bluuebunny/crossref_metadata_2025 huggingface dataset:
DeepSOCIAL: Social Distancing Monitoring and Infection Risk Assessment in COVID-19 Pandemic
Authors: Rezaei Mahdi , Azarmi Mohsen
Published: September 2020

Social distancing is a recommended solution by the World Health Organisation (WHO) to minimise the spread of COVID-19 in public places. The majority of governments and national health authorities have set the 2-meter physical distancing as a mandatory safety measure in shopping centres, schools and other covered areas. In this research, we develop a generic Deep Neural Network-Based model for automated people detection, tracking, and inter-people distances estimation in the crowd, using common CCTV security cameras. The proposed model includes a YOLOv4-based framework and inverse perspective mapping for accurate people detection and social distancing monitoring in challenging conditions, including people occlusion, partial visibility, and lighting variations. We also provide an online risk assessment scheme by statistical analysis of the Spatio-temporal data from the moving trajectories and the rate of social distancing violations. We identify high-risk zones with the highest possibility of virus spread and infection. This may help authorities to redesign the layout of a public place or to take precaution actions to mitigate high-risk zones. The efficiency of the proposed methodology is evaluated on the Oxford Town Centre dataset, with superior performance in terms of accuracy and speed compared to three state-of-the-art methods.
The predictive factors that are associated with the number of sutures used during meniscal repair
Authors: Song Xiaoxiao , Chen Dongyang , Xinsheng Qi , Jiang Qing , Xia Caiwei
Published: September 2020

PurposeTo investigate factors associated with the consumption of a large number of sutures during arthroscopic meniscus repair procedures.MethodsAll patients who received meniscal repair, with or without concomitant anterior cruciate ligament (ACL) reconstruction, in our hospital from January 2015 to December 2019 were included in the current study. Demographic data (sex, age, body mass index (BMI), and injury-to-surgery interval) and surgical data (the site of the tear, side of the meniscus, presence of an ACL rupture or not and the number of sutures) were retrospectively collected from our medical records. The number of sutures was divided into two groups (1–2 sutures versus > 2 sutures). The stitching process was implemented through an all-inside technique using a meniscal repair device (Fast-Fix; Smith & Nephew). According to the length and stability of the meniscal tear, one to seven sutures were used. Univariate analysis consisted of chi-square tests. Multivariate logistic regression was then performed to adjust for confounding factors.ResultsA total of 242 patients, including 168 males and 57 females, was finally included. In the univariate analysis, we found that those patients who underwent meniscus repair within one month after meniscus tear were more likely to need fewer sutures than those who underwent surgery more than one month after injury (70/110 versus 59/115, p = 0.062). In total, 75/109 (68.8%) lateral meniscal tears were repaired with fewer sutures than medial (34/72, 47.2%) and bilateral meniscus injuries (20/44, 45.4%; p = 0.003). In the multivariate analysis, we found that the duration of injury (OR, 2.06; 95% CI, 1.16–3.64, p = 0.013), presence of an ACL injury (OR, 3.76; 95% CI, 1.97–7.21, p < 0.001) and the side of the meniscus (OR, 0.31; 95% CI, 0.14–0.65, p = 0.002) were associated with the number of sutures used during meniscal repair procedures.ConclusionsPatients who underwent meniscal repair within one month after meniscus tear, especially lateral menisci tears, were more likely to need fewer sutures.Study DesignCase-control study; level of evidence, 3.
Association of vitamin D receptor gene polymorphisms with gestational diabetes mellitus-a case control study in Wuhan, China
Authors: liu jianqiong , Dai Qiong , Li Wei , Guo Yan , Dai Anna , Wang Yanqing , Deng Mengyao , Tang Zhao , She Lu , Chen Xiaohong , Yang Mei
Published: September 2020

Background
Gestational diabetes mellitus (GDM) is extremely harmful to both the women and the fetuses. The association between the vitamin D receptor (VDR) gene and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. In addition, we aimed to explore their combined effect on the risk of GDM.
Methods
Pregnant women who had prenatal examination at 24 to 28 weeks’ gestation in our hospital were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood sample were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted by the Sequenom MassARRAY platform. Statistical analyses such as t-test, chi-square test and logistic regression etc. were performed to the data with SPSS Software. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM.
Results
Differences in age, pre-pregnancy BMI, family history of diabetes and morning sickness between the case and control groups were statistically significant (P < 0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P > 0.05). There were no significant differences at allele and genotype distributions of the examined VDR gene SNPs (P > 0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes and morning sickness, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs.
Conclusion
The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.
A Highly Thermotolerant Laccase Produced by Cerrena Unicolor Strain CGMCC 5.1011 for Complete and Stable Malachite Green Decolorization
Authors: Yao Yanhua , Zhou Guimei , Lin Yonghui , Xu Xinqi , Yang Jie
Published: September 2020

Laccases are a class of multi-copper oxidases with important industrial values. A thermotolerant laccase produced by a basidiomycete fungal strain Cerrena unicolor CGMCC 5.1011 was studied. With glycerin and peptone as the carbon and nitrogen sources, respectively, a maximal laccase activity of 121.7 U/mL was attained after cultivation in the shaking flask for 15 days. Transcriptomics analysis revealed an expressed laccase gene family of 12 members in C. unicolor strain CGMCC 5.1011, and the gene and cDNA sequences were cloned. A glycosylated laccase was purified from the fermentation broth of Cerrena unicolor CGMCC 5.1011 and corresponded to Lac2 based on MALDI-TOF MS/MS identification. Lac2 was stable at pH 5.0 and above, and was resistant to organic solvents. Lac2 displayed remarkable thermostability, with half-life time of 1.67 h at 70 ºC. Consistently, Lac2 was able to completely decolorize malachite green (MG) at high temperatures, whereas Lac7 from Cerrena sp. HYB07 resulted in accumulation of colored MG transformation intermediates. Molecular dynamics simulation of Lac2 was conducted, and possible mechanisms underlying Lac2 thermostability were discussed. The robustness of C. unicolor CGMCC 5.1011 laccase would not only be useful for industrial applications, but also provide a template for future work to develop thermostable laccases.
Outcome of COVID-19 with Co-Existing Surgical Emergencies in Children: Our Initial Experiences and Recommendations
Authors: Hasan Samiul , Ali Md Ayub , Huq Umama
Published: September 2020

Background: COVID-19 has changed the practice of surgery vividly all over the world. This has already lead to a huge burden of rescheduled pediatric surgical cases worldwide. Though children are less likely to be infected and suffer less when infected, there is a growing fear among health care workers of being self-infected, which is limiting the surgical care of children globally. This study aims to share our experiences with the outcome of COVID-19 in children who had a co-existing surgical emergency, which might help the pediatric surgeons globally to mitigate the effect of COVID 19 on pediatric surgery.Methods: This is a retrospective observational study. We reviewed the epidemiological, clinical, and laboratory data of all patients admitted in our surgery department through the emergency department and later diagnosed to have COVID-19 by RT-PCR. During April 2020 – June 2020. A nasopharyngeal swab was taken from all patients irrespective of symptoms to detect SARS CoV 2 by RT-PCR to identify and isolate asymptomatic patients and patients with atypical symptoms. We divided the test positive patients into 4 age groups for the convenience of data analysis. Data were retrieved from hospital records and analyzed using SPSS (version 25) software. Ethical permission was taken from the hospital ethical review board.Results: Total patients were 32. Seven (21.9%) of them were neonates. Twenty-four (75%) patients were male. The predominant diagnosis was acute abdomen followed by infantile hypertrophic pyloric stenosis (IHPS), myelomeningocele, and intussusception. Only two patients had mild respiratory symptoms (dry cough). Fever was present in 13 (40.6%) patients. Fourteen (43.8%) patients required surgical treatment. The mean duration of hospital stay was 5.5 days. One neonate with ARM died in the post-operative ward due to cardiac arrest. No patient had hypoxemia or organ failure. Seven health care workers (5.51%) including doctors & nurses got infected with SARS Co V2 during this period.Conclusion: Our study has revealed a milder course of COVID-19 in children with minimal infectivity even when present in association with emergency surgical conditions. This might encourage a gradual restart to mitigate the impact of COVID-19 on children’s surgery.
Lateral Position: A Friendly Surgical Position for Intramedullary Nailing of Tibial Shaft Fractures Via Infrapatellar Approach
Authors: zhao jinzhu , Qu Liang , Li Peng , Tan Changlong , Tao Chunsheng
Published: September 2020

Purpose The purpose of this study was to investigate the utility of the lateral position in intramedullary nailing of tibial shaft fractures via the infrapatellar approach.Methods The present study was a retrospective analysis of 112 patients who sustained closed tibial shaft fractures and treated with intramedullary nailing via the infrapatellar approach. Patients were divided into two groups according to surgical position: lateral or supine. The demographic and clinical data were collected and analyzed. Results There were 54 patients in the lateral and 58 in the supine position groups. The duration of surgery and fluoroscopy was shorter in the lateral group than the supine group (p < 0.05). Blood loss during surgery was lower in the lateral compared with supine position group (p < 0.05). The malunion rate was lower in the lateral position group as compared with the supine position group (p < 0.05); moreover, fewer surgical assistants were needed than in the supine group (p < 0.05). There were no significant differences in fracture healing time, other complications between the two groups (p > 0.05). Conclusions The lateral position was a more convenient choice for intramedullary nailing of tibial shaft fractures via infrapatellar approach.
Osteopontin as a Novel Biomarker for the Prognosis and Clinical Pathology of Prostate Cancer: A Systematic Review and Meta-Analysis
Authors: Yu Anze , Xie Kai , Xing Changsheng , Qin Qilin , Liu Longfei , Zu Xiongbing
Published: September 2020

Background: Evaluation of the feasibility for osteopontin (OPN) to serve as a biomarker in the prognosis and clinical pathological features of prostate cancer patients.Methods: The original publications related to osteopontin and prostate cancer were comprehensively searched in the online databases, including PubMed, Embase, Cochrane Library, Web of Science, Medline, Wanfang database and China National Knowledge Infrastructure up to August 2019. Results were analyzed by software Revman 5.3 and Stata 12.0. Results: A total of 21 studies were included in the analysis and the result showed that the positive OPN expression group had a lower overall survival than the negative expression group (univariate: HR=2.32, 95%CI [1.74, 3.10], multivariate: HR=2.41, 95%CI [1.63, 3.57]) and a lower biochemical relapse-free survival than the negative group (univariate: HR=1.42, 95%CI [0.92, 2.17], multivariate: HR=1.61, 95%CI [1.39, 1.87]). In addition, there was a higher expression level of OPN in prostate cancer tissues than in normal prostate tissues (OR=46.55, 95%CI [12.85, 168.59], p<0.00001) and benign prostatic hyperplasia tissues (OR=11.07, 95%CI [3.43, 35.75], p<0.0001). Moreover, OPN positive expression was also related to high Gleason score (OR=2.64, 95%CI [1.49, 4.70], p=0.0009), high TNM stage (OR=3.15, 95%CI [1.60, 6.20, p=0.0009), high Whitmore-Jewett stage (OR=2.53, 95%CI [1.06, 6.03], p=0.04), high lymph node (OR=3.69, 95%CI [1.88, 7.23], p=0.0001), and distant metastasis (OR=8.10, 95%CI [2.94, 22.35], p=0.01). There was no difference observed in the differentiation of prostate cancer (OR=1.79, 95%CI [0.39, 8.33], p=0.46).Conclusion: Osteopontin could be recognized as a promising novel diagnostic and prognostic biomarker for prostate cancer patients.
Characterization of Bone Metabolism in Hungarian Psoriatic Arthritis Patients: A Case–Control Study.
Authors: Petho Zsofia , Kalina Edit , Pap Zoltan , Hodosi Katalin , Falcsik Rebeka , Balogh Adam , Szekanecz Zoltan , Bhattoa Harjit Pal
Published: September 2020

Background: Skeletal manifestations are predominant in psoriatic arthritis (PsA). The aim of this cross-sectional, case-controlled study is the complex assessment of areal and volumetric bone mineral density (BMD), fracture risk, vitamin D status and bone turnover markers, and its association with disease-related variables.Methods: Lumbar spine (L1-L4) and femur neck (FN) areal, and distal radius (DR) volumetric BMD, 10-year probability of major and hip osteoporotic fracture as assessed by the fracture risk assessment (FRAX) tool, markers of bone metabolism and disease activity were assessed.Results: Upon comparison of the disease and age- and sex-matched control groups, there was a statistically significant difference in FN areal (0.955±0.145 g/cm2 vs. 1.034±0.148 g/cm2; p=0.001) and DR total volumetric (285.7±61.8 mg/cm3 vs. 369.6±23.6 mg/cm3; p<0.001) BMD, 10 year probability for major osteoporotic (5.0% (0.7%-32%) vs. 3.5% (0%-17.5%); p=0.003) and hip (1.1% (0%-16%) vs. 0.5% (0%-6.1%); p=0.002) fracture and 25-hydroxyvitamin D status (53 (10-120) nmol/L vs. 67 (10-137; p<0.001) nmol/L). As compared to areal assessment, volumetric BMD measurements identified a significantly higher number of patients with low bone mass (T-Score £ -1.00) (34% vs. 88%, p<0.001). Upon multiple linear regression analysis, disease activity score, as determined by DAS28 assessment, was an independent predictor of 10-year probability for major osteoporotic fracture (B (95%CI) = 1.351 (0.379–2.323); p = 0.007).Conclusion: In the studied PsA cohort, disease activity was an independent predictor of 10-year probability for a major osteoporotic fracture, and complemented assessment of volumetric and areal BMD assured better efficacy at identifying those with low bone mass.
CSF Biomarker Profiles in CNS Infection Associated with HSV and VZV Mimic Pattern in Alzheimer’s Disease.
Authors: Shinomoto Makiko , Kasai Takashi , Tatebe Harutsugu , Kitani-Morii Fukiko , Ohmichi Takuma , Fujino Yuzo , Allsop David , Mizuno Toshiki , Tokuda Takahiko
Published: September 2020

Alzheimer’s disease (AD) is the most common cause of dementia. Although AD was initially considered to be a cell autonomous neurodegenerative disorder, marked neuroinflammation is observed in the brains of patients with AD, alongside Aβ and tau pathology. Based on genetic and molecular biological findings, central nervous system (CNS) inflammatory processes have been postulated to be involved in the etiopathogenesis of AD, in which activated microglia play a key role. This has also been supported by the epidemiological observation that CNS infections were associated with the development of AD, and in particular the relationship between herpetic virus and AD has been well-investigated. For example, the presence of anti-herpes simplex virus (HSV) antibody was associated with an elevated risk of developing AD [1]. Moreover, anti-herpetic medication was associated with a reduced risk of dementia in a population-based study [2]. Similar results were also observed in the case of varicella zoster virus (VZV) infections [3]. Taking into consideration the reports above, we hypothesized that the biomarker signature representing AD might be observed in patients with herpetic viral CNS infections as a prognostic biomarker of AD development. In the current study, we aimed to determine whether or not the biomarkers related to AD and neurodegeneration were changed in patients with CNS infection by HSV and VZV compared with controls. This study focused on CSF levels of Aβ1-42, Aβ1-40, total-tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) as molecules representing the AD signature; neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (p-NfH) as indicators of axonal injury; soluble triggering receptor expressed on myeloid cells 2 (sTREM2) as a potential biomarker for microglia activity; and glial fibrillary acidic protein (GFAP) as a biomarker for astrocytic damage. We also measured serum levels of NfL as a blood based biomarker for axonal injury. (For detailed methods, see Supplementary methods) The demographic characteristics, diagnosis, CSF profiles, results of viral detection, magnetic resonance imaging (MRI) findings, lowest score of the Glasgow coma scale (GCS) during the hospitalization period, and modified Rankin Scale (mRS) at discharge are summarized in Supplementary Table 1 and 2. There was no significant difference in age or sex among the HSV, VZV, and control groups.
Overexpression of miR-140-3p Could Reverse Radioresistance of Nasopharyngeal Carcinoma by Targeting XIAP
Authors: Wu Qi , Zhu Zhenhua
Published: September 2020

BackgroundMalignant behavior and radioresistance, which severely limits the efficacy of radiotherapy (RT) in nasopharyngeal carcinoma (NPC), lead to tumor progression and poor prognosis. The aim of this study was to investigate the underlying molecular mechanism of miR-140-3p on NPC development and radioresistance.MethodsThe expression of genes and proteins was detected by Western blotting, and quantitative reverse transcription PCR (qRT-PCR). Proliferation, apoptosis, and radioresistance of NPC were detected. Luciferase reporter assays were used to detect the interactions of miR-140-3p with its downstream targets.ResultsThe expression of miR-140-3p was associated with the occurrence and radiation resistance of NPC. XIAP as the direct target of miR-140-3p was verified. We found alleviated radioresistance of NPC cells upon miR-140-3p overexpression or XIAP knockdown.ConclusionmiR-140-3p is downregulated in radioresistant NPC. miR-140-3p could hamber radioresistance of NPC via directly target XIAP, suggesting miR-140-3p/XIAP axis is vital in the regulation of irradiation sensitivity.
Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism
Authors: Schuermann Matthias , Oppel Felix , Shao Senyao , Volland-Thurn Verena , Kaltschmidt Christian , Kaltschmid Barbara , Scholtz Lars-Uwe , Sudhoff Holger
Published: September 2020

BackgroundCholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies.MethodsWe isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry.ResultsUnder standard culture conditions, we detected a tissue-independent higher expression of IL-1β and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1β, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation.ConclusionWe propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence.
Perception of Malaria Chemoprevention Interventions in Infants and Children in Eight Sub-Saharan African Countries: an End-User Perspective Study
Authors: Audibert Celine , Tchouatieu Andre-Marie
Published: September 2020

Background: Preventive chemotherapy interventions have been identified as key tools for malaria prevention and control. Seasonal malaria chemoprevention (SMC) and intermittent preventive treatment of infants (IPTi) represent the two major chemoprevention measures recommended by the WHO since 2012. A large number of publications of clinical trials have reported on the efficacy and safety profile of these interventions. However, little literature exists on end-user experience. The objective of this study was to provide insights on the perceptions and attitudes towards SMC and IPTi to identify drivers of and barriers to acceptance.Methods: a total of 179 in-depth qualitative interviews were conducted with community health workers (CHWs), health center managers, parents of children receiving chemoprevention, and national decision-makers across eight countries in sub-Saharan Africa. Questionnaires were adapted to the malaria chemoprevention intervention in place in each country. The transcribed verbatim responses were coded and analyzed using a thematic approach.Results: Study data indicate that SMC is largely well perceived and accepted by end-users, mainly due to its generally favorable efficacy and safety profile. Despite this largely positive perception, coverage remained below 100%, with health-center managers and CHWs who participated in our survey estimating, respectively, that 88% and 92% of eligible children received the first dose each month. The main causes mentioned for missing doses were children’s absenteeism, children being sick, parents’ reluctance, and lack of staff. Regarding IPTi, results from participants based in Sierra Leone showed that the intervention was generally well accepted and integrated into the Expanded Programme on Immunization (EPI) program. High infant mortality rate due to malaria and supportive efficacy data led Sierra Leone to implement IPTi, although these arguments were not sufficient for respondents from other countries. At the field level, parents and CHWs from Sierra Leone recognized the efficacy of the intervention in protecting their infants from malaria. The main challenges encountered were access to water, crushing the tablets, and high staff turnover.Conclusions: SMC and IPTi are perceived as valuable interventions. Our study identified the key elements that need to be considered to facilitate the expansion of these two interventions to different geographies or age groups.
Unveiling the origin of steep decay in γ-ray bursts
Authors: Ronchini Samuele , Oganesyan Gor , Branchesi Marica , Ascenzi Stefano , Bernardini Maria Grazia , Brighenti Francesco , Dall'Osso Simone , D'Avanzo Paolo , Ghirlanda Giancarlo , Ghisellini Gabriele , Ravasio Maria Edvige , Salafia Om Sharan
Published: September 2020

γ-ray bursts (GRBs) are short-lived transients releasing a large amount of energy (10^51-10^53 erg) in the keV-MeV energy range. GRBs are thought to originate from internal dissipation of the energy carried by ultra-relativistic jets launched by the remnant of a massive star’s death or a compact binary coalescence. While thousands of GRBs have been observed over the last thirty years, we still have an incomplete understanding of where and how the radiation is generated in the jet. A novel investigation of the GRB emission mechanism, via time-resolved spectral analysis of the X-ray tails of bright GRB pulses, enables us to discover a unique relation between the spectral index and the flux. This relation is incompatible with the long standing scenario invoked to interpret X-ray tails, that is, the delayed arrival of pho-tons from high-latitude parts of the jet. We show that our results provide for the first time evidence of adiabatic cooling and efficient energy exchange between the emitting particles in the relativistic outflows of GRBs.
Optimization of the Separation of Unburned Coal from a Selected Fly Ash
Authors: Wierzchowski Krzysztof , Klupa Agnieszka , Białecka Barbara , Moszko Joanna Całus
Published: September 2020

Unburned coal grains often hinder the economic utilization of fly ash and also represent energy loss of the fuel. This paper addresses the possibility of separating unburned coal from a selected fly ash with typical mineralogical and chemical characteristics. To assess the possibility of separating the unburned coal, the analysis of the grain density and composition of ash was used. The unburned coal was separated using one wet gravity and three dry methods. The highest amount of unburned coal, 62% in the concentrate, was obtained using the fluidized bed method with separation. The largest weight yield of concentrate equal to 17.8% was obtained using the electrostatic method.
Sea Urchin-like Microstructures Pressure Sensors with Ultra-sensitivity and Super Working Range
Authors: Wang Xiu , Tao Lu-Qi , Yuan Min , Wang Ze-Ping , Yu Jiabing , Xie Ding , Luo Feng , Chen Xian-Ping , Wong Ching-Ping
Published: September 2020

Sensitivity and pressure range are two significant parameters of pressure sensors. The existing pressure sensors are difficult to achieve both high sensitivity and a wide pressure range. In this regard, we proposed a new pressure sensor with a ternary nanocomposite Fe2O3/C@SnO2. Notably, the sea urchin-like Fe2O3 structure promoted signal transduction and protected Fe2O3 needles from mechanical breaking; while, acetylene carbon black improved the conductivity of Fe2O3. Moreover, one part of SnO2 nanoparticles adhered to the surface of Fe2O3 needles and formed Fe2O3/SnO2 heterostructures whereas its other part of nanoparticles dispersed into the carbon layer and formed SnO2@C structures. Collectively, the synergy of the three structures (Fe2O3/C, Fe2O3/SnO2 and SnO2@C) improved the limited pressure response range of a single structure. The experimental results demonstrated that the Fe2O3/C@SnO2 pressure sensor exhibits high sensitivity (680 kPa-1), fast response (10 ms), broad range (up to 150 kPa), and good reproducibility (over 3500 cycles under a pressure of 110 kPa). This implies that the new pressure sensor has wide application prospects especially in wearable electronic devices and health monitoring.
NRG1 Fusions in Breast Cancer
Authors: Howarth Karen D , Mirza Tashfina , Cooke Susanna L , Chin Suet-Feung , Pole Jessica C , Turro Ernest , Eldridge Matthew D , Garcia Raquel Manzano , Rueda Oscar M , Boursnell Chris , Abraham Jean E , Caldas Carlos , Edwards Paul A W
Published: September 2020

Background NRG1 gene fusions may be clinically actionable, since cancers carrying the fusion transcripts can be sensitive to tyrosine kinase inhibitors. The NRG1 gene encodes ligands for the HER2(ERBB2)-ERBB3 heterodimeric receptor tyrosine kinase, and the gene fusions are thought to lead to autocrine stimulation of the receptor. The NRG1 fusion expressed in the breast cancer cell line MDA-MB-175 serves as a model example of such fusions, showing the proposed autocrine loop and exceptional drug sensitivity. However, its structure has not been properly characterised, its oncogenic activity has not been fully explained, and there is limited data on such fusions in breast cancer. Methods We analysed genomic rearrangements and transcripts of NRG1 in MDA-MB-175 and a panel of 572 breast cancers.Results We found that the MDA-MB-175 fusion—originally reported as a DOC4(TENM4)-NRG1 fusion, lacking the cytoplasmic tail of NRG1—is in reality a double fusion, PPP6R3-TENM4-NRG1, producing multiple transcripts, some of which include the cytoplasmic tail. We hypothesize that many NRG1 fusions may be oncogenic not for lacking the cytoplasmic domain but because they do not encode NRG1’s nuclear-localised form. The fusion in MDA-MB-175 is the result of a very complex genomic rearrangement, which we partially characterized, that creates additional expressed gene fusions, RSF1-TENM4, TPCN2-RSF1, and MRPL48-GAB2. We searched for NRG1 rearrangements in 572 breast cancers subjected to genome sequencing and transcriptome sequencing and found four cases (0.7%) with fusions, WRN-NRG1, FAM91A1-NRG1, ARHGEF39-NRG1 and ZNF704-NRG1, all splicing into NRG1 at the same exon as in MDA-MB-175. However, the WRN-NRG1 and ARHGEF39-NRG1 fusions were out of frame. We identified rearrangements of NRG1 in many more (8% of) cases that seemed more likely to inactivate than to create activating fusions, or whose outcome could not be predicted because they were complex, or both. This is not surprising because NRG1 can be pro-apoptotic and is inactivated in some breast cancers.Conclusions Our results highlight the complexity of rearrangements of NRG1 in breast cancers, and confirm that some do not activate but inactivate. Careful interpretation of NRG1 rearrangements will therefore be necessary for appropriate patient management.
Cranial Manipulation Modulates Cholinergic Pathway Gene Expression in an Animal Model of Age-related Cognitive Decline
Authors: Anandakrishnan Ramu , Tobey Hope , Nguyen Steven , Sandoval Osscar Gonzalez , Klein Bradley G. , Costa Blaise M.
Published: September 2020

Age dependent dementia is a devastating disorder afflicting the growing older population around the world. Although pharmacological agents improve symptoms of dementia, age related co-morbidities combined with adverse effects often outweigh their clinical benefits. Therefore, non-pharmacological therapies are being investigated as an alternative. Randomized controlled trials and observational studies have shown promising results for cranial manipulation as a treatment for dementia and other nervous system disorders. In this study we examine the effect of osteopathic cranial manipulative medicine (OCMM) on gene expression, in an animal model for age-related cognitive decline (aged rats). We found that OCMM significantly affected the expression of 36 genes in the neuronal pathway (False Discovery Rate (FDR) < 0.004). The top five neuronal genes with the largest fold-change (Slc5a7, Chat, Slc18a3, Adcy5 and Cacna2d2, >2-fold change, FDR<0.004) are part of the cholinergic neurotransmission mechanism, which is known to affect cognitive function. Slc5a7, the highest overexpressed neuronal gene (3-fold change) encodes a sodium and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. This is the pathway enhanced by the clinically used Alzheimer’s disease drug Donepezil, which selectively inhibits acetylcholinesterase, an enzyme that catalyzes endogenous acetylcholine degradation. In addition, 40% of significant differentially expressed (SDE) genes (FDR<0.004), have been previously implicated in neurological disorders. Overall, SDE genes and their role in central nervous system signaling pathways suggest a connection to previously reported OCMM induced behavioral and biochemical changes in rat models of age-dependent dementia. Further investigation in this direction will provide a better understanding of the molecular mechanisms of OCMM and its potential in clinical applications. With clinical validation, OCMM could represent a much needed low-risk adjunct treatment for age-related dementia including Alzheimer’s disease.
Gene Expression Patterns Associated With Tumor-infiltrating CD4+  and CD8+ T Cells in Invasive Breast Carcinomas 
Authors: Wang Zhanwei , Yang Xi , Xu Jiamin , Pan Yuefen , Shen Junjun , Liu Jin , Han Shuwen
Published: September 2020

Objective: This study investigated the gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas.Methods: The gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4+ and CD8+ T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted.Results: In total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4+ T cell-related genes and 78 CD8+ T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4+ T cell-related genes, the chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8+ T cell-related genes.Conclusions: The chr22-38_28785274-29006793.1-–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4+ and CD8+ T cell infiltration, respectively, in BRCA.
Effect of Dietary Standardized Ileal Digestible Arginine to Lysine Ratio on the Reproductive Performance, Plasma Free Amino Acid Profile, and Colostrum Composition in Gestating Sows
Authors: Wen XiaoLu , Gao Kaiguo , Wang Li , Yang Xuefen , Guo Chunyan , Zhu Cui , Xiao Hao , Ban Wenjie , Jiang Zongyong
Published: September 2020

Background: The objective of the present study was to determine the optimal standardized ileal digestible arginine to lysine (SID Arg: Lys) ratio on the reproductive performance, plasma free amino acids and biochemical parameters of sows during gestation , as well as colostrum compositions and performance of their offspring litter . Methods: A total of 174 multiparous sows (3+ parity,Landrace × Large white ) were randomly allocated to five treatment groups with different dietary SID Arg: Lys ratios (0.91, 1.02, 1.14, 1.25 and 1.38) by modifying the supplementation of Arg or alanine (Ala) for isonitrogenous equilibrium. All diets were formulated with the same composition levels including DE at 3.14 Mcal/kg and SID Lys at 0.64%. The reproductive performance of sows during gestation and lactation and the performance of offspring litters during lactation were evaluated. Blood samples were obtained on days 90 and 110 of gestation for analyses of plasma biochemical indexes and free amino acids, and colostrum samples were collected for determination of the composition. Results: The results showed that increasing the dietary SID Arg: Lys ratio increased litter size alive linearly ( P =0.001) and quadratically ( P =0.001), and decreased the number of stillborns linearly ( P <0.001) and quadratically ( P <0.001), and decreased the mummified size quadratically ( P =0.033). The birth weight variation of born alive was linearly ( P= 0.002) and quadratically ( P =0.008) reduced by increasing the dietary SID Arg: Lys ratio. The broken-line regression analysis indicated that the optimal SID Arg: Lys ratio requirement for gestating sows to maximize the litter size alive was 1.25. Birth intervals were decreased linearly ( P =0.025) and quadratically ( P =0.013) with increasing the dietary SID Arg: Lys ratio. There were linear and quadratic increases ( P <0.05) in the concentrations of colostrum compositions including non-fat solid, total solid, protein, and energy by increasing dietary SID Arg: Lys ratio. The plasma nitric oxide (NO) and total protein in serum were increased linearly as dietary SID Arg: Lys ratio increased. Similarly, sows feed the diet with higher SID Arg: Lys ratio significantly increased the concentrations of plasma arginine in sows at day 90 of gestation and ornithine ( P <0.05). Conclusion: Collectively, the current study indicated that increasing the dietary SID Arg: Lys ratio during gestation resulted in the increase of litter size alive, reduction of birth intervals, and improvement of colostrum composition. The requirement of optimal SID Arg:Lys ratio for gestating sows to maximize the litter size alive was 1.25 using a linear broken-line model.
Association of Parenting With Suicidal Ideation and Attempts in Children and Youth: Protocol for A Systematic Review and Meta-Analysis of Observational Studies.
Authors: Perquier Florence , Hetrick Sarah , Rodak Terri , Jing Xin , Wang Wei , Cost Katherine , Szatmari Peter , Aitken Madison
Published: September 2020

Background: Suicide is a leading cause of death in children and youth, with suicidal thoughts and suicide attempt (referred to as non-fatal suicidal behaviors; NFSB) being among its strongest predictors. Parenting, including positive parenting (e.g. warmth, responsiveness), negative parenting (e.g. control, hostility) and parent-child relationship (e.g. trust, communication), may be associated with differences in NFSB in children and youth. But the overall strength of these associations remains unclear. To date, no comprehensive systematic review has considered together the wide range of parenting factors studied in relation to NFSB, and no meta-analysis of existing findings has been conducted. The present study will critically appraise and synthesize the existing evidence from observational studies that examine the relationships between parenting factors and i) suicidal ideation and ii) suicide attempt in people aged less than 25.Methods: Our systematic review and meta-analysis will include cross-sectional and longitudinal studies, published as articles and dissertations, and identified in APA PsycInfo, Medline, CINAHL, Embase, Scopus and the Cochrane Library databases. Two reviewers will select articles after title and abstract screening and full-text assessment of relevant citations. They will extract relevant information using double data entry and will appraise studies’ quality. Any disagreements will be discussed with a third reviewer. In addition to a narrative summary of results, when at least three studies are available, meta-analyses will be conducted using three-level random effect models that will derive pooled estimates from dependent effect sizes (obtained from the same sample or study). In case of significant heterogeneity, moderation analyses will be performed considering study design, age, gender, ethnicity of participants, type of informant(s), countries and their income economy indicators. If possible, separate analyses will be conducted according to study setting. Certainty of evidence will be assessed using the GRADE approach.Discussion: Our findings will identify parenting factors associated with NFSB and better estimate the strength of associations in children and youth. The results will inform further intervention and prevention strategies designed for young people experiencing NFSB and their families by highlighting parenting factors that are important to target and in identifying high-risk population subgroups. Systematic review registration: PROSPERO CRD42020165345
Unified Gas-Kinetic Wave-Particle Method IV: Multi-Species Gas Mixture and Plasma Transport
Authors: Liu Chang , Xu Kun
Published: September 2020

In this paper, we extend the unified gas-kinetic wave-particle (UGKWP) method to the multi-species gas mixture and multiscale plasma transport. The construction of the scheme is based on the direct modeling on the mesh size and time step scales, and the local cell's Knudsen number determines the flow physics. The proposed scheme has the multiscale and asymptotic complexity diminishing properties. The multiscale property means that according to cell's Knudsen number the scheme can capture the non-equilibrium flow physics in the rarefied flow regime, and preserve the asymptotic Euler, Navier-Stokes, and magnetohydrodynamics limit in the continuum regime. The asymptotic complexity diminishing property means that the total degree of freedom of the scheme automatically decreases as cell's Knudsen number decreases. In the continuum regime, the scheme automatically degenerates from a kinetic solver to a hydrodynamic solver. In UGKWP, the evolution of microscopic velocity distribution is coupled with the evolution of macroscopic variables, and the particle evolution as well as the macroscopic fluxes are modeled from the time accumulating solution up to a time step scale from the kinetic model equation. For plasma transport, current scheme provides a smooth transition from particle in cell (PIC) method in the rarefied regime to the magnetohydrodynamic (MHD) solver in the continuum regime. In the continuum limit, the cell size and time step of the UGKWP method is not restricted to be less than the mean free path and mean collision time. In the highly magnetized regime, the cell size and time step are not restricted by the Debye length and plasma cyclotron period. The multiscale and asymptotic complexity diminishing properties of the scheme are verified by numerical tests in multiple flow regimes.
What is the Impact of Infrapopliteal Endovascular Intervention on Free Flap Survival in Diabetic Foot Reconstruction?
Authors: Thai Duy Quang , Lee Dong Hwan , Lee Woo Beom , Hahn Hyung Min , Lee Il Jae
Published: September 2020

BackgroundThe combination of endovascular intervention and microvascular free flap transfer has been effectively used for the chronic ischemic wounds of lower limb. This study aimed to indicate the influence of angioplasty on the free flap survival in diabetic foot ulcer reconstruction.MethodsA retrospective research was conducted of 46 diabetic patients with chronic ulcer of the foot. All the patients underwent the free flap reconstruction because of their non-healing wound with tendon or bone exposure. Patient’s demography, clinical data related to vascular status, vascular intervention, free flap transfer procedure were collected. Flap survival rate was compared between the group of severe arterial stenosis and non-severe group and between the different revascularization result groups as well. ResultsThe average was 56.2 ± 10.8 years with 14 men (30.4%) and 32 women (69.6%). All of 23 patients (50%) who had severe infrapopliteal arterial stenosis underwent endovascular intervention. The final result of the pedal arch was type 1 in 13/23 patients (56.5%), type 2A and 2B in 7/23 and 2/23 patients respectively and type 3 in only one patient. Total flap necrosis was in 5 cases (10.9%), marginal necrosis in 4 cases (8.7%) and wound dehiscence in 4 cases (8.7%). There was no significant difference of flap loss between the severe arterial stenosis patients and non-severe arterial stenosis patients. In severe arterial stenosis group, after endovascular intervention, patients with type 1 of pedal arch had a significantly lower rate of total flap necrosis compared to the others. There was also no association between using of revascularized recipient artery and flap survival.ConclusionsOur study revealed the crucial of quality of pedal arch on free flap survival. The PTA should aim to re-establish the complete pedal arch to increase the rate of wound healing as well as the flap success.
The Effect of Improved Dietary Control on Cognitive and Psychiatric Functioning in Adults With Phenylketonuria: The ReDAPT Study
Authors: Burgess Nicholas M. , Kelso Wendy , Malpas Charles B. , Winton-Brown Toby , Fazio Timothy , Panetta Julie , De Jong Gerard , Neath Joanna , Atherton Sonny , Velakoulis Dennis , Walterfang Mark
Published: September 2020

Background Phenylketonuria (PKU) is an autosomal recessive inherited disorder characterised by a deficiency in phenylalanine hydroxylase (PAH). Untreated, PKU is associated with a wide range of cognitive and psychiatric sequelae. Contemporary management guidelines recommend lifetime dietary control of phenylalanine (Phe) levels, however many individuals may – due to erroneous treatment recommendations or patient factors – discontinue dietary control and subsequently suffer symptoms of anxiety, depression and disturbances to cognition. We undertook a prospective cohort study of patients with early-treated phenylketonuria who had ceased dietary control to test the hypothesis that resumption of dietary control of PKU is associated with improvements in measures of psychiatric morbidity and cognitive functioning. Methods We re-initiated dietary control for early-treated patients with PKU and monitored cognitive and psychiatric outcomes over a twelve-month period. Assessments included objective cognitive function (measured by cognitive proficiency index (CPI)), anxiety and depression scales. General linear mixed model (GLMM) analyses were performed to assess change in psychometric variables from baseline over twelve months after resumption of dietary control. Results A total of nine patients were recruited. Mean age was 34 years, five were female. Mean time off dietary control was 20.4 years, and mean baseline phenylalanine (Phe) levels were 1108 µmol/L. GLMM analysis demonstrated a positive relationship between CPI and time on diet (b = 0.56 [95% CI = 0.17, 0.95]). Age, time off diet, Phe levels and depression scores were not associated with cognitive function. There was a negative relationship between time on diet and anxiety (b = -0.88 95% CI = [-1.26, -0.50]) and depression ratings (b = -0.61, 95% CI = [-0.95, -0.26]). Conclusions This study demonstrated improvements in cognitive function, anxiety, and depression ratings associated with resumption of dietary control of PKU. Raw Phe levels were not strongly associated with psychiatric or cognitive scores in this cohort. These findings support the importance of lifelong treatment for PKU, and demonstrate the reversibility of cognitive and psychiatric sequelae of the disease.