bluuebunny/crossref_metadata_2025 huggingface dataset:
Annotation of Gene Alteration in Amniotic Fluid Cell Free RNA Transcriptome via Weighted Gene Co-expression Network Analysis
Authors: Yang Shufa , Yin Chenghong , Liu Yan , Zhuang Taifeng
Published: September 2020

BackgroundHuman amniotic fluid (AF) cells are commonly used in prenatal diagnosis. The AF cell-free mRNA (cfRNA) derived from necrotic or apoptotic cells of fetus may provide feasible marker of organ development and fetal malformation. Analysis of gene co-expression network will help to annotate AF cfRNA gene variations in fetal diseases.MethodsDatasets of amniotic fluid free RNA were downloaded from the Gene Expression Omnibus database. Co-expressed modules based on normal fetus AF cfRNA transcriptome were established via Weighted Gene Co-expression Network Analysis. The relationship between modules and tissues were set up via tissue-specific gene expression analysis of genes in modules. Differential expressed genes in Down syndrome (DS), Edwards syndrome (ES), and Turner syndrome (TS) were analyzed via linear models implemented in the limma package. Gene Ontology (GO) analysis of modular specific differential expressed genes for these three syndrome fetus was performed separately. Based on relationship of GO terms, GO graph of all enriched GO terms were constructed. The associated enriched GO terms in GO graph were considered as the same subset. Numbers of GO terms of the same subset with diseases and modules were calculated.ResultsA total of 22 co-expressed modules were constructed. Most of co-expressed module eigengenes showed no correlation with gestation weeks. Probe sets with higher expression values showed significant clustering tendencies. Dominant tissues and modules were different for different modules and tissues respectively through analysis of tissue-specific genes distribution in modules. The total numbers of enriched GO terms in six major modules were related to diseases severity for ES, DS, and TS. Disease-specific modules for ES, DS, and TS were detected in relation to biological processes through GO analysis. Differential expressed genes in disease-specific module were identified for DS, ES, and TS.ConclusionsThe gene co-expression network for functional classification provides a potential tool for annotating AF cfRNA variations in fetal diseases.
Concurrent cerebral arterial and venous sinus thrombosis revealing celiac disease - A case report and literature review
Authors: Alhosain Dalia , Kouba Lamia
Published: September 2020

Background: Celiac disease is an autoimmune condition characterized by an inappropriate immune reaction against gluten. It classically presents as chronic diarrhea, bloating, and nausea in addition to malabsorption symptoms such as weight loss and micronutrient deficiency. We report the first case of coinciding cerebral infarction and venous sinus thrombosis unveiling the diagnosis of celiac disease.Case Presentation: A 40-year old female patient with a four-day history of severe diarrhea presented with right hemiplegia and altered mental status. Imaging revealed left middle cerebral artery occlusion and left transverse and sigmoid venous sinus thrombosis, along with left jugular vein thrombosis. Her laboratory evaluation was notable for profound iron deficiency anemia, thrombocytosis, and hyperhomocysteinemia. Her positive anti-tissue transglutaminase IgA antibodies and ensuing duodenal biopsy confirmed the diagnosis of celiac disease.Conclusions: Celiac disease has a wide range of intestinal and extra-intestinal manifestations and can present with thrombotic events in young patients with iron deficiency and hyperhomocysteinemia.
Examining the Determinants of Contraceptive Use in Northern Nigeria
Authors: Aduloju-Ajijola Natasha M , Idogho Omokhudu , Yusuf Farouk , Muhammed Fatima , Anyanti Jennifer
Published: September 2020

Background: The Northern part of Nigeria, has higher rates of child marriage, lower levels of contraceptive use, lower rates of antenatal care, fewer births delivered in a health facility, and higher total fertility rates and adolescent fertility rates than Southern regions. The purpose of this study is to identify predictors of current and intentions to use contraception, among young women of Northern Nigeria. Methods: The data analyzed in this study are from 2018 Nigeria Demographic and Health Survey, part of the Demographic and Health Survey by USAID. Results: Participants (N = 10066) ranged in age from 15 to 24 (mean = 19, sd = 2.76) from the three northern regions of Nigeria, primarily lived in rural areas (68.7%, n = 7107). We found that, 83.3 percent of the sample had heard of modern contraceptive methods, though only 3.6 (n = 357.2) were currently using a modern contraceptive method, and 43.4 (n = 4286.4) intended to use them. Conclusion: The primary predictors of contraceptive use include literacy, wealth, educational levels, being the decision maker regarding contraceptives, age of first sex, wanting more children, and decisional autonomy in the home. Since the literacy is low, interventions should utilize pictures and radio programs, traditional and religious leaders, and incorporate men.
Large carbon sink potential of Amazonian Secondary Forests to mitigate climate change
Authors: Heinrich Viola , Dalagnol Ricardo , Cassol Henrique , Rosan Thais , Almeida Catherine Torres de , Junior Celso H. L. Silva , Campanharo Wesley , House Joanna , Sitch Stephen , Hales Tristram , Adami Marcos , Anderson Liana , Aragão Luiz
Published: September 2020

Secondary forests (SF) have a large climate mitigation potential, given their ability to sequester carbon up to 20 times faster than old-growth forests. Environmental variability and anthropogenic disturbances lead to uncertainties in estimating spatial patterns of SF carbon sequestration rates. Here we quantify the influence of environmental and disturbance drivers on the rate and spatial patterns of regrowth in the Brazilian Amazon, by integrating a 33-year land cover timeseries with a 2017 Aboveground Biomass dataset. Carbon sequestration rates of young Amazonian SF (<20 years old) are at least twice as high in the west (3.0±1.0 MgC ha-1 yr-1) than in the east (1.3±0.3 MgC ha-1 yr-1). Disturbances reduce SF regrowth rates by 8–50% (0.6 – 1.3 MgC ha-1 yr-1). We estimate the 2017 SF carbon stock to be 294 TgC, which could be 8% higher by avoiding fires and repeated deforestation. Maintaining the 2017 SF area has the potential to accumulate ~15 TgC yr-1 until 2030, contributing ~5% to Brazil’s 2030 net emissions reduction target. Supporting SF and old-growth forests conservation alongside the expansion of SF in deforested areas is therefore a viable nature-based climate mitigation solution.
LncRNA Profiling of Exosomes Derived From Staphylococcus Aureus-induced Bovine Mammary Epithelial Cell Lines MAC-T
Authors: Chen Yu , Jing Hongyuan , Chen Miaoyu , Liang Wan , Guo Mengyao
Published: September 2020

Background: Exosomes (carrying proteins, miRNA, lncRNA, etc.) play a vital role in participating in the occurrence and development of mastitis. LncRNA can play a variety of regulatory roles by combining with protein, RNA, and DNA. The expression of mRNA and lncRNA in exosomes derived from bovine mammary epithelial cells infected by S. aureus is rarely understood.Methods: We used ultracentrifugation to separate exosomes derived from S. aureus- stimulated MAC-T cells. After extracting exosomal RNA, RNA sequencing was performed. We screened differentially expressed genes, mRNA and lncRNA, and predicted their functions through KEGG and GO analysis. 6 mRNA and lncRNA were randomly selected for RT-qPCR verification.Results: Analysis of the sequencing results showed that there were 186 differentially expressed genes, 431 differentially expressed mRNAs and 19 differentially expressed lncRNAs in the exosomes derived from S. aureus-infected and non-infected MAC-T acells. By predicting lncRNA target genes, it was found that 19 differentially expressed lncRNAs all acted on multiple mRNAs in cis and trans. GO analysis revealed that differentially expressed genes and lncRNA target genes played significant roles in such metabolism, transmembrane transport, cellular response to DNA damage stimulus, response to cytokines. KEGG enrichment indicated that lncRNA target genes gathered in the TNF pathway, Notch pathway, phosphatidylinositol signaling system and p53 pathway. Conclusion: The data suggested that S. aureus induced changes in genes, mRNA, and lncRNA in exosomes secreted by MAC-T cells, which furtherly triggered other cells damage through exosomal delivery. This study would provide valuable resource for understanding the lncRNA information in exosomes derived from dairy cow mammary epithelial cells, and conduced to the study of S. aureus infection in dairy cow mammary glands.
The Improvement of Parturition Progress by High Intake of Dietary Fibre in Late Gestation is Associated with the Altered Gut Microbiome and Metabolome in Sows
Authors: Liu Yang , Jiang Pingping , Chen Nan , Zhang Ruinan , Jiang Yannan , Fang Zhengfeng , Lin Yan , Xu Shengyu , Feng Bin , Zhuo Yong , Wu De , Theil Peter Kappel , Che Lianqiang
Published: September 2020

Background: Gestational intake of dietary fibre improves the parturition progress, which largely affects developmental outcomes of the offspring. Dietary fibre can alter the gut microbiome and production of symbiotic metabolites, e.g. short chain fatty acids (SCFAs). We hypothesized that the improvement of parturition progress by dietary fibre is associated with the symbiotic metabolites generated by the gut microbiome. Methods: Yorkshire sows were randomly given diet containing normal level of fibre (NDF, 16.2% dietary fibre, n = 20) or high level (HDF, 30.1%, n = 20) with other nutrients identical from days 90 of gestation to parturition. Faecal microbiome profiled with 16S amplicon sequencing, SCFAs and metabolome in the faeces and plasma around parturition were compared between the dietary groups. Correlation analysis was conducted to further explore the potential associations between specific bacterial taxa and metabolites. Results: HDF significantly improved the parturition progress, indicated by the shorter parturition duration. HDF increased abundance of the phyla Bacteroidetes and Synergistetes and multiple genera. Except for butyrate, SCFAs levels in the faeces and plasma of sows at parturition were increased in HDF group. The abundances of 15 and 12 metabolites in the faeces and plasma, respectively, markedly differ between HDF and NDF sows. These metabolites are involved in the bacterial metabolism of amino acids, bile acids, SCFAs and dietary fibre. Correlation analysis also showed associations between specific taxa (genera Cellulosilytica and Lachnoclostridia) and metabolites (acetate and isobutyrate).Conclusions: The improvement of parturition process by high fibre intake in late gestation is associated with altered gut microbiome, production of SCFAs and other metabolites, potentially serving for energy metabolism.
Transcriptome-wide assessment of the m6A methylome of intestinal porcine epithelial cells treated with deoxynivalenol
Authors: Wu Zhengchang , Xu Chao , Wang Haifei , Gao Song , Wu Shenglong , Bao Wenbin
Published: September 2020

Background: Deoxynivalenol (DON) is a cytotoxic compound found in various food and feed products. N6-Methyladenosine (m6A) is a highly abundant epitranscriptomic marker that modifies a wide range of mRNA molecules in mammalian cells. However, the role of the m6A methylome in DON-induced damage remains poorly understood.Results: In this study, we assessed the transcriptome-wide m6A profile of intestinal porcine epithelial cells (IPEC-J2) treated with 1000 ng/mL DON by m6A sequencing and RNA sequencing. Overall, 5406 new m6A peaks appeared with the disappearance of 2615 peaks in DON-treated IPEC-J2 cells. Genes that were uniquely m6A-modified following DON treatment were found to be associated with the tumor necrosis factor (TNF) signaling pathway. On comparing DON-treated and control cells, we identified 733 differentially expressed mRNAs bearing hyper- or hypomethylated m6A peaks. Further experimental data suggested that METTL3-dependent m6A methylation might also play a role in DON-induced inflammatory response, and CSF2 marker is key functional relevance in the context of DON-induced toxicity. Conclusions: This is the first study to perform a transcriptome-wide assessment of the m6A methylome of IPEC-J2 cells treated with DON. We believe that our findings should be useful for identifying mechanisms whereby m6A modifications influence the outcomes of DON exposure.
Multimodal Monitoring With Haemodynamic Optimisations May Offer Some Benefit for Patients Undergoing Major Abdominal Surgery. A Randomised, Controlled Trial.
Authors: Jenko Matej , Mencin Katarina , Novak-Jankovic Vesna , Spindler-Vesel Alenka
Published: September 2020

Background: Combined monitoring of blood flow with assessment of fluid status and cerebral tissue oxygenation improve perioperative management and outcome of high-risk surgical patients. The study tests if intraoperative multimodal monitoring reduces postoperative morbidity and duration of hospitalisation in patients undergoing major abdominal surgery managed by same anaesthetic protocols with epidural analgesia.Methods: Prospective study was conducted in 2 parallel groups. High risk surgical patients undergoing major abdominal surgery were randomised in control group (CG), where standard monitoring was applied and protocol group (PG), where cerebral oxygenation and haemodynamic monitoring were used with protocol for intraoperative interventions.Results: There was no difference in median length of hospital stay, CG 9 days (IQR 8 days), PG 9 (5.5), p= 0.851. There was no difference in postoperative renal of cardiac impairment. Procalcitonin was significantly higher (highest postoperative value in first 3 days) in CG, 0.75 mcg/L (IQR 3.19mcg/L), than in PG 0.3 mcg/L (0.88 mcg/L), p= 0.001. Patents in PG received larger intraoperative amount of fluids; median intraoperative fluid balance +1300 ml (IQR 1063ml) than CG; +375 ml (IQR 438ml), p<0.00.Conclusions: There was no difference in postoperative morbidity or hospital stay. Median postoperative value of procalcitonin was significantly higher in CG and was above laboratory reference range. There were significant differences in intraoperative fluid management.Trial registration: ClinicalTrials.gov, NCT02293473, Registered June 10, 2014, https://clinicaltrials.gov/
Adverse Neonatal Birth Outcomes Among Adolescent Pregnancies in Kampala, Uganda Between 2015 –2018
Authors: Serunjogi Robert , Barlow-Mosha Linda , Mumpe-Mwanja Daniel , Williamson Dhelia , Valencia Diana , Tinker Sarah C , Adler Michelle R , Namale-Matovu Joyce , Kalibbala Dennis , Nankunda Jolly , Nabunya Evelyn , Birabwa-Male Doreen , Byamugisha Josaphat , Musoke Philippa
Published: September 2020

Background: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and older mothers (age 20-34 years) in four urban hospitals.Methods: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson’s chi-square. Adjusted odds ratios (aORs) and 95% Confidence Intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to older mothers.Results: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. A significantly higher proportion of HIV-infected adolescents were not initiated on antiretroviral therapy by the time of delivery compared to HIV-infected older mothers (8.8% vs 4.4%, p<0.001). Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI: 1.06-1.23), low birth weight (aOR: 1.46; CI: 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI: 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI: 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI: 1.12-9.13) compared to older mothers.Conclusions: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to older mothers, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population.
Deviations in Hippocampal Subregion Associated With Cognitive and Physical Frailty in Older Adults With Cognitive Frailty
Authors: Wan Mingyue , Ye Yu , Lin Huiying , Xu Ying , Liang Shengxiang , Xia Rui , He Jianquan , Qiu Pingting , Huang Chengwu , Tao Jing , Chen Lidian , Zheng Guohua
Published: September 2020

Background The hippocampus is a complex, heterogeneous structure that is composed of widely different and interacting subregions. Atrophy of these subregions has been implicated in a variety of neurodegenerative diseases. Cognitive frailty is a kind of neurodegenerative disease with unclear neuropathological changes. The aim of this study was to explore the changes in hippocampal subregions in older adults with cognitive frailty and the relationship between subregions and cognitive decline as well as physical frailty.Methods Twenty-six older adults with cognitive frailty and 26 matched healthy controls were included in this study. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA) scale (Fuzhou version) and Wechsler's Memory Scale, while physical frailty was tested with the Chinese version of the Edmonton Frailty Scale (EFS) and grip strength. The volume of the hippocampal subregions was measured with structural brain magnetic resonance imaging. Partial correlation analysis was carried out between the volumes of hippocampal subregions and MoCA scores, Wechsler’s Memory Quotient and physical frailty indexes.Results A significant volume decrease was found in six hippocampal subregions, including the bilateral presubiculum, the left parasubiculum, molecular layer of the HP, and HATA, and the right CA1 area, in older adults with cognitive frailty (P<0.05/12), while the proportion of brain parenchyma and total number of white matter fibers were lower than those in the healthy controls (P<0.05). Positive correlations were found between Wechsler’s Memory Quotient and the size of the left molecular layer of the HP and HATA and the right presubiculum (P<0.05). The sizes of the left presubiculum, molecular of the layer HP, and HATA and right CA1 and presubiculum were found to be positively correlated with MoCA score (P<0.05). The sizes of the left parasubiculum, molecular layer of the HP and HATA were found to be negatively correlated with the physical frailty index (P<0.05).Conclusion Significant volume decrease occurs in hippocampal subregions of older adults with cognitive frailty, and these changes are correlated with cognitive decline and physical frailty. Therefore, the atrophy of hippocampal subregions could participate in the pathological progression of cognitive frailty.
Nonalcoholic Fatty Liver Disease in Non-Obese Subjects With Abdominal Obesity is Associated With A Higher Risk of Advanced Cardiovascular Disease: A 14 Year Prospective Cohort Study
Authors: Son Mi Kyoung , Park Ji Hye , Lee Joung-won , Kim Seungwoo , Kim Won Ho
Published: September 2020

Background Obese nonalcoholic fatty liver disease (NAFLD) is closely associated with an increased risk of cardiovascular disease (CVD). However, the association between non-obese NAFLD and the incidence of CVD is still unclear and little is known about deleterious factors related to their inter-relationship. Here, we investigated the effects of abdominal obesity (AO) and/or NAFLD on CVD risk.Methods We enrolled 8,422 patients who did not have CVD or consume excessive amounts of alcohol at baseline from the Korean Genome and Epidemiology Study (KoGES). NAFLD was defined using the Fatty Liver Index (FLI). Obesity was defined as a body mass index (BMI) ≥25 kg/m2, and AO was defined as a waist circumference (WC) ≥90 cm in men and ≥85 cm in women. Subjects were sub-divided into eight groups depending on whether they were obese, AO, and/or NAFLD.Results In the full cohort, during a median 11.6 years of follow-up period, the incidence rate (IR) of CVD was 8.07%. The IR of CVD in participants with NAFLD was 1.9-fold higher than in those without NAFLD. The IR per 1,000 person-years for CVD was highest in the non-obese abdominal obesity subjects with NAFLD (15.76 [95% confidence interval (CI), 11.76–20.69]). Compared with participants who did not have obesity, AO, or NAFLD, the adjusted hazard ratio for CVD was 1.67 (95% CI: 1.16–2.41) in non-obese NAFLD patients with AO, 1.60 (95% CI: 1.21–2.11) in NAFLD patients with obesity and AO, and 0.54 (95% CI: 0.32–0.91) in obese subjects without either NAFLD or AO.Conclusions The co-occurrence of AO with NAFLD appears to be strongly associated with an increased risk of CVD regardless of obesity; but its risk is higher in non-obese subjects. By contrast, obese individuals without AO or NAFLD appear to be at lower risk. Therefore, early prevention and control of AO and NAFLD is an important means of reducing the risk of CVD, even in subjects with a normal BMI.
Gunshot Injuries: Patterns, Presentations, and Outcomes of Civilian Hospital Experiences in a Developing Country Setting
Authors: GISMALLA MOHAMED Daffalla Awadalla , Bakhiet Mohammed , Koko Mohammedbabalrahma Bashier Ahmed , Kabbashi Abdelrahim
Published: September 2020

BackgroundGunshot injuries are considered a burden as well as one of the intricate emergencies in civilian medical practice. In this study, we aim to determine the pattern of presentation and management outcome in a general hospital in a sub-Saharan country.MethodsThis is a retrospective, descriptive, hospital-based study conducted between January 2015- December 2019 in a general teaching hospital, to review the clinical presentation and management outcome of gunshot injuries. All patients’ records were reviewed during the study period.ResultsOne hundred fifty-seven patients were included in the study, with male predominant 83%. 40% are between 19-30 years of age, with patients under 18 years of age comprising 17% of the population. The common cause of gunshot injuries was personal enmity in 49%. The anatomical sites most affected by gunshot were the lower limb (41.4%) and upper limb (22.9%), and the least impacted site is the perineum (1.9%). The most common diagnoses among the patients in this study were limb fractures (49.7%) and soft tissue injuries (28.7%). Specific treatment in this study is wound debridement, which was done for 91 (58.0 %) patients. Bone fixation, laparotomy, and chest tube insertion were done for the rest of the patients. More than 120 (75%) of patients were treated and discharge in a good condition and 27 (17.2%). The in-hospital mortality rate in this study group was 3.2 %.Conclusion Most of the patients in this study were young males. Upper and lower limb fractures are the most common presentations. Wound debridement, bone fixation, and laparotomy are the most common treatments with significant success rates, despite prolonged hospital stay.
Psychosocial Interventions for Reducing Depression Among the Elderly in Low and Middle Income Countries: A Systematic Review Protocol
Authors: Amanyire Jordan Mutambi , Aheisibwe Irene , Rukundo Godfrey Zari
Published: September 2020

Background: According to the World Health Organization, depression is expected to be the largest contributor to the global disease burden by 2030. Depression is the most frequent cause of emotional distress and reduced quality of life among older people affecting over 12% of the individuals aged 65 or older, . Psychosocial interventions have been proven to be effective in the management of depression. Most of the available evidence is from high income settings, with paucity of information in low and middle income countries which carry the biggest burden of depression and other health challenges. In this systematic review, we will document evidence on psychosocial interventions that have been effective in treatment of depression among elderly people in low and middle income countries. Methods: The review will be conducted and reported in accordance to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. We will include journal articles that have documented the psychosocial interventions in the primary prevention of depressive symptoms in elderly people aged 60 or older. We will also include accessible grey literature about the topic. We will include articles that have documented the psychosocial interventions to address depression in elderly patients in low and middle income countries. We will search different search engines and data bases including PubMed, EMBASE, Psych-INFO, Cochrane Library. We will use a meta-analysis, should we find that there is no heterogeneity between included studies.Discussion: This protocol describes a planned systematic review of observational studies reporting psychosocial interventions in the management of depressive symptoms in elderly people aged 60 or older. We anticipate that once this review is complete and published, our findings will be of interest to the elderly with depressive symptoms, their families and caregivers, students, and other healthcare professionals, scientists and policy makers.Systematic review registration: This protocol will not be registered with PROSPERO International prospective register of systematic reviews since the system is no longer accepting new protocols.
Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life
Authors: Mulette Pauline , Ravoninjatovo Bruno , Guguen Camille , Barbe Coralie , Dury Sandra , Dumazet Antoine , Perdu Dominique , Perotin Jeanne-Marie , Guillard Thomas , Lebargy François , Deslee Gaetan , Launois Claire
Published: September 2020

Background: While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients.Methods: Twenty-eight CF patients (18M/10F), with a mean age of 28.2 ± 8.5 (mean ± standard deviation) years and a mean forced expiratory volume in one second of 69 ± 31% predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Respiratory assessment data, including symptoms, sputum analysis, arterial blood gases, 6-minute walking test, pulmonary function tests and polysomnographic variables, were also analyzed. Results: Forty-three percent of patients were insomniac (ISI > 7). Compared with non-insomniac patients (ISI ≤ 7), insomniac patients had more severely impaired quality of life and a higher HAD score: mean anxiety score of 8.9 ± 2.4 vs 4.0 ± 2.4 (p <0.001), mean depression score of 7.3 ± 3.4 vs 2.1 ± 2.2 (p <0.01), with a positive correlation between ISI and HAD anxiety/depression scores (r=0.674/r=0.724, respectively, p <0.001). Insomnia was also associated with restless legs syndrome, pain and lower SpO2 during sleep. Conclusions: The strong association between insomnia, impaired quality of life and increased HAD score should prompt physicians to be particularly attentive to the management of anxiety and depression in adult CF patients with insomnia.Trial registration: on clinicaltrials.gov (NCT02924818)
Tacholess Rotational Speed Estimation via The Integration of Continuous Wavelet Transform and Time-Dependent Autoregression
Authors: Zhang Ran , Liu Xingxing , Zheng Yongjun , Lv Haotun , Li Baosheng , Yang Shenghui , Tan Yu
Published: September 2020

Speed estimation is crucial to monitor the conditions of rotational machinery. Most speed measurements are carried out by installing encoders or tachometers inside the machines. In many cases, such method could be cumbersome or even inaccessible. This paper proposes a vibration-based speed estimation method. The vibration sensors are often cheaper and easier to install than angle encoders. In the proposed method, the continuous wavelet transform (CWT) is used as a preprocessing technique to extract the signal of importance. Then, the time-varying autoregressive (TAR) model is applied to analyze the rotational frequency. Additionally, the paper presents a fast algorithm for implementation. The proposed method is validated by both synthetic and empirical data.
Dopamine Reduced Pyroptosis and Improved Functional Recovery After Spinal Cord Injury 
Authors: Zhu Liulong , Ding Guoming , He Fan , Li Maoqiang , Jiang Wu
Published: September 2020

The authors have requested that this preprint be removed from Research Square.
Clinicopathological Characteristics and Prognosis of Gastric Cancer With Old Tuberculosis: A Propensity Score Matching Analysis
Authors: Yan Meng-Hua , Song Xiao-Hai , Zhang Wei-Han , Liu Kai , Chen Xiao-Long , Zhao Lin-Yong , Chen Xin-Zu , Yang Kun , Song Bin , Wu Bing , Hu Jian-Kun
Published: September 2020

Background: It is known that Bacillus Calmette–Guérin (BCG), which serves as an adjuvant immunotherapy, has certain beneficial effects on the prognosis for gastric cancer. However, no existing reports have probed into the impact of old tuberculosis (TB) lesion on patients with gastric cancer. Methods: Using the database from a high-volume center, 2649 consecutive gastric cancer patients admitted to West China Hospital undergoing curative-intent gastrectomy were identified between 2009 and 2016. Patients were divided into TB group and non-tuberculosis (NTB) group based on the presence or absence of a coexistent old pulmonary TB lesion. Then, multinomial logistic regression models tested the risk factors for the postoperative pulmonary complications (PPCs). Kaplan-Meier analyses and Cox regression models tested the effect of old TB lesion on overall survival (OS) rate. The propensity score-matching (PSM) method was used to assemble a well-balanced cohort.Results: Altogether 81 of the enrolled patients had old pulmonary TB lesions. The presence of an old TB lesion was associated with superior overall survival (OS). Besides, the 3-year OS rates were 84.7% in TB group and 69.2% in NTB group, and the difference between two groups was statistically significant (p=0.005). Similarly, in the following analysis on 73 pairs of matched patients, significant differences were also noted between the two cohorts (p=0.001), with the 3-year OS rates of 90.4% and 69.2%, respectively. Further, multivariable Cox regression analysis showed that old TB was an independent positive factor for OS before and after propensity score-matching (PSM) (p=0.002/p<0.001, HR=0.471/0.220, respectively). Additionally, the old TB lesion appeared to be an independent risk factor for postoperative pulmonary complications (PPCs) (both p<0.001, HR=3.375 and HR=3.415 in univariate and multivariate logistic regression, respectively).Conclusions: Old TB lesion is a risk factor for PPCs. Despite that, it represented as an independent positive factor for the prognosis of gastric cancer in general. This study may shed light on further immune therapy for gastric cancer.
Coconut Online: Collection of Open Natural Products Database
Authors: Sorokina Maria , Merseburger Peter , Rajan Kohulan , Yirik Mehmet Aziz , Steinbeck Christoph
Published: September 2020

Natural products (NPs) are small molecules produced by living organisms with potential applications in pharmacology and other industries for their high bioactivities. Over the years a multiplication of thematic NP databases has been observed. However, there is no online resource regrouping all known NPs in just one place, which would greatly simplify NP research and allow computational screening and other in silico applications. Here we present the COlleCtion of Open Natural prodUcTs (COCONUT): an aggregated dataset of NPs available in different open sources and a subsequent web interface to browse, search and easily and quickly download NPs. COCONUT web is freely available at https://coconut.naturalproducts.net.
High-elevational occurrence of two tick species, Ixodes ricinus and I. trianguliceps, at their northern distributional limit
Authors: De Pelsmaeker Nicolas , Korslund Lars , Steifetten Øyvind
Published: September 2020

Background: During the last decades a northward and upward range shift has been observed among many organisms across different taxa. In the northern hemisphere, ticks have been observed to have increased their latitudinal and altitudinal range limit. However, the elevational expansion at its northern distribution limit remains largely unstudied. In this study we investigated the altitudinal distribution of the exophilic Ixodes ricinus and endophilic I. trianguliceps on two mountain slopes in Norway by assessing larval infestation rates on bank voles (Myodes glareolus).Methods: During 2017 and 2018, 1325 bank voles were captured during spring, summer and autumn at 10 trapping stations ranging from 100 m to 1000 m.a.s.l in two study areas in southern Norway. We used generalized logistic regression models to estimate the prevalence of infestation of both tick species along altitude, considering study area, collection year and season, temperature, humidity and altitude interactions as extrinsic variables; and host body mass and sex as intrinsic predictor variables.Results: We found that both I. ricinus and I. trianguliceps infested bank voles at altitudes up to 1000 m.a.s.l., which is a substantial increase in altitude compared to previous findings for I. ricinus in this region. The infestation rates declined more rapidly for I. ricinus compared to I. trianguliceps, indicating that the endophilic ecology of I. trianguliceps may provide shelter from limiting factors tied to altitude. Seasonal effects limited the occurrence of I. ricinus during autumn, but I. trianguliceps was found to infest rodents at all altitudes during all seasons of both years.Conclusions: This study provides new insights into the altitudinal distribution of two tick species at their northern distributional limit, one with the potential to transmit zoonotic pathogens to both humans and livestock. With warming temperatures predicted to increase, and especially so in the northern regions, the risk of tick-borne infections is likely to become a concern at increasingly higher altitudes in the future.
Laboratory based Retrospective Study to determine the start of SARS-CoV-2 in Patients with Severe Acute Respiratory Illness in Egypt at El-Demerdash tertiary hospitals
Authors: H.A.Agwa Sara , Elghazaly Hesham , El-Nakeep Sarah , Moustafa Ahmad , El-Sayed Manal H , Hafez Hala , abdo Samia , Matboli Marwa , Saad Maha , M.Elsayed Shaimaa , Elsamie Aya M.Abd , M.Dar Reham , elarab Hoda ezz , Ebeid Fatma S. E. , Makkeyah Sara , Meteini Mahmoud S El
Published: September 2020

Subject Area: SARS-CoV-2Purpose: COVID-19 is the most recent pandemic causing morbidity and mortality. Although a part of the pathogens causing SARI, it is unique in causing pulmonary thrombosis and lung fibrosis. Thus different management is needed. We aimed o explore the start of SARS-CoV-2 in preserved SARI samples to know the exact time of its emergence in our hospital, to conduct whole-genome sequencing in positive SARS-CoV-2 samples to define its strain. To assess the clinical characteristics of the severe respiratory infection admitted to El-Demerdash hospitals in that same period from our own file reports.Methods: We conducted a retrospective cohort study among SARI patients who were admitted to Ain Shams university hospitals. preserved nasopharyngeal& oropharyngeal swabs from 333 SARI patients were used in SARS-CoV-2 detection by RT-Real time PCR. Moreover, whole-genome sequencing of SARS-CoV-2 positive samples was performed. Clinical characteristics of the SARI patients were analyzed in the same period to show the relation to morbidity and mortality.Results: The first case of SARS-CoV-2 was detected in a 6months aged female patient on mid-April 2020, B.1.1.7, clade GR. Co-infection (with both bacterial and viral) was most prevalent in pediatrics than adults, but mortality was higher in adults than pediatrics (18.1% versus 7.1%). ICU admission was higher in adults than in the pediatric group (65% versus 12.8%). Co-morbidities were associated with higher mortality and more severe infection. The most common bacterial infection in both adults and pediatrics was Klebsiella pneumoniae, followed by Staphylococcus aureus and Streptococcus pneumoniae. Conclusion: COVID-19 didn’t start till mid-April in the Egyptian hospitals as remarked by this tertiary hospital’s data. Co-infection is the most prevalent in children and further research is needed in this area.
An aptamer/ siRNA Chimera against The SARS-CoV-2: A Dual Therapeutic Strategy for The Virus Neutralizing and RNA Interfering
Authors: Khanali Javad , Azangou-khyavy Mohammadreza , Asaadi Yasaman , Jamalkhah Monire , Kiani Jafar
Published: September 2020

During the ongoing COVID-19 pandemic, besides the vaccines, there is an urgent need for the development of effective therapeutics. Although significant efforts have been made to develop such therapies, there are currently no approved treatments for COVID-19. One of the potential therapeutic targets is the spike (S) protein of SARS-CoV-2, which mediates viral entry into host cells. It has been shown that targeting S protein could neutralize viruses and hinder their binding to the cells. Among known viral neutralizing agents, aptamers’ potential in neutralizing the SARS-Cov-2 virus has not yet been revealed. In addition, aptamers could also be used for targeted delivery of drugs and other genetic elements, such as siRNAs, to the cells. Small interfering RNAs (siRNAs) are reliable tools for gene knockdown via RNA degradation. siRNAs have been implemented previously against some viruses, including SARS-CoV, to target its genome. Recently, potential siRNA sequences and their targets in the SARS-CoV-2 genome have been reported, and the efficiency of siRNAs in inhibiting SARS-CoV-2 infection is being revealed. An alternative antiviral approach we propose here relies on an aptamer-siRNA-based system for the treatment of COVID-19. These aptamers could neutralize viruses by hindering their receptor-mediated endocytosis, and siRNAs could suppress the expression of viral genes and halt various aspects of its pathogenesis whenever the aptamers fail to neutralize the virus.
Comorbidities role on death in diabetic patients with COVID-19 
Authors: Emami Amir , Mohammadzadeh Khalil Ali , Akbari Ali , Falahati Farshad , Basirat Atefeh , Zare Hamid
Published: September 2020

Purpose: According to the possible role of other comorbidities in increase the risk of mortality in diabetes patient, recent study was designed to manage complications and mortality rate in this group of patients.Methods: In this cross-sectional study (25 February to 10 July 2020) total of 458 diabetic patients were enrolled based on their characteristics, symptoms and signs, and presence of underlying diseases. Multiple logistic regression and χ2 test analysis used to check the effectiveness of comorbidities on the mortality outcome among diabetic patients.Results: Of 458 diabetic patients, 306 (67%) were with underlying diseases (200 (65.4%) hypertension, 103 (33.7%) cardiovascular diseases and 29 (9.5%) kidney diseases). The rate of fatality was significantly high in patients with chronic kidney and liver diseases. The odds of mortality outcome increase 3.1 fold for patients over 55 years as compared to under 55 years (P =0.011), and the odds of mortality outcome was more than 5.1 folds for those who had chronic kidney disease (P <0.001).Conclusions: The presentation of SARS-CoV-2 in older diabetic patients with comorbidities (chronic kidney and liver diseases) is more severe in risk of mortality.
Measurement Operators in Conjugate Transformation Structure - Conjugate Hierarchy of Multiple Levels on Logic Constructions, Pairs of 0-1 Feature Vectors and Hamiltonian Dynamics
Authors: Zheng Jeffrey
Published: September 2020

Hamiltonian dynamics play a key role in the foundation of modern physics and mathematics with wider applications in multiple advanced sciences and technologies.This paper proposes a conjugate transformation structure and its measurement operators on a hierarchy of multiple levels to support intermediate transforming structures from pairs of logic states as micro-ensembles to feature vector transformations as global measurements.Using logic equations and pairs of partitions on phase spaces, conjugate 0-1 vectors provide hypercomplex number systems. Multiple operators can be created and linked with Hamiltonian operators.The main constructions of conjugate transformation structures are described and complex conjugate operators are discussed under a pair of symmetric and antisymmetric parameters with O(2^{2^n}x2^N); 1 =< n =< 2m structural complexity.Using new operators, the Yang-Mills equations are briefly described as an example.
Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome
Authors: Gong Yan , Luo Shan , Fan Ping , Zhu Huili , Li Yujing , Huang Wei
Published: September 2020

Background: Growth hormone (GH) can reduce oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in GCs of patients with polycystic ovary syndrome (PCOS). Methods: Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to receive treatment with GH (PCOS-GH, n = 30) or without GH (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and ﬂuorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels were determined by enzyme-linked immunosorbent assay. Result(s): The present study found that compared with those in the non-PCOS and PCOS-GH groups, the ROS levels and apoptotic rates were significantly increased, whereas MMP was significantly decreased in the PCOS-C group GCs (P < 0.05). Compared with those in non-PCOS and PCOS-GH groups, mRNA levels of FOXO1, Bax, caspase-9, and caspase-3 were significantly increased, whereas Bcl-2 was decreased in the GCs of the PCOS-C group (P < 0.05). The protein levels of FOXO1, Bax, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3 were increased, whereas p-PI3K/PI3K, p-Akt/Akt, p-FOXO1 and Bcl-2 were decreased in the GCs of the PCOS-C group, compared with those in the non-PCOS and PCOS-GH groups (P < 0.05). Conclusion: OS induced apoptosis and inactivated the PI3K/Akt signaling pathway in patients with PCOS. GH could improve apoptosis and activate the PI3K/Akt signaling pathway.Clinical Trial Registration Number: Chinese Clinical Trial Registry (www.chictr.org.cn/index.aspx). ChiCTR1800019437. Prospectively registered on October 20, 2018, http://www.chictr.org.cn/edit.aspx?pid=28663&htm= 4
Investigation of genetic variations of IL6 and IL6R as potential prognostic and pharmacogenetics biomarkers: implications for COVID19 and neuroinflammatory disorders.
Authors: Strafella Claudia , Caputo Valerio , Termine Andrea , Barati Shila , Caltagirone Carlo , Giardina Emiliano , Cascella Raffaella
Published: September 2020

In the present study, we investigated the distribution of genetic variations in IL6 and IL6R genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in IL6 and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within IL6R, respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. The Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID19 severity and mortality as well as with neurodegenerative diseases mediated by neuroinflammation. Thus, the availability of IL6-IL6R-related biomarkers for COVID19 disease may be helpful to counteract harmful complications and prevent multi-organ failure. At the same time, IL6-IL6R-related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders and undertake the most suitable treatment strategies to improve patients’ prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize precision medicine protocols for chronic, age-related and modern public health emergencies.
COVID-19 outbreak, social distancing and mass testing in Kenya - Insights from a mathematical model 
Authors: Mbogo Rachel Waema , Oddhiambo John W.
Published: September 2020

As reported by the World Health Organization (WHO), the world is currently facing a devastating pandemic of a novel coronavirus ( COVID -19), which started as an outbreak of pneumonia of unknown cause in the Wuhan city of China in December 2019. Within days and weeks, the COVID -19 pandemic had spread to over 210 countries. By the end of April, COVID -19 had caused over three million confirmed cases of infections and 230,000 fatalities globally. The trend poses a huge threat to global public health. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas.We employed a SEIHCRD delay differential mathematical transmission model with reported Kenyan data on cases of COVID -19 to estimate how transmission varies over time and which population to target for mass testing. The model is concise in structure, and successfully captures the course of the COVID -19 outbreak, and thus sheds light on understanding the trends of the outbreak and the vulnerable populations. The results from the model gives insights to the government on the population to target for mass testing. The government should target population in the informal settlement for mass testing. People with pre-existing medical and non-medical conditions should be identified and given special medical care. With aggressive effective mass testing and adhering to the government directives and guidelines, we can get rid of COVID -19 epidemic.
Acute kidney injury caused by darunavir in a patient with COVID-19: A Case Report
Authors: Abdalla Shiema , Elgassim Lenah , Rustom Fatima , Othman Muftah
Published: September 2020

BackgroundA highly contagious virus known as SARS-CoV-2 has been a pandemic globally. HIV medications were one of the suggested treatments for COVID-19. Here, we report an unusual adverse drug reaction with darunavir in a SARS-CoV-2-infected patient.Case presentationThis is a case presentation of a 53-year-old male with no past medical history who was diagnosed with COVID-19. One week after initiating treatment, the patient developed acute kidney injury, and his serum creatinine increased significantly.ConclusionAs there was no clear justification for renal impairment such as a prerenal or postrenal cause, acute kidney injury, possibly crystal-induced nephropathy, was considered an adverse drug reaction from darunavir.