bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of Ribosomal DNA (ITS2) of hard ticks of Iran, in understanding the conspecificity of Dermacentor marginatus and D. niveus
Authors: Soltan-Alinejad Parisa , Ramezani Zahra , Edalat Hamideh , Telmadarraiy Zakkyeh , Dabiri Farrokh , Vatandoost Hassan , Oshaghi Mohammad Ali , Mohebali Mehdi , Seyyed-Zadeh Seyyed Javad , Zarei Zabihollah , Hanifian Haleh , faghihi faham , Abolhasani Mandan , Bavani Mulood Mohammadi , Musavi Jalil , Terenius Olle , Chavshin Ali Reza
Published: August 2020

Objectives: Hard ticks (Acari: Ixodidae) are ectoparasites of human and animals and transmit a wide range of pathogens. The species identification of ticks is normally based on morphological keys. However, considering the importance of proper identification of the species and their bio-ecological characteristics, relying on morphological characteristics alone can be questionable. In this study, ITS2 and COI were selected for phylogenetic evaluation of Iranian species belonging to three genera: Dermacentor, Hyalomma and Rhipicephalus. Results: The ticks were from 10 populations from three different climatic and zoogeographical zones of Iran. The study of important morphological characteristics revealed notable differences in these characteristics between different populations of D. marginatus species.Contrary to the results of ITS2 sequence analysis which giving additional support for the view that D. niveus and D. marginatus should be viewed as one species only, the sequence analysis of COI and phylogeny favored the separation of the two species of D. niveus and D. marginatus. Given the greater importance of COI in identifying and distinguishing species, the Being two species should be considered.
Sociodemographic, health-related, and social predictors of subjective well-being among Chinese oldest-old: a national community-based cohort study
Authors: Cheng Gang , Yan Yan
Published: August 2020

Background: There is still a lack of a systematic and comprehensive multifactor analysis of subjective well-being (SWB) among Chinese oldest-old. This study aimed to explore sociodemographic, health-related, and social predictors of SWB among Chinese oldest-old using a large and representative sample.Methods: The study included 49,069 individuals aged 80 and older from the Chinese Longitudinal Healthy Longevity Survey, a prospective, nationwide, community-based study conducted from 1998 to 2014. SWB was measured by eight items covering life satisfaction, positive affect (optimism, happiness, personal control, and conscientiousness) and negative affect (anxiety, loneliness, and uselessness). Generalized estimating equation models were used to explore the predictors of SWB.Results: We found that age, gender, ethnic group, education, primary occupation before retirement, current marital status, and place of residence were sociodemographic predictors of SWB among the Chinese oldest-old. The health-related predictors included self-rated health, visual function, hearing function, diet quality, smoking status, and exercise status. SWB was influenced by some social factors, such as co-residence, number of biological siblings, number of children, leisure activities, financial independence, and access to adequate medical service. In particular, self-rated health, access to adequate medical services, exercise status, and place of residence exert a stronger effect than other factors.Conclusions: SWB in the oldest-old is influenced by a large number of complex sociodemographic, health-related, and social factors. Special attention should be paid to the mental health of centenarians, women, rural residents, widowed, physically disabled, and childless oldest-old people. Relevant agencies can improve physical activities, leisure activities, financial support, and medical services to promote the well-being of the oldest-old.
The Economic Burden of Coronavirus Disease 2019 (COVID-19): Evidence from Iran
Authors: Darab Mohsen Ghaffari , Keshavarz Khosro , Sadeghi Elnaz , Shahmohamadi Javad , Kavosi Zahra
Published: August 2020

This study aimed to estimate both direct medical and indirect costs of treating the Coronavirus disease 2019 (COVID-19) from a societal perspective in the patients at a referral hospital in Fars province as well as the economic burden of COVID-19 in Iran in 2020.Methods:This is a partial economic evaluation and a cross-sectional cost-description study conducted descriptively-analytically and based on the data of the COVID-19 patients referred to a referral university hospital in Fars province between March and July 2020. The data were collected by examining the patients' records and accounting information systems. The subjects included all the inpatients with COVID-19 (477 individuals) who admitted to the medical centre during the four months. Bottom-up costing, incidence-based and income-based human capital approaches were used as the main methodological features of this study.Results: The mean direct medical costs were estimated 28,240,025,968 Rials ($ 1,791,172) in total and 59,203,409 Rials ($ 3,755) per person, a significant part of which (41 %) was that of intensive and general care beds (11,596,217,487 Rials equal to $ 735,510. (The second to which were the costs of medicines and medical consumables (28 %). The mean indirect costs including income loss due to premature death, economic production loss due to hospitalization and job absenteeism during recovery course were estimated 129,870,974 Rials ($ 11634) per person. Furthermore, the economic burden of the disease in the country for inpatient cases with the definitive diagnosis was 22,688,925,933,095 Rial equal to $ 1,439,083,784.Conclusion: The results of this study showed that the severe status of the disease would bring about the extremely high cost of illness in this case. It is estimated that the high prevalence rate of COVID-19 has been imposing a heavy economic burden on the country and health system directly that may result in rationing or painful cost-control approaches.
Refractory Multi-inflammatory Syndrome in a two weeks old neonate with COVID-19 Treated Successfully with Intravenous Immunoglobulin, Steroids and Anakinra
Authors: Magboul Samar , Khalil Ahmed , Alshami Ahmad , Alaido Mohamed , Alhothi Abdulla , Ellithy khaled , Amri Mohamed Al , Hassan Manasik
Published: August 2020

Background: World Health Organization (WHO) and other Health officials alert clinicians about a rare but severe inflammatory condition seen in children and linked to Corona Virus Disease 2019(COVID-19). The WHO is describing the condition as a multisystem inflammatory syndrome in children (MIS-C) and is recommending clinicians to report those cases to get a better understanding of the disease and clinicians can learn more.Case presentation: We are reporting the clinical course of the youngest case of COVID-19 related MIS-c; a two-week-old term neonate with COVID-19 infection and features suggestive of MIS-C , managed with intravenous immunoglobulin (IVIG), pulse steroid, and interleukin-1 inhibitor (Anakinra).By reviewing the literature, our baby is the first neonatal case who has been diagnosed with MIS-C.Conclusion: COVID-19 infection in pediatrics are likely to present with a mild course; however, some may develop a hyper-inflammatory syndrome. Pediatricians should be aware of such presentation, the clinical course, the management modalities, and inform parents and caregivers about common signs and symptoms. Anakinra may consider as effective second agent in (IVIG and steroid-refractory pediatric cases).
Activated breast stromal fibroblasts exhibit myoepithelial and mammary stem cells features
Authors: Aboussekhra Abdelilah , Islam Syed S , Alraouji Noura N.
Published: August 2020

Background: Active breast cancer-associated fibroblasts (CAFs) promote tumor growth and spread, and like tumor cells they are also heterogeneous with various molecular sub-types and different pro-tumorigenic capacities.Methods: We have used immunoblotting as well as quantitative RT-PCR to assess the expression of various epithelial/mesenchymal as well as stemness markers in breast stromal fibroblasts. Immunofluorescence was utilized to assess the level of different myoepithelial and luminal markers at the cellular level. Flow cytometry allowed to determine the proportion of CD44- and ALDH1-positive breast fibroblasts, while sphere formation assay was used to test the ability of these cells to form mammospheres.Results: We have shown here that IL-6-dependent activation of breast and skin fibroblasts promotes mesenchymal-to-epithelial transition in a STAT3- and p16-dependent manner. Interestingly, most primary CAFs isolated from breast cancer patients exhibited such transition and expressed lower levels of the mesenchymal markers N-cadherin and vimentin as compared to their adjacent normal fibroblasts (TCFs) isolated from the same patients. We have also shown that while CAFs and IL-6-activated fibroblasts express high levels of several myoepithelial markers such as cytokeratin 5/6, cytokeratin 14, cytokeratin 19 and c-KIT, they do not express the luminal marker cytokeratin 18. Furthermore, we present clear evidence that IL-6 treatment promotes mammary stemness characteristics (CD44high/CD24low/ALDHhigh) in stromal fibroblasts in a STAT3- and p16-dependent manner. Similar features were also identified in 12 CAFs isolated from breast tumors, which showed higher proportions of CD44high and ALDHhigh cells, compared to their corresponding TCF cells. Importantly, these CD44high cells have higher abilities to form mammospheres and to enhance cell proliferation of breast cancer cells in a paracrine manner relative to their corresponding CD44low cells.Conclusions: Together, the present findings show novel characteristics of active breast stromal fibroblasts, which exhibit additional myoepithelial/progenitor features.
Prognostic Significance and Immune Infiltration of Microenvironment‐related Signatures in Pancreatic Cancer
Authors: Lu Qian , Zhang Yu , Gu Weihong , Ji Xinrong , Chen Zhong
Published: August 2020

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal and most aggressive types of malignancies and accounts for the vast majority of Pancreatic Cancer (PC). Numerous studies have reported that the tumor microenvironment (TME) was significantly correlated with the oncogenesis, progress, and prognosis of various malignancies. Therefore, mining of TME-related genes is reasonably important to improve the overall survival (OS) of patients with PDAC. Methods: The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to identify differential expressed genes (DEGs). Functional and pathway enrichment analyses, protein–protein interaction (PPI) network construction and module analysis, overall survival analysis and tumor immune estimation resource (TIMER) database analysis were then performed on DEGs. Results: Data analysis indicated that higher immune scores were correlated with better overall survival (P = 0.033). Differential expression analysis obtained 90 intersection genes influencing both stromal and immune scores. Among these intersection genes, CA9, EBI3, SPOCK2, WDFY4, CD1D and CCL22 were significantly correlated with OS in PDAC patients. Moreover, multivariate Cox analysis revealed that CA9, SPOCK2 and CD1D were the most significant prognostic genes, and were closely correlated with immune infiltration in TCGA cohort. Further analysis indicated that CD1D were significantly related with immune cell biomarkers for PDAC patients. Conclusions: In summary, our findings provide a more comprehensive insight into TME and show a list of prognostic immune associated genes in PDAC. However, further studies on these genes need to be performed to gain additional understanding of the association between TME and prognosis in PDAC.
Up-Regulation of LINC00158 Contributes to Endometrial Carcinoma Progression by Interacting with HMGB2
Authors: Cai Yixuan , Hao Min , Chang Yue , Liu Yun
Published: August 2020

Background: Increasing evidence has reported lncRNAs exhibit significant biological functions in regulating endometrial carcinoma (EC) progression. LINC00158 has been identified as a crucial modulator in various diseases. Nevertheless, the specific molecular mechanism of LINC00158 in EC remains to be investigated.Methods:q-PCR and Western blot analysis were performed to determine the expression of LINC00158 and HMGB2 in EC tissues and cells. Cell viability assay, EdU assay, flow cytometry, wound healing assay and transwell invasion assay were used to evaluate their effects on EC cell proliferation, migration and invasion. RIP assay was used to verify the interactions between LINC00158 and HMGB2. Xenograft tumor model was established to confirm the effects of LINC00158 in vivo.Results:INC00158 was obviously up-regulated in EC tissues in comparison to the normal endometrium. LINC00158 was greatly increased in EC cells than in the immortalized endometrial fibroblast cell T-HESCs. Cell viability of EC cells was reduced as indicated using CCK-8 assay and EdU experiments by knockdown of LINC00158. Loss of LINC00158 obviously induced EC cell apoptosis and blocked cell cycle, repressed EC cell migration and invasion capacity. HMGB2 was remarkably increased in EC tissues and it was positively correlated with LINC00158 expression. RIP assay was carried out and confirmed the direct binding relationship between LINC00158 and HMGB2. Decrease of LINC00158 was able to reduced HMGB2 expression in AN3CA and HEC1-A cells. LINC00158 activated HMGB2 to promote EC progression in vivo.Conclusions: Our findings implied high expression of LINC00158 promoted EC progression via interacting with HMGB2.
Local Persistence of Novel Regional Variants of La Crosse Virus in the Northeast United States
Authors: Eastwood Gillian , Shepard John J , Misencik Michael J , Andreadis Theodore G , Armstrong Philip M
Published: August 2020

Background: La Crosse virus [LACV] (genus Orthobunyavirus, family Peribunyaviridae) is a mosquito-borne virus that causes pediatric encephalitis and accounts for 50-150 human cases annually in the USA. Human cases occur primarily in the Midwest and Appalachian regions whereas documented human cases occur very rarely in the northeastern USA. Methods: Following detection of a LACV isolate from a field-collected mosquito in Connecticut during 2005, we evaluated the prevalence of LACV infection in local mosquito populations and genetically characterized virus isolates to determine whether the virus is maintained focally in this region. Results: During 2018, we detected LACV in multiple species of mosquitoes, including those not previously associated with the virus. We also evaluated the phylogenetic relationship of LACV strains isolated from 2005-2018 in Connecticut and found that they formed a genetically homogeneous clade that was most similar to strains from New York State. Conclusion: Our analysis argues for local isolation and long-term persistence of a genetically distinct lineage of LACV within this region. We highlight the need to determine more about the phenotypic behavior of these isolates, and whether this virus lineage poses a threat to public health.
Incoming Flow Turbulence Reduction Increases the Efficiency of Aerosolized Medication Delivery to 3D Oral Mucosal Tissue Models.
Authors: Haroutunian G. Greg , Tsagikian Ashot , Zheng Haiyan , Mosoian Arevik
Published: August 2020

Background: Inhalable medication devices on the market deliver aerosolized drugs in a turbulent flow, which creates significant obstacles for reaching the lower lungs. The complexity of the interaction of external turbulent flow from an inhalation device with complex anatomy of the upper airways, including the oropharyngeal cavity, makes the fidelity of aerosolized medication delivery to the lungs extremely low. Unpredictable outcomes, waste, and side effects result from unintended upper airway drug deposition. Methods: Here we compared the efficiency of aerosolized medication (fluticasone) delivery via a novel Flow Modification Device (ModiFlow) to that of a Standard Spacer (SS) device. The ability of ModiFlow to minimize the turbulence in the flow was assessed preliminarily by measuring the length of the Laminar Outflow using video recording. Oral mucosal 3D tissue culture (SkinAxis) was used as a target for delivery, and was placed either “well within” the range of the length of the oro-pharyngeal cavity (5cm) or “well outside” of it (20cm) from exit points of each device. The efficiency of fluticasone delivery to the surface of tissue cultures was quantified by mass spectrometry. Results: The results of the study demonstrated a statistically significant advantage of ModiFlow over a Standard Spacer in delivering aerosolized fluticasone to target tissue at both distances. The difference in the efficiency of delivery between the two spacers was more pronounced at a longer distance.Conclusions: Lamination of the outflow using internal septi helps improve the delivery of aerosolized medication to target tissue despite an increased inner surface area of the spacer device, which also indicates lesser deposition of the medication on the walls of the test tube. This suggests that the use of ModiFlow will potentially result in the more efficient delivery of aerosolized medications to the lungs with lesser deposition in the oral cavity and fewer side effects.
Digital Insecticide-treated nets (ITNs) mass distribution campaign in the particular context of covid-19 pandemic in Benin: lessons learned and challenges
Authors: AIKPON ROCK , Affoukou Cyriaque , Hounkpatin Benjamin , Eclou Dieu-Donné , Cyaka Yves , Egwu Elijah , Agbessi Narcisse , Tokponon Filémon , Salifou Sahidou , Salami Lamidhi , Hounto Aurore Ogouyemi
Published: August 2020

Background
In 2020, Benin has implemented a digital Insecticide-treated nets (ITNs) mass distribution campaign in the particular context of covid-19 pandemic and then, offered important lessons to share. This paper aims to describe the implementation process as well as the lessons learned and challenges from this campaign.
Methods
A descriptive design was used for reporting the planning and implementation process of ITNs campaign. Moreover, the changes and adaptations related to covid-19 pandemic are well described.
Results
A total of 3,175,773 households were registered corresponding to a total of 14,423,998 persons (13.55% more from projection). Moreover, 94.16% (13,581,637 people) of enumerated population were protected. A total of 7,652,166 ITNs were distributed countrywide.
Conclusions
High political commitment, engagement and support add to the financial and technical supports from partners were the essential factors that make 2020 ITNs mass campaign success in Benin despite the particular context of COVID-19 pandemic. It is essential to maintain the prevention activities for malaria and this could substantially reduce the overall impact of the COVID-19 pandemic in the populations at malaria risk.
Single amino acid bionanozyme for environmental remediation
Authors: Makam Pandeeswar , Yamijala Sharma , Shimon Linda , Wong Bryan , Gazit Ehud
Published: August 2020

Enzymes are extremely complex catalytic structures with immense biological and technological importance. Nevertheless, their widespread environmental implementation faces several challenges, including high production costs, low operational stability, and intricate recovery and reusability. Therefore, the de novo design of minimalistic biomolecular nanomaterials that can efficiently mimic the biocatalytic function (bionanozyme) and overcome the limitations of natural enzymes is a key goal in biomolecular engineering. Here, we report an exceptionally simple yet highly active and robust single amino acid bionanozyme that can catalyze the rapid oxidation of environmentally toxic phenolic contaminates and serves as an ultrasensitive tool to detect biologically important neurotransmitters, similar to the laccase enzyme. While inspired by the laccase catalytic site, the substantially simpler copper-coordinated bionanozyme is ∼5400-fold more cost-effective, 10-fold more efficient, and 36-fold more sensitive compared to the natural protein. Furthermore, the designed mimic is stable under extreme conditions (pH, ionic strength, temperature, storage time), markedly reusable for several cycles and display broad substrate specificity. These findings hold great promise in the development of efficient bionanozyme for analytical chemistry, environmental protection, and biotechnology.
Transient Responses of the Hepatic Lipidome to Acute Exercise Bouts in Mice
Authors: Henderson Gregory C , Tenorio Valeria P Martinez , Tuazon Marc A
Published: August 2020

BACKGROUND: The content of triacylglycerol (TAG) in the liver is known to rapidly increase after a single bout of exercise followed by recovery to sedentary levels. The response of other hepatic lipids, and acyl chain composition of lipid classes, would provide a deeper understanding of the response of hepatic lipid metabolism to acute exercise. METHODS: Female mice performed a single bout of continuous exercise (CE), high-intensity interval exercise (HIIE), or no exercise (CON). The total content of various lipids in the liver, and fatty acids within lipid classes, were measured in tissues collected 3 hours after exercise (Day 1) and the day following exercise (Day 2). RESULTS: The total concentration of TAG rose on Day 1 after exercise (P < 0.05), with a greater elevation in HIIE than CE (P < 0.05), followed by a decline toward CON levels on Day 2. The total concentration of other measured lipid classes was not significantly altered by exercise. However, n-6 polyunsaturated fatty acid relative abundance in diacylglycerol (DAG) was increased by HIIE (P < 0.05). In CON liver, TAG content was positively correlated with DAG and phosphatidylethanolamine (P < 0.05), while these statistical associations were disrupted in exercised mice on Day 1. CONCLUSIONS: Overall, the results characterize flexibility of the hepatic TAG pool size in the liver, and the relationship between TAG and other lipid abundances is altered during the transient TAG pool expansion after exercise. The transient expansion of the hepatic TAG pool and remodeling of the DAG pool may be fundamental components of the physiological response to intense exercise.
LncRNA CASC2 Plays an Indicative Role in Diagnosing Bladder Cancer
Authors: Zi Hao , Tao Wen-Lin , Gao Lei , Yu Zhao-Hua , Bai Xiao-Dong , Li Xiao-Dong
Published: August 2020

Background: Bladder cancer is a common cancer of urinary system, with high incidence and mortality. LncRNA CASC2 as a tumor suppressor has been reported to be involved in many human tumors. In this study, we aimed to explore the diagnostic value of CASC2 for bladder cancer patients.Methods: qRT-PCR was used to detect the expression level of CASC2 in 140 bladder cancer patients and 90 healthy volunteers. The differences of CASC2 expression between the cancer group and healthy group were analyzed using student’s t test. The correlation of CASC2 expression with clinical characteristics of the bladder cancer patients was estimated with Chi-square test. In addition, ROC curve was plotted to evaluate the diagnostic value of CASC2 for bladder cancer patients.Results: Serum CASC2 level was lower in bladder cancer patients than that in healthy group (P<0.05). The expression level of CASC2 was significantly associated with histological grade (P=0.000), TNM stage (P=0.000), and lymph node metastasis (P=0.001). The area under the ROC curve (AUC) was 0.864 and the optimal cutoff value was 0.955, suggesting the diagnostic value of CASC2 for bladder cancer. The diagnostic sensitivity was 77.8% and specificity was 85.7%.Conclusion: CASC2 may be a novel biomarker for early diagnosis of bladder cancer.
Chemotherapy Sensitizing Effects of Methadone in Glioblastoma Cells Are Drug- and Cell Line-dependent
Authors: Haas Bodo , Ciftcioglu Janine , Jermar Sanja , Weickhardt Sandra , Eckstein Niels , Kaina Bernd
Published: August 2020

Background

D,L-methadone (MET), an analgesic drug used for pain treatment and opiate addiction has achieved attention from oncologist and social media as possible chemosensitizing agent in glioblastoma multiforme (GBM) treatment. MET has been reported to enhance doxorubicin-induced cytotoxicity in GBM cells via activation of the µ-opioid receptor (MOR) and subsequent apoptosis induction. Here, we further aimed at quantifying MET effects in comparison to other opioids alone and in combination with doxorubicin and clinically more relevant temozolomide (TMZ) in a set of GBM cell lines and primary GBM cells.
Methods

MOR expression in GBM cells was investigated by immunofluorescence and immunoblotting. Resistance to drugs alone or in combination was assessed by MTT assays. Concentration effect curves were fitted to data points by nonlinear regression analysis and IC50 values were calculated. Apoptotic rates were determined by Annexin V staining.
Results

We found that MET alone was cytotoxic to GBM cells at high micromolar concentrations in MTT assays by induction of apoptosis and necrosis while morphine and oxycodone were hardly cytotoxic. Naloxone was not able to block MET-induced cytotoxicity, indicating that cell death inducing effects of MET are not MOR dependent. We recorded doxorubicin and TMZ concentration response curves by MTT assays in combination with fixed MET concentrations. MET only enhanced doxorubicin cytotoxicity in one cell line and in part in primary cells at certain MET concentrations. MET was not effective in sensitizing cells towards TMZ. Contrarily, in two cell lines MET even decreased sensitivity towards TMZ.
Conclusions

MET can be considered cytotoxic to GBM cells only at clinically not relevant concentrations by induction of apoptosis and necrosis. Sensitizing effects are only observed in combination with doxorubicin but not with TMZ and are highly dependent on cell line and applied drug concentrations.
Adherence to Veterinary Recommendations for Ectoparasiticides Purchased by Cat Owners in the United States.
Authors: Lavan Robert Philip , Armstrong Rob , Normile Dorothy , Vaala Wendy
Published: August 2020

Background: Safe and effective flea and tick treatment options for cats are important in companion animal practice because of feline ectoparasite infestation prevalence and the potential for parasitic disease transmission. Retrospective cat owner purchasing transactions at U.S. veterinary clinics were obtained for three topical feline flea and tick ectoparasiticides. One medication, fluralaner, had a 12-week redosing interval, while two other medications were approved for monthly redosing. The annual number of doses purchased by cat owners was determined for each of the three medications and then compared between medications. The objective was to evaluate whether 12-week retreatment intervals resulted in a different duration of coverage compared to monthly treatments for ectoparasiticide products. Methods: Study results were obtained by analyzing the transactional records from a commercial database derived from veterinary practice management software. The study database consisted of cat owner purchasing records from January 2017 through June 2019 from 671 veterinary practices representing approximately 46,700 cats.Results: Cat owners purchased an average of 1.5 doses of fluralaner per year which, based on a 12-week redosing interval, provides 4.2 months of treatment coverage. Cat owners who used monthly flea and tick medications purchased 3.6 months (fipronil combination) and 2.8 months (imidacloprid combination) annually of each of the two medications. Average yearly cat owner purchases of fluralaner provide a longer duration of coverage than for cat owners purchasing fipronil combination (17% more) or imidacloprid combination (50% more). Conclusion: Cat owners who obtained a flea and tick treatment with a 12-week redosing interval (fluralaner) protected their cats for up to 50% longer duration each year compared to the duration of protection obtained by cat owners who used a medication re-dosed monthly. Cat owners should increase their duration of flea and tick coverage to come closer to achieving veterinary recommendations.
Comparing Surgical and Conservative Treatment on Achilles Tendon Rupture: A Comprehensive Meta-Analysis of RCTs
Authors: She Guorong , Teng Qiang , Li Jieruo , Zheng Xiaofei , Chen Lin , Hou Huige
Published: August 2020

Background Achilles tendon is the strongest tendon in human and frequently injured mainly in young to middle age active population. Increasing incidence of Achilles tendon rupture (ATR) is still reported in several studies. Surgical repair and conservative treatment are two major management strategy widely adopted in ATR patients but the consensus of optimal treatment strategy is still debated. We aimed at fully reviewing the ATR topic with additional assessments and performed a most comprehensive meta-analysis of randomized controlled trials (RCTs).Method We comprehensively searched database of PubMed, Embase, Cochrane and ClinicalTrial.gov and retrieved all randomized controlled trials comparing surgical and conservative treatment on achilles tendon rupture for further analysis. Data extraction was performed by two independent reviewer and random effect model was adopted when I2 > 50%, with data presentation of risk ratio, risk difference or mean difference and 95% confidence interval. Results A total of 13 randomized control trials were included in this meta-analysis. Significant difference was observed in events of re-rupture, complication rate, adhesion to underlying tendon, sural nerve injury and superficial infection. For surgical treatment, significant reduction in re-rupture rate could be observed while complication rate was higher compared with conservative treatment. Conclusion Surgical treatment was revealed significance in reduction of re-rupture rate but associated with higher complication rate while conservative treatment showed similar outcomes with lower complication rate. Collectively, we recommend conservative treatment if patients’ status and expectation are suitable, but surgeon as well as physician’s discretion is also important in decision making.
Landlessness, Economic Activities and Household Income in the Red River Delta, Vietnam
Authors: Vu Quang , Tran Tuyen Quang
Published: August 2020

The authors have requested that this preprint be removed from Research Square.
The Whole Cell Proteome-based Study on The Mechanism of Apoptosis Induced by Soybean Agglutinin on IPEC-J2
Authors: Pan Li , Liu Yan , Farouk Mohammed Hamdy , Bao Nan , Zhao Yuan , Sun Hui , Qin Guixin
Published: August 2020

Background: Soybean agglutinin (SBA), a major anti-nutritional factor in soybean, may induce abnormal health and metabolism of intestinal cells, resulting in the reduction of the production performance of animals. The anti-nutritional mechanisms of SBA are not fully understood, in terms of the cell life activities and metabolism of intestinal cells. This research aims to find the effects of SBA on the cell cycle, apoptosis and proteomic, and furtherly to get more findings for verifying the mechanism of SBA anti-nutritional characters.Methods: The IPEC-J2 cell line was cultured with the medium containing 0.0, 0.5 or 2.0 mg/mL SBA, respectively, for 24 h. The percentage of the cells at different cell cycle phases (G0/G1 phase, S phase and G2 phase) and cell apoptosis rates were measured with flow cytometry. The expressions of Cyclin D1, active p21, Bcl-2, and Bax were determined by western blotting. The activity of caspase-3 (Casp-3) and caspase-9 (Casp-9) were tested with ELISA. The whole-cell quantitative proteome were detected by TMT/iTRAQ Labeling, HPLC fractionation and LC-MS/MS Analysis. The functions and characteristics of the differential expressed proteins in the proteome results were analyzed from the aspects of GO annotation and KEGG pathway. The relationship between the results of proteomics and apoptosis or cell cycle were analyzed and discussed.Results: The percentage of the cells at G0/G1 phase, cell apoptosis rates, expressions of Bax and p21, and the activities of Casp-3 and Casp-9 were increased, cyclin D1 and Bcl-2 expression were declined with the increased of the SBA treatment levels (p<0.05). The proteomic measurements showed that a numbers of differentially expressed proteins, caused by SBA treatment, were mainly enriched in the DNA replication, base excision repair, nucleus excision repair, mismatch repair, ubiquitin-mediated proteolysis pathway, cell structural-proteins, and structures and functions of mitochondria. Moreover, the differential expressed proteins enriched in AMP-activated protein kinase (AMPK) pathway and the process of synthesis and metabolism of proteins were only found in 2.0 mg/mL SBA treatment.Conclusion: The results of this experiment demonstrated that cell cycle arrest and apoptosis induced by SBA may be resulted from the downregulating the expression of the proteins related to DNA replication and repair, protein translation, signal-conducting relation, cell structure, and subcellular structure and function.
Lack of Cross-resistance Between Non-steroidal and Steroidal Aromatase Inhibitors in Breast Cancer Patients: The Potential Role of the Adipokine Leptin.
Authors: Bahrami Nazli , Jabeen Shakila , Sauer Torill , Ødegård Hilde Presterud , Geisler Stephanie Beate , Gravdehaug Berit , Reitsma Laurens Cornelus , Selsås Knut , Kristensen Vessela , Geisler Jürgen
Published: August 2020

Background: The aromatase inactivator exemestane may cause clinical disease stabilization following progression on non-steroidal aromatase inhibitors like letrozole in patients with metastatic breast cancer, indicating that additional therapeutic effects, not necessarily related to estrogen-suppression, may be involved in this well-known “lack of cross-resistance”. Experimental design: Postmenopausal women with ER positive, HER-2 negative, locally advanced breast cancer were enrolled in the NEOLETEXE-trial and randomized to sequential treatment starting with either letrozole (2.5 mg o.d.) or exemestane (25 mg o.d.) followed by the alternative aromatase inhibitor. Serum levels of 54 cytokines, including 12 adipokines were assessed using the Luminex xMAP technology (multiple ELISA). Results: Serum levels of leptin were significantly decreased during treatment with exemestane (p < 0.001), regardless whether exemestane was given as first or second neoadjuvant therapy. In contrast, letrozole caused a non-significant increase in serum leptin levels in vivo. Conclusions: Our findings suggest an additional and direct effect of exemestane on CYP-19 (aromatase) synthesis presumably due to effects on the CYP19 promoter use that is not present during therapy with non-steroidal aromatase inhibitors. Our findings provide a reasonable explanation for the clinically observed lack of cross-resistance between nonsteroidal and steroidal aromatase inhibitors in breast cancer patients.Trial registration: registered on March 23rd. 2015 in the National trial database of Norway (Registration number: REK-SØ-84-2015).
A rapid review of the impact of COVID-19 on the mental health of health and social care workers: implications for psychological interventions
Authors: De Kock Johannes H. , Latham Helen Ann , Leslie Stephen J , Grindle Mark , Munoz Sarah-Anne , Ellis Liz , Polson Rob , O’Malley Christopher M
Published: August 2020

BackgroundHealth and social care workers (HSCWs) have carried a heavy burden during the COVID-19 crisis and in the challenge to control the virus have directly faced its consequences. Supporting their psychological wellbeing continues therefore to be a priority. This rapid review was carried out to identify whether there are any identifiable risk factors for adverse mental health outcomes amongst HSCWs during the COVID-19 crisis. The review also sought to identify a participant population for the trial of a digital intervention to support HSCW’s psychological wellbeing during the pandemic. MethodsWe undertook a rapid review of the literature following guidelines by the WHO and the COVID-19 Cochrane Collaboration’s recommendations. We searched across 14 databases, executing the search at two different time points. We included published observational and experimental studies that reported the psychological effects on health and care workers during the COVID-19 pandemic. ResultsThe 24 studies included in this review reported data predominantly from China (18 out of 24 included studies) and most sampled urban hospital staff. Our study indicates that COVID-19 has a considerable impact on the psychological wellbeing of front line hospital staff. Results suggest that nurses may be at higher risk of adverse mental health outcomes during this pandemic, but no studies compare this group with the social care or primary care workforce. Other risk factors identified were underlying organic illness, gender (female), concern about family, fear of infection, lack of personal protective equipment (PPE) and close contact with COVID-19. Resilience was identified as a factor protecting against adverse mental health outcomes. ConclusionsThe evidence to date suggests that female nurses with close contact with COVID-19 patients may have the most to gain from psychological interventions. However, inconsistencies in findings and a lack of data outside of hospital settings, suggest that we should not exclude any groups when addressing psychological wellbeing in health and social care workers. Psychological interventions aimed at enhancing psychological resilience and utilising innovative methods to personalise treatments without excluding groups may be of benefit.
Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1
Authors: Benedetti Francesca , Snyder Greg , Giovanetti Marta , Angeletti Silvia , Gallo Robert C. , Ciccozzi Massimo , Zella Davide
Published: August 2020

Background:The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was ﬁrst detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic.Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by i) the presence of specific amino acid residues of nsp1 and b) the interaction between the protein and the host’s small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects.Methods: A total of 17928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host’s gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and ii) correlate these changes in nsp1 with potential decreased viral pathogenicity.
 On Classification of the Earth's Crust Areas by the Level of Geodynamic Threat
Authors: Batugin Andrian
Published: August 2020

It is accepted as a well-known fact that a similar anthropogenic impact on the Earth's crust in different places causes dissimilar response. Seismic zoning maps are not designed to predict such geodynamic hazards as rock bursts, induced earthquakes, reactivation of tectonic faults, etc., and require careful adjustment in places of intense impact on the subsurface strata. In this regard, we consider the classification of the Earth's crust areas according to the degree of geodynamic hazard, i.e. its potential geodynamic response to anthropogenic intervention. This classification is based on the concept that there exists a critically stressed layer within the Earth’s crust. It is believed that such critically stressed layer within the Earth’s crust extends from the Earth's surface to a certain depth, which at each point depends on the nature of the interaction between crustal blocks of different hierarchical levels.From this perspective, anthropogenic impact, such as mining operations, represents a direct impact upon the critically stressed zone. The hypothesis is accepted that the thicker is the critical stressed rock layer, the stronger might be the response to anthropogenic intervention, as it has more accumulated energy. Four categorized of the geodynamic threat were found and mapped. To verify this classification, the manifestations of the geodynamic hazards were studied. The intensity of geodynamic hazard increases from the 1st area to the 4th area. The phenomenon of large induced seismic events with hypocenters at great depths is explained by the base of this idea and could be associated with anthropogenic impacts from the surface directly on the regional zone of the critical stressed rock massif. The approach can be used to assess the geodynamic consequences of human exposure to the Earth's crust.
Maternal Folic Acid Impacts DNA Methylation Profile in Male Rat Offspring Associated With Neurodevelopment and Learning/Memory Abilities
Authors: Wang Xinyan , Li Zhenshu , Zhu Yun , Yan Jing , Liu Huan , Huang Guowei , Li Wen
Published: August 2020

Background: Periconceptional folic acid (FA) supplementation not only reduces the incidence of neural tube defects, but also improves cognitive performances in offspring. However, the genes or pathways that are epigenetically regulated by FA in neurodevelopment were rarely reported. Methods: To elucidate the underlying mechanism, the effect of FA on the methylation profiles in brain tissue of male rat offspring was assessed by methylated DNA immunoprecipitation chip. Differentially methylated genes (DMGs) and gene network analysis were identified using DAVID and KEGG pathway analysis. Results: Compared with the FA-N group, 1939 DMGs were identified in the FA-D group, and 1498 DMGs were identified in the FA-S group, among which 298 DMGs were overlapped. The pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in response to maternal FA intake during pregnancy, and there were some identical and distinctive potential mechanisms under FA deficiency or supplemented conditions. Conclusions: In conclusion, genes and pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in male rat offspring in response to maternal FA deficiency or supplementation during pregnancy.
“My first 48 hours out”: Drug users’ perspectives on challenges and strategies upon release from prison
Authors: Jamin Daniela , Stöver Heino , Vanderplasschen Wouter , Sys Orphée , Jauffret-Roustide Marie , Michel Laurent , Trouiller Philippe , Neisa Andreia , Homem Mariana , Mendes Vania
Published: August 2020

Background Prisoners report much higher prevalence rates of drug use and more harmful patterns of use than the general population [1]. People who use drugs have also an above-average experience with the criminal justice system in general, the prison system and the subsequent release situation in particular. Release from prison is associated with increased mortality rates among drug users due to the risk of overdose [2–5]. The EU-funded project ‘My first 48h out’ aimed to address the gaps in the continuity of care for long-term drug users in prison and upon release and had a special focus on drug user’s perspectives on challenges upon release.Methods A multi-country (Belgium, France, Germany and Portugal) qualitative study was set up to explore drug users’ perceptions of drug use and risk behaviour upon prison release, experiences of incarceration, knowledge of risks and overdose prevention, individual risk reduction mechanisms and strategies to avoid risks when being released. Therefore, interviews and focus groups based on a semi-structured interview with (ex-) prisoners in four countries were implemented.Results 104 (Ex-) prisoners pointed out that there are a lot of challenges for people who use drugs at release from prison. Mainly named are a lack of housing and employment support and also a complex administrative procedure regarding services, health insurance and welfare benefits. Beside these structural challenges there are individual challenges like old habits, drug use (overdose) and the situation outside prison. As a result of a lack of support (ex-) prisoners use individual strategies to cope with the risks and challenges at release.Conclusion There are measures to prepare prisoners for release, but mostly they do not focus on individual and specific challanges of poeple who use drugs. Mainly psychosocial and medical support need to be improved and adjusted inside and outside prison. To implement measures the individual needs and strategies of people who use drugs should be utilized, as they show the specific needs of drug users at release.
Surgical Treatment for Anomalous Origin of the Right Coronary Artery from the Pulmonary Artery: A Case Report with Five-Year Follow-up
Authors: Teng Peng , Li Weidong , Ni Yiming
Published: August 2020

Background: Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital heart disease affecting about 0.002% of the population. Knowledge of ARCAPA is almost collected from case reports. The aim of this study was to provide a rare case to better understand this rare congenital coronary anomaly.Case presentation: We report a rare case of an 18-year-old male who was initially referred because of heart murmur. Dilated and tortuous coronary arteries were detected by echocardiography and congenital coronary anomaly was suggested. Further coronary CT angiography confirmed the diagnosis of ARCAPA. Although dual coronary system provides favorable long-term outcome, bypass surgery was considered technically difficult due to the huge mismatch of caliber between the right coronary artery and graft vessels. Eventually, simple right coronary artery ligation was performed. The patient was followed up for about 5 years without evidence of atherosclerosis or myocardial ischemia.Conclusions: ARCAPA presents as a rare congenital heart disease with variable clinical manifestations. Surgical treatment is highly recommended to re-establish dual coronary system and prevent further complications. To our best knowledge, only about 200 cases of ARCAPA has been reported.