood lymphocytes was analyzed by statistical method .
Results

Irradiation dose is dominant ; At each dose point, “(dicentric chromosome + centric rings) /cell” is proportional to "dose rate", that is, Y = k X + b;Between 1-5Gy dose, “(dicentric chromosome + centric rings) /Cell ” holds a quadratic linear relationship with dose rate, that is,y = ax2 + bx + c.
Conclusion

The fraction of “dicentric + ring” caused by dose rate was calculated, if “Dose rate” is Z Gy•min− 1, it corresponds to an increase in linear relationships. Biological dose estimation curve :Y = 3.318 × 10− 3+2.0541 × 10− 2 x + 7.1721 × 10− 2x2(1.16Gy•min− 1༛R2 = 0.9997)(3).Dose rate :Y Dose rate = 1.2534 × 10− 2 x 2+6.6164 × 10− 2 x -2.732 × 10− 3༈0.01Gy•min− 1༛R2 = 0.999༉(1).The estimated dose is formula (3) – (1.16-Z) × formula (1).
A multipronged deep omics-based investigation of COVID-19 plasma samples identifies key molecular networks of disease severity progression
Authors: Suvarna Kruthi , Srivast Sanjeeva
Published: December 2020

Prognosis and management of COVID-19 severity is a challenge even after months of the pandemic. We employed high resolution mass spectrometry-based deep proteomics and metabolomics based investigation to study a cohort of 186 patients plasma samples to understand the COVID-19 disease severity mechanism. A cohort of patients displayed COVID-19 like symptoms but were negative for the virus while the COVID-19 positive patients were classified as non-severe or severe groups based on the clinical manifestation of the disease. Of the 1200 proteins detected, 27 were differentially regulated in COVID positive group while 38 were found to be differentially expressed between non-severe and severe groups. GO enrichment analysis highlighted the involvement of regulation of peptidase activity, regulated exocytosis, extracellular structure organization, blood coagulation, fibrin clot formation, complement activation, leukocyte activation involved in immune response, and response to glucocorticoid biological processes to be dysregulated in severe SARS-CoV-2 infection. Further, metabolomics identified 15 significant metabolites indicating dysregulation in tryptophan, glycine, serine, threonine, arginine, proline, and porphyrin metabolism pathways. We validated the potential severity biomarkers such as angiotensinogen, apolipoprotein B, SERPINA3, SERPING1, and Fibrinogen gamma chain using targeted proteomics. Moreover, using our proteomics dataset and docking studies we found FDA-approved drugs Selinexor and Ponatinib having potential to be repurposed for the therapeutics intervention of COVID-19.
Assessing The Feasibility and Acceptability of A Cluster-Randomized Study of Cognitive Behavioral Therapy For Chronic Insomnia In A Primary Care Setting
Authors: Torrens Isabel , Esteva Magdalena , Vicens Caterina , Vidal-Thomas Maria Clara , Pizà-Portell Maria Rosa , Vidal-Ribas Cristina , Lorente-Montalvo Patricia , Torres-Solera Elena
Published: December 2020

Background: Cognitive behavioral therapy (CBT) is the treatment of choice for chronic insomnia but is underutilized in patients in primary care. The purpose of this study was to assess the feasibility and acceptability of a pilot cluster-randomized study of CBT for chronic insomnia (CBT-i) in a primary care setting. Methods: This pilot-feasibility study with a parallel cluster-randomized design comparing CBT-i-intervention group (IG) and usual care (UC) was performed at two primary health care centers in Majorca, Spain. Patients were included if they were 18 to 65 years-old; had diagnoses of chronic insomnia according to the Insomnia Severity Index (ISI ³ 8) and had insomnia longer than 3 months; and did or did not use a hypnotic medication. A total of 25 GPs and nurses and 32 patients were randomly allocated to two groups. The outcome of the intervention was improvement in quality of sleep. Other primary outcomes were the feasibility and applicability of the intervention, which were defined using nominal groups. UC was defined based on previous studies. The recruitment process, compliance with intervention sessions, and patient retention were also assessed.Results: We adapted the CBT-i approach of Morin to a primary care context. After intervention training, primary care providers (PCPs) expressed the need for more extensive training in the different aspects of the therapy and the discussion of more cases. PCPs considered the intervention as adequate but wanted fewer and shorter sessions as well as to discard the cognitive restructuring component. PCPs considered it crucial to prepare each session in advance and to establish a specific agenda for the CBT-i. Regular reminders given to PCPs and patients were suggested to improve study participation. Compared to the UC group, significantly higher proportions of patients in the IG had short sleep latency, slept for longer than 5 h, and had fewer sleep disruptions. Conclusions: This pilot-feasibility study identified several key issues that must be addressed before performing CBT-i intervention in future clinical trials in a primary care setting. Trial registration: NCT04565223. (Clinical trials.gov) Registered 1 September 2020 - Retrospectively registered.
‘Too old to test?’: A life course approach to HIV-related risk and self-testing among midlife-older adults in Malawi
Authors: Johnson Cheryl , Kumwenda Moses , Meghji Jamilah , Choko Augustine , Phiri Mackwellings , Hatzold Karin , Baggaley Rachel , Taegtmeyer Miriam , Terris-Prestholt Fern , Desmond Nicola , Corbett Elizabeth L
Published: December 2020

Background: Despite the aging HIV epidemic, increasing age can be associated with hesitancy to test. Addressing this gap is a critical policy concern and highlights the urgent need to identify the underlying factors, to improve knowledge of HIV-related risks as well as uptake of HIV testing and prevention services, in midlife-older adults. Methods: We conducted five focus group discussions and 12 in-depth interviews between April 2013 and November 2016 among rural and urban Malawian midlife-older ( ≥ 30 years) men and women. Using a life-course theoretical framework we explored how age is enacted socially and its implications on HIV testing and sexual risk behaviours. We also explore the potential for HIVST to be part of a broader strategy for engaging midlife-older adults in HIV testing, prevention and care. Thematic analysis was used to identify recurrent themes and variations. Results: Midlife-older adults associated their age with respectability and identified HIV as “a disease of youth” that would not affect them, with age protecting them against infidelity and sexual risk-taking. HIV testing was felt to be stigmatizing, challenging age norms, threatening social status, and implying “lack of wisdom”. These norms drove self-testing preferences at home or other locations deemed age and gender appropriate. Awareness of the potential for long-standing undiagnosed HIV to be carried forward from past relationships was minimal, as was understanding of treatment-as-prevention. These norms led to HIV testing being perceived as a threat to status by older adults, contributing to low levels of recent HIV testing compared to younger adults. Conclusions: Characteristics associated with age-gender norms and social position encourage self-testing but drive poor HIV-risk perception and unacceptability of conventional HIV testing in midlife-older adults. There is an urgent need to provide targeted messages and services more appropriate to midlife-older adults in sub-Saharan Africa. HIVST which has often been highlighted as a tool for reaching young people, may be a valuable tool for engaging midlife-older age groups who may not otherwise test.
QTL Mapping of Agronomic and Economic Traits for Four F2 Populations of Upland Cotton
Authors: Li Hongge , Pan Zhaoe , He Shoupu , Jia Yinhua , Geng Xiaoli , Chen Baojun , Wang Liru , Pang Baoyin , Du Xiongming
Published: December 2020

Background: Upland cotton (Gossypium hirsutum) accounts for more than 90% of the annual world cotton output because of its high yield potential. However, yield and fiber quality traits often show negative correlations. We constructed four F2 populations of unland cotton, using two normal lines (4133B and SGK9708) with high yield potential but moderate fiber quality and two introgression lines (Suyuan04-3 and J02-247) with superior fiber quality, and used them to investigate the genetic basis underlying complex traits such as yield and fiber quality in upland cotton. We also phenotyped eight agronomic and economic traits and mapped quantitative trait loci (QTLs). Results: Extensive phenotype variations and transgressive segregation were found across the segregation populations. We constructed four genetic maps of 585.97 cM, 752.45 cM, 752.45 cM and 1 163.66 cM, one for each of the four F2 populations.. Fifty QTLs were identified across the four populations (7 for plant height, 27 for fiber quality and 16 for yield). The same QTLs were identified in different populations, including qBW4 and qBW2, which were linked to a common simple sequence repeat (SSR) marker, NAU1255. A QTL cluster containing eight QTLs for six different traits was characterized on linkage group 9 of the 4133B×Suyuan04-3 population. Conclusions: These findings will provide insights into the genetic basis of simultaneous improvement of yield and fiber quality in upland cotton breeding.
Physical mapping and InDel marker development for the restorer gene Rf2 in cytoplasmic male sterile CMS-D8 cotton
Authors: Feng Juanjuan , Zhang Xuexian , Zhang Meng , Guo Liping , QI Tingxiang , Tang Huini , Zhu Haiyong , Wang Hailin , Qiao Xiuqin , Xing Chaozhu , Wu Jianyong
Published: December 2020

Background: Cytoplasmic male sterile (CMS) with cytoplasm from Gossypium Trilobum (D8) fails to produce functional pollen. It is useful for commercial hybrid cotton seed production. The restore line of CMS-D8 containing Rf 2 gene can restore the fertility of the corresponding sterile line. This study combined the whole genome resequencing bulked segregant analysis (BSA) with high-throughput SNP genotyping to accelerate the physical mapping of Rf 2 locus in CMS-D8 cotton. Methods: The fertility of backcross population ((sterile line×restorer line)×maintainer line) comprising of 1623 individuals was investigated in the field. The fertile pool (100 plants with fertile phenotypes, F-pool) and the sterile pool (100 plants with sterile phenotypes, S-pool) were constructed for BSA resequencing. The selection of 24 single nucleotide polymorphisms (SNP) through high-throughput genotyping and the development insertion and deletion (InDel) markers were conducted to narrow down the candidate interval. The pentapeptide repeat (PPR) family genes and upregulated genes in restore line in the candidate interval were analysed by qRT-PCR. Results: The fertility investigation results showed that fertile and sterile separation ratio was consistent with 1:1. BSA resequencing technology, high-throughput SNP genotyping, and InDel markers were used to identify Rf 2 locus on candidate interval of 1.48 Mb on Chromosome D05. Furthermore, it was quantified in this experiment that InDel markers co-segregated with Rf 2 enhanced the selection of the restorer line. The qRT-PCR analysis revealed PPR family gene Gh_D05G3391 located in candidate interval had significantly lower expression than sterile and maintainer lines. In addition, utilization of anther RNA-Seq data of CMS-D8 identified that the expression level of Gh_D05G3374 encoding NB-ARC domain-containing disease resistance protein in restorer lines was significantly higher than that in sterile and maintainer lines. Conclusions: This study not only enabled us to precisely locate the restore gene Rf 2 but also evaluated the utilization of InDel markers for marker assisted selection in the CMS-D8 Rf 2 cotton breeding line. The results of this study provide an important foundation for further studies on the mapping and cloning of restorer genes.
Hypoxia-preconditioned adipose-derived stem cells combined with scaffold promote urethral reconstruction by up-regulation of angiogenesis and glycolysis
Authors: Wan Xiang , Xie Min-kai , Xu Huan , Wei Zi-wei , Yao Hai-jun , Wang Zhong , Zheng Dachao
Published: December 2020

Rationale: Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia preconditioned ADSCs, compared to normxia preconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism.Methods: In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits.Results: The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxia-preconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology and enhanced angiogenesis (p < 0.05). Conclusions: Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction.
Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy
Authors: Kasahara Yuko Nitahara , Kuraoka Mutsuki , Oda Yuki , Kinoh Hiromi Hayashita , Takeda Shin’ichi , Okada Takashi
Published: December 2020

Background: Multipotent mesenchymal stromal cells (MSCs) are potentially therapeutic for muscle disease because they can accumulate at the sites of injury and act as immunosuppressants. MSCs are attractive candidates for cell-based strategies that target diseases with chronic inflammation, such as Duchenne muscular disease (DMD). We focused on the anti-inflammatory properties of IL-10 and hypothesized that IL-10 could increase the typically low survival of MSCs by exerting a paracrine effect after transplantation.Methods: We developed a continuous IL-10 expression system of MSCs using an adeno-associated virus (AAV) vector. To investigate the potential benefits of IL-10 expressing AAV vector-transduced MSCs (IL-10-MSCs), we examined the cell survival rates in the skeletal muscles after intramuscular injection into mice and dogs. Systemic treatment with IL-10-MSCs derived from dental pulp (DPSCs) was comprehensively analyzed using the canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to that of DMD patients.Results: In vivo bioluminescence imaging analysis revealed higher retention of IL-10-MSCs injected into the hind-limb muscle of mice. In the muscles of dogs, myofiber-like tissue was formed after the stable engraftment of IL-10-MSCs. Repeated systemic administration of IL-10-DPSCs into the CXMDJ model resulted in long-term engraftment of cells and slightly increased the serum levels of IL-10. IL-10-hDPSCs showed significantly reduced expression of pro-inflammatory MCP-1 and upregulation of stromal-derived factor-1 (SDF-1). MRI and histopathology of the hDPSC-treated CXMDJ indicated the regulation of inflammation in the muscles, but not myogenic differentiation from treated cells. hDPSC-treated CXMDJ showed improved running capability and recovery in tetanic force with concomitant increase in physical activity. Serum creatine kinase levels, which increased immediately after exercise, were suppressed in IL-10-hDPSC-treated CXMDJ.Conclusions: In case of local injection, IL-10-MSCs could maintain the long-term engraftment status and facilitate associated tissue repair. In case of repeated systemic administration, IL-10-MSCs facilitated the long-term retention of the cells in the skeletal muscle and also protected muscles from physical damage-induced injury, which improved muscle dysfunction in DMD. We can conclude that the local and systemic administration of IL-10-producing MSCs offers potential benefits for DMD therapy through the beneficial paracrine effects of IL-10 involving SDF-1.
Risk factors for multiple drug resistant tuberculosis relapses
Authors: Аlliluev А. S. , Filinyuk O. V. , Shnayder E. E. , Golubchikov P. N. , Аmichba D. E.
Published: December 2020

The objective of the study: to identify risk factors for relapses in patients after the effective course of chemotherapy for multiple drug resistant tuberculosis (MDR TB). Subjects and methods. Medical files of 346 adult MDR TB patients were analyzed, they all had the effective treatment as per regimen IV in Tomsk Phthisiopulmonology Medical Center in 2009-2011. They were divided into 2 groups: Group 1 included 35 patients who developed a relapse of tuberculosis over the next 5 years; Group 2 consisted of 311 patients who had no relapse of the disease over the next 5 years. Results. The relapse rate in effectively treated MDR TB patients made 10.1% (35/346 patients). The following social factors contributed to higher chances of the relapse: retirement age (p = 0.045; OR = 2.86 [1.14-7.20]) and disability due to somatic diseases (p < 0.001; OR = 4.82 [2.13-10.90]); while biomedical factors were the following: HIV infection (OR = 19.19 [5.29-69.56]), mental illness (OR = 5.85 [2.27-15.03]), tobacco smoking (OR = 3.16 [1.08-9.20]). People with history of tuberculosis relapses (OR = 12.17 [4.19-35.34]) have higher chances of relapse, as well as those having the following characteristics of the tuberculosis disease during the effective chemotherapy course: destruction of lung tissue (OR = 7.48 [1.76-31.80]), positive results of sputum smear microscopy (OR = 2.91 [1.28-6.61]), persisting bacterial excretion (by culture) after 2 months of chemotherapy (OR = 4.98 [2.41-10.29]).
Professional Development of English Teachers at a State Islamic Senior High School in Palembang
Authors: Fadhliyah Rizki , Mirizon Soni , Petrus Ismail
Published: December 2020

The objectives of this study were to investigate teachers’ professional development, the obstacles faced by the teachers, teachers’ efforts to resolve the obstacles, and school support for the teachers in continuing professional development. To reveal the phenomenon, qualitative case study design was used. This study combined observation, questionnaires, and interviews in data collection. English teachers, vice-principal of the curriculum, teachers who taught other subjects, and students who had been taught by the English teachers were the participants of this study. Findings revealed that English teachers’ professional development was good. The results also revealed that teachers’ scientific publications were in the poor category. Innovative works for both English teachers were in the average category. Lack of time and information were the obstacles faced by the English teachers in continuing professional development. Teachers attempted to resolve the obstacles by looking for information needed through the internet. They also had discussions with other teachers to gain information for their knowledge. The school frequently conducted some programs related to teachers’ professional development and allowed them to attend professional development activities held by other institutions.
ENSINO REMOTO E FORMAÇÃO DE PROFESSORES: UM ESTUDO COM OS LICENCIANDOS DE PEDAGOGIA
Authors: Silva Cinthia Luiz da , Altino Filho Humberto Vinício
Published: December 2020

Este estudo tem como foco a investigação das relações dos licenciando do curso de Pedagogia de uma Instituição de Ensino Superior do Leste de Minas Gerais com o Ensino Remoto Emergencial. Sabe-se que o contexto da pandemia do COVID-19 trouxe efeitos e impactos nos mais diversos setores da sociedade, inclusive na educação. Para conhecer as relações mencionadas, além da contextualização do estudo, os dados foram coletados por meio de um questionário on-line. Os resultados apontam que, em linhas gerais, o Ensino Remoto superou as expectativas dos estudantes e as percepções sobre os pontos que foram, de certa forma, mais desafiadores nesse modelo, mostram que os ideias de educação para esses futuros professores encontram-se em consonância com as discussões sobre o ensino e aprendizagem atuais.
Acute Issues of Strateging and Functioning of Information Space on Territory in Conditions of Restrictive Measures
Authors: Odintsova T. M. , Matushevskaya E. A. , Shipilov N. Yu. , Rozhkova M. G.
Published: December 2020

The article studies such issues as strateging of sustainable development of regions, developing the system of information support of strategic development of the region, risks connected with sanctions imposed by Western countries. These subjects were analyzed with the help of literature sources and further lines of research were proposed. The system of information support of strategic development of regions includes strategic goals and figures of development, which require correction in conditions of growing pressure on behalf of Western countries, as well as political and economic restriction of external environment. The authors came to the conclusion about the necessity to correct the system of indicators of the region strategic development by social and economic expediency, managerial supervision and possibility of monitoring. During designing, realizing and monitoring of strategy of region development it is necessary to take into account the impact not only of conventional restrictions coming from the external environment but also specific restrictions in conditions of sanctions imposed by Western countries. Such restrictions during the last decade turned into a trend, which affects life of territories with uncertain status, unrecognized and questionable territories and tend to be used as tools of political pressure or economic wars.
Prospects of Developing Municipal Structures in the 21st Century (Illustrated by the Republic of Armenia)
Authors: Martirosyan G. K. , Avetyan A. A.
Published: December 2020

Nowadays many democratic states face the acute problem of even and sustainable regional development. The article studies different trends of organizational changes in the development of local self-governance in connection with social and economic changes. It is found out that the key hindrances for effective development of local selfgovernance are the standard of living of the population, the resource potential, investment appeal, the scale of local self-governance authority, the level of municipal facility infrastructure and low use of informational and advanced technologies in municipal services being rendered. In this aspect we focus on the issue of upgrading the system of strategic management of municipal structures’ development, which could provide an opportunity of identifying their promising directions and with the help of advanced information technologies reach a new level of development. The authors by analyzing academic data, key parameters of development and legislative and organizational principles of local self-governance in the Republic of Armenia prepared recommendations aimed at modernizing the system of municipal structures’ management, which would allow us to build an efficient, flexible and economical system of local self-governance. Findings of the research could be used both in the system of state and municipal governance and in academic research in the field of local self-governance development.
Credit Market Imbalances in Russia: Dynamics and Risks
Authors: Belyaninov A. Yu. , Garnov A. P. , Perepelitsa D. G.
Published: December 2020

Digital-marketing market is growing exponentially. There are a lot of services, platforms and technologies that are used for business promotion. While 10 years ago only Google and Facebook were available, today we can see thousands of various solutions. Analysts forecast transit of all industries to digital space. Changes in behavioral skills of customer finance services and growing competitive pressure on the part of start-ups ruin conventional business-models and induce us to develop new strategies. Therefore banks and other regulated finance intermediaries try, with due regard to their budgets, to master as quickly as possible innovations in the field of finance technologies and alter formats of client service. A typical feature of today’s society development is increasing innovation of all spheres of human activity. For example, now we can observe break-through innovation in technology, which changes not only technical and technological foundations of economy but drastically influence different processes in the social sphere. Researching credit strategies within the frames of economic behavior of the population is connected mainly with studying the grounds, key trends and consequences of individuals’ operations on finance service market. The article investigates specific features of Russian citizens’ behavior in the segment of mortgage crediting and auto-crediting, analyzes figures of banks in crediting individuals and shows risks of repayment delay. The authors systematized key concepts of regulating credit and finance markets, which is needed for the process of designing the effective regulatory model that takes into account specific features of markets. The findings of the research can be used in assessing the efficiency and improvements in international coordination of national regulators on finance markets.
State Viewed by Economists
Authors: Makarov V. L. , Kozyrev A. N. , Dementiev V. E. , Ustyuzhanina E. V.
Published: December 2020

The article studies issues of transforming the institution of state in today’s conditions. Special attention is paid to the following questions: characteristic features of state as a specific social and economic institution; immanent contradictions of the institution; lines in state development in conditions of world economic ties globalization; digitalization of the communication system and ecological interdependence. The given approach to research is characterized by its focus on economic aspects of current changes. The goal of the article is to find out key spots of mutual impact of state and economic system. The authors discuss such problems as reshaping the system of contacts inside state and among them, the role of state in controlling key resources, dubious nature of state as an institution, watering state borders, citizenship in conditions of cosmopolitanism, feasibility of such form of public life organization as people’s rule, the role of culture in forming and retaining the institution of state, the impact of pandemia on evolution of interstate relations. Co-authors’ opinions are not always the same, however, they adhere to the common approach to researching the phenomenon of state as a developing and transforming institution. The article was written on the basis of materials of the seminar held in the Central Institute of Economics and Mathematics RAN within the frames of the ‘Makarov’s Gathering’ Club.
Investigating the Impact of Different Acrylamide (Electrophilic Warhead) on Osimertinib’s Pharmacological Spectrum by Molecular Mechanic and Quantum Mechanic Approach
Authors: Patel Harun , Ahmad Iqrar , Jadhav Harsha , Pawara Rahul , Lokwani Deepak , Surana Sanjay
Published: December 2020

Background:

Lung cancer has become the prominent cause of the cancer-related deaths
globally. More than 80 % of all lung cancers have been diagnosed with Non- Small Cell Lung
Cancer (NSCLC). The USFDA approved osimertinib to treat patients with metastatic T790M
EGFR NSCLC on a regular basis in March 2017. Recently, C797S mutation to osimertinib has
been reported, which indicates the need for structural modification to overcome the problem of
mutation.

Methods:

In this bioinformatics study, we have evaluated the impact of various acrylamide as an
electrophilic warhead on the activity and selectivity of osimertinib.

Results:

Osimertinib analouge 48, 50, 60, 61, 67, 75, 80, 86, 89, 92, 93, 116 and 124 were the most
active and selective compounds against T790M EGFR mutants compared to Osimertinib.

Conclusion:

These compounds also showed less inclination towards WT-EGFR.
Neobavaisoflavone Demonstrates Valid Anti-tumor Effects in Non-Small- Cell Lung Cancer by Inhibiting STAT3
Authors: Cai Xueding , Zhou Feng , Xie Xiaona , Zheng Dandan , Yao Yulei , Zhao Chengguang , Huang Xiaoying , Hu Ke
Published: December 2020

Aim and Objective :

Lung cancer is the most commonly occurring cancer, which
contributes to the majority of death caused by cancer, where non-small-cell lung cancer (NSCLC)
accounts for approximately 85% of lung cancer. To treat NSCLC, STAT3 has been identified as a
target with therapeutic potential. The neobavaisoflavone (NBIF) is one of the flavonoids of
traditional Chinese medicine Psoralea corylifolial.

Materials and Methods:

Human NSCLC cell lines, PC-9, H460 and A549, were applied to determine NBIF’s antiproliferative effects through cell viability and colony formation detection. The effect of NBIF on cell apoptosis was
determined through Flow cytometry-based assay. Western blotting was used in this study to confirm the levels of P-STAT3
and Bcl-2 and Bax which are apoptotic proteins.

Results:

It was observed that NBIF could decrease the cell viability and migration and induce apoptosis in human NSCLC
cell lines dose-dependently. Levels of P-STAT3, as well as the downstream signals of STAT3 pathway, were
downregulated, suggesting that the tumor-suppression effects of NBIF might be related to the inhibition of STAT3
signaling. Furthermore, NBIF could contribute to the upregulation of BAX and downregulation of BCL2.

Conclusion:

NBIF might perform the anti-NSCLC efficacy as a result of the inhibition on STAT3 pathway. Besides, our
work suggests that NBIF could provide therapeutic alternatives for NSCLC.
Synthetic and Semi-synthetic Drugs as a Promising Therapeutic Option for the Treatment of COVID-19
Authors: Shirbhate Ekta , Patel Preeti , Patel Vijay K , Veerasamy Ravichandran , Sharma Prabodh C , Sinha Barij N , Rajak Harish
Published: December 2020

The novel coronavirus disease-19 (COVID-19) is a global pandemic that emerged from
Wuhan, China, and has spread all around the world, affecting 216 countries or territories with
21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 updates of August
18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for
combating this infection. Despite, to date, no certified antiviral treatment or vaccine exists. Although,
few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-
19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity
in clinical uses or studies on COVID-19 and also focuses on the mode of action of drugs being
repositioned against COVID-19.
Detection of Natural Inhibitors against Human Liver Cancer Cell Lines through QSAR, Molecular Docking and ADMET Studies
Authors: Alam Sarfaraz , Nasreen Sadaf , Ahmad Ateeque , Darokar Mahendra Pandurang , Khan Feroz
Published: December 2020

Background:

Liver cancer is ranked as the fifth most prevalent and third most lethal cancer
worldwide. The incidence rates of this cancer are on the rise, and only limited treatment options
are available.

Methods:

To identify and optimize the inhibitors of liver cancer cell-lines, a QSAR model was developed
by using multiple linear regression methods. The robustness of the model was validated
through statistical methods and wet-lab experiments.

Results:

The developed QSAR models yielded high activity descriptor relationship accuracy of
91%, referred to by regression coefficient (r2= 0.91), and a high activity prediction accuracy of
89%. The external predicted (pred_r2) ability of the model was found to be 90%.

Conclusion:

The QSAR study indicates that chemical descriptors such as to measure of electronegative
atom count (Epsilon3), atom type count descriptors (MMFF_10), number of a carbon atom
connected with four single bonds (SssssCE- index), molecular weight and, number of oxygen atom
connected with two aromatic bonds (SaaOE-index) are significantly correlated with anticancer activity.
The model, which was validated statistically and through wet-lab experiments, was further
used in the virtual screening of potential inhibitors against the liver cancer cell line WRL68. ADMET
risk screening, synthetic accessibility, and Lipinski's rule of five are used to filter false positive
hits. AfterwardS, to achieve a set of aligned ligand poses and rank the predicted active compounds,
docking studies were carried out. The studied compounds and their metabolites were also
analyzed for different pharmacokinetics parameters. Finally, a series of compounds was proposed as
anticancer agents.