bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Characteristics and Determinants of CD4 at Diagnosis of HIV in Mexico from 2008 to 2017: A 10-Year Population-Based Study
Authors: Alonso Amilcar Azamar , Bautista-Arredondo Sergio A , Smaill Fiona , Mbuagbaw Lawrence , Costa Andrew P , Tarride Jean-Eric
Published: November 2020

Background: Worldwide, around 37.9 million people are living with HIV, of which 220,000 live in Mexico. In 2007-2012 the Mexican government launched the National HIV program and there was a major change in HIV policies implemented in 2013-2018, when efforts focused on prevention, increase in early diagnosis and timely treatment. Thus, the objectives of this study were to identify the determinants of late HIV diagnosis (i.e. CD4 count less than 200 cells/mm3) in Mexico from 2008 to 2017 and to evaluate the impact of the 2013-2017 National HIV program. Methods: Using patient level data from the SALVAR database, which includes 64% of the population receiving HIV care in Mexico, an adjusted logistic model was conducted. Main study outcomes were HIV late diagnosis which was defined as CD4 count less than 200 cells/mm3 at diagnosis. Results: the study included 106,830 individuals newly diagnosed with HIV and treated in Mexican public health facilities between 2008 and 2017 (mean age: 33 years old, 80% male). HIV late diagnosis decreased from 45% to 43% (P <0.001) between 2008-2012 and 2013-2017 (i.e. before and after the implementation of the 2013-2017 policy). Multivariable logistic regressions indicated that being diagnosed between 2013-2017 (odds ratio [OR]= 0.96 [95% Confidence interval [CI]: [0.93, 0.98]) or in health facilities specialized in HIV (OR=0.64 [95% CI: 0.60, 0.69]) was associated with early diagnosis. Being male, older than 29 years old, diagnosed in Central East, the South region of Mexico or in high-marginalized locality increased the odds of a late diagnosis.Conclusions: The results of this study indicate that the 2013-2017 National HIV program in Mexico has been marginally successful in decreasing the proportion of individuals with late HIV diagnosis in Mexico.
Long-term Remission of AIDS-related Primary Central Nervous System Lymphoma in a Patient Under Antiretroviral Therapy: A Case Report and Review of the Literature
Authors: Gijs Pieter-Jan , Clerc Olivier
Published: November 2020

Background: Acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/ml. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2-3 months if left untreated.Case description: a 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/ml and a viral load of 260’000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AIDS-related primary central nervous system lymphoma. HAART was initiated with whole-brain radiotherapy, and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission of the brain lesions. At 3-year follow-up, the patient remains in complete remission, but presented mild neurocognitive dysfunction possibly secondary to whole-brain radiotherapy.Conclusion: Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of whole-brain radiotherapy is questionable because of late neurotoxic effects.
Sexual Behaviour Problems : Current State of Knowledge and Representations by Medico-Social Professionals in France
Authors: Simon Charlie , Ulrich Morgane , Oriez Baptiste , Demonte Charlotte , Horrach Pierre , Ligier Fabienne
Published: November 2020

BackgroundThere are no studies identified that address professionals' knowledge of sexual behaviour problems in children aged 0-12 years. However, it seems essential for child professionals to be able to identify the healthy or pathological nature of sexual behaviour.Case presentationWe proposed a cross-sectional, descriptive and comparative observational study using anonymous questionnaires distributed to medico-social professionals in France. They were questioned on their knowledge of normal sexual development, risk factors for developing sexual behaviour problems, and the future of minors presenting these behaviours.Conclusions﻿Among the 93 respondents whose questionnaires were usable, there were 12 men and 81 women. The majority of respondents didn’t know the age at which psychosexual and emotional child development begins (73.1%) or didn’t know the age limits for sexual behaviour problems (95.7%). Very often, these professionals represented children with sexual behaviour problems as "children who have been abused" (81.72% of respondents) and/or who "will become child perpetrators of sexual violence" (70.87% of respondents). All these answers highlight the lack of training of these professionals, at the risk of proposing a reply that is not adapted to children with these disorders. So, it seems essential to offer more systematic and adapted courses to professionals who take care of minors in institutions.
HMMR Functions as a Prognostic Biomarker in Uterine Carcinosarcoma Identified by Comprehensive Bioinformatics Analysis
Authors: Sun Hui , Ma Li , Chen Jie
Published: November 2020

BackgroundUterine carcinosarcoma (UCS) is a rare aggressive tumor with a high metastasis rate and poor prognosis. Bioinformatics analysis has been widely applied to screen and analyze genes in linkage to various types of cancer progression. This study aims to explore the molecular mechanism of UCS. MethodsFirst, transcriptional different expression data between UCS and normal samples were got from the GEPIA database. Subsequently, differentially expressed genes were analyzed through the Metascape with Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then, the STRING website and Cytoscape software were applied to construct the protein-protein interaction network. Finally, the top 30 genes obtained through the MCC algorithm were selected as hub genes, which was finally validated in TIMER, and UALCAN databases. ResultsA total of 1894 DEGs (579 up-regulated and 1315 down-regulated) were identified, GO and KEGG functional enrichment analysis were performed for the DEGs. The PPI network was constructed based on DEGs, and four clusters were excavated for further analysis and the top 30 genes were identified as hub genes. Our data showed that the expression of HMMR is significantly higher in UCS tissues compared to the paired normal tissues (p<0.05) and the elevated expression of HMMR is related to poor prognosis in patients with UCS (p= 0.0031). TPX2, AURKA, BRCA1 and BARD1 are essential for the function of HMMR. TPX2 and AURKA were found to be significantly higher in UCS compared to the normal tissue (p<0.05), and there was a statistically significant positive correlation between the expression of HMMR and AURKA, TPX2, BRCA1, BARD1 in UCS (p=1.08e-07, p=1.62e-05, p=2.02e-3, p=6.54e-6). Conclusions﻿Our study suggested that HMMR may be a potential biomarker for predicting the prognosis of UCS patients.
Gender and Age Differences in Risk Factors of Lymph Node Metastasis in Patients With Early Gastric Cancer and Analysis Prognosis of Early Gastric Cancer
Authors: Wang Jingjing , Wang Jingjing , Meng Tao , Meng Tao , Chen Ke , Chen Ke , wang zhengguang , wang zhengguang
Published: November 2020

ObjectiveTo explore the effects of gender and age differences in the risk factors for lymph node metastasis in patients and analysis prognosis of patients of early gastric cancer (EGC). MethodsA total of 411 patients with EGC who underwent surgical treatment at the First Affiliated Hospital of Anhui Medical University from 2011 to 2017 were included in this study and grouped according to gender and age. Retrospective analysis of the effects of gender and age on tumor size, histological type, depth of invasion, and ulcer type was performed, and differences in the clinicopathological characteristics of lymphovascular invasion were noted. Follow-up of the postoperative recurrence and metastasis of the patients and analysis of their prognosis were finally conducted. All follow-ups ended in August 2020. ResultThe participants in this study ranged in age from 25 years to 85 years (average, 60.27 ± 10.77 years). A total of 57 (13.9%) of the patients showed lymph node metastasis. Females accounted for 25.5% (105/411) while males accounted for 74.5% (306/411) of the study population. Patients aged ≤60 years accounted for 55.5% (228/411) while patients aged >60 years accounted for 44.5% (183/411) of the study population. Univariate analysis of male patients showed that tumor size, depth of tumor invasion, ulcerative tumors, and lymphovascular invasion are related to lymph node metastasis (P < 0.05). Univariate analysis of female patients showed that tumor size, depth of tumor invasion, tumor histology, and lymphovascular invasion are related to lymph node metastasis (P < 0.05). Univariate analysis of patients aged ≤60 years showed that depth of tumor invasion, ulcerative tumors, and lymphovascular invasion are related to lymph node metastasis (P < 0.05). Univariate analysis of patients aged >60 years showed that depth of tumor invasion, ulcerative tumors, and lymphovascular invasion are related to lymph node metastasis (P < 0.05). Multivariate analysis of male patients, female patients, and patients aged ≤60 years showed that depth of tumor invasion is an independent risk factor for lymph node metastasis. Multivariate analysis of patients aged >60 years showed that depth of tumor invasion, ulcerative tumors, and lymphovascular invasion are independent risk factors for lymph node metastasis. ConclusionThe risk factors for lymph node metastasis in patients with EGC differed according to gender and age. The results provide a reference for choosing suitable treatment options for these patients.
Study of the Comparison of Endoscopic Closure and Laparoscopic Repair of Defect of Gastric Wall
Authors: Qiao Qiao , Tu Huiming , Fei Bojian , Xu Kebin , Yang Fan , Li Jie , Gao Qizhong
Published: November 2020

Objective: To make analysis on the curative effect on the technique of endoscopic closure and laparoscopic closure, and explore the effect and safety of acute perforation of the endoscopic closure technique. Methods: Analysis on the 40 therapeutic cases of laparoscopic repair and endoscopic closure treatments, respectively, to submucosal tumours (SMT) of the stomach removed through ESE/EFR. According to the double-sample t-test, the differences of operation time and medical expenses between the two closure methods were compared and analyzed. And used the chi-square test to compare the difference in terms of operational difficulty and effects. Results: Postoperative pathology of 76 therapeutic cases operated through ESE and EFR was diagnosed as mesenchymal tumor and 4 cases as leiomyoma, among which 34 cases were in fundus ventriculi, 30 in corpus ventriculi and 16 in antrum. Endoscopic closure is significantly lower than laparoscopic closure in operation time span (endoscopic closure VS laparoscopic repair 74.70±23.55min vs 178.35±38.98min, p < 0.001) , medical expenses (endoscopic closure VS laparoscopic repair 28463.55±8228.96rmb vs 61848.75±8812.12rmb, p < 0.001) and inpatient days (endoscopic closure VS laparoscopic repair 10.50±3.49days vs. 16.95±4.58days, P < 0.01), while there is no significant difference in terms of technical difficulty and effects (P > 0.05). Conclusion: With the training and technical progress of endoscopic closure, it is safe, effective and quick in recovery to have non-laparoscopic assisted surgery on gastric wall closure.
Temperature Sensation in Parkinson’s Disease Measured by Quantitative Sensory Testing
Authors: Kaiserova Michaela , Grambalova Zuzana , Otruba Pavel , Janova Anetta , Zapletalova Jana , Mensikova Katerina , Kanovsky Petr
Published: November 2020

BackgroundThe pathophysiology of abnormal temperature sensation in Parkinson’s disease (PD) remains unclear. Abnormal thermal detection does not seem to depend on the dopaminergic deficit, suggesting that other systems play a role in these changes, probably both central and peripheral.MethodsWe measured thermal detection thresholds (TDT) using quantitative sensory testing (QST) in 28 patients with PD and compared them with 15 healthy controls.ResultsOf 28 patients, 21 % had increased TDT according to the normative data. TDT were higher on the dominant side. No correlation between TDT and disease duration, severity of motor impairment, and dopaminergic therapy was observed. 50 % of the patients had difficulty differentiating between warm and cold stimuli, as TDT were within the normal range in most of these patients.ConclusionsThese results suggest that abnormal thermal detection may be present from early stages of the disease and is more pronounced on the dominant side. Abnormal differentiation between the thermal stimuli suggest impaired central processing of thermal information.
Chronic Hypoperfusion is not Associated with Cerebral Amyloidosis
Authors: Fan Dong-Yu , Li Hui-Yun , Chen Dong-Wan , Chen Yang , Yi Xu , Yang Heng , Shi Qian-Qian , Jiao Fang-Yang , Tang Yi , Li Qi-Ming , Wang Fang-Yang , Wang Shu-Nan , Jin Rong-Bing , Zeng Fan , Wang Yan-Jiang
Published: November 2020

Background Insufficient cerebral perfusion is suggested to play a role in the development of AD. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology, including β-amyloid (Aβ) deposition and brain atrophy in humans. Methods We enrolled 10 cognitively normal patients (median age: 64 years old) with unilateral chronic cerebral hypoperfusion. Volumes of interest (VOIs) and regions of interest (ROIs) with the most pronounced hypoperfusion changes were created in the hypoperfused region, and were then mirrored into the contralateral hemisphere to create a control region with normal perfusion respectively.11C-Pittsburgh compound-PET (PiB-PET) imaging standard uptake ratios (SUVRs) and several brain atrophy indices from the CT images of each patient were calculated. Results We found that there were no differences in SUVRs of PiB-PET imaging and brain atrophy indices between the hypoperfused regions and contralateral normally-perfused regions. Conclusion Our findings suggest that chronic hypoperfusion may not directly induce cerebral Aβ deposition and neurodegeneration in humans.
Structural and Functional Analysis of Tomato Sterol C22 Desaturase
Authors: Gutiérrez-García Laura , Arró Montserrat , Altabella Teresa , Ferrer Albert , Boronat Albert
Published: November 2020

Background: Sterols are essential components of eukaryotic cells that modulate membrane biophysical properties and function. Plants produce a complex mixture of sterols, among which β-sitosterol, stigmasterol, campesterol, and cholesterol in some Solanaceae, are the most abundant species. Many reports have shown that the stigmasterol to β-sitosterol ratio changes during plant development and in response to stresses, suggesting that it may play a role in the regulation of these processes. In tomato (Solanum lycopersicum), changes in the stigmasterol to β-sitosterol ratio correlate with the induction of the only gene encoding sterol C22-desaturase (C22DES), the enzyme specifically involved in the conversion of β-sitosterol to stigmasterol. However, despite the biological interest of this enzyme, there is still a lack of knowledge about several relevant aspects related to its structure and function.Results: In this study we report the subcellular localization of tomato C22DES in the endoplasmic reticulum (ER) based on confocal fluorescence microscopy and cell fractionation analyses. Modeling studies have also revealed that C22DES consists of two well-differentiated domains: a single N-terminal transmembrane-helix domain (TMH) anchored in the ER-membrane and a globular (or catalytic) domain that is oriented towards the cytosol. Although TMH is sufficient for the targeting and retention of the enzyme in the ER, the globular domain may also interact and be retained in the ER in the absence of the N-terminal transmembrane domain. The observation that a truncated version of C22DES lacking the TMH is enzymatically inactive revealed that the N-terminal membrane domain is essential for enzyme activity. The in silico analysis of the TMH region of plant C22DES revealed several structural features that could be involved in substrate recognition and binding.Conclusions: Overall, this study contributes to expand the current knowledge on the structure and function of plant C22DES and to unveil novel aspects related with plant sterol metabolism.
Placental Pathology of the Third Trimester Pregnant Women from COVID-19
Authors: Gao Likun , Ren Jiacai , Xu Li , Ke Xiaokang , Xiong Lin , Tian Xiaoli , Fan Cuifang , Yan Honglin , Yuan Jingping
Published: November 2020

Aims: To explore the clinical characteristics and placental pathological changes of pregnant women with 2019 novel coronavirus (CoV) disease (COVID-19) in the third trimester, and to assess the possibility of vertical transmission.Methods and results: The placenta tissues were evaluated by using immunohistochemistry for inflammatory cells and Hofbauer cells, and using severe acute respiratory syndrome (SARS) CoV-2 RNA Fluorescence In-Situ Hybridization (FISH) and SARS-CoV-2 spike protein immunoﬂuorescence (IF) double staining. All Eight placentas from the third trimester pregnancy women were studied. all patients were cured, no clinical or serological evidence pointed to vertical transmission of SARS-CoV-2. Features of maternal vascular malperfusion (MVM) such as increased syncytial knots were present in all 8 cases (8/8), and increased focal perivillous fibrin depositions were presented in 7 cases (7/8). No significate inflammatory cell reaction was noted in the placenta. The number of macrophages and inflammatory cells such as T cells, B cells and plasma cells in the placental villous was not significantly increased in all cases. Moreover, all of eight cases demonstrated negative results by FISH using a SARS-CoV-2 virus RNA probe and by IF using a monoclonal antibody against SARS-CoV-2 spike protein. Conclusions: We found no evidence of vertical transmission and adverse maternal-fetal outcomes in the placentas of third trimester COVID-19 pregnancy women, which provided further information for the clinical management of those women in the third trimester. However, further studies are still needed for patients with infections in different stage of gestation, especially in first and second trimester.
Birthweight DNA Methylation Signatures in Infant Saliva 
Authors: Moccia Chiara , Popovic Maja , Isaevska Elena , Fiano Valentina , Trevisan Morena , Rusconi Franca , Polidoro Silvia , Richiardi Lorenzo
Published: November 2020

Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to investigate whether cord blood birthweight-associated CpG sites identified by the PACE Consortium replicate in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 141 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7-17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in replication and exploratory EWAS analyses.Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was replicated in infant saliva. In saliva EWAS analyses, birthweight as continuous variable was associated with DNA methylation variation in 44 CpG sites, while being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation variation in 44 CpGs (all false discovery rate p-values<0.05), with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes identified also by the PACE consortium (MACROD1 and RPTOR).Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.
Facilitators and Barriers of Preconception Care in Women With Inflammatory Bowel Disease and Rheumatic Diseases
Authors: Admiraal Laura , Rosman Ageeth , Dolhain Radboud , West Rachel , Mulders Annemarie
Published: November 2020

Background: Preconception care (PCC) is care prior to conception to optimize parental health, and health of the future child, through biomedical and behavioral changes. Providing PCC to all women with a wish to conceive will improve perinatal health. PCC is especially important for women with a chronic disease, such as inflammatory bowel disease (IBD) and rheumatic diseases (RD). However, at present PCC is not part of routine care for these women. The aim of this study is to identify facilitators and barriers on a patient and professional level regarding the provision of PCC in women with IBD and RD.Methods: A survey study among women with IBD and RD, their treating physicians as well as obstetric professionals was performed. Patients, visiting the outpatient clinic of a university medical center and a secondary hospital located in the Netherlands with a wish to conceive, pregnant women or those with a recent pregnancy (<1 year ago) and involved physicians and obstetric professionals were eligible. Results: A total of 71% of the IBD patients (n=22/31) and 35% of the RD patients (n=20/58) received a PCC consultation. PCC consultation was considered easy to enter, short in time and patients felt comfortable. Patients (71% IBD; 62% RD) preferred a personal PCC consultation with their disease specific specialist together with an obstetrician. Patients specifically wanted to receive information about the safety of medication use and disease activity following delivery. A total of 67% (n=31) of the included healthcare professionals agreed PCC was applicable to their patients. Main barrier to providing PCC was lack of time and unavailability of professionals. In total 41% (n=16) of obstetric professionals felt they had the knowledge and skills to provide PCC compared to 33% (n=1) and 75% (n=3) of gastroenterologists and rheumatologists, respectively. Conclusion: Facilitators and barriers have been reported both on a patient and healthcare professional level. Despite the positive attitude towards PCC on both levels, realization of PCC remains difficult. In the future, in order to facilitate optimal PCC to high risk patients as standard of care, it is necessary to remove these barriers. Trial Registration: not applicable.
Assessing Fetal Movements in Pregnancy: A Qualitative Evidence Synthesis of Women’s Views, Perspectives and Experiences
Authors: Smith Valerie , Muldoon Kathryn , Brady Vivienne , Delaney Hannah
Published: November 2020

Background: Raising awareness of the importance of fetal movements (FMs) and advising women on the appropriate action to take if they experience reduced FMs, is critical for minimising or avoiding adverse perinatal outcomes. To gain insight and understanding of women’s perspectives of assessing FMs in pregnancy, we conducted a qualitative evidence synthesis. Methods: A qualitative evidence synthesis using thematic synthesis was conducted. Studies were eligible if they included pregnant women who were at least 20 weeks gestation and reported qualitative data from women on assessing FMs in pregnancy. MEDLINE, CINAHL, EMBASE, PsycINFO and Social Science Citation Index, from inception to July 2020, were searched. The methodological quality of included studies was assessed by at least two reviewers using an EPPI-Centre quality assessment tool. Data analysis, using the Thomas and Harden framework, involved line by line coding of extracted data, establishing descriptive themes, and determining analytical themes. Confidence in the findings was assessed using GRADE CER-Qual. Results: Nine studies, involving 2193 women, were included in the review. The methodological quality of the studies was overall generally high. The synthesis revealed three dominant themes, and seven sub-themes that reflected women’s perspectives of assessing FMs in pregnancy. These were; 1) How women engage with FMs, with subthemes of informal engagement, formal engagement, and strategies to stimulate FMs; 2) ‘…like a feather inside my belly’ - articulating and describing FMs, with sub-themes of sensations associated with FMs and timing and frequency of FMs; and 3) FMs and help/health seeking, with sub-themes of information sources and interacting with healthcare professionals. Confidence in the findings was either high or moderate, although two findings were rated low confidence and one very low.Conclusion: This qualitative evidence synthesis reveals that women informally engage with FMs during pregnancy. Women commonly adopt strategies to stimulate FMs when concerned. The use of the internet was a common source of obtaining information regarding FMS. Women require better support when contacting healthcare professionals about FMs. As only three of the nine included studies were exclusively qualitative in design, further qualitative studies exploring women’s perspective of assessing FMs in pregnancy are required.
Investigation of Immune Microenvironment in Children with Langerhans Cell Histiocytosis
Authors: Zhang Fuyong , Wang Weihong , Zhen Yunfang , Dai Jin , Zhu Lunqing , Liang Peirong , Su Guanghao , Zhang Min , Fang Jianfeng , Yuan Quanwen , Liu Ya , Zhuang Ting , Wang Xiaodong , Liu Yao
Published: November 2020

Background: Langerhans cell histiocytosis (LCH) is a rare disease that mainly occur in children. The aim of this investigation is to explore the immune microenvironment of LCH and feasibility of immunotherapy for children with LCH. Methods: Tissue samples were collected from 15 children with LCH and their clinical characteristics were recorded. The expressions of PD-1 ligand 1(PD-L1) and the presence of CD8 T lymphocytes were assessed by immunohistochemistry (IHC). Results: Of the total 15 patients, 8 of them were PD-L1 positive and it accounted for 53.33% and 9 of them were CD8 T lymphocytes positive and it accounted for 60%. There were 8 out of the 15 patients that were both PD-L1 positive and CD8 positive and they accounted for 53.33%.Conclusions: Our results showed that the expression of PD-L1 and presence of CD8 T lymphocytes occurred in the microenvironment of LCH. The findings indicated a possible new treatment option for LCH in children.
Analyzing the value of NUSAP1 in hepatocellular carcinoma from clinical and molecular mechanism perspectives: Bioinformatics-based approach.
Authors: Zhu Wenjie , Wang Jie , Chen Zehao , Jiang Jianxin
Published: November 2020

Background: Hepatocellular carcinoma (HCC) is one of the most common and highest mortality rates carcinomas worldwide. At present, there are varies of therapeutic methods can be provided for HCC patients. However, there is no one method can inhibit occurrence and development of HCC very well, and prognosis of HCC patients is still very poor. Herein, our study aims to identify a key gene closely related to occurrence, development, poor prognosis of HCC and explore its underlying mechanism from molecular level.Methods: GSE62232, GSE102079, GSE112790 and GSE121248 genes expression profile datasets were screened from Gene Expression Omnibus (GEO) database. R studio was used to identify DEGs of each dataset. Venn online tool was used to generate a Venn diagram and screen overlapping DEGs of the four datasets. Search Tool for the Retrieval of Interacting Genes (String) online tool was used to draw Protein–Protein Interaction (PPI) network. And the most significant module and the key gene NUSAP1 in PPI network were identified by MCODE and cytoHubba plug-in in Cytoscape software. Oncomine database and Kaplan–Meier Plotter database were used to analyze relationships between expression of NUSAP1 and occurrence, development, prognosis of HCC. The cBioPortal online tool was used to identify co-expression genes of NUSAP1 in HCC patients from TCGA database. Then, KEGG pathway analysis was carried out by DAVID online tool and Cell cycle pathway map was generated by Kyoto Encyclopedia of Genes and Genomes (KEGG) online tool.Results: A total of 86 overlapping DEGs were screened, which included 55 up-regulated DEGs and 31 down-regulated DEGs. Then the key gene NUSAP1 in the PPI network were screened using cytoHubba plug-in in Cytoscape software. We found NUSAP1 may be associated with occurrence, development and poor prognosis of HCC by analyzing HCC patients in Oncomine database and Kaplan–Meier Plotter. Co-expression genes of NUSAP1 in TCGA database were obtained by cBioPortal. And KEGG pathway analysis was produced using the top 300 co-expression genes of NUSAP1, the result showed most co-expression genes closely related to the expression of NUSAP1 were concentrated in Cell cycle. Thus, we generate a KEGG pathway map of Cell cycle and found that most of these genes were located in S phase and G2/M phase of the Cell cycle and they could regulate the genes in G1 phase, hence, we inferred that NUSAP1 may regulate the progression of HCC by promoting the transition from the G1 phase to the S phase.Conclusion: NUSAP1 may influence occurrence, development and prognosis of HCC and might be a new molecular marker in HCC.
ANGPTL4 supports glutamine metabolism and promotes fatty acid oxidation in nonsmall cell lung cancer cells
Authors: Xiao Song , Nai-Dong Wang , Yan Jin-Xiang , Tian Long , Lu Xiu-Rong , Gao Hong , Yan Jie-Cheng , Zhang Fei
Published: November 2020

Background Angiopoietin-like proteins (ANGPTLs) 4 is key factor in the regulation of lipid and glucose metabolism in metabolic diseases. It also has been demonstrated highly expressed in cancers, but the regulation of energy metabolism on tumor remains to be determined.Methods Two different NSCLC cells A549 and H1299 were used to investigate the role of ANGPTLs 4 in energy metabolism by tracer technique and seahorse XF technology in ANGPTLs4 knockdown cell. RNA microarray and specific inhibitors were used in identification targets in overexpression ANGPTLs4 cells.Results Knockdown ANGPTLs4 could inhibit the energy metabolism and proliferation of NSCLC cells. Knockdown ANGPTLs4 had no significant effect on glycolysis, but affected the glutamine consumption and fatty acid oxidation. Knockdown ANGPTLs4 also significantly inhibited the growth of metastasis and energy metabolism of tumor in mice, but had a weak effect on glycolysis. RNA microarray analysis showed that ANGPTLs4 significantly affected GLS and CPT1. ANGPTLs4 overexpression cells exposed to glutamine deprivation, the effect on cell proliferation and energy metabolism were significantly decreased, but still has difference compared with normal NSCLC cells. ANGPTLs4 overexpression cells treated with GLS and CPT1 inhibitor at the same time, the regulatory effects on cell proliferation and energy metabolism were disappeared.Conclusions ANGPTLs4 could promote the glutamine consumption and fatty acid oxidation, but not glycolysis, and accelerated the energy metabolism in NSCLC.
Saline collection media and an extraction free workflow enables massively scalable, highly sensitive, and cost-effective SARS-CoV-2 testing
Authors: Lim Yan Wei , Leonetti Nicole , Amin Aakash , Machado Henrique , Bonilla Natasha , Lu James , Becker K.David
Published: November 2020

The challenges in scaling up SARS-CoV-2 testing capacity include shortages in the supply chain for consumables and reagents. Improvements in consumption patterns can be obtained through removal of key processing steps, including RNA extraction. Here, we present a scalable and validated extraction-free method for the detection of SARS-CoV-2 from swab specimens in saline, with a limit of detection at 1,000 GCE/mL and a sensitivity and specificity of 100%.
Larval habitats of Anopheles gambiae senso lato (Diptera-Culicidae) in Anger Gute resettlement villages, western Ethiopia
Authors: Kenea Oljira , Dufera Mebrate
Published: November 2020

Background: Anger Gute is one of the national malaria surveillance Sentinel Sites in Ethiopia targeted to generate malaria data for the disease control, elimination and eradication. The objective of this work was to obtain information about the habitat characterization of An. gambiae s.l. larvae in western Ethiopian lowlands particularly in Anger Gute resettlement villages. Methods: A longitudinal mosquito larval habitat survey was undertaken every month from January to December 2018. The study covered three rural farming villages namely Tulu Lencha, Warabo and Dalasa Makanisa. All anopheline positive larval habitats present within a 500 m radius of each village and 700 m along the major streams which were located adjacent to the villages were sampled year round to study the mosquito larval density and the habitat characteristics. Larval collections were done from various aquatic habitats in all the villages using the standard dipping method. All III and IV instar anopheline larvae collected were preserved in 70% alcohol. In Wollega University Entomology laboratory, each larva was individually mounted on a microscope slide and identified to An. gambiae s.l. by morphological criteria using identification keys for the Ethiopian mosquitoes. Characteristics of the larval habitats were determined using mean comparison of the mosquito larval density using one-way analysis of variance (ANOVA). Results: The mosquito larvae were found in many diverse habitats and were collected most abundantly from rain pool puddles (35.0%) followed by river edge pools (23.5%). During wet season, most of (83.3%) the larval habitats were accessed along roads. Whereas during dry season the habitats were most accessible along streams in the study localities. Significantly higher mean densities of the mosquito larvae were obtained from aquatic habitats that had turbid standing water and in habitats near to human dwellings (<500 m). Conclusions: The malaria mosquito An gambiae s.l. breeds most abundantly in rain pool puddles along footways and roads closer to human habitation during wet season and in stream edges along local streams in dry season in Anger Gute Resettlement villages. These findings suggest that targeting malaria mosquito larval intervention along footways and roads in wet season and on stream edges along local streams in the dry season could result in effective larval control of the malaria vector in the study setting.
Patterns and Effects of Admission Hyperglycemia And Inflammatory Response in Trauma Patients: A Prospective Study
Authors: El-Menyar Ayman , Asim Mohammad , Mir Fayaz , Hakim Suhail , Kanbar Ahad , Siddiqui Tariq , Younis Basil , Ahmed Khalid , Mahmood Ismail , Atique Sajid , Jogol Hisham Al , Taha Ibrahim , Mustafa Fuad , Alabdallat Mohammad , Abdelrahman Husham , Peralta Ruben , Al-Thani Hassan
Published: November 2020

Background: Hyperglycemia following trauma could be a response to stress. The constellation of the initial hyperglycemia, proinflammatory cytokines and severity of injury among trauma patients is understudied. We aimed to evaluate the patterns and effects of on-admission hyperglycemia and inflammatory response in a level 1 trauma center admissions. Methods: A prospective, observational study was conducted for adult trauma patients who were admitted and tested for on-admission blood glucose, hemoglobin A1c, interleukin (IL)-6 ,Il-18 and hs-CRP. Patients were categorized into 4 groups (non-diabetic normoglycemic, diabetic normoglycemic, diabetic hyperglycemic (DH) and stress-induced hyperglycemic (SIH)). The inflammatory markers were measured on 3 time points (admission, 24 h, and 48 h). Pearson’s correlation test and logistic regression analysis were performed. We hypothesized that higher initial readings of blood glucose and cytokines are associated with severe injuries and worse in-hospital outcomes in trauma patients.Results: During the study period, 250 adult trauma patients were enrolled. Almost 13% of patients presented with hyperglycemia (SIH&DH); of whom 50% had SIH. Compared to the other 3 groups; SIH patients were younger, had significantly higher ISS, higher IL-6 readings, prolonged hospital length of stay and higher mortality. The SIH group had lower Revised Trauma Score (p=0.005), lower Trauma Injury Severity Score (p=0.01) and lower GCS (p=0.001). IL-18 and hs-CRP were comparable among the study groups. Compared to the normoglycemia groups, patients with hyperglycemia had elevated high- sensitive troponin T (p=0.001) and required more blood transfusion (p=0.03). Patients with hyperglycemia had 3-times higher in-hospital mortality than the normoglycemia groups (p=0.02). A significant correlation was identified between initial blood glucose and serum lactate, IL-6, ISS and hospital length of stay. IL-6 correlated well with ISS (r=0.40, p=0.001). On- admission blood glucose had age-sex-GCS adjusted odd ratio 1.20(95% CI 1.06-1.33, p=0.003) for severe injury (ISS≥16).Conclusions: On-admission hyperglycemia is associated with a significant severer injury than normoglycemia patients. Initial blood glucose correlates with serum IL-6 which indicates a potential role of the systemic inflammatory response in the disease pathogenesis among the injured patients. On-admission glucose level could be a useful marker of injury severity, triage and risk assessment in trauma patients.This study was registered at the ClinicalTrials.gov (Identifier: NCT02999386), retrospectively Registered on December 21, 2016 https://clinicaltrials.gov/ct2/show/NCT02999386.
Trends in reasons for emergency calls during the COVID-19 crisis in the department of Gironde, France using automatic classification.
Authors: Gil-Jardiné Cédric , Chenais Gabrielle , Pradeau Catherine , Tentillier Eric , Revel Philipe , Combes Xavier , Galinski Michel , Tellier Eric , Lagarde Emmanuel
Published: November 2020

Objectives During periods such as the COVID-19 crisis, there is a need for responsive public health surveillance indicators related to the epidemic and to preventative measures such as lockdown. The automatic classification of the content of calls to emergency medical communication centers could provide relevant and responsive indicators. Methods We retrieved all 796,209 free-text call reports from the emergency medical communication center of the Gironde department, France, between 2018 and 2020. We trained a natural language processing neural network model with a mixed unsupervised/supervised method to classify all reasons for calls in 2020. Validation and parameter adjustment were performed using a sample of 20,000 manually-coded free-text reports. Results The number of daily calls for flu-like symptoms began to increase from February 21, 2020 and reached an unprecedented level by February 28, 2020 and peaked on March 14, 2020, 3 days before lockdown. It was strongly correlated with daily emergency room admissions, with a delay of 14 days. Calls for chest pain, stress, but also those mentioning dyspnea, ageusia and anosmia peaked 12 days later. Calls for malaises with loss of consciousness, non-voluntary injuries and alcohol intoxications sharply decreased, starting one month before lockdown. Discussion This example of the COVID-19 crisis shows how the availability of reliable and unbiased surveillance platforms can be useful for a timely and relevant monitoring of all events with public health consequences. The use of an automatic classification system using artificial intelligence makes it possible to free itself from the context that could influence a human coder, especially in a crisis situation. Conclusion The content of calls to emergency medical communication centers is an efficient epidemiological surveillance data source that provides insights into the societal upheavals induced by a health crisis.
Sigmoid colon perforation caused by three living loaches inserted into anus: a case report
Authors: Li Jun , Zhao Ning , Pang Kai , Zhang Tingting , Wu Yadong , An Yongbo , Wu Guocong , Yang Yingchi , Yin Jie , Wang Jin , Zhang Jun , Jin Lan , Yao Hongwei , Zhang Zhongtao
Published: November 2020

BACKGROUND Colorectal perforation are common surgical emergencies. Yet perforation caused by living animals has not been reported with no record found on Medline. CASE PRESENTATION A 47-year-old male arrived at our surgical emergency room for "severe abdominal pain with itchy rash for 5 hours", who explained that "three big living loaches" had been squeezed into the anus 1 hour before the onset of symptoms. Thorough physical and auxiliary examinations suggested lower gastrointestinal perforation. After prompt anti-shock, anti-allergy, analgesia and gastrointestinal decompression, we performed exploratory laparotomy, sigmoid colon repair and double-lacuna ileostomy. The patient underwent uneventful postoperative recovery and was discharged on the 10th day after surgery. CONCLUSIONS CT examination is critical for diagnosing colorectal perforation caused by living animals (3 loaches as reported in our case). Specifically, due attention should be given to the serious allergic reaction induced by exogenous organisms entering the abdominal cavity. Surgery should be performed as soon as possible to fundamentally address the allergic shock. As to colorectal perforation caused by multiple living organisms, considering the restricted condition for thorough exploration during emergency surgery (particularly the exploration of the posterior wall of the colon), colostomy should be selected with caution.
Pretreatment with LCK Inhibitors Chemosensitizes Cisplatin-Resistant Endometrioid Ovarian Tumors
Authors: Crean-Tate Katie , Braley Chad , Dey Goutam , Esakov Emily , Saygin Caner , Trestan Alexandria , Silver Daniel , Turaga Soumya M. , Connor Elizabeth V. , Debernardo Robert , Michener Chad M. , Rose Peter G. , Lathia Justin , Reizes Ofer
Published: November 2020

Background: Ovarian cancer is the most fatal gynecologic malignancy in the United States. While chemotherapy is effective in the vast majority of ovarian cancer patients, recurrence and resistance to standard systemic therapy is nearly inevitable. We discovered that CD55 via activation of the non-receptor tyrosine kinase Lymphocyte Cell-Specific Protein-Tyrosine Kinase (LCK) promoted cisplatin resistance. Here, we hypothesized that treating high grade, platinum resistant endometrioid cancer cells with an LCK inhibitor (LCKi) followed by co-treatment with cisplatin would lead to increased cisplatin efficacy. Our objective was to assess clinical outcomes associated with increased LCK expression, test our hypothesis of utilizing LCKi as pre-treatment followed by co-treatment with cisplatin in platinum resistant ovarian cancer in vitro, and evaluate our findings in vivo to assess LCKi applicability as a therapeutic agent. Results: Kaplan-Meier (KM) plotter data indicated LCK expression is associated with significantly worse median progression-free survival (HR 3.19, p=0.02), and a trend toward decreased overall survival in endometrioid ovarian tumors with elevated LCK expression (HR 2.45, p=0.41). In vitro, cisplatin resistant ovarian endometrioid cells treated first with LCKi followed by combination LCKi-cisplatin treatment showed decreased cell viability and increased apoptosis. Immunoblot studies revealed LCKi led to increased expression of phosphorylated H2A histone family X (-H2AX), a marker for DNA damage. In vivo results demonstrate treatment with LCKi followed by LCKi-cisplatin leads to significantly slowed tumor growth.Conclusions: We identified a strategy to therapeutically target cisplatin resistant endometrioid ovarian cancer leading to chemosensitization to platinum chemotherapy via treatment with LCKi followed by co-treatment with LCKi-cisplatin.
The role of computed tomography in predicting peritoneal carcinomatosis and upfront surgery outcome in advanced ovarian cancer
Authors: Asp Mihaela , Malander Susanne , Wallengren NilsOlof , Pudaric Sonja , Bengtsson Johan , Sartor Hanna , Kannisto Päivi
Published: November 2020

Background Epithelial ovarian cancer is usually diagnosed at advanced stages. To choose the best therapeutic approach, an accurate assessment of the tumor spread is crucial. This study aimed to determine whether numeric scoring, the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT), can predict the tumor extent and improve the outcome of AOC upfront surgery. Methods This single center retrospective analysis of 194 patients diagnosed with AOC included 119 patients treated with upfront surgery at the Skåne University Hospital, Lund, Sweden, from January 2016 to December 2018. CT based peritoneal cancer index (PCI) scores, enlarged cardiophrenic lymph nodes (CPLNs), and the amount of ascites were correlated to the surgical PCI (S-PCI) and the completeness of the cytoreductive surgery.The patients were grouped according to the residual disease (RD) and the overall survival (OS) rates for the three groups were determined using Kaplan-Meier curves. Linear regression and the interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. Results The survival rate was significantly higher in patients with no macroscopic residual disease compared those with residual disease <10 mm (p<0.03) or residual disease ≥10 mm (p<0.005). S-PCI and large ascites volumes were correlated with the risk of suboptimal residual disease (for ascites > 1000 ml, OR 5.5626 (1.665-19.007) p<0.019; for S-PCI, OR 1.24 (1.141-1.348), p<0.001). CT-PCI, CA-125 level and CPLN were not predictive of the cytoreductive surgery results in the adjusted data to days from CT to operation and for ascites. CT-PCI correlated well to S-PCI ((95%) CI: 0.397 (0.252-0.541) p<0.001). Conclusions CT is a reliable tool for assessing the extent of the disease in AOC, but it has limitations in predicting surgical outcome. This study was unable to show an association between the CT-PCI and surgical outcome when the data were adjusted and ascites, CA-125 level, days between the CT examination to surgery and CPLN. Ascites volumes exceeding 1000 ml increased the risk of residual disease and thereby worse outcome. That certain areas (e.g., small bowel region) are particularly critical when evaluating surgical outcome using preoperative CT-PCI warrants further investigation.