bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate reactions of newly-diagnosed HIV-positive persons to the initial news of being HIV-positive: Implications for public health
Authors: Owusu Adobea Yaa
Published: October 2020

Background: Ready acceptance of the first news of HIV-positive diagnosis is a known personal and public health safety-net. Its beneficial effects include prompt commencement and sustenance of HIV-positive treatment and care, better management of transmission risk, and disclosure of the HIV-positive status to significant others. Yet, no known study has explored this topic in Ghana; despite Ghana’s generalised HIV/AIDS infection rate. Existing studies have illuminated the effects of such reactions on affected significant others; not the infected.Methods: This paper studied qualitatively the initial reactions of 26 persons living with HIV/AIDS upon receiving the initial news of their diagnosis. Sample selection was combined purposive and random, from two hospitals in a district in Ghana heavily affected by HIV/AIDS. The paper applied the theory of hopelessness.Results: As expected, the vast majority of respondents reacted to the initial announcement of their HIV-positive infection with a myriad of negative psychosocial reactions, including thoughts of committing suicide. Yet, few of them received the news with resignation. For the vast majority of respondents, having comorbidities from AIDS prior to the diagnosis primarily shaped their initial reactions to their diagnosis. The respondents’ transitioning to self-acceptance of their HIV-positive status was mostly facilitated by receiving counselling from healthcare workers.Conclusions: Although the first news of an HIV-positive diagnosis was immobilising to most respondents, the trauma faded, paving the way for beneficial public health actions. The results imply the critical need for continuous education on HIV/AIDS by public health advocates, using mass media, particularly, TV. Healthcare workers in VCTs should empathise with persons who are informed of their HIV-positive status for the first time.
8q24 Clear Cell Renal Cell Carcinoma Germline Variant is Associated with VHL Mutation Status and Clinical Aggressiveness
Authors: Eckel-Passow Jeanette E , Yan Huihuang , Kosel Matthew , Serie Daniel , Decker Paul , Jenkins Robert , Costello Brian , Leibovich Bradley , Ho Thai , Parker Alexander
Published: October 2020

Background: The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown.Methods: We analyzed 420 ccRCC patients from The Cancer Genome Atlas (TCGA). Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results: The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR=1.6, p=0.0037) and SSIGN score (OR=1.9, p=0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes.Conclusions: These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.
Minimal invasive versus open esophagectomy for patients with esophageal squamous cell carcinoma after neoadjuvant treatments
Authors: Chen Dongni , Wang Weidong , Mo Junxian , Ren Qiannan , Miao Huikai , Chen Youfang , wen zhesheng
Published: October 2020

Background Although previous studies have discussed whether the minimally invasive esophagectomy (MIE) is superior to open surgery, the data concerning esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant treatment followed by radical resection is limited. The purpose of our study was to compare the short- and long-term clinical outcomes of the two surgical approaches in treating ESCC patients.MethodsBetween January 2010 and December 2016, ESCC patients who had received neoadjuvant therapy and underwent Mckeown esophagectomy at our institute were eligible. The baseline characteristics, pathological data, short-and long-term outcomes of these patients were collected and compared based on the surgical approach. ResultsA total of 195 patients was included in the current study. Compared to patients underwent open surgery, patients underwent MIE had shorter operative time and less intraoperative bleeding (390 min vs 330 min, P=0.001; 204 ml vs 167 ml, P=0.021). In addition, the risk of anastomotic leakage was decreased in MIE group (20.0% vs 3.3%, P<0.001), while the occurrence of other complications did not have statistical significance between two groups. Overall survival (OS) and disease-free survival (DFS) was no difference in patients received neoadjuvant chemotherapy between the two approaches. For the patients underwent neoadjuvant chemoradiotherapy, OS was significantly better in the MIE group (log rank=6.197; P=0.013). ConclusionMinimally invasive Mckeown esophagectomy is safe and feasible for ESCC patients who underwent neoadjuvant therapy. MIE approach presented better perioperative results than open esophagectomy. The effect of surgical approaches on survival was depending on the scheme of neoadjuvant treatment.
Genomic analysis of circular RNAs in heart
Authors: Dong Kunzhe , He Xiangqin , Su Huabo , F David J.R. , Zhou Jiliang
Published: October 2020

Background: Heart failure (HF) is a leading cause of human morbidity and mortality. Circular RNAs (circRNAs) are a newly discovered class of RNA that have been found to have important physiological and pathological roles. In the current study, we de novo analyzed existing whole transcriptome data from 5 normal and 5 dilated cardiomyopathy (DCM) human heart samples and compared the results with circRNAs that have been previously reported in human, mouse and rat hearts. Results: Our analysis identifies a list of cardiac circRNAs that are reliably detected in multiple studies. We have also defined the top 30 most abundant circRNAs in healthy human hearts which include some with previously unrecognized cardiac roles such as circHIPK3_11 and circTULP4_1. We further found that many circRNAs are dysregulated in DCM, particularly transcripts originating from DCM-related gene loci, such as TTN and RYR2. In addition, we predict the potential of cardiac circRNAs to sponge miRNAs that have reported roles in heart disease. We found that circALMS1_6 has the highest potential to bind miR-133, a microRNA that can regulate cardiac remodeling. Interestingly, we detected a novel class of circRNAs, referred to as read-though (rt)-circRNAs which are produced from exons of two different neighboring genes. Specifically, rt-circRNAs from SCAF8 and TIAM2 were observed to be dysregulated in DCM and these rt-circRNAs have the potential to sponge multiple heart disease-related miRNAs.Conclusions: In summary, this study provides a valuable resource for exploring the function of circRNAs in human heart disease and establishes a functional paradigm for identifying novel circRNAs in other tissues.
Intraventricular neuroepithelial tumors: Surgical outcome, technical considerations and review of literature
Authors: Aftahy Amir Kaywan , Barz Melanie , Krauss Philipp , Liesche Friederike , Wiestler Benedikt , Combs Stephanie E. , Straube Christoph , Meyer Bernhard , Gempt Jens
Published: October 2020

Background: Intraventricular neuroepithelial tumors (IVT) are rare lesions and comprise different pathological entities such as ependymomas, subependymomas and central neurocytomas. The treatment of choice is neurosurgical resection, which can be challenging due to their intraventricular location. Different surgical approaches to the ventricles are described. Here we report a large series of IVTs, its postoperative outcome at a single tertiary center and discuss suitable surgical approaches. Methods: We performed a retrospective chart review at a single tertiary neurosurgical center between 03/2009-05/2019. We included patients that underwent resection of an IVT emphasizing on surgical approach, extent of resection, clinical outcome and postoperative complications.Results: 45 IVTs were resected from 03/2009 to 05/2019, 13 ependymomas, 21 subependymomas, 10 central neurocytomas and one glioependymal cyst. Median age was 52,5 years with 55.6% (25) male and 44.4% (20) female patients. Gross total resection was achieved in 93.3% (42/45). 84.6% (11/13) of ependymomas, 100% (12/21) of subependymomas, 90% (9/10) of central neurocytomas and one glioependymal cyst were completely removed. Postoperative rate of new neurological deficits was 26.6% (12/45). Postoperative new permanent cranial nerve deficits occurred in one case with 4th ventricle subependymoma and one in 4th ventricle ependymoma. Postoperative KPSS was 90% (IR 80-100). 31.1% of the patients improved in KPSS, 48.9% remained unchanged and 20% declined. Postoperative adverse events rate was 20.0%. Surgery-related mortality was 2.2%. The rate of shunt/cisternostomy-dependent hydrocephalus was 13.3% (6/45). 15.4% of resected ependymomas underwent adjuvant radiotherapy. Mean follow-up was 26,9 (±30.1) months.Conclusion: Our surgical findings emphasize satisfactory complete resection throughout all entities. Surgical treatment can remain feasible, if institutional experience is given. Satisfying long-term survival and cure is possible by complete removal. Gross total resection should always be performed under function-remaining aspects due to mostly benign or slow growing nature of IVTs. Further data is needed to evaluate standard of care and alternative therapy options in rare cases of tumor recurrence or in case of patient collective not suitable for operative resection.
A novel “Three-port” trocar placement technique for laparoscopic radical prostatectomy
Authors: Xu Ben , Peng Yi-ji , Ma Guo-Zhong , Zhang Qian
Published: October 2020

Background: To introduce a novel “three-port” trocar placement technique for laparoscopic radical prostatectomy (LRP) in prostate cancer (PCa) patients.Methods: We retrospectively reviewed 300 patients with PCa who received surgical treatment between November 2010 and June 2015 at our institution. They were divided into group A: three-port LRP, group B: conventional four-five port LRP, group C: open RP (ORP) and group D: robotic-assisted RP (RARP). A learning curve was analyzed by dividing patients of group A into the early and late stages.Results: All groups were comparable with regard to the preoperative characteristics except for the relatively smaller prostate volume in group A. The three-port LRP operations were performed successfully with only 8 cases conversion to the conventional LRP. None of any severe complications or conversion to ORP occurred. In group A, the mean operative time (OT) duration was 113.8min, the mean estimated blood loss (EBL) was 94.2ml, the mean drainage days was 4.0d, the mean hospitalization was 5.1d, and 27.8% of the prostate specimen margins (PSM) were positive. The differences of OT, EBL, drainage days, hospitalization and transfusion in group A were statistically significant among the majority of the other groups (p<0.05). After undergoing the early stages of a learning curve analysis in three-port LRP, the EBL was obviously decreased.Conclusions: Three-port LRP is a novel technique that exhibits superior intraoperative advantages to the conventional LRP. Due to its less OT, EBL, drainage days, hospitalization and transfusion with a shorter learning curve, it should be recommended and popularized in the clinical practice!
Understanding the barriers to using oral anticoagulants among long-term aspirin users with atrial fibrillation – A qualitative study
Authors: Ng Vanessa WS , Siu Chung-Wah , Chiu Patrick KC , Kng Carolyn PL , Jamieson Elizabeth , Wong Ian CK , Lam May PS
Published: October 2020

Background: Despite international treatment guidelines currently advocating oral anticoagulants (OACs) as the only appropriate stroke prevention therapy for patients with atrial fibrillation (AF) and evidence that OACs can greatly reduce the risk of stroke with similar risk of bleeding compared with aspirin, the underuse of OACs in patients with AF is common globally, especially in Asia. This study aimed to identify the barriers to prescribing and using OACs among long-term aspirin users with AF.Method: Face-to-face interviews were conducted with fourteen eligible patients with AF using a semi-structured interview guide. The interview recordings were transcribed verbatim and data was analyzed according to the principles of thematic analysis.Results: Five themes were developed: awareness of AF symptoms and diagnosis; knowledge and understanding of AF and stroke prevention therapy; role of decision-making in prescribing; willingness to switch from aspirin to OACs; and impact of OAC regimen on daily living. The majority of the patients were not aware of the symptoms and diagnosis of AF and only had a vague understanding of the illness and stroke prevention therapy, leading to their minimal involvement in decisions relating to their treatment. Some patients and their caregivers were particularly concerned about the bleeding complications from OACs and perceived aspirin to be a suitable alternative as they find the adverse effects from aspirin manageable and so preferred to remain on aspirin if switching to OACs was not compulsory. Lastly, the lifestyle modifications required when using warfarin, e.g. alternative dosing regimen, diet restriction, were seen as barriers to some patients and caregivers.Conclusion: The findings revealed patients’ knowledge gap in AF management which may be targeted using educational interventions to improve patients’ understanding of AF and its management and hence encourage active participation in the decision-making of their treatment in the future.
Dose- and time-dependent effects of hyaluronidase on structural cells and the extracellular matrix of the skin
Authors: Buhren Bettina , Schrumpf Holger , Gorges Katharina , Reiners Oliver , Boelke Edwin , Fischer Jens , Homey Bernhard , Gerber Arne
Published: October 2020

Hyaluronic acid (hyaluronan; HA) is an essential component of the extracellular matrix (ECM) of the skin. The HA-degrading enzyme hyaluronidase (HYAL) is critically involved in the HA-metabolism. Yet, only little information is available regarding the skin´s HA-HYAL interactions on the molecular and cellular levels.OBJECTIVE To analyze the dose- and time-dependent molecular and cellular effects of HYAL on structural cells and the HA-metabolism in the skin.MATERIALS AND METHODS Chip-based, genome-wide expression analyses (Affymetrix® GeneChip PrimeView™ Human Gene Expression Array), quantitative real-time PCR analyses, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (DAB), and in vitro wound healing assays were performed to assess dose-dependent and time-kinetic effects of HA and HYAL (bovine hyaluronidase, Hylase “Dessau”) on normal human dermal fibroblasts (NHDF), primary human keratinocytes in vitro and human skin samples ex vivo.RESULTS Genome-wide expression analyses revealed an upregulation of HA synthases (HAS) up to 1.8-fold change in HA- and HYAL-treated NHDF. HA and HYAL significantly accelerated wound closure in an in vitro model for cutaneous wound healing. HYAL induced HAS1 and HAS2 mRNA gene expression in NHDF. Interestingly, low concentrations of HYAL (0.015 U/ml) resulted in a significantly higher induction of HAS compared to moderate (0.15 and 1.5 U/ml) and high concentrations (15 U/ml) of HYAL. This observation corresponded to increased concentrations of HA measured by ELISA in conditioned supernatants of HYAL-treated NHDF with the highest concentrations observed for 0.015 U/ml of HYAL. Finally, immunohistochemical analysis of human skin samples incubated with HYAL for up to 48 h ex vivo demonstrated that low concentrations of HYAL (0.015 U/ml) led to a pronounced accumulation of HA, whereas high concentrations of HYAL (15 U/ml) reduced dermal HA-levels.CONCLUSION HYAL is a bioactive enzyme that exerts multiple effects on the HA-metabolism as well as on the structural cells of the skin. Our results indicate that HYAL promotes wound healing and exerts a dose-dependent induction of HA-synthesis in structural cells of the skin. Herein, interestingly the most significant induction of HAS and HA were observed for the lowest concentration of HYAL.
A cross-sectional study on the burden and impact of migraine on work productivity and quality of life in selected workplaces in the Philippines
Authors: Haw Nel Jason , Cabaluna Ian Theodore , Kaw Germaine Erika , Cortez Joanna Feliz , Chua Maria Pamela , Guce Kristel
Published: October 2020

Background: Migraine imposes a substantial personal and economic burden to many working age individuals. This study aimed to evaluate the burden and impact of migraine on work productivity in selected workplaces in the Philippines. Methods: A cross-sectional survey was conducted among employees suspected or diagnosed with migraine February to May 2020. Volunteer employees were screened for migraine using the ID-Migraine™ test. Eligible employees were tested for migraine severity and impact on work productivity using the Migraine Disability Assessment (MIDAS) questionnaire. Quality of life was measured using the Short Form-36 (SF-36) questionnaire and additional questions on triggers, coping mechanisms, workplace assistance, and health care utilization were asked. Multiple logistic regression was used to identify significant predictors of migraine disability (high – MIDAS Grade III/IV vs. low – MIDAS Grade I/II). Differences in quality of life scores by migraine disability were measured using multiple linear regression. Productivity costs lost to migraine disability were calculated as the number of days lost to migraine multiplied by the self-reported wage rate, and costs according to migraine severity were measured using a two-part model (logistic then generalized linear model). Results: From around 24,000 employees who were invited to participate in the survey, 954 respondents provided consent and attempted to respond to the survey resulting to a response rate of around 4.1%. A total of 511 positive migraine screens were included in the final sample. Females comprised two-thirds of all positive migraine screens and were more likely to have high migraine disability (odds ratio: 1.60, 95% CI: 1.03 - 2.49) than males. Those with high migraine disability scored lower on role limitations compared to those with low migraine disability. Stress and looking at computer screens were cited as the top trigger for migraine, while sleeping enough hours and getting a massage were cited as top coping mechanisms. Three in four (77%) visited their company clinic within the past three months, which meant that most doctors seen for migraine-related symptoms were general practitioners. Five in six (85%) took medication for migraine, almost all of which were over-the-counter medications. Mean annual productivity costs lost due to migraine disability were PHP27 794 (USD556) per person. Conclusion: Migraine poses a significant threat to work productivity in the Philippines. Many opportunities, such as disease management and introduction of alternative options for migraine treatment, may be introduced to help address these issues.
A Rare Primary Intraosseous Schwannoma of the Tibia
Authors: Liu Xueqing , Ding Yunlong , Shen Yanling , Yang Wensheng
Published: October 2020

Background: Primary intraosseous schwannoma is a rare benign tumor derived from schwanncells that cover myelinated nerve fibers, accounting for less than 0.2% of all primary bone tumors. Because of its rarity, the new World Health Organization classification of bone tumors has deleted it.Case presentation: A 29-year-old woman presented with a history of intermittent pain on her right ankle over three years. Radiological examination revealed a multilocular cystic and lytic lesion in the distal tibia. Histologically, the tumor was composed of spindle shaped cells, similar to soft tissue neurilemmoma. The patient underwent a surgical resection of the intraosseous lesion. After a 38-month follow-up, the symptoms were significantly relieved and there was no clinical or radiological recurrence.Conclusion: Primary intraosseous schwannoma is a rare benign bone tumor. The pathologists should be aware of the incidence of the tumor, although WHO has deleted it.
Updated evaluation of clinicopathologic landscape in histopathologic subtypes of endometrial carcinoma with MMR gene mutation
Authors: Wang Aifen , Hu Weidong , Zhang Qinfu , Ren Hongjiu , Zhao Zihan , Zhang Ziyue , Chen Youguo
Published: October 2020

Background: This study aimed to identify an optimal screening strategy to detect mismatch repair (MMR) mutation for each histologic subtype of endometrial carcinoma. Methods:We performed a comparative analysis of the demographic, clinical, pathologic, and molecular data for 562 patients from The Cancer Genome Atlas database, stratified by tumor histologic subtype.Results: Molecular data, including MLH1, MLH3, PMS1, PMS2, MSH2, MSH3, MSH6, and EPCAM, was available for 562 patients, of which 162 (28.8%) had tumors that were positive for MMR gene mutations. Of these tumors, the penetrate rate of grade 3 endometrioid endometrial carcinoma (84/184, 45.7%) was significantly higher than that of uterine serous carcinoma (35/156, 22.4%) (p < 0.001), grade 2 endometrioid endometrial carcinoma (26/129, 20.2%) (p < 0.001), and grade 1 endometrioid endometrial carcinoma (17/93, 18.3%) (p < 0.001). Of 562 endometrial carcinomas, alterations in MSH2 (n = 55), MSH6 (n = 54), and MSH3 (n = 50) were the most frequent mutations. There were no differences in overall survival and progression-free interval (PFI) between MMR mutation carriers and nonmutation carriers (p >0.05) except that PFI with MMR gene mutation was higher than with MMR proficiency in grade 3 endometrioid endometrial carcinoma (p = 0.014). Conclusions: Grade 3 endometrioid endometrial carcinoma harbored more MMR mutations than grade 1 endometrioid endometrial carcinoma, grade 2 endometrioid endometrial carcinoma, and uterine serous carcinoma. Besides MLH1, MSH2, MSH6, PMS2, and EPCAM mutation, MLH3, MSH3, and PMS1 mutation may be necessary to be screened in patients with newly diagnosed endometrial carcinoma.
How Large is The Burden of Depression in A Medical School? A Cross-Sectional Study Among Medical Students in Nigeria
Authors: Ossai Edmund Ndudi , Eze Irene Ifeyinwa , Onyenakazi Rejoice Chinecherem , Ugebe Elias Ifeyinwa , Eze Basil C , Obasi Obinna C
Published: October 2020

Background: Mental health of students deteriorate when they begin studies in a medical school and remains poor throughout the period of training. Notwithstanding that medical students of today are the physicians of tomorrow who need to have stable mental health for effective performance, mental status of this group have not been adequately explored in the Nigeria context. The study aimed to determine the prevalence of depression and associated factors among medical students in Nigeria. Methods: A cross-sectional study was carried out on all matriculated medical students of Ebonyi state University Abakaliki, Nigeria. Information was obtained from 522 medical students that were eligible to participate in the study using self-administered structured questionnaire. Becks Depression Inventory was used to determine the prevalence of depression. Chi square test was used in the analysis to ascertain association between variables. Level of statistical significance was determined by a p value of <0.05.Results: Mean age of the students was 23.2±3.3 years and majority, 60.2% were males. Prevalence of depression was 17.4%. Third-year class (major examination class) had the highest proportion of students who were depressed, 24.2% while final year class had the least, 8.8%. Coping mechanisms for low moods included sleeping, 50.4% and having interactions with colleagues, 46.9%. Factors associated with depression included being <25 years, (p=0.008), being in clinical school, (p=0.023) and being afraid some students may not graduate from medical school, (p=0.030).Conclusions: Burden of depression was high among the students and most pronounced among third year students. There is need for proper orientation of newly admitted medical students on the medical curriculum by authorities of the university. Medical students preparing for major examinations should be well supported and encouraged by their colleagues and efforts should be made to decrease undue anxiety among the students. Adequate measures should be put in place for early detection and prompt management of cases of depression among the students.
Applying Deep Learning for Genome Detection of Coronavirus
Authors: Rani Geeta , Oza Meet Ganpatlal , Dhaka Vijaypal Singh , Pradhan Nitesh , Verma Sahil , Rodrigues Joel J. P. C.
Published: October 2020

Amidst the global pandemic and catastrophe created by ‘COVID-19’, every research institution and scientists are doing their best efforts to invent or find the vaccine or medicine for the disease. The objective of this research is to design and develop a deep learning model for finding the degree of similarity of the genome of the Severe Acute Respiratory Syndrome-Coronavirus 2 (‘SARS-CoV-2’) with a given genome. This research also aims at detecting the genome of ‘SARS-CoV-2’ in the host human beings. The experimental results on the dataset publicly available at National Centre for Biotechnology Information, show that the model is effective in predicting the similarity score of the genomic sequence of ‘SARS-CoV-2’ and other prevalent viruses such as Severe Acute Respiratory Syndrome-Coronavirus, Middle East Respiratory Syndrome Coronavirus, Human Immunodeficiency Virus, and Human T- cell Leukaemia Virus. This is successful in detecting the genome of ‘SARS-CoV-2’ in the host genome with an accuracy of 99.27%. It may prove a useful tool for doctors to quickly classify the infected and non-infected genomes. It can also be useful in finding the most effective drug from the available drugs for the treatment of ‘COVID-19’.
Positive Feedback Regulation between USP15 and ERK2 Promotes Cartilage Repair Through the TGF-β/SMAD2 signaling
Authors: Wang Wenjuan , Zhu Yanhui , Sun Zhenyu , Jin Chen , Wang Xiang
Published: October 2020

The transforming growth factor-β (TGF-β) signaling pathway plays an essential role in maintaining homeostasis in joints affected by osteoarthritis (OA). Here, we detected that overexpression of USP15, rather than USP15 C269S (a USP15 mutant), activated p-SMAD2 in ATDC5 cells, which also went down by USP15 knocked out followed by the latest gene editing technology Crispr/Cas9. And we established rat knee OA models through anterior cruciate ligament transection and partial medial meniscectomy (ACLT+pMMx) after 8 weeks and conducted the corresponding Adeno-associated virus (AAV) intraarticular injections. Next, experimental data including immunohistochemical staining, HE/Safranin-O fast green staining, histological evidence analysis, relevant Osteoarthritis Research Society International (OARSI) scores, expression of molecules involved in cartilage anabolism and so on indicated that USP15 can reduce damaged cartilage by activating TGF-β signaling pathway in vivo. We further observed that ERK2 of non-SMAD signaling can maintain the cartilage phenotype by regulating the TGF-β signaling pathway through USP15 in vitro and in vivo. Most importantly, USP15 is required during this process and can form a complex with ERK2 to regulate ubiquitination of ERK2. Specifically, USP15, instead of USP15 C269S, deubiquitinates and activates ERK2, followed by translocation of phosphorylated ERK2 from the cytoplasm to the nucleus. Taken together, our study revealed a positive feedback regulation between USP15 and ERK2, which plays a critical role in the interaction of SMAD and non-SMAD signaling pathways to promote cartilage repair in experimental OA. Therefore, this specific mechanism can guide clinical treatments of OA.
Apolipoprotein L1 Risk Genotypes in Ghanaian Systemic Lupus Erythematosus Patients: A Prospective Cohort Study
Authors: Blazer Ashira , Dey Ida Dzifa , Nwaukoni Janet , Reynolds Margret , Ankrah Festus , Algasas Huda , Ahmed Tasneem , Divers Jasmin
Published: October 2020

Objective: Two Apolipoprotein L1 (APOL1) risk variants (RV) are enriched in sub-Saharan African populations due to a conferred resistance to Trypanosoma brucei. This comes at the cost of progressive renal disease by multiple causes including systemic lupus erythematosus (SLE). In African Americans, APOL1 high-risk genotypes have emerged as an important risk factor for progressive lupus nephritis. Despite emerging reports that SLE is common in Ghana, where APOL1 variant allelic frequencies are high, the regional contribution to SLE outcomes has not been described. Accordingly, this prospective longitudinal cohort study tested the associations between APOL1 high-risk genotypes and kidney outcomes, organ damage accrual, and death in 100 Ghanaian SLE patients.Methods: A prospective cohort of 100 SLE outpatients met four 1982 American College of Rheumatology SLE criteria. Patients were assessed for demographics, SLE activity, and organ injury as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at baseline and every 6 months for 1 year. Serum, plasma, and saliva samples were taken for serologic testing and APOL1 genotyping. Outcomes of interest were kidney function, SDI, and case fatality. Results: Assuming a recessive model of inheritance, the APOL1 high-risk genotype (2RV) associated with developing end stage renal disease (ESRD) at an odds ratio of 14 (p=0.008). These patients accrued more SDI points particularly in renal, neurologic, and cardio/pulmonary domains. The SDI was 81.3% higher in 2RV patients compared to 0RV or 1RV patients despite no difference in SLE activity (p=0.02). After a 12 month period of observation, 3/12 (25%) of the 2RV patients died compared to 2/88 (2.3%) of the 0RV or 1RV carriers (odds ratio=13.6, p=0.01). Deaths were due to end stage kidney disease and heart failure. Conclusion: Our results suggest that in Ghanaian SLE patients, APOL1 risk variants are heritable risk factors for morbidity and mortality. Despite no appreciable differences in SLE severity, APOL1 high-risk patients exhibited progressive renal disease, organ damage accrual, and a 13-fold higher case fatality rate.
Assessment of Causal Relationship Between Rheumatoid Arthritis and Inflammatory Bowel Disease: A Bi-Directional Mendelian Randomization Study
Authors: Zhang Xueer , Zhuang Zhenhuang , Du Jie , Wang Wenxiu , Yang Ruotong , Liu Zhonghua , Huang Tao
Published: October 2020

Objective: Observational studies have shown that rheumatoid arthritis (RA) was associated with a higher risk of inflammatory bowel disease (IBD), and vice versa. However, if such associations reflect causality remains unclear. We aimed to examine the bidirectional causal associations of RA with IBD, ulcerative colitis (UC), and Crohn’s disease (CD).Method: A Bi-directional Mendelian randomization (MR) analysis and Linkage Disequilibrium Score regression (LDSC) were used to investigate the causality between RA and IBD subtypes. Summary data was extracted from the Rheumatoid Arthritis Consortium International for Immunochip (RACI) consortium and the Genetics and Allied research in Rheumatic diseases Networking (GARNET) consortium (29,880 cases of RA and 73,758 controls); and the International IBD Genetics Consortium (38,155 cases of IBD and 48,485 controls; 17,647 cases of UC and 47,179 controls; 20,550 cases of CD and 41,642 controls). Results: Genetically predicted RA was associated with higher risks of IBD (per 1-unit higher log odds: odds ratio: 1.13; 95% confidence interval: 1.04-1.21; P=0.002) and UC (1.16; 1.07-1.25; P=1.5 × 10−4) after a Bonferroni correction (P<0.05/3). In addition, the weighted median method showed a suggestive association of RA with a higher risk of CD (1.16; 1.05-1.28; P=0.003). However, there was no evidence showing a causal relation of IBD, UC or CD with RA risk. Conclusion: Our findings provide novel evidence supporting a significant causality of RA with IBD or UC, whereas IBD is unlikely to increase the risk of RA, indicating the importance of keeping gut microbiota composition healthy for RA patients to prevent IBD.
A Mechanistic Insight into Doxorubicin Adsorption on N-isopropyl Acrylamide Grafted Nanotube: Optimization Study of Loading Temperature
Authors: Maleki Reza , Dahri Mohammad , Ghasemy Ebrahim , Akbarialiabad Hossein
Published: October 2020

Background: The drug development process is costly and time-consuming; hence, nowadays, enormous efforts have been established through computational studies for finding appropriate strategies, methods and solutions for enhancing the drug production and administration procedures. Hydrogels that undertake deformation upon pertinent changes in temperature have significant aptitude as drug delivery systems. These biomaterials have made a substantial impact on the development of drugs for critical diseases, especially cancer therapy. Drug loading and uptake are primary and fundamental steps of the drug development and discovery process. N-isopropyl acrylamide is a common and well-known thermo-sensitive and injectable hydrogel for the drug uptake under the lower critical solution temperature (LCST). In the current study, carbon nanotube (CNT) as a nanocarrier was modified via N-isopropyl acrylamide. On the other hand, Doxorubicin as an anti-cancer drug applied on mentionted systems to develop drug packing at three different temperatures. Results: After computational parametrization of the system via bioinformatics software and databases, Molecular dynamics (MD) simulation was run. To this end, the detailed simulations were carried out to reveal the interaction energy, numbers of hydrogen bonds, the gyration radius, mean square displacement, and radial distribution function as well as Gibss free energy. Besides, the optimal loading temperature for doxorubicin was determined. The results achieved from simulating the polymer demonstrated a decrease in the gyration radius at a higher temperature. A decrease of gyration radius resulted in more concentrated aggregation with stronger bonds.Conclusions: Therefore, at the higher temperature, the more stable polymer interaction and better doxorubicin loading were acquired. The smart absorption of doxorubicin onto the CNT modified via N-iso-propyl acrylamide (NIPA) give a significant and valuable view on the future studies regarding the drug development and novel, biocompatible, and biodegradable stimuli-sensitive drug delivery system.
Potential Biomarkers of Diabetic Kidney Disease Based on Weighted Gene Co-expression Network Analysis
Authors: Chen Yang , Xiao Kangli , Shi Ningjie , Yang Fengying , Cui Zhenhai , Zhang Jiaoyue , Li Huiqing
Published: October 2020

Background: Diabetic kidney disease (DKD) is one of the serious complications of diabetes. However, there is no unified and clear understanding of the pathogenesis of DKD at present. The evidence suggests that genetic predispositions play a significant role in an individual’s susceptibility to DKD. WGCNA analysis may provide a new way to search for genes closely related to DKD. Methods: In this study we analysed key genes and pathways involved in DKD from RNA-seq count results using 23 peripheral blood samples from patients with DKD. Weighted gene co-expression network analysis (WGCNA) was performed with the WGCNA package.Results: We found turquoise and purple module were characterized as having the highest correlation with large proteinuria stage in DKD. Furthermore, the key genes, including DCN, F2R, LTBP2, B2M, PSMB8, and NLRC5, were evaluated through a protein-protein interaction (PPI) network combined with a co-expression network, which were expected to be potential diagnostic and therapeutic targets of DKD. Conclusions: These signalling pathways and hub genes will provide effective targets and ideas for further study of the pathogenesis of DKD and are expected to have roles in the prevention of, early screening for, and the treatment of DKD.
PCR-based Genotyping Assays to Detect Germline APC mutations Associated with Hereditary Gastrointestinal Polyposis in Jack Russell Terriers
Authors: Yoshizaki Kyoko , Hirata Akihiro , Matsushita Hiroyuki , Nishii Naohito , Kawabe Mifumi , Mori Takashi , Sakai Hiroki
Published: October 2020

Background: The prevalence of gastrointestinal (GI) neoplastic polyps in Jack Russell Terriers (JRTs) has increased in Japan since the late 2000s. Recently, we demonstrated that JRTs with GI polyps harbor identical germline mutations in the APC gene (c.[462A>T; 463A>T]) in the heterozygous state. Thus, this disease is an autosomal dominant hereditary disorder. Although the affected JRTs have distinct features, such as the development of multiple GI polyps and an early age of disease onset, genetic testing is indispensable for a definitive diagnosis. Here, polymerase chain reaction (PCR)-based assays capable of detecting germline APC mutations were designed and validated using synthetic wild-type and mutant DNAs and genomic DNAs from carrier and non-carrier dogs.Result: First, the PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed by taking advantage of the germline APC mutations creating a new restriction site for MseI. In the PCR-RFLP assay, the 156-bp region containing the mutation site was amplified by PCR and subsequently digested with MseI, yielding diagnostic 51 and 58 bp fragments from the mutant allele and allowing determination of the APC genotypes. It was possible to determine the genotypes using genomic DNA extracted from the peripheral blood, buccal swab, or formalin-fixed paraffin-embedded tissue. Next, a TaqMan duplex real-time PCR assay was developed, where a 78-bp region flanking the mutation was amplified in the presence of wild-type allele- and mutant allele-specific fluorescent probes. Using blood-derived DNA, altogether 40 cycles of PCR amplification determined the APC genotypes of all examined samples by measuring the fluorescence intensities. Importantly, false-positive and false-negative errors were never detected in both assays. Conclusion: In this study, we developed highly reliable genetic tests for hereditary GI polyposis in JRTs, providing accurate assessment of the presence of the causative germline APC mutations. The genotyping assays could contribute to the diagnosis and prevention of hereditary GI polyposis in dogs.
First Report of Spirocerca Lupi Larva in Dung Beetles (Scarabaeus Armeniacus) in Iran: A Morphological and Molecular Identification
Authors: Mohtasebi Sina , Teimouri Aref , Afshar Mohammad Javad Abbaszadeh , Mobedi Iraj , Abbasian Hamed , Totonchian Niloofar , Mohtasebi Alireza , Allahmoradi Mahya , Mowlavi Gholamreza
Published: October 2020

Background: Dung beetles are detritivores insects. They naturally use feces of vertebrates as foods and reproduction beds. This leads to frequent contacts between dung beetles and parasitic helminths. The current study was carried out to assess infections of dung beetles with larval stages of helminths in rural areas of Taleqan County, Alborz Province, Iran. In total, 200 dung beetles were randomly collected in June 2017 from the highlands of Taleqan County. Beetles were dissected in normal saline and carefully studied using stereomicroscopy. Morphological characteristics of the recovered larvae were drawn using camera lucida equipped microscope at 400× magnification. Furthermore, genomic DNAs of the recovered larvae were extracted and PCR amplifications of the mitochondrial cytochrome c oxidase subunit 1 (cox1) genes were carried out and the amplicons were sequenced. Results: All collected dung beetles were identified as Scarabaeus armeniacus from Scarabaeidae family (55.5% were male and 44.5% female). Three females of the beetles were infected with nematode larva, morphologically identified as the third-stage of Spirocerca lupi larvae. The average length and width of the larvae were 2.95 (2.81–3.15; CI 95%) and 0.12 (0.1–0.15; CI 95%) mm, respectively. The phylogenetic analysis showed that S. lupi belonged to a clade within Spirocercidae family, well separated from Onchocercidae family. Conclusions: In the current study, S. armeniacus was introduced as a potentially biological vector for the transmission of S. lupi to vertebrates in the region. To the best of the authors’ knowledge, this is the first reported on larval stages of S. lupi in S. armeniacus.
Experimental Infection of Domestic Cats with Feline Herpesvirus-1 Strain CH-B Isolated from British Shorthair Cat
Authors: Niu Jiangting , Zhao Han , Zhang Shuang , Guo Yanbing , Zhang Qian , Bao Di , Dong Hao , Meng Fanxing , Zhao Yanli , Huang Hailong , Wang Junzheng , Wang Kai , Hu Guixue , Yi Shu-Shuai
Published: October 2020

Background: Feline herpesvirus-1 (FHV-1) is a most common virus that cause viral rhinotracheitis and ocular diseases in domestic cats and wild felids. As other alpha-herpesviruses, acute FHV-1 infection is responsible for severe upper respiratory tract and ocular disease, followed by lifelong latency that persist the limited virus in sensory neuronal cells. While latency reactivation can result in recrudescence, leading sever ocular lesions. Hence, FHV-1 infection in cats can be considered as a good natural host model to study alpha-herpesvirus pathogenesis. Results: In this study, the FHV-1 CH-B was isolated from nasal discharge collected from a British shorthair cat in China, and was further identified via transmission electron microscopy (TEM) observation, indirect immunofluorescence assay (IFA) and genome analysis. Experimental infection of domestic cats with different dose of isolate CH-B, ranging from 104 to 107 TCID50, showed that cats inoculated with 105 TCID50 not only showed typical upper respiratory track and ocular symptoms, but also could copy the progress of disease development. Therefore, the FHV-1 infection model was established by intranasally inoculated with 105 TCID50 of FHV-1 isolate CH-B. Infected cats began to show clinical signs at days 5 post inoculated (dpi), developed severe upper respiratory tract and ocular symptoms at 10-15 dpi, began to recover at 20 dpi, and recovered almost completely by 25 dpi. During acute infection period, virus mainly replicates in turbinate, conjunctiva, cornea and sensory neuronal cells, while virus only persists in trigeminal ganglia (TG) at lifelong latency. Viremia and viral infections in lungs do not appear in FHV-1 CH-B infected cats, with only one exception. We also demonstrate that FHV-1 CH-B infection can induce severe inflammatory responses and lung, trachea, and tonsils tissues damage in cats. In addition, we found that FHV-1 infected cats can shed virus via nasal and ocular discharge, resulting FHV-1 infection in in-contact cats. Conclusions: This natural host model of FHV-1 infection will be valuable for the screen and assessment of antiviral drugs and vaccines, as well as the studies of the pathogenesis of alpha-herpesvirus infection in animals and humans.
Autonomic Nervous System Activity and the Risk of Nosocomial Infection in Critically Ill Patients With Brain Injury
Authors: Wirtz Mathijs , Moekotte Jiri , Balvers Kirsten , Admiraal Marjolein , Pittet Jean-Francois , Colombo Joe , Wagener Brant , Goslings Carel , Juffermans Nicole
Published: October 2020

Purpose: Nosocomial infection contributes to adverse outcome after brain injury. This study investigates whether autonomic nervous system activity is associated with a decreased host immune response in patients following stroke or traumatic brain injury (TBI).Methods: A prospective study was performed in adult patients with TBI or stroke who were admitted to the Intensive Care Unit of our tertiary university hospital between 2013 and 2016. Heart rate variability (HRV) was recorded daily and assessed for autonomic nervous system activity. Outcomes were nosocomial infections and immunosuppression, which was assessed ex vivo using whole blood stimulations with plasma of patients with infections, matched not-infected patients and healthy controls.Results: Out of 64 brain injured patients, 23 (36%) developed an infection during their hospital stay. The ability of brain injured patients to generate a host response to LPS was diminished compared to healthy controls. Patients who developed an infection yielded significantly lower TNF-α and higher IL-10 values following ex vivo whole blood stimulations when compared to patients not developing an infection. This decreased host immune response was associated with altered admission HRV values. Brain-injured patients who developed an infection showed increased normalized high frequency power compared to patients not developing an infection, whereas normalized low frequency power was lower in infected patients.Conclusion: Brain injured patients developing a nosocomial infection show parasympathetic predominance in the acute phase following brain injury, reflected by alterations in HRV, which parallels a decreased ability to generate an immune response to stimulation with LPS.
Screening, Assessment and Management of Perioperative Malnutrition: A Survey of UK Practice
Authors: Matthews Lewis , Wootton Stephen , Davies Sarah , Levett Denny
Published: October 2020

BackgroundPerioperative malnutrition is common and is associated with increased mortality, complications and healthcare costs. Patients having surgery for cancer and gastro-intestinal disease are at particular risk. It is a modifiable pre-operative risk factor and perioperative clinicians are well placed to identify those at risk and instigate interventions shown to improve outcome. Thus, we conducted a survey of Perioperative Medicine Leads with the aim of assessing the current provision of nutritional screening and intervention pathways in the United Kingdom.MethodsPerioperative Medicine Leads registered with the Royal College of Anaesthetists were asked to complete an online survey exploring current practice in screening, assessment and management of malnutrition in the perioperative period. The survey included a mixture of open and closed questions, graded response questions and options for free text. Where a response was not received departments were phoned directly and e-mails sent to non-responders.Results121 completed questionnaires were received from 167 Perioperative Medicine Leads (response rate of 72.5%). Seventy respondents (57.9%) reported using the Malnutrition Universal Screening Tool to screen patients, however only 61 (50.4%) referred patients at nutritional risk onto a dietitian. Sixty (49.6%) lacked confidence in local ability to identify and manage malnutrition perioperatively, with 28 (23.1%) reporting having a structured pathway for managing malnourished patients. 111 respondents (91.7%) agreed that malnutrition impacts on quality of life after surgery and 105 (86.8%) felt adopting a standard protocol would improve outcomes for patients. Those reporting a lack of confidence in dealing with malnutrition perioperatively cited a lack of organisational support, patients being seen too close to surgery and lack of clarity around responsibility as key reasons for difficulties in managing this group of patients.ConclusionsMalnutrition in the perioperative period is a modifiable risk factor which is common and results in increased morbidity for patients and increased cost to healthcare systems. This survey highlights areas of practice where perioperative clinicians can improve the assessment and management of patients at nutritional risk prior to elective surgery.Trial registrationNot applicable.