bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations of White Matter Integrity in Cerebral Small Vessel Disease and Their Correlation with Cognitive Performance: A Trace-Based Spatial Statistics Study
Authors: Wang Yifan , Wang Tianyao , Yu Zekuan , Huang Bo , Liu Biao , Liu Xianwei , Yin Huabin , Liu Jun
Published: January 2021

Background: This study aimed to understand the injury of white matter (WM) microstructure behind white matter hyperintensities (WMH) and identify the regions where injury was more pronounced with increasing WMH severity. Moreover, we analyzed whether this microstructural injury is related to cognition. Methods: 110 patients with WMH were recruited in this research. All subjects underwent 3.0T MRI scans and neuropsychological cognitive assessments. Simple mental state examination (MMSE) along with Montreal Cognitive Assessment (MoCA) were applied to assess the patient's overall cognitive ability. WMH of each subject was graded according to Fazekas grade scale and was divided into two groups: (A) WMH score of 1-2 points (n=64), (b) WMH score of 3-6 points (n=46). Trace-based spatial statistics (TBSS) was applied for the analysis of diffusion tensor imaging (DTI) data. All statistical analyses were performed in SPSS 26.0 statistical software. Results: The results indicate that patients with higher WMH scores showed extensively symmetrical areas of increased mean diffusion, axial diffusion and radial diffusion involving bilateral anterior limb, posterior limb and retrolenticular part of internal capsule, posterior corona radiata, external capsule, superior longitudinal fasciculus, and superior fronto-occipital fasciculus (P < 0.01). Conclusions: Finally, we come to the conclusion that cognition-related WM fiber tracts tend to be more vulnerable to be injured in patients of cerebral small vessel disease (CSVD). Moreover, changes in WM microstructure often predate changes of cognition. Early detection of microstructural changes and timely intervention can delay cognitive decline to some extent.
Risk Factors for Ectopic Pregnancy: A Multi-center Case Control Study
Authors: Atta Nooria , Aram Fahima , Naseri Nafisa , Sahak Mahbooba
Published: January 2021

Background: Ectopic pregnancy (EP) is defined as a pregnancy in which fertilized oocyte implants outside the endometrial cavity. Although there is no known etiology for ectopic pregnancy, some risk factors of EP have been determined. It has been evident that ectopic pregnancy can be of multifactorial origin. This multicenter research aims to study risk factors associated with increased risk of ectopic pregnancy in women living in Kabul. Methods: A multicenter case control study was conducted in five tertiary maternity hospitals located in Kabul, Afghanistan. A total of 457 pregnant women were included in this study. In the case group, women with diagnosed ectopic pregnancy, while in control group women with intrauterine pregnancy were included. For each case in this study, two controls were enrolled. Results: The mean (SD) age of women in case group was 27.9 (6) years while in control group it was 26.4 (5.5) years. This difference was not statistically significant. We found a significant association between history of abortion and EP (Adj. OR=1.57; 95%CI: 1.02, 2.42). Having history of abdominal/pelvic surgery was a risk factor for EP with adjusted OR 1.94 (95%CI: 1.15, 3.30). In this study we found an increasing risk of EP in women of 35 years or older compared to younger women (Crude OR=2.26; p= 0.024). In women reporting prior EP, the chance of its recurrence was increased (Crude OR= 9.64; 95%CI: 1.1, 83.2). No association of gravidity and parity was found with EP incidence. Conclusions: In this study we found a statistically significant association between history of abdominal/pelvic surgery and EP. In addition, history of abortion was suggested as a risk factor for ectopic pregnancy. In case of having a previous EP probability of its recurrence will be increased. Women with advanced age having other potential risk factors will be facing higher risk of EP.
Superlinear scaling of riverine biogeochemical function with watershed size
Authors: Wollheim Wilfred , Harms Tamara , Robison Andrew , Koenig Lauren , Helton Ashley , Song Chao , Bowden William , Finlay Jacques
Published: January 2021

River networks are a crucial component of the earth system because they regulate carbon and nutrient exchange between continents, the atmosphere, and oceans. Quantifying the role of river networks at broad spatial scales must accommodate spatial heterogeneity, discharge variability, and upstream-downstream connectivity. Allometric scaling relationships of cumulative biogeochemical function with watershed size integrate these factors, providing an approach for understanding the role of fluvial networks in the earth system. Here we demonstrate that allometric scaling relationships of cumulative river network function are linear (power exponent ~ 1) when biogeochemical reactivity is high and river discharges are low, but become increasingly superlinear (power exponent > 1) as reactivity declines or discharge increases. Superlinear scaling indicates that biogeochemical function of entire river networks within a watershed is an emergent property that increases disproportionately with increasing watershed size. Expanding observation networks will increase precision in riverine fluxes of carbon and nutrients estimated by allometric scaling functions.
Starfish-inspired Ultrasound Ciliary Bands for Microrobotic Systems
Authors: Dillinger Cornel , Nama Nitesh , Ahmed Daniel
Published: January 2021

Cilia are short, hair-like appendages ubiquitous in various biological systems, which have evolved to manipulate and gather food in liquids at regimes where viscosity dominates inertia. Inspired by these natural systems, synthetic cilia have been developed and cleverly utilized in microfluidics and microrobotics to achieve functionalities such as propulsion, liquid pumping and mixing, and particle manipulation. In this article, we present the first demonstration of ultrasound-activated synthetic ciliary bands that mimic the natural arrangements of ciliary bands on the surface of starfish larva. Our system leverages nonlinear acoustics at microscales to drive bulk fluid motion via acoustically actuated small-amplitude oscillations of synthetic cilia. By arranging the planar ciliary bands angled towards (+) or away (–) from each other, we achieve bulk fluid motion akin to a flow source or sink. We further combine these flow characteristics with a novel physical principle to circumvent the scallop theorem and realize acoustic-based propulsion at microscales. Finally, inspired by the feeding mechanism of a starfish larva, we demonstrate an analogous microparticle trap by arranging + and – ciliary bands adjacent to each other.
Evaluation of the Expression Levels of Cannabinoid Type-1 (CB1) Receptor and Phosphorylated Extracellular Signal-Regulated Kinase (p-ERK) in Gliomas
Authors: Choucair Nader , Sakr Zahraa , Eddine Hassane Kheir , Zaarour Mariana , Harati Hayat , Fares Youssef , Bahmad Hisham , Nabha Sanaa
Published: January 2021

Background

Gliomas are the most frequent primary brain tumors and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new cancer-therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors, CB1 and CB2. The aim of this study was to investigate the expression levels of cannabinoid type-1 (CB1) receptors and phosphorylated extracellular signal-regulated kinase (p-ERK) in human glioma samples and evaluate their clinicopathologic significance.
Materials and Methods

We analyzed the expressions of CB1 receptors (CB1R) and p-ERK in 61 paraffin-embedded gliomas and 4 normal brain tissues using automated immunohistochemical assay. CB1R and p-ERK expressions were categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and p-ERK expression levels and the clinicopathologic features and overall survival.
Results

Our results showed that CB1R is down-expressed in glioma tissues compared to normal brain tissues. However, the low expression of CB1R was found to be not related to the malignancy grade of gliomas. Conversely, higher expression of p-ERK was noted in gliomas compared to normal brain tissues, with no association observed with tumor grades. In addition, CB1R expression was not observed to be associated with clinicopathologic features of gliomas, except for p-ERK expression.
Conclusion

Our findings indicate a down-expression of CB1R and overexpression of p-ERK in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas may contribute to further research on the therapeutic effects of cannabinoids in human gliomas.
Alkaline Phosphatase Downregulation Promotes Lung Adenocarcinoma Metastasis via the C-Myc/RhoA Axis
Authors: Lou Zhefeng , Lin Weiwei , Zhao Huirong , Jiao Xueli , Wang Cong , Zhao He , Liu Lu , Liu Yu , Xie Qipeng , Huang Xing , Huang Haishan , Zhao Lingling
Published: January 2021

Background: Lung adenocarcinoma (LUAD) metastasis significantly reduces patient survival; hence inhibiting the metastatic ability of lung cancer cells will greatly prolong patient survival. Alkaline phosphatase (ALPL), a homodimeric cell surface phosphohydrolase, is reported to play a controversial role in prostate cancer and ovarian cancer cell migration; however, the function of ALPL in LUAD and the related mechanisms remain unclear.Methods: TCGA database was used to analysis the expression of ALPL, and further verification was performed in a cohort of 36 LUAD samples by qPCR and western blot. Soft-agar assay, transwell assay and lung metastasis assay were employed to detect the function of ALPL in LUAD progression. The qPCR, luciferase promoter reporter assay and western blot were used to clarify the molecular mechanisms of ALPL in promoting metastasis in LUAD.Results: ALPL was downregulated in LUAD, and the disease-free survival rate of patients with low ALPL was significantly reduced. Further studies showed that overexpression of ALPL in LUAD cell lines did not significantly affect cell proliferation, but it did significantly attenuate lung metastasis in a mouse model. ALPL downregulation in LUAD led to a decrease in the amount of phosphorylated (p)-ERK. Because p-ERK promotes the classical c-Myc degradation pathway, the decrease in p-ERK led to the accumulation of c-Myc and therefore to an increase in RhoA transcription, which enhanced LUAD cell metastasis.Conclusion: ALPL specially inhibits the metastasis of LUAD cells by affecting the p-ERK/c-Myc/RhoA axis, providing a theoretical basis for the targeted therapy of clinical LUAD.
The CAFs Related Gene CALD1 Is a Prognostic Biomarker and Correlated With Immune Infiltration in Bladder Cancer
Authors: Du YiHeng , Jiang Xiang , Wang Bo , Cao Jin , Wang Yi , Yu Jiang , Wang XiZhi , Liu HaiTao
Published: January 2021

Background: Stromal components of the tumor microenvironment contribute to bladder cancer progression, and Cancer-Associated Fibroblasts (CAFs) were reported to play an important role. Accumulating pieces of evidence indicate that CAFs participate in the crosstalk with tumor cells and have a complex interaction network with immune components. Further study of the role of CAFs in the bladder cancer microenvironment and the search for possible specific markers are important for a deeper understanding of the roles of CAFs in bladder cancer progression and immunomodulation.Methods: In the present study, we examined the abundance of CAFs in the TCGA and GEO datasets using the MCP-Counter algorithm. Additionally, the expression of genes related to CAFs was analyzed through the Weighted Gene Co-expression Network Analysis (WGCNA). The CIBERSORT and ESTIMATE algorithms were used for the correlation analysis between the key CAFs related gene and the tumor microenvironment components.Immunohistochemistry analysis in clinical samples was used to validate the results of bioinformatics analysis.Results: The results showed that CAFs were closely associated with the progression and prognosis of bladder cancer. WGCNA also revealed that CALD1 was a key gene significantly associated with CAFs in bladder cancer. Moreover, the further in-depth analysis showed that CALD1 significantly affected the progression and prognosis of bladder cancer. The CIBERSORT and ESTIMATE algorithms significant correlations between CALD1 and the tumor microenvironment components, including CAFs, macrophages, T cells, and multiple immune checkpoint related genes. Finally, immunohistochemistry results of clinical samples' validated the strong association between CALD1, CAFs, and macrophages.Conclusions: In the present study, we confirmed the cancer-promoting roles of CAFs in bladder cancer. Being a key gene associated with CAFs, CALD1 may promote bladder cancer progression by remodeling the tumor microenvironment. The bioinformatics methods, including the CIBERSORT, MCP-COUNTER and ESTIMATE algorithms, may provide important value for studying the tumor microenvironment.
LAMC1, Upregulated by TGFβ in Tumor Cells, Contributed to The Formation of Inflammatory Cancer-Associated Fibroblasts Via NF-kB/CXCL1/STAT3 in Esophageal Squamous Cell Carcinoma.
Authors: Fang Lingling , Che Yun , Zhang Chaoqi , Huang Jianbing , Lei Yuanyuan , Lu Zhiliang , Sun Nan , He Jie
Published: January 2021

Background: The tumor microenvironment (TME) consists of a variety of cells that interact with each other through cytokines. As an important member of the TME, cancer-associated fibroblasts (CAFs) play an important role in the development of tumor cells, which is influenced by the heterogeneity of CAFs. Transforming growth factor β (TGFβ) not only plays a dual role in the progression of tumor cells directly but also influences tumor cells by regulating the heterogeneity of CAFs. Methods: we explored oncogenes regulated by TGFβ, which were involved in signaling molecules and interactions in the TME. We analyzed sequencing data of TCGA and GSE53625, as well as ESCC cell lines with or without TGFβ1 stimulation, and then we focused on laminin subunit gamma 1 (LAMC1). The upregulation of LAMC1 after TGF-β1 stimulation was examined by western blot (WB), quantitative real time PCR (qRT-PCR) and Chromatin immunoprecipitation (ChIP). We performed gain-of-function and loss-of-function assays to examine the effect of LAMC1 on proliferation and migration of ESCC cells. CAFs were isolated and cocultured with ESCC cells. And conditional medium of shLAMC1 ESCC cells and CAFs with different treatments were collected. RNA-seq of those cells were also performed. Luminex liquid suspension chip detection, ELISA, WB, qRT-PCR and rescue experiments were carried out to reveal the interaction of between ESCC cells and CAFs.Results: LAMC1 was highly expressed in ESCC, affecting the prognosis of patients. Moreover, LAMC1 could be upregulated by TGFβ1 through SMAD4 and SP1 synergistic activation. Further experiments showed that LAMC1 would promote the proliferation and migration of tumor cells mainly via Akt/NF-κB/MMP9 and MMP14. Additionally, LAMC1 would promote CXCL1 secretion mainly by activating NF-κB. Tumor-secreted CXCL1 remodeled the formation of inflammatory CAFs (iCAFs) through CXCR2/pSTAT3. The conditioned medium of iCAFs promoted the proliferation and migration of tumor cells.Conclusions: Our study identified the mechanism by which upregulation of LAMC1 by TGFβ in tumor cells not only promoted ESCC progression but also indirectly induced carcinogenesis by stimulating CXCL1 secretion and promoting the formation of iCAFs. This suggests that LAMC1 could be a potential therapeutic target and prognostic marker for ESCC.
APOE is a Prognostic Biomarker and Correlates With Immune Infiltrates in Papillary Thyroid Carcinoma
Authors: Lin Xu , Zhang Wen-Jing , Xue Gang , Wu Jing-Fang , Chao Liu-ya
Published: January 2021

Background: Recent research showed that abnormal lipid metabolism was associated with cancers. As one of the genes that can regulate the level of lipid metabolism, abnormal APOE expression was associated with carcinogenesis. However, the biological role of APOE in papillary thyroid carcinoma (PTC) remains to be determined.Methods: ONCOMINE, GEPIA, UALCAN, STRING, GeneMANIA, LinkedOmics, GSCALite, TISIDB, EPIC and TIMER were utilized to achieve comprehensively bioinformatics analysis of APOE in this study. And the immunohistochemical staining of APOE was used to verify the predicted results.Results: The mRNA level and protein level of APOE of PTC tissues were significantly elevated in TCGA cohort and Shanghai cohort. And APOE expression was positively correlated with the pathological stage and lymph node metastasis in PTC. PTC patients with low mRNA level of APOE were associated with a bad prognosis. The functions of APOE co-expressed genes were mainly enriched in adaptive immune response, protein-lipid complex subunit organization, actin cytoskeleton reorganization, cell chemotaxis, protein activation cascade and transcriptional misregulation in cancer. APOE level was significantly correlated with tumor-infiltrating cells (B cells, CD8+ T cells, neutrophils, and dendritic) and immune biomarkers in PTC.Conclusions: APOE is a potential independent biomarker for PTC and APOE expression is positively correlated with immune cell infiltration in PTC.
Alteration of 3d Matrix Stiffness Regulates Viscoelasticity of Human Mesenchymal Stem Cells
Authors: Kao Ting-Wei , Chiou Arthur , Lin Keng-Hui , Liu Yi-Shiuan , Lee Oscar
Published: January 2021

Background: Human mesenchymal stem cells (hMSCs) possess potential of bone formation and were proposed as ideal material for tissue regeneration against osteoporosis. Although a plethora of elucidation regarding the directing effect on lineage specification by physical cues has been proposed, how mechanical stimulations impact the intracellular viscoelasticity during osteo-lineage commitment remained enigmatic. Methods: Cyto-friendly 3D matrix was prepared on soft-lithographed device. The substrate was basically polyacrylamide and conjugated with fibronectin. Stiffness of the scaffolds was determined by the mixing ratio of monomer and crosslinker. The hMSCs were injected with fluorescent beads by gene gun before being cultured in the matrix and chemically induced toward osteogenesis. The mechanical properties were assessed using video particle tracking microrheology. On post-induction day 0, 7, 14, 21, inverted epifluorescence microscope with charge-coupled camera was exploited to capture the projected Brownian trajectory of indwelling hMSCs. Mean square displacement thereof was calculated and transformed into intracellular viscoelasticity by generalized Stokes-Einstein equation.Results: Two different stiffness of 3D culture microspheres (12 kPa, 1 kPa) were established. A total of 45 cells were assessed. Initially, hMSCs possessed equivalent mechanical traits in the first week. Nonetheless, cells cultured in rigid matrix displayed statistically significant elevation over elastic (G’) and viscous moduli (G”) on day 7 (G’: 192±8 vs. 114±8, p<0.01; G” 204±9 vs. 169±10 Pa, p<0.01) and day 14 (G’: 190±6 vs. 129±7, p<0.01; G” 222±10 vs. 161±9 Pa, p<0.01). To appreciate the trend of fluctuation, subsequent measurements were compared with the respective modulus at day 0. The soft niches no longer facilitated stiffening hMSCs, whereas the effect by rigid substrates was consistently during the entire differentiation course.Conclusions: Stiffness of the matrix impacted the viscoelasticity of hMSCs. Detailed elucidation on how microenvironment impacts mechanical properties and differentiation of hMSCs will facilitate the advancement of tissue engineering and regenerative medicine.
LncRNA FBXL19-AS1 Promotes Proliferation and Metastasis of Cervical Cancer Through Upregulating COL1A1 as a Sponge of MiR-193a-5p
Authors: Huang Xiaoyong , Shi Haiyan , Shi Xinghai , Jiang Xuemei
Published: January 2021

Background: Cervical cancer (CC) is one of the most common and malignant tumors in women. In this study, we aim to explore the role and mechanism of FBXL19-AS1, a novel long-chain non coding RNA with marked roles in a variety of tumors, in regulating the proliferation and metastasis of CC. The expression of FBXL19-AS1, miR-193a-5p and COL1A1 were detected by RT-PCR and western blot. Gain-and loss- of functions of FBXL19-AS1 and miR-193a-5p were performed in CC cell lines in vitro. The proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT) level were determined. Results: FBXL19-AS1 and COL1A1 were significantly up-regulated in CC, while miR-193a-5p was significantly down-regulated. Overexpression of FBXL19-AS1 significantly promoted the proliferation, migration, invasion and EMT of CC cells and inhibited apoptosis, while knockdown of FBXL19-AS1 had the opposite effects. On the other hand, miR-193a-5p inhibited the proliferation and metastasis of CC cells. Mechanistically, FBXL19-AS1 functioned as a competitive endogenous RNA and inhibited the expression of miR-193a-5p, which targeted at the 3'-UTR site of COL1A1 and negatively regulated COL1A1 expression. Concluson: FBXL19-AS1 can promote the proliferation and metastasis of CC by sponging miR-193a-5p and up-regulating COL1A1.
Premorbid cardioselective (but not non-selective) β-blocker exposure reduces intensive care unit mortality among septic patients
Authors: Kuo Ming-Jen , Chou Ruey-Hsing , Lu Ya-Wen , Guo Jiun-Yu , Tsai Yi-Lin , Wu Cheng-Hsueh , Huang Po-Hsun , Lin Shing-Jong
Published: January 2021

Background

β blockers may protect against catecholaminergic myocardial injury in critically ill patients. Long-term β-blocker users are known to have lower lactate concentrations and favorable sepsis outcomes. However, the effects of cardioselective and nonselective β-blockers on sepsis outcomes have not been compared. This study was conducted to investigate the impacts of different β-blocker classes on the mortality rate in septic patients.
Methods

We retrospectively screened 2678 patients admitted to the medical or surgical intensive care unit (ICU) between December 2015 and July 2017. Data from patients who met the Sepsis-3 criteria at ICU admission were included in the analysis. Premorbid β-blocker exposure was defined as the prescription of any β-blocker for at least 1 month. Bisoprolol, metoprolol, and atenolol were classified as cardioselective β-blockers, and others were classified as nonselective β-blockers. All patients were followed for 28 days or until death.
Results

Among 1262 septic patients, 209 (16.6%) patients were long-term β-blocker users. Patients with premorbid β-blocker exposure had lower heart rates, initial lactate concentrations, and ICU mortality. After adjustment for disease severity, comorbidities, blood pressure, heart rate, and laboratory data, reduced ICU mortality was associated with premorbid cardioselective [adjusted hazard ratio (HR), 0.28; 95% confidence interval (CI), 0.11–0.74; P = 0.010], but not non-selective (adjusted HR, 0.78; 95% CI, 0.30–2.05; P = 0.611), β-blocker use.
Conclusion

Premorbid cardioselective, but not non-selective, β-blocker use was associated with improved mortality in septic patients. This finding supports the protective effect of cardioselective β-blockers in septic patients. Prospective studies are needed to confirm it.
Serum lithium test requesting across three UK regions: An evaluation of adherence to monitoring guidelines
Authors: Parfitt Ceri , Duff Christopher J , Scargill Jonathan , Green Lewis , Holland David , Heald Adrian H , Fryer Anthony A
Published: January 2021

Background: Bipolar disorder is the fourth most common mental health condition, affecting ~1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is widely recommended as a first-line treatment. We previously showed in other areas that laboratory testing patterns are variable with sub-optimal conformity to guidance. We therefore examined lithium results and requesting patterns relative to monitoring recommendations.Methods: Data on serum lithium levels and intervals between requests were extracted from Clinical Biochemistry laboratory information systems at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012-2018 (46,555 requests; 3,371 individuals). Data were examined with respect to region/source of request, age and sex.Results: Across all sites, lithium levels on many requests were outside the recommended UK therapeutic range (0.4-0.99 mmol/L); 19.2% below the range and 6.1% above the range (median [Li]: 0.60 mmol/L). A small percentage were found at the extremes (3.2% at <0.1mmol/L, 1.0% at ≥1.4mmol/L). Most requests were from general practice (56.3%) or mental health units (34.4%), though those in the toxic range (≥1.4 mmol/L) were more likely to be from secondary care (63.9%). For requesting intervals, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak at 6 months, as recommended for those aged <65 years on unchanging therapy, though re-test intervals in this age group were more likely to be longer. There was a peak at 0-7 days, reflecting those requiring closer monitoring (e.g. treatment initiation, toxicity). However, for those with initial lithium concentrations within the BNF range (0.4-0.99 mmol/L), 69.4% of tests were requested outside expected testing frequencies.Conclusions: Our data showed: (a) lithium levels are often maintained at the lower end of the recommended therapeutic range, (b) patterns of lithium results and testing frequency were comparable across three UK sites with differing models of care and, (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly, but not at 6-monthly intervals. Many tests were repeated outside expected frequencies, indicating the need for measures to minimise inappropriate testing.
School trajectory disruption among adolescents living with perinatal HIV receiving antiretroviral treatments: a case-control study in Thailand
Authors: Merville Ophélie , Puangmala Patcharee , Suksawas Pranee , Kliangpiboon Woranut , Keawvilai Waraporn , Tunkam Chorkanikar , Yama Suvimon , Sukhaphan Usa , Sathan Somporn , Marasri Siriporn , Rolland-guillard Louise , Sirirungsi Wasna , Coeur Sophie Le
Published: January 2021

Background: Adolescents living with perinatal HIV often experience difficult living circumstances that can impact educational achievement and thus their transition to adult life. We explored their school trajectories and evaluated the contribution of perinatal HIV-infection, in Thailand, where education is free and compulsory until the age of 15.Methods: We used data from the Teens Living with Antiretrovirals (TEEWA) study, a cross-sectional case-control study conducted from 2011 to 2014 in Thailand. Participants were 707 adolescents living with perinatal HIV (ALPHIV, cases) aged 12–19 receiving antiretroviral therapy in 19 hospitals throughout Thailand and 689 HIV-uninfected adolescents (controls) living in the same institutions or, for those living in family settings, randomly selected from the general population and individually matched for sex, age, and place of residence. School trajectory disruption was defined as ≥ 1 year of academic delay or as early school dropout (before 15 years of age). Logistic regression models were used to assess factors independently associated with disrupted school trajectory and to estimate the proportion of school disruption attributable to HIV-infection. We used multivariate imputations by chained equations (MICE) to manage missing data and performed two sensitivity analyses to evaluate the main model’s reliability.Results: The study population’s median age was 14.5 years (58% female). School trajectory disruption was experienced by 37% of ALPHIV and 12% of the controls. After adjusting for sociodemographic factors, ALPHIV were 5 times more likely to experience disruption than controls ( =5.2 [3.7-7.2]). About 50% of school trajectory disruption was attributable to HIV-infection. Boys and adolescents living in institutions were more likely to experience school trajectory disruption ( =1.8 [1.3-2.4] and =11.0 [7.7-15.8], respectively). Among ALPHIV, neurocognitive difficulties and growth delay were significantly associated with disruption ( =3.3 [2.1-5.2] and =1.8 [1.3-2.6], respectively). For those living in families, disruption was also associated with having a caregiver who had less than a secondary-level education ( =2.1 [1.1-3.9]) or having experienced stigmatization ( =1.9 [1.2-3.1]). Conclusions: HIV and contextual factors combine to aggravate the educational disadvantage among ALPHIV. The impact of this disadvantage on their life prospects, especially regarding access to higher education and professional achievement, should be further explored.
Validation of multiplex PCR sequencing assay of SIV
Authors: Moriarty Ryan V , Fesser Nico , Sutton Matthew S , Venturi Vanessa , Davenport Miles P , Schlub Timothy , O'Connor Shelby L
Published: January 2021

Background: The generation of accurate and reproducible viral sequence data is necessary to understand the diversity present in populations of RNA viruses isolated from clinical samples. While various sequencing methods are available, they often require high quality templates and high viral titer to ensure reliable data.Methods: We modified a multiplex PCR and sequencing approach to characterize populations of simian immunodeficiency virus (SIV) isolated from nonhuman primates. We chose this approach with the aim of reducing the number of required input templates while maintaining fidelity and sensitivity. We conducted replicate sequencing experiments using different numbers of quantified viral RNA (vRNA) or viral cDNA as input material. We performed assays with clonal SIVmac239 to detect false positives, and we mixed SIVmac239 and a variant with 24 point mutations (SIVmac239-24X) to measure variant detection sensitivity.Results: We found that utilizing a starting material of quantified viral cDNA templates had a lower rate of false positives and increased reproducibility when compared to that of quantified vRNA templates. This study identifies the importance of rigorously validating deep sequencing methods and including replicate samples when using a new method to characterize low frequency variants in a population with a small number of templates.Conclusions: Because the need to generate reproducible and accurate sequencing data from diverse viruses from low titer samples, we modified a multiplex PCR and sequencing approach to characterize SIV from populations from non-human primates. We found that increasing starting template numbers increased the reproducibility and decreased the number of false positives identified, and this was further seen when cDNA was used as a starting material. Ultimately, we highlight the importance of vigorously validating methods to prevent overinterpretation of low frequency variants in a sample.
How joint line orientation affects the amount of bone resected in mechanically aligned TKA: a retrospective clinical-radiographic correlational study
Authors: Wang Zhiwei , Yu Yang , Wen Liang , Ma Desi , Qu Tiebing
Published: January 2021

Background: Discrepancies in bone resection between the medial and lateral compartments is very common in total knee replacement (TKA) when mechanical alignment (MA) is used. The purpose of this study was to explore whether and how joint line orientation affects the gross amount of bone resected in mechanically aligned TKA.Methods: A total of 112 patients (137 knees) diagnosed with osteoarthritis (OA) were included. Bone resection simulations were conducted in the coronal view using full-length weight-bearing radiographs per the technical parameters of MA, and the feasibility of simulated osteotomy was verified via intraoperative caliper measurement. Correlation and regression analyses were conducted comparing the amount of bone resected and various parameters, including hip-knee-ankle (HKA) angle, mechanical lateral distal femoral angle (mLDFA), joint line congruency angle (JLCA), and medial proximal tibial angle (MPTA). Moreover, any intraoperative bone resection adjustments that were made were retrospectively collected using a medical record query system.Results: All knees in the current case series could be artificially divided into 4 subgroups: 84 varus knees (61.3%) with valgus femurs in subgroup 1, 32 varus knees (23.4%) with varus femurs in subgroup 2, 14 valgus knees (10.2%) with varus tibias in subgroup 3, and 7 valgus knees (5.1%) with valgus tibias in subgroup 4. Simulated bone resection thickness was highly consistent with intraoperative measurements. MPTA and mLDFA were positively correlated with the amount of bone resected in subgroup 1. The regression equation was: Maximum resection thickness (mm) = 0.556*mLDFA (deg.) + 0.098*MPTA (deg.) -39.74; R2=0.808. Similarly, intraoperative bone resection adjustments also showed a correlation with mLDFA in subgroup 1.Conclusions: Deformities in knee OA can be divided into 4 subgroups based on the alignment of extremities and the joint line orientation. When TKA is performed in varus knees with valgus femurs using conventional instruments and mechanical alignment techniques, the amount of bone resected in the coronal plane demonstrates a linear relationship with the patient’s mLDFA.
DSSAM: Digitally Signed Secure Acknowledgement Method for Mobile Ad-hoc Network
Authors: Srivast Ashutosh , Gupta Sachin Kumar , Najim Mohd , Sahu Nitesh , Aggarwal Geetika , Mazumdar Bireshwar Dass
Published: January 2021

Mobile Ad-hoc Networks (MANETs) is an infrastructure-less, self-motivated, arbitrary, self-configuring, rapidly changing, multi-hop network that is self-possessing wireless bandwidth-conscious links without centrally managed router support. In such a network, wireless media is easy to snoop. It is firm to the surety to access any node, easier to insertion of bad elements or attackers for malicious activities in the network. Therefore, security issues become one of the significant considerations for such kind of networks. The deployment of an effective intrusion detection system is important in order to provide protection against various attacks. In this paper, a Digitally Signed Secure Acknowledgement Method (DSSAM) with the use of the RSA digital signature has been proposed and simulated. Three different parameters are considered viz. secure acknowledgment, node authentication and packet authentication for study. This article observes the DSSAM performance and compares it with two existing standard methods, namely, Watchdog and 2-ACK under standard Dynamic Source Routing (DSR) routing environment. In the end, it is noticed that the rate of detection of malicious behaviour is better in the case of the proposed method. However, associated overheads are high. A trade-off between performance and overhead has been considered.
Analysis of pain markers and epidural fibrosis caused by repeated spinal surgery in Sprague–Dawley rats
Authors: Quan Meiling , Kim Jae-Hoon , Hwang Won-Ha , KIM Young-Yul
Published: January 2021

Background: Epidural fibrosis is one of the aetiologies of pain following a spinal revision surgery. It is reported that the specific members of the mitogen – activated protein kinases (MAPK) family might mediate neuropathic pain. However, roles of epidural fibrosis caused by repeated spinal surgeries and pain-related proteins in causing the post spinal surgery syndrome remain unknown. Using a rat spinal surgery epidural fibrosis and adhesion model, in this study, we evaluated and investigated the relationship between pain markers and epidural fibrosis. Methods: Sprague–Dawley rats that underwent the spinal surgery were divided into three groups: group A (single laminectomy), group B (two repeated surgeries) and group C (three repeated surgeries). Dural thickness was measured in each experimental group, and immunohistochemical analysis and western blotting of mitogen-activated protein kinases were performed (ERK, p38 and JNK) using the spine cord. Results: Dural thickness was 6.363 ± 1.911 µm in group A, 13.238 ± 2.123 µm in group B and 19.4 ± 2.115 µm in group C, respectively. In the western blotting, phosphorylated ERK expression gradually increased with the number of repeated surgeries, and expression in groups B (1.77-fold) and C (2.42-fold) increased as compared to expression in group A. Phosphorylated p38 showed an increasing trend with the number of repeated surgeries, and groups B (1.17-fold) and C (1.33-fold) expression increased compared with group A. However, phosphorylated JNK expression did not gradually increase with the number of repeated surgeries, and groups B (1.62-fold) and C (1.43-fold) expression increased compared with group A. Excluding phosphorylated JNK, immunohistochemical analysis revealed that phosphorylated ERK and p38 expression gradually increased with the number of repeated surgeries in the spine dorsal horn, as evidenced by western blotting. Conclusions: Repeated spinal surgeries may increase dural thickness and expression of phosphorylated ERK and p38 in the spinal dorsal horn, and it suggests that the neuropathic pain is likely induced by epidural fibrosis and that the pain increases with the number of repeated surgeries.
Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke
Authors: Manwani Bharti , Fall Pamela , Zhu Liang , O’Reilly Meaghan Roy , Conway Sarah , Staff Ilene , McCullough Louise D.
Published: January 2021

Background: Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes. Methods: Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 hours of symptom onset. 17-β estradiol, testosterone and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as difference of premorbid and discharge mRS) using multivariate regression. Results: We found no significant difference in estradiol levels 24 hours after stroke in men (p=0.86) or women (p=0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83±0.12 vs 2.86±0.65, p=0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27±0.22 vs 0.97±0.22, p=0.002), but not in men (p=0.84). Estradiol levels positively correlated with change in mRS in both women (r=0.38, p=0.02) and men (r=0.3, p=0.04).Conclusions: Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 hours) of stroke. However, no significant difference in estradiol levels is seen 24 hours post stroke in men or women. Testosterone levels decrease at 24 hours after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.
Left hemispheric deficit in the sustained neuromagnetic response to periodic click trains in children with ASD.
Authors: Stroganova Tatiana A , Komarov Kirill S , Sysoeva Olga V , Goiaeva Dzerasa E , Obukhova Tatiana S , Ovsiannikova Tatiana M , Prokofiev Andrey O , Orekhova Elena V
Published: January 2021

Background: Deficits in perception and production of vocal pitch are often observed in people with autism spectrum disorder (ASD), but the neural basis of these deficits is unknown. In magnetoencephalogram (MEG), spectrally complex periodic sounds trigger two continuous neural responses – the auditory steady state response (ASSR) and the sustained field (SF). It has been shown that the SF in neurotypical individuals is associated with low-level analysis of pitch in the ‘pitch processing center’ of the Heschl’s gyrus. Therefore, alternations in this auditory response may reflect atypical processing of vocal pitch. The SF, however, has never been studied in people with ASD. Methods: We used MEG and individual brain models to investigate the ASSR and SF evoked by monaural 40 Hz click trains in boys with ASD (N=35) and neurotypical (NT) boys (N=35) aged 7-12-years.Results: In agreement with the previous research in adults, the cortical sources of the SF in children were located in the left and right Heschl’s gyri, anterolateral to those of the ASSR. In both groups, the SF and ASSR dominated in the right hemisphere and were higher in the hemisphere contralateral to the stimulated ear. The ASSR increased with age in both NT and ASD children and did not differ between the groups. The SF amplitude did not significantly change between the ages of 7 and 12 years. It was moderately attenuated in both hemispheres and was markedly delayed and displaced in the left hemisphere in boys with ASD. The SF delay in participants with ASD was present irrespective of their intelligence level and severity of autism symptoms. Limitations: We did not test the language abilities of our participants. Therefore, the link between SF and processing of vocal pitch in children with ASD remains speculative. Conclusion: Children with ASD demonstrate atypical processing of spectrally complex periodic sound at the level of the core auditory cortex of the left-hemisphere. The observed neural deficit may contribute to speech perception difficulties experienced by children with ASD, including their poor perception and production of linguistic prosody.
Generation and Selection of Driver-Behavior-Based Transferable Motion Primitives
Authors: Guan Haijie , Wang Boyang , Wei Jiaming , Lu Yaomin , Chen Huiyan , Gong Jianwei
Published: January 2021

In order to achieve the integration of driver experience and heterogeneous vehicle platform characteristics in the motion planning algorithm, based on the driver-behavior-based transferable motion primitives, a general motion planning framework for offline generation and online selection of motion primitives (MPs) is proposed. The optimal control theory is applied to solve the boundary value problems in the process of generating MPs, where the driver behaviors and the vehicle motion characteristics are integrated into the optimization in the form of constraints. Moreover, this paper proposes a layered, unequal-weighted MPs selection framework and utilizes the combination of environmental constraints, nonholonomic vehicle constraints, trajectory smoothness, and collision risk as the single-step extension evaluation index. The library of MPs generated offline demonstrates that the proposed generation method realizes the effective expansion of the MP types and achieves the diverse generation of MPs with various velocity attributes and platform types. We also present how the MP selection algorithm utilizes the unique MP library to achieve the online extension of MP sequences. The results show that the proposed motion planning framework can not only improve the efficiency and rationality of the algorithm based on driving experience but also can transfer between heterogeneous vehicle platforms and highlight the unique motion characteristics of the platform.
Parent-perceived barriers to accessing services for their child’s mental health problems.
Authors: Hansen Anna Sofie , Telléus Gry Kjaersdam , Mohr-Jensen Christina , Lauritsen Marlene Briciet
Published: January 2021

Background Many children and adolescents with impairing mental health disorders are not in contact with specialized child and adolescent mental health services (CAMHS). In order to close the service gap, it is important to increase our knowledge of barriers to access. The aim of this study was to investigate parent perceived barriers to accessing services for their child’s mental health problems to identify potential areas for improvement of access to CAMHS. Method In this cross-sectional observational study 244 parents of children and adolescents referred to outpatient psychiatric assessment were interviewed using the Children’s services interview regarding barriers to accessing child mental health services across healthcare, educational services and social services. Parent reported barriers were analyzed in relation to the child’s age, referral reason, symptom duration and impairment of the child. Results The most commonly reported barriers were lack of information about were to seek help (60.3%), the perception that professionals did not listen (59.8%) and professionals refusing to initiate interventions or provide referral to services (53.7%). Lack of knowledge, stigmatization and unavailability of services were common themes across barriers to help-seeking. Long symptom duration and parent rated impairment was associated with increased risk of reporting several barriers to help-seeking.Conclusion Parents seeking help for their child’s mental health encounter numerous barriers that could explain part of the treatment gap and long duration of mental health problems in children prior to referral to CAMHS.
A telephone assessment and advice service within an ED Physiotherapy clinic: A single-site quality improvement cohort study
Authors: Kelly Marie , Higgins Anna , Murphy Adrian , McCreesh Karen
Published: January 2021

BackgroundIn response to issues with timely access and high non-attendance rates for Emergency Department (ED) physiotherapy, a telephone assessment and advice service was evaluated as part of a quality improvement project. This telehealth option requires minimal resources, with the added benefit of allowing the healthcare professional streamline care. A primary aim was to investigate whether this service model can reduce wait times and non-attendance rates, compared to usual care. A secondary aim was to evaluate service user acceptability.MethodsThis was a single-site quality improvement cohort study that compares data on wait time to first physiotherapy contact, non-attendance rates and participant satisfaction between patients that opted for a service based on initial telephone assessment and advice, versus routine face-to-face appointments. 116 patients were referred for ED physiotherapy over the 3-month pilot at the ED and out-patient physiotherapy department, X, Ireland. 91 patients (78%) opted for the telephone assessment and advice service, with 40% (n=36) contacting the service. 25 patients (22%) opted for the face-to-face service. Data on wait time and non-attendance rates was gathered using the hospital data reporting system. Satisfaction data was collected on discharge using a satisfaction survey adapted from the General Practice Assessment Questionnaire. Independent-samples t-test or Mann Whitney U Test was utilised depending on the distribution of the data. For categorical data, Chi-Square tests were performed. A level of significance of p ≤ 0.05 was set for this study.ResultsThose that contacted the telephone assessment and advice service had a significantly reduced wait time (median 6 days; 3 – 8 days) compared to those that opted for usual care (median 35 days; 19 – 39 days) (p ≤ 0.05). There was no significant between-group differences for non-attendance rates or satisfaction.ConclusionA telephone assessment and advice service may be useful in minimising delays for advice for those referred to ED Physiotherapy for musculoskeleltal problems. This telehealth option appears to be broadly acceptable and since it can be introduced rapidly, it may be helpful in triaging referrals and minimising face-to-face consultations, in line with COVID-19 recommendations. However, a large scale randomised controlled trial is warranted to confirm these findings.