bluuebunny/crossref_metadata_2025 huggingface dataset:
p38β - MAPK11 and its role in female cancers
Authors: Katopodis Periklis , Kerslake Rachel , Zikopoulos Athanasios , Beri Nefeli Eirini , Anikin Vladimir
Published: November 2020

Background The p38MAPK family of Mitogen Activated Protein Kinases are a group of signalling molecules involved in cell growth, survival, proliferation and differentiation. The widely studied p38α isoform is ubiquitously expressed and is implicated in a number of cancer pathologies, as are p38γ and p38δ. However, the mechanistic role of the isoform, p38β, remains fairly elusive. Recent studies suggest a possible role of p38β in both breast and endometrial cancer with research suggesting involvement in bone metastasis and cancer cell survival. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment however require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using an in-silico approach. Methods A detailed gene expression and methylation analysis was performed using datasets from cBioportal, CanSar and MEXPRESS. Breast, Uterine Endometrial, Cervical, Ovarian and Uterine Carcinosarcoma TCGA cancer datasets were used and analysed.Results Data using cBioportal and CanSAR suggest that expression of p38β is lower in cancers: BRCA, UCEC, UCS, CESC and OV compared to normal tissue. Methylation data from SMART and MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene MAPK11. Analysis of the genes’ two CpG islands shows that the gene was hypermethylated in the CpG1 with increased methylation seen in BRCA, CESC and UCEC cancer data sets with a slight increase of expression recorded in cancer samples. CpG2 exhibited hypomethylation with no significant difference between samples and high levels of expression. Further analysis from MEXPRESS revealed no significance between probe methylation and altered levels of expression. In addition, no difference in the expression of BRCA oestrogen/progesterone/HER2 status was seen. Conclusion This data provides an overview of the expression of p38β in female tissue specific cancers, showing a decrease in expression of the gene in BRCA, UCEC, CESC, UCS and OV, increasing the understanding of p38β MAPK expression and offering insight for future in-vitro investigation and therapeutic application.
Role of doxycycline, oral steroids, and nasal steroid in treatment of anosmia due to COVID-19 with the new insights into the doxycycline activity.
Authors: Husain Parvez , Ahmed Shaheen Khalil , Husain Benazeer
Published: November 2020

Background All over the world, severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has been the most important public health issue this year; recently this was re-named as corona virus disease 2019 (COVID-19) by the World Health Organization (WHO). Olfactory or gustatory dysfunction is often reported as a symptom.Aims Aim of the study is to evaluate the role and effectiveness of Doxycycline, Oral Methyl Prednisolone, and Topical Nasal Steroid (Mometasone) in the treatment of COVID-19 related anosmia/hyposmiaMaterial and Methods Total 64 patients were evaluated randomly who were COVID-19 positive and developed recent onset of anosmia/hyposmia. They were divided into two groups 32 each. First group was treated with Doxycycline, Oral Methyl Prednisolone, and Topical Nasal Steroid (Mometasone). Second group was the control group and was given placebo and Olfactory training.Results Out of 32 patients 27 patients completely recover after only 2 days of the administration of above treatment. Out of the remaining 5 patients 4 had partial resolution of the anosmia after 2 days and near complete resolution after 5-7 days, and 1 patient did not responded at all with the above treatment. Out of the control group 19 patient had near complete recovery after 7 days and rest 13 patient did not recover after 10 days.Conclusion The above study showed a very promising results but many more similar studies are needed following the similar treatment protocol on a larger group of patients suffering from olfactory dysfunction.
Rapid Serological Tests for SARS-COV-2: Diagnostic Performance of Four Commercial Assays
Authors: de Almeida Sérgio Monteiro , Spalanzani Regiane Nogueira , Nogueira Meri Bordignon , Spiri Beatriz Sanada , Cavalli Barbara Maria , Rotta Indianara , Takahashi Gislene Reche de Almeida , Pereira Luciane Aparecida , Moreira Francielli Brusco , Dino Carolina Lumi Tanaka , Graf Maria Esther , de Almeida Bernardo Montesanti Machado , Domino Natalia Ramos , Genelhoud Gustavo , Bueno Lucas Bochnia , Raboni Sonia Mara
Published: November 2020

Background. This study aimed to assess the diagnostic performance of lateral flow immunochromatographic assays (LFA) of four different manufacturers to identify SARS-CoV-2 antibodies (IgM, IgG or total), comparing them with the nucleic acid amplification test (NAAT) or clinical defined (definite or probable SARS-CoV-2 infection respectively). Methods. 119 serum samples were randomly selected by convenience and distributed in the groups: (1) Group with SARS-CoV-2 infection [n=82; RT-qPCR positive (definite, n=70), and probable (n=12)]; (2) other diseases [n= 27; other viruses identified (n=8), SARS of other etiologies (n=19)]; (3) healthy control group (n=10). LFA essays of four manufacturers were compared: MedTest Coronavírus (COVID-19) IgG/IgM (MedLevensohn, Brazil); COVID-19 IgG/IgM ECO Test (Ecodiagnóstica, Brazil); Camtech COVID-19 IgM/IgG Rapid Test Kit (Camtech Diagnostics Pte Ltd, Singapore); and one Step COVID-19 Test for total antibodies (Guangzhou Wondfo Biotech Co, China).Results. The four tests studied showed high diagnostic performance characteristics for the diagnoses of definite or probable SARS-CoV-2 infection. The best measures were for the Wondfo test: sensitivity (86.59%; 95%CI, 77.26-93.11%); specificity (100%; 90.51-100%); DOR (257; 60-1008); LR+ (33.43; 4.82-231.85); LR− (0.13; 0.08 - 0.23); accuracy (90.76%; 84.06- 95.29%); Matthews Correlation coefficient (MCC) 0.82. Although considering only the probable SARS-CoV-2 infection (PCR-) cases, all the kits studied showed limited values.Conclusion. Our data demonstrate the excellent performance of LFA for the diagnoses of definite or probable SARS-CoV-2 infection. There was substantial heterogeneity in sensitivities of IgM and IgG antibodies among the manufacturers. LFA tests cannot replace molecular diagnostics, but should be used as additional screening tool.
Long Non-coding RNA LINC02085 Mediates Cell Growth and Inflammatory Response of Fibroblast-Like Synoviocytes by Activating PI3K/AKT Signals in Rheumatoid Arthritisis
Authors: Wen Jianting , Liu Jian , Wang Xin , Wang Jie
Published: November 2020

Background: The present study explored the possible functions and the underlying mechanism of Long Non-coding RNA LINC02085 in rheumatoid arthritis (RA). Methods: Peripheral blood mononuclear cells (PBMCs) were collected from patients with RA. Primary fibroblast-like synoviocytes (FLS) were separated from synovial tissues and was established cell lines, then cultured for subsequent cell experiments by transfecting different vectors. The RT-qPCR analysis was employed for evaluating the levels of LINC02085 in the PBMCs and RA-FLS. ELISA analysis was employed to detect the levels of inflammatory cytokines. CCK8 assay, migration and invasion assays were used to evaluate the proliferation, migration and invasion abilities of cells, respectively. Besides, the levels of the the PI3K/AKT pathway-related proteins were measured by WB and IF. Spearman correlation analysis, association rule analysis, logistic regression analysis were used to assess the correlation between LINC02085 and clinical parameters. Results: The expression level of LINC02085 was significant high in patients with RA, and positively associated with age, ESR, CRP, RF, CCP and DAS28. Moreover, logistic regression analysis indicated that ESR, CRP, RF and DAS28 were risk factors for LINC02085. We found that LINC02085 was upregulated in RA -FLS and TNF-αstimulated. And overexpression of LINC02085 could promote proliferation, migration and invasion induced by TNF-α, through upregulating the levels of TNF-αand TNFAIP2 and promoting the activation of PI3K/AKT pathway. Whereas knockdown of LINC02085 received the opposite results. ﻿Conclusion: In conclusion, the present study revealed that LINC02085 could regulate cell growth and inflammatory response of RA-FLS by activating the PI3K/ AKT signaling pathway, subsequently playing important roles in promoting the occurrence and development of RA.
APEX1 regulates alternative splicing of key tumorigenesis genes in non-small-cell lung cancer
Authors: Peng Li , Liu Yuwei , Chen Jing , Du Xuebei , Zhang Renwei , Cheng Mengxin , Wu Ying , Chen Min , Zhong Ya , Shen Dan , Chen Ling , Ye Xujun
Published: November 2020

Background: Aberrant alternative splicing (AS) contributes to tumor progression. Previous studies have shown that apurinic-apyrimidinic endonuclease-1 (APEX1) is involved in tumor progression. It is unknown whether APEX1 functions in tumor progression by regulation of AS. It is also unknown whether APEX1 can regulate non-small-cell lung cancer (NSCLC) proliferation and apoptosis. Methods: We analyzed APEX1 expression levels in 517 lung NSCLC samples from the TCGA (Cancer Genome Atlas) database. The impact of APEX1 over expression on A549 cell proliferation and apoptosis was detected by the methyl thiazolyl tetrazolium assay and by flow cytometry. The transcriptome of A549 cells with and without APEX1 over expression was determined by Illumina sequencing, followed by analysis of AS. RT-qPCR validated APEX1 in A549 cells. Results: We have successfully applied RNA-seq technology to demonstrate APEX1 regulation of AS. APEX1 expression was shown to be upregulated in NSCLC samples and to reduce cell proliferation and induce apoptosis of A549 cells. Further, APEX1 regulated AS of key tumorigenesis genes involved in cancer proliferation and apoptosis within the MAPK and Wnt signaling pathways. Each of these pathways are involved in lung cancer progression. Validated AS events regulated by APEX1 were located in key tumorigenesis genes; AXIN1 (axis inhibition protein 1), GCNT2 (N-acetyl glucosaminyl transferase 2), and SMAD3 (SMAD Family Member 3). These genes encode signaling pathway transcription regulatory factors. Conclusions: We found that increased expression of APEX1 in NSCLC is an independent prognostic factor related to tumor progression. Therefore, APEX1 regulation of AS may serve as a molecular marker or therapeutic target for NSCLC treatment.
Lightweight Model For The Prediction of COVID-19 Through The Detection And Segmentation of Lesions in Chest CT Scans
Authors: Ter-Sarkisov Aram
Published: November 2020

We introduce a lightweight Mask R-CNN model that segments areas with the Ground Glass Opacity and Consolidation in chest CT scans. The model uses truncated ResNet18 and ResNet34 nets with a single layer of Feature Pyramid Network as a backbone net, thus substantially reducing the number of the parameters and the training time compared to similar solutions using deeper networks. Without any data balancing and manipulations, and using only a small fraction of the training data, COVID-CT-Mask-Net classification model with 6.12M total and 600K trainable parameters derived from Mask R-CNN, achieves 91.35% COVID-19 sensitivity, 91.63% Common Pneumonia sensitivity, 96.98% true negative rate and 93.95% overall accuracy on COVIDx-CT dataset (21191 images). We also present a thorough analysis of the regional features critical to the correct classification of the image. The full source code, models and pretrained weights are available on https://github.com/AlexTS1980/COVID-CT-Mask-Net.
A simulation is worth a thousand worlds - Importance sampling Monte Carlo applied to COVID-19 contingency
Authors: Rapuzzi Andrea , Vairo Tomaso
Published: November 2020

COVID-19 outbreak has become a global pandemic that affected more than 200 countries worldwide. Predicting the behavior of this outbreak has a crucial role in organizing preventive and protective actions, and in improving the decision making process.The aim of predicting the number of people who contract the virus has so far been pursued with regression models (exponential, logistics, ...), but regressions can integrate the variable context only a posteriori. The regression models are all dependent on their own history, thus, they can not display anything which did not happen before.The pandemic infection of COVID-19 presents a transmission behavior that is widely changing over time. This is due to the growth of the efficiency in the detection of infected, for the changes in social distancing measures and for the widespread use of individual protection devices.The approach presented in this paper, starting from the definition of simplified risk assessment framework, aims at designing a probabilistic model for the virus transmission and detection, keeping into account this context changes, binding the correct set of variables to them, and at inferring the distribution for the underlying stochastic variables. This is a key to unlock innovative and valuable insights from the current events. The model has been built in Gen, a probabilistic programming system, built at MIT and embedded in Julia.
Evaluation of image quality at the detector’s edge of dedicated breast positron emission tomography
Authors: Satoh Yoko , Motosugi Utaroh , Imai Masamichi , Omiya Yoshie , Onishi Hiroshi
Published: November 2020

Background: Using phantoms and clinical studies in prone hanging breast imaging, we assessed the image quality of a commercially available dedicated breast PET (dbPET) at the detector's edge, where mammary glands near the chest wall are located. These are compared to supine PET/CT breast images of the same clinical subjects.Methods: A breast phantom with four spheres (16, 10, 7.5, and 5 mm diameter) was filled with 18F-fluorodeoxyglucose solution (sphere-to-background activity concentration ratio, 8:1). The spheres occupied five different positions from the top edge to the centre of the detector and were scanned for 5 min in each position. Reconstructed images were visually evaluated, and the contrast-to-noise ratio (CNR), contrast recovery coefficient (CRC) for the 5-mm sphere, and coefficient of variation of the background (CVB) were calculated. Subsequently, clinical images obtained with standard supine PET/CT and prone dbPET were retrospectively analysed. Tumour-to-background ratios (TBRs) between breast cancer near the chest wall (close to the detector’s edge; peripheral group) and at other locations (non-peripheral group) were compared. The TBR of each lesion was compared between dbPET and PET/CT.Results: Closer to the detector’s edge, the CNR and CRC decreased while the CVB increased in the phantom study for all sphere sizes. The disadvantages of this placement were visually confirmed. Regarding clinical images, TBR of dbPET was significantly higher than that of PET/CT in both the peripheral (12.38±6.41 vs 6.73±3.5, p=0.0006) and non-peripheral (12.44±5.94 vs 7.71±7.1, p=0.0183) groups. There was no significant difference in TBR of dbPET between the peripheral and non-peripheral groups.Conclusion: The phantom study revealed poorer image quality at <2 cm distance from the detector's edge than at other more central parts. In clinical studies, however, the visibility of breast lesions with dbPET was the same regardless of the lesion position, and it was higher than that in PET/CT. dbPET has a great potential for detecting breast lesions near the chest wall if they are at least 2 cm from the edge of the FOV, even in young women with small breasts.
Understanding Social Media Beyond Text: A Reliable Practice on Twitter
Authors: Hou Qixuan , Han Meng , Qu Feiyang , He Jing (Selena)
Published: November 2020

Social media provides high-volume and real-time data, which has been broadly used in diverse applications in sales, marketing, disaster management, health surveillance, etc. However, distinguishing between noises and reliable information can be challenging, since social media, a user-generated content system, has a great number of users who update massive information every second. The rich information is not only included in the short textual content but also embedded in the images and videos. In this paper, we introduce an effective and efficient framework for event detection with social media data. The framework integrates both textual and imagery content in the hope to fully utilize the information. The approach has been demonstrated to be more accurate than the text-only approach by removing 58 (66.7%) false-positive events. The precision of event detection is improved by 6.5%. Besides, based on our analysis, we also look into the content of these images to further explore the space of social media studies. Finally, the closely related text and image from social media offer us valuable text-image mapping, which can enable knowledge transfer between two media types.
Geographic location of health facility and immunization program performance in Hoima district, western Uganda: A health facility level assessment
Authors: Kwikiriza Nicholas Magambo , Bajunirwe Francis , Bagenda Fred
Published: November 2020

Background: Globally, immunization coverage for childhood vaccines is below the immunization target of achieving at least 90% coverage with the pentavalent vaccine. In Uganda, a recent survey shows 80% of districts had poor immunization program performance. However, there is significant variation in performance within and between districts. We hypothesized that geographic location of a health facility may influence performance of its immunization programs. Therefore, the purpose of this study was to examine whether geographical location of a health facility within a district is associated with performance of the immunization program in Hoima district, western Uganda.Methods: We conducted a cross sectional study using a mixed methods approach. The main study unit was a health center and we also interviewed health workers in-charge of the facilities and reviewed their health facility records. We reviewed the Uganda Health Management Information System (HMIS) 105 reports of six months to obtain data on immunization program performance. Performance was categorized using World Health Organization’s Reach Every District (RED) criteria and classified as poor if a facility fell in category 3 or 4 and good if 1 or 2. We also conducted key informant interviews with immunization focal persons in the district. We examined the association between dependent and independent variables using Fisher’s exact test. Results: We collected data at 49 health facilities. Most of these facilities (55.1%) had poor immunization program performance. Proximal location to the central district headquarters was significantly associated with poor immunization program performance (p<0.05). Attitudes of health workers in the more urban areas, differences in strategies for outreach site selection and community mobilization in the rural and urban areas were suggested as possible explanations.Conclusions: Proximal location to the urban setting near district headquarters was strongly associated with poor immunization program performance. To be able to reach larger numbers of children for vaccination, interventions to improve performance should target health facilities in urban settings.
Design and validation of Brucellosis prevention questionnaire focused on animal vaccination
Authors: Bahadori Farhad , Ghofranipour Fazlollah , Ghaﬀarifar Saeideh , Ziaei Reza
Published: November 2020

Background: Inadequate awareness of livestock breeders concerning the transmission of brucellosis and their improper knowledge with regard to the prevention of brucellosis are among important barriers to vaccinate animals against brucellosis. The aim of this study is design and validation of a Brucellosis prevention questionnaire focused on animal vaccination. This valid questionnaire is used to design, implement and evaluate an interventional training program.Methods: In this exploratory psychometric study, a brucellosis prevention questionnaire (BPQ) was developed. Face-to-face interviews were conducted to develop the initial items of BPQ. The findings from interviews were merged with those of literature review. Face, content and construct validity of BPQ were assessed by participation of livestock breeders, veterinarians and health educationists. Impact Score (IS), Content Validity Ratio (CVR) and Content Validity Index (CVI) of the items were calculated. Construct validity of BPQ was evaluated through factor analysis. Cronbach’s alpha, Intra-class correlation coefficient (ICC), composite reliability and standard error of measurement (SEM) were measured to assess the reliability of the findings by BPQ.Results: BPQ was finalized by 53 items and its validity was confirmed by CVI, CVR, and IS of 0.90, 0.74 and 4.30, respectively. The items were loaded into three constructs of awareness, attitude and practice. The predictive power of the awareness, attitude and practice was 43.43%, 15.81% and 15.78%, respectively. The fitness of the proposed model among those constructs was confirmed by Root Mean Square Error of Approximation (RMSEA) <0.08, Normed chi-square (x 2/ df) < 5.0, Comparative Fit Index (CFI) ≥ 0.90, Tucker- Lewis Index (TLI) ≥ 0.9. Conclusion: The brucellosis prevention questionnaire has acceptable psychometric properties. Applying BPQ, veterinarians and educational planners can identify factors influencing preventive behavior of livestock breeders.
A Model to Illustrate the Potential Pairing of Animal Biotelemetry with Individual-Based Modeling
Authors: Brosnan Ian G , Welch David W
Published: November 2020

Background. Animal biotelemetry and individual-based modeling (IBM) are natural complements, but there are few published examples where they are applied together to address fundamental or applied ecological questions. Existing studies are often found in the modeling literature and frequently re-use small datasets collected for purposes other than the model application. Animal biotelemetry can provide the robust measurements that capture relevant ecological patterns needed to parameterize, calibrate, and assess hypotheses in IBMs; together they could help meet demand for predictive modeling and decision-support in the face of environmental change. Results. We used an simple exemplar IBM that uses spatio-temporal movement patterns of 103 acoustic-tagged juvenile yearling Chinook salmon (Oncorhynchus tshawytscha), termed ‘smolts’, to quantitatively assess plausibility of two migratory strategies that smolts are hypothesized to use while migrating north through the plume of the Columbia River (United States of America). We find that model smolts that seek to maximize growth demonstrate movement patterns consistent with those of tagged smolts. Model smolts that seek to move quickly out of the plume region by seeking favorable currents do not reproduce the same patterns. Conclusions. Animal biotelemetry and individual-based modeling are maturing fields of inquiry. Our hope is that this model description and the basic analytical techniques will effectively illustrate individual-based models for the biotelemetry community, and perhaps inspire new collaborations between biotelemetry researchers and individual-based modelers.
Barriers to women's disclosure of Domestic Violence in health services in Palestine: qualitative interview-based study
Authors: Shaheen Amira , Ashkar Suzy , Alkaiyat Abdulsalam , Bacchus Loraine , Colombini Manuela , Feder Gene , Evans Maggie
Published: November 2020

Background Domestic violence (DV) damages health and requires a global public health response and engagement of clinical services. Recent surveys show that 27% of married Palestinian women experienced some form of violence from their husbands over a 12 month’s period, but only 5% had sought formal help, and rarely from health services. Across the globe, barriers to disclosure of DV have been recorded, including self-blame, fear of the consequences and lack of knowledge of services. This is the first qualitative study to address barriers to disclosure within health services for Palestinian women.Methods In-depth interviews were carried out with 20 women who had experienced DV. They were recruited from a non-governmental organisation offering social and legal support. Interviews were recorded, transcribed and translated into English and the data were analysed thematically.Results Women encountered barriers at individual, health care service and societal levels. Lack of knowledge of available services, concern about the health care primary focus on physical issues, lack of privacy in health consultations, lack of trust in confidentiality, fear of being labelled ‘mentally ill’ and losing access to their children were all highlighted. Women wished for health professionals to take the initiative in enquiring about DV. Wider issues concerned women’s social and economic dependency on their husbands which led to fears about transgressing social and cultural norms by speaking out. Women feared being blamed and ostracised by family members and others, or experiencing an escalation of violence.Conclusions Palestinian women’s agency to be proactive in help-seeking for DV is clearly limited. Our findings can inform training of health professionals in Palestine to address these barriers, to increase awareness of the link between DV and many common presentations such as depression, to ask sensitively about DV in private, reassure women about confidentiality, and increase awareness among women of the role that health services can play in DV.
Frequent avoidable admissions amongst Aboriginal and non-Aboriginal people with chronic conditions in New South Wales, Australia: a historical cohort study
Authors: Jayakody Amanda Anne , Oldmeadow Christopher , Carey Mariko , Bryant Jamie , Evans Tiffany , Ella Stephen , Attia John , Towle Simon , Sanson-Fisher Robert
Published: November 2020

Background: Aboriginal and Torres Strait Islander people have high rates of avoidable hospital admissions for chronic conditions, however little is known about the frequency of avoidable admissions for this population. This study examined trends in avoidable admissions among Aboriginal and non-Aboriginal people with chronic conditions in New South Wales (NSW), Australia. Methods: A historical cohort analysis using de-identified linked administrative data of Aboriginal patients and an equal number of randomly sampled non-Aboriginal patients between 2005/06 to 2013/14. Eligible patients were admitted to a NSW public hospital and who had one or more of the following ambulatory care sensitive chronic conditions as a principal diagnosis: diabetic complications, asthma, angina, hypertension, congestive heart failure and/or chronic obstructive pulmonary disease. The primary outcomes were the number of avoidable admissions for an individual in each financial year, and whether an individual had three or more admissions compared with one to two avoidable admissions in each financial year. Poisson and logistic regression models and a test for differences in yearly trends were used to assess the frequency of avoidable admissions over time, adjusting for sociodemographic variables and restricted to those aged ≤75 years.Results: Once eligibility criteria had been applied, there were 27,467 avoidable admissions corresponding to 19,025 patients between 2005/06 to 2013/14 (71.2% Aboriginal; 28.8% non-Aboriginal). Aboriginal patients were 15% more likely than non-Aboriginal patients to have a higher number of avoidable admissions per financial year (IRR=1.15; 95% CI: 1.11, 1.20). Aboriginal patients were almost twice as likely as non-Aboriginal patients to experience three or more avoidable admissions per financial year (OR=1.90; 95% CI=1.60, 2.26). There were no significant differences between Aboriginal and non-Aboriginal people in yearly trends for either the number of avoidable admissions, or whether or not an individual experienced three or more avoidable admissions per financial year (p=0.859; 0.860 respectively). Conclusion: Aboriginal people were significantly more likely to experience frequent avoidable admissions over a nine-year period compared to non-Aboriginal people. These high rates reflect the need for further research into which interventions are able to successfully reduce avoidable admissions among Aboriginal people, and the importance of culturally appropriate community health care.
Simultaneous rupture on conjugate faults during the 2018 Anchorage, Alaska, intraslab earthquake (MW 7.1) inverted from strong-motion waveforms
Authors: Guo Yujia , Miyakoshi Ken , Tsurugi Masato
Published: November 2020

An MW 7.1 ~50-km-deep intraslab earthquake within the Pacific/Yakutat slab underlying the North American Plate struck Anchorage, southern Alaska, on November 30, 2018. The ground-motion records very close to the source region of the Anchorage earthquake provide an important opportunity to better understand the source characteristics of intraslab earthquakes in this subduction zone. We estimated the kinematic rupture process during this earthquake using a series of strong-motion waveform (0.05–0.4 Hz) inversions. Our inversions clearly indicate that the Anchorage earthquake was a rare intraslab event with simultaneous rupture on two conjugate faults, which are recognized sometimes for shallow crustal earthquakes but rarely for deep intraslab earthquakes. Interestingly, one of the conjugate faults had low aftershock productivity. This fault extends to great depth and may reflect a deep oceanic Moho or a local low-velocity and high-VP/VS zone within the oceanic mantle. Even though the Anchorage earthquake was a rare event due to the conjugate faults, we found that its kinematic source parameters such as the slip amplitude and large-slip area nearly equal the global averages derived from source scaling relationships for intraslab earthquakes. Because the source parameters comparable to the global averages were also found for another large intraslab earthquake in the subducting Pacific/Yakutat slab, these source parameters are likely an important source characteristic common to this subduction zone.
Genetic characterization of a Marek’s disease virus strain isolated in Japan
Authors: Murata Shiro , Machida Yuka , Isezaki Masayoshi , Maekawa Naoya , Okagawa Tomohiro , Konnai Satoru , Ohashi Kazuhiko
Published: November 2020

Background: Marek’s disease virus (MDV) causes malignant lymphomas in chickens (Marek’s disease, MD). MD is currently controlled by vaccination; however, MDV strains have a tendency to develop increased virulence. Distinct diversity and point mutations are present in the Meq proteins, the oncoproteins of MDV, suggesting that changes in protein function induced by amino acid substitutions might affect MDV virulence. We previously reported that recent MDV isolates in Japan display distinct mutations in Meq proteins from those observed in traditional MDV isolates in Japan, but similar to those in MDV strains isolated from other countries.Methods: To further investigate the genetic characteristics in Japanese field strains, we sequenced the whole genome of an MDV strain that was successfully isolated from a chicken with MD in Japan. A phylogenetic analysis of the meq gene was also performed.Results: Phylogenetic analysis revealed that the Meq proteins in most of the Japanese isolates were similar to those of Chinese and European strains, and the genomic sequence of the Japanese strain was classified into the Eurasian cluster. Comparison of coding region sequences among the Japanese strain and MDV strains from other countries revealed that the genetic characteristics of the Japanese strain were similar to those of Chinese and European strains.Conclusions: The MDV strains distributed in Asian and European countries including Japan seem to be genetically closer to each other than to MDV strains from North America. These findings indicate that the genetic diversities of MDV strains that emerged may have been dependent on the different vaccination-based control approaches.
Developing a Comprehensive School-Based Physical Activity Program with Flexible Design – From Pilot to National Program
Authors: Mooses Kerli , Vihalemm Triin , Uibu Marko , Mägi Katrin , Korp Leene , Kalma Maarja , Mäestu Evelin , Kull Merike
Published: November 2020

This article focuses on the process of designing the vital, participatory school-based intervention program aiming to increase the physical activity in schools. The program analyzed is Estonian nationwide comprehensive physical activity program Schools in Motion (SiM) that recently received European Commission’s #BeActive Education Award. The program has a good performance in terms of willingness of schools to participate in co-creation of program development, the high interest to join the program and zero dropouts, and strong partnership with ministries which enables to actively participate in policy making. Authors analyze the key elements of the planning, piloting, implementation, and scaling phases of the SiM program and share their lessons learnt in co-working with schools. The difficulties faced during the development process, the strengths and challenges associated with an interdisciplinary approach, and involvement of schools as experts have been addressed.
Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients: Implications for Interferon Response and Coagulation
Authors: Gill Sean E. , Santos Claudia C. dos , O’Gorman David B. , Carter David E. , Patterson Eric K. , Slessarev Marat , Martin Claudio , Daley Mark , Miller Michael R. , Cepinskas Gediminas , Fraser Douglas D.
Published: November 2020

Background: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19 associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.Results: We enrolled seven COVID19+ (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia. The mortality rate for this cohort of COVID19+ ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19+ ICU patients were: (i) a robust overrepresentation of interferon related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor/interleukin 6 signalling. Conclusions: Our findings demonstrate that critically ill COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.
Integration of Deep and Ensemble Learning for Detecting COVID-19 in Computed Tomography Images
Authors: Haidar Ali , Holloway Lois
Published: November 2020

This paper presents an approach for detecting covid-19 in Computed Tomography (CT) images by integrating deep convolutional neural networks and ensembles of decision trees. The proposed approach consisted of three steps. In the first step, the CT images slices were collected and processed. In the second step, a deep convolutional neural network was trained to predict covid-19 in the CT images. In the third step, deep features were extracted and were used to train an ensemble of decision trees. Six types/packages of ensembles of decision trees were investigated: extreme gradient boosting (XGBoost), bagged decision trees (BDT), random forest (RF), adaptive boosting decision trees (Adaboost), gradient boosting decision trees (GBDT), and dropouts meet multiple additive regression trees (DART). The accuracy, sensitivity, specificity, f1-score, precision, and area under the ROC curve (AUC) were calculated to compare the models against each other. The proposed approach revealed the highest performance with a RF that reported 0.87 accuracy, 0.87 f1-score, and 0.90 AUC. The developed models revealed similar performance when compared to previously published models. This highlights the efficiency of combining deep networks with ensembles of decision trees for detecting covid-19.
Experience in managing psoriasis patients receiving targeted therapy during the COVID-19 pandemic
Authors: Potekaev N. N. , Zhukova O. V. , Artemyeva S. I. , Ostretsova M. N.
Published: November 2020

Introduction. With the onset of the COVID-19 pandemic the dermatological manifestations of the infection are widely discussed along with the correct management tactics for patients with severe chronic dermatoses, primarily those on immunosuppressive therapy. Immunocompromised patients are overly vulnerable to infections, which is especially important in the context of the pandemic. The article provides up-to-date literature information regarding the general risks of infection in patients receiving systemic immunomodulatory agents for the treatment of psoriasis, as well as evidence based treatment recommendations, including the example of our own clinical experience of using targeted therapy during the COVID-19 pandemic.Purpose of the study. The aim of the study was to analyze the therapeutic efficacy and safety of the systemic immunomodulatory drugs therapy in the context of the global COVID-19 pandemic.Materials and methods. The study included 142 patients with psoriasis receiving GEBD and small molecules therapy at the Department of Anti-Cytokine Therapy and Efferent Methods of Treatment of MNPCDK DZM. All patients were examined to determine their level of IgM and IgG antibodies to the SARS-CoV-2 virus strain in the blood serum. All patients continued to receive therapy according to their individual dosing regimen. The study was conducted at a time of high morbidity in the city of Moscow.

Results. The overall morbidity among the studied patients was 13.4% of which the majority were patients with an asymptomatic course of the disease. It should be noted that there was a low incidence rate among patients receiving therapy with IL-17 inhibitors (secukinumab, netakimab).Conclusion. Our study confirms worldwide records that there is no evidence of an increased risk of COVID-19 among patients receiving targeted therapy for psoriasis. In our opinion, the discuntinuation of the current treatment can lead to unjustified risks, such as a relapse of psoriasis, including with severe manifestations and subsequent possible ineffectiveness when resuming therapy.Potentially, the termination of therapy that suppresses the production of proinflammatory cytokines will lead to an increase in the “cytokine storm” and a worsening of the course of viral infection when it occurs.
The patient's path to AD: a study of patients adherence to therapy
Authors: Kruglova L. S. , Griazeva N. V.
Published: November 2020

Introduction. Atopic dermatitis (AD) is one of the most common skin diseases. The prevalence of atopic dermatitis among children is up to 20%, among adults - 2-8%. According to the form, there are mild, moderate and severe AD. Over the past decades, there has been an increase in the incidence of AD, its course is becoming more complicated, and the outcome is becoming more difficult. In this regard, the search for new successful treatment methods, as well as a detailed analysis of the currently used treatment regimens, is an urgent task. Goal. Measure the distribution of patients with AD by type of course (mild, moderate, severe) with a description of the patient's path, including the most important moments of decision-making, drivers of switching, changes in therapy, the main groups of influence and identify the main information requests/needs of patients with AD.Materials and methods. The study involved 700 patients, including 96 patients with moderate to severe form and 116 with severe form. All patients were diagnosed with AD and had at least one exacerbation in the last year. The age of the patients was 18-60 years. Results. The data obtained show that patients with moderate to severe AD make up about 25% of all patients with AD, including patients with severe ad - about 5%. Antihistamines are most often used by patients with AD, and the drug in this category is most often referred to by patients as the “main” drug for AD. More than half of patients (60%) with moderate to severe AD have used systemic steroids and/or cyclosporins over the past year. Patients with severe AD are significantly more likely than other groups to use steroids and immunosuppressants. The recommendation of a doctor (most often - a dermatologist in a municipal clinic or a skin and venereal clinic) is the most significant factor determining the choice of a drug for the treatment of atopic dermatitis. Conclusions. The data obtained indicate the need to conduct special educational activities with patients such as “schools of atopic dermatitis”, informing patients about the features of lifestyle in AD, theoretical aspects of treatment and skin care.
Successful use of Netakimab in the treatment of psoriasis accompanied by the psoriatic onychodystrophy
Authors: Potekaev N. N. , Zhukova O. V. , Artemyeva S. I.
Published: November 2020

Psoriasis is a chronic immune-mediated disease that is accompanied by a significant number of comorbid pathologies. Damage to the nail plates (psoriatic onychodystrophy) is widespread among patients with psoriasis and is associated with significant functional as well as psychosocial impairments. Despite the fact that nails constitute a small percentage of the surface of the human body, the damage to this particular area can lead to a deterioration in the quality of life and irreversible disability. In addition, studies have shown that nail psoriasis is indicative of a more severe course of the disease and it can also be associated with psoriatic arthritis or it can be a predictor of its development. Current treatment options for psoriasis accompanied by the nail plates damage include many topical and systemic methods, however, patients often report dissatisfaction with the results of treatment due to low efficacy or many side effects. Achieving higher efficiency is possible with the use of biologic therapy. Currently, a wide range of biologics have been developed that modulate key elements in the immunopathogenesis of psoriasis.The pathogenesis of psoriasis is a multifactorial process, however, it is the IL23 / Th17 signaling pathway that is key in this process. Interleukin-17A is the principal effector of this pathway and overexpression of IL-17A leads to epidermal hyperplasia and an excessive inflammatory response seen in psoriasis. Therefore, interleukin-17A is a promising therapeutic target.Considering the critical pathogenetic role as well as the high efficacy and safety of IL-17A inhibitors, the study of their effect on the psoriatic onychodystrophy manifestations is of great clinical importance.Netakimab is the first Russian original IL-17 inhibitor which is a promising modern agent for the treatment of moderate-to-severe plaque psoriasis. The obtained real clinical data indicate the high efficacy and safety of the use of Netakimab in patients with both plaque psoriasis and «severe» psoriasis in difficult to treat localizations, such as damage of the nail plate.
Rhinitis: differential diagnosis and treatment principles
Authors: Guseva A. L. , Derbeneva M. L.
Published: November 2020

Rhinitis is inflammation of the mucous membrane inside the nose. The clinical symptoms of this disease include nasal congestion, sneezing, itching of the nose and roof of mouth, rhinorrhea, and mucus draining down the back of the throat. Both allergic and non-allergic factors can play a role in the development of rhinitis. The most commonly used classification of rhinitis includes allergic rhinitis, non-allergic rhinitis, infectious rhinitis, and its specific forms. Allergic rhinitis is classified into the intermittent or persistent types, and may also be classified as mild, moderate and severe according to the severity of symptoms. Treatment of allergic rhinitis includes elimination of contact with allergen, allergen-specific immunotherapy and pharmacotherapy, which is selected depending on the severity of the symptoms. Infectious rhinitis develops in acute viral infection, and rhinitis symptoms are present in acute and chronic rhinosinusitis. Non-allergic rhinitis comprises conditions ranging from vasomotor rhinitis and gustatory rhinitis to non-allergic rhinitis with eosinophilia syndrome. Mixed rhinitis has components of allergic and non-allergic rhinitis. In addition, there are CPAP rhinitis, occupational rhinitis, medication rhinitis, rhinitis in systemic administration of drugs, rhinitis of pregnant women, atrophic rhinitis, rhinitis in systemic diseases. The type of rhinitis is diagnosed based on the patient’s complaints, anamnesis and clinical picture, some cases require laboratory tests and CT scan of the paranasal sinuses to differentiate the diagnosis. Approaches to the treatment of rhinitis depend on its type and include elimination of allergens or provoking factors, administration of saline solutions, intranasal glucocorticosteroids, systemic antihistamines, intranasal cromones, decongestants, antibacterial drugs may be prescribed to treat infectious rhinitis. Rhinitis should be differentiated from structural abnormalities, including congenital features, acquired conditions, neoplasms, gastroesophageal reflux, nasal liquorrhea.