bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling
Authors: Khoshnejat Maryam , Kavousi Kaveh , Banaei-Moghaddam Ali Mohammad , Moosavi-Movahedi Ali Akbar
Published: July 2020

Background Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempted to provide a better understanding of abnormalities in this tissue. Methods We have explored the muscle gene expression pattern in healthy and newly diagnosed T2DM individuals using supervised and unsupervised classification along with examining the potential of sub-typing based on the gene expression pattern in patients.Results A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminate between normoglycemic and diabetic groups. A gene set comprises 26 genes identified, which was able to discriminate healthy from diabetic individuals with 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct clusters with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion This study implies that it seems the disease has triggered through different cellular/molecular mechanisms and it has the potential to be sub-typing. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.
Prevalence and associated factors of chlamydial infection among patients seeking clinic-based STI services in Shenzhen, China
Authors: Wang Hong-Lin , Cai Yu-Mao , Chen Xiang-Sheng , Yu Wei-Ye , Hong Fu-Chang , Feng Tie-Jian , Liu Jin-Hong , Zhang Chun-Lai , Wen Li-Zhang , Wang Feng , Ye Jian-Bin , Weng Rong-Xing , Tang Fen
Published: July 2020

The authors have withdrawn this preprint due to erroneous posting.
Recovery and Maintenance of NESTIN Expression in Umbilical Cord-MSC Using a Novel Culture Medium
Authors: Liu Yuncheng , Xiao Feidi , Hu Xiang , Tang Zan , Fu Zeqin , Liang Xiao , Zeng Guifang , Zeng Weijie , Liao Yan , Ren Yuan , Liu Zhiyu , Peng Hao , Mei Qiuhong , Liu Muyun
Published: July 2020

Mesenchymal stem cells (MSC) are a popular candidate in cellular therapy for many diseases. MSCs are well known by their feature of self-renewal and their differentiation potential. NESTIN is a cytoskeletal protein expressed in MSC that functions directly in cell proliferation and differentiation. Here, we demonstrated that adding UltraGRO, a medium supplement, could maintain and partially recover the expression of NESTIN in human umbilical cord derived MSCs (UC-MSCs). Furthermore, the UC-MSCs cultured with UltraGRO showed a better immunomodulation ability in a colitis mouse model compared with those cultured in other types of media. This indicates that the use of novel culture medium benefits the maintenance of NESTIN expression and NESTIN may be one of the vital factors that regulates the performance of MSCs.
Patients’ perceptions of frequent hospital admissions: A qualitative interview study with older people above 65 years of age
Authors: Huang Miaolin , Borght Carolien Van der , Leithaus Merel , Flamaing Johan , Goderis Geert
Published: July 2020

Background: Although ‘frequent flyer’ hospital admissions represent barely 3 to 8% of the total patient population in a hospital, they are responsible for a disproportionately high percentage (12 to 28%) of all admissions. Moreover, hospital admissions are an important contributor to health care costs and overpopulation in various hospitals. The aim of this research is to obtain a deeper insight into the phenomenon of frequent flyer hospital admissions. Our objectives were to understand the patients’ perspectives on the cause of their frequent hospital admissions and to identify the perceived consequences of the frequent flyer status.Methods: This qualitative study took place at the University Hospital of Leuven. The COREQ guidelines were followed to provide rigor to the study. Patients were included when they had at least four overnight admissions in the past 12 months, an age above 65 years and hospital admission at the time of the study. Data were collected via semi-structured interviews and encoded in NVivo.Results: Thirteen interviews were collected. A total of 17 perceived causes for frequent hospital admission were identified, which could be divided into the following six themes: patient, drugs, primary care, secondary care, home and family. Most of the causes were preventable or modifiable. The perceived consequences of being a frequent flyer were divided into the following six themes: body, daily life functioning, social participation, mental status and spiritual dimension. Negative experiences were linked to frequent flying and could be situated mainly in the categories of social participation, mental status and spiritual dimensions.Conclusions: Frequent hospital admissions may be conceived as an indicator, i.e., a ‘red flag’, of patients’ situations characterized by physical, mental, spiritual and social deprivation in their home situation.
Remote ischaemic preconditioning influences the levels of acylcarnitines in vascular surgery: a randomised clinical trial
Authors: Kasepalu Teele , Kuusik Karl , Lepner Urmas , Starkopf Joel , Zilmer Mihkel , Eha Jaan , Vähi Mare , Kals Jaak
Published: July 2020

Background Vascular surgery affects tissues` blood supply and microcirculation and might lead to mitochondrial dysfunction, which may result in the accumulation of acylcarnitines (ACs). It has been suggested that remote ischaemic preconditioning (RIPC) has its organ protective effect via promoting mitochondrial function. The aim of this study was to evaluate the effect of RIPC on the profile of ACs in the vascular surgery patients. Methods. This is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 minutes of ischaemia, followed by 5 minutes of reperfusion, was applied. A blood pressure cuff was used for RIPC or a sham procedure. Blood was collected preoperatively and approximately 24 hours postoperatively. The profile of ACs was analysed using the AbsoluteIDQp180 kit (Biocrates Life Sciences AG, Innsbruck, Austria). Results Ninety-eight patients were recruited and randomised into the study groups and 45 patients from the RIPC group and 47 patients from the sham group were included in final analysis. There was a statistically significant difference between the groups regarding the changes in C3-OH (p=0.023) - there was a decrease (-0.007 µmol/L, ± 0.020 µmol/L, p=0.0233) in the RIPC group and increase (0.002 µmol/L, ±0.015 µmol/L, p=0.481) in the sham group. Additionally, a decrease from baseline to 24 hours after surgery (p<0.05) was detected both in the sham and the RIPC group in the levels of following ACs: C2, C8, C10, C10:1, C12, C12:1, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2. In the sham group, there was an increase (p<0.05) in the levels of C0 (carnitine) and a decrease in the level of C18:1-OH. In the RIPC group, a decrease (p<0.05) was noted in the levels of C3-OH, C3-DC (C4-OH), C6:1, C9, C10:2. Conclusions It can be concluded that RIPC may have an effect on the levels of ACs and might therefore have protective effects on mitochondria in the vascular surgery patients. Further studies conducted on metabolically more homogenous populations are needed to make more definite conclusions about the effect of RIPC on the levels of ACs. Trial registration: ClinicalTrials.gov database, NCT02689414. Registered 24 February 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02689414.
miRNA-23b as a biomarker of culture-positive neonatal sepsis
Authors: Fatmi Ahlam , Rebiahi Sid Ahmed , Chabni Nafissa , Zerrouki Hanane , Azzaoui Hafsa , Elhabiri Yamina , Benmassour Souheila , Ibáñez-Cabellos José Santiago , Aribi Mourad , García-Giménez José Luis , Pallardó Federico V
Published: July 2020

Background: Neonatal sepsis remains an important cause of morbidity and mortality. The ability to quickly and accurately diagnose neonatal sepsis based on clinical assessments and laboratory blood tests remains difficult, where haemoculture is the gold standard for detecting bacterial sepsis in blood culture. It is also very difficult to study because neonatal samples are lacking. Methods : Forty-eight newborns suspected of sepsis admitted to the Neonatology Department of the Mother-Child Specialized Hospital of Tlemcen. From each newborn, a minimum of 1-2 ml of blood was drawn by standard sterile procedures for blood culture. The miRNA-23b level in haemoculture was evaluated by RT-qPCR. Results : miR-23b levels increased in premature and full-term newborns in early onset sepsis ( p < 0.001 and p < 0.005 respectively), but lowered in late onset sepsis in full-term neonates ( p < 0.05) compared to the respective negative controls. miR-23b levels also increased in late sepsis in the negative versus early sepsis negative controls ( p < 0.05). miR-23b levels significantly lowered in the newborns who died from both sepsis types ( p < 0.0001 and p < 0.05 respectively). In early sepsis, miR-23b and death strongly and negatively correlated (correlation coefficient = -0.96, p = 0.0019). In late sepsis, miRNA-23b and number of survivors (correlation coefficient = 0.70, p = 0.506) positively correlated. Conclusions : Lowering miR-23b levels is an important factor that favours sepsis development, which would confirm their vital protective role, and strongly suggest that they act as a good marker in molecular diagnosis and patient monitoring.
Twin-chain polymer networks loaded with nanostructured fluids for the selective removal of a non-original varnish from the Picasso “L’Atelier” at the Peggy Guggenheim Collection, Venice
Authors: Buemi Luciano Pensabene , Petruzzellis Maria Laura , Chelazzi David , Baglioni Michele , Mastrangelo Rosangela , Giorgi Rodorico , Baglioni Piero
Published: July 2020

This paper reports on the evaluation of a polyvinyl alcohol (PVA) “twin-chain” polymer network (TC-PN) combined with an oil-in-water nanostructured fluid (NSF) for the removal of a polyvinyl acetate (PVAc) varnish. Small Angle X-ray Scattering, Confocal Laser Scanning Microscopy, and Fluorescence Correlation Spectroscopy showed that the structure of the gel and the NSF are only minimally altered by loading the fluid into the gel. The NSF is partially free to diffuse through the network, but also interacts with the gel walls. During the cleaning, the dynamics of the fluid at the gel-substrate interface are controlled by the osmotic balance taking place among the interconnected pores. These features grant effective and controlled cleaning performances. The case study identified for this research is Pablo Picasso’s The Studio (L’Atelier, 1928), one of the masterpieces in the Peggy Guggenheim Collection, Venice (PGC). In 1969 the oil painting, originally unprotected, was wax-lined and then varnished using a PVAc varnish. Over the years, the white shades of the painting have been compromised by the yellowing of the varnish and soiling of deposits. On painting mock-ups, the NSF-loaded hydrogels allowed the swelling and softening of PVAc varnish and wax layers, which were then removed with gentle mechanical action. Effective varnish and wax removal at the micron scale, and the absence of residues from the cleaning system (gel and NSF), were confirmed by Fourier Transform Infrared Spectroscopy (FTIR) 2D imaging. The effective and safe removal of the aged PVAc varnish and wax layer from the surface of the painting was then carried out using the same cleaning protocol successfully tested on the mock-ups, setting the NSF-loaded PVA TC-PNs as robust and reliable tools for the cleaning of sensitive works of art.
Uncertainty analysis of tumour absorbed dose calculations in Molecular Radiotherapy
Authors: Finocchiaro Domenico , Gear Jonathan I , Fioroni Federica , Flux Glenn D , Murray Iain , Castellani Gastone , Versari Annibale , Iori Mauro , Grassi Elisa
Published: July 2020

Background: Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results. Recently, the EANM published a practical guidance on uncertainty analysis for molecular radiotherapy based on the application of the law of propagation of uncertainty. In this study, we investigated the overall uncertainty on a sample of patient following the EANM guidelines. The aim of this study was to provide an indication of the typical uncertainties that may be expected from performing dosimetry, to determine parameters that have the greatest effect on the accuracy of calculations and to consider the potential improvements that could be made if these effects were reduced.Results: Absorbed doses and the relative uncertainties were calculated for a sample of 49 patients and a total of 154 tumours. A wide range of relative absorbed dose uncertainty values was observed (14 - 102%). Uncertainties associated with each quantity along the absorbed dose calculation chain (i.e. Volume, Recovery Coefficient, Calibration Factor, Activity, Time-Activity Curve Fitting, Time-Integrated Activity and Absorbed Dose) were estimated. An equation was derived to describe relationship between the uncertainty in the absorbed dose and the volume. The largest source of error was the VOI delineation. By postulating different values of FWHM, the impact of the imaging system spatial resolution on the uncertainties was investigated.Discussion: To the best of our knowledge, this is the first analysis of uncertainty in molecular radiotherapy based on a cohort of clinical cases. Wide inter-lesion variability of absorbed dose uncertainty was observed. Hence, a proper assessment of the uncertainties associated with the calculations should be considered as a basic scientific standard. A model for a quick estimate of uncertainty without implementing the entire error propagation schema, which may be useful in clinical practice, was presented. Ameliorating spatial resolution may be in future the key factor for accurate absorbed dose assessment.
Antibiotic resistance genes in different animal manures and their derived organic fertilizer
Authors: Xu Yan , Li Houyu , Shi Rongguang , Lv Jiapei , Li Bihan , Yang Fengxia , Zheng Xiangqun , Xu Jian
Published: July 2020

Background: The prevalence of antibiotic resistance genes (ARGs) in animal manure poses a threat to environmental safety. Organic fertilizers fermented by livestock and poultry manure are directly applied to farmland and have the potential to cause outbreaks of bacterial resistance in agricultural environments. This study investigated the composition of ARGs in different animal manures and their derived organic fertilizers. Results: The results showed that the abundance of several ARGs, such as sul 2, Tet B-01, Tet G-01 and Tet M-01, in organic fertilizer samples was 12%~96% lower than that in animal manure. However, the abundance of Tet K and erm C was higher in animal manure than in organic fertilizers. No correlation between ARGs and environmental factors such as pH, TN, and antibiotics was observed by redundancy analysis (RDA). Procrustes analysis revealed a significant correlation between bacterial community structures and ARG abundance (r=0.799, p<0.01). Nonmetric multidimensional scaling (NMDS) analysis suggested that microorganisms in organic fertilizer may be derived from animal manure. Additionally, the abundance of pathogenic bacteria (especially Actinomadura ) would increase rather than decrease in manure compared to organic fertilizer. Conclusion: The diversity and abundance of most ARGs significantly decreased from animal manure to organic fertilizer. Microorganisms in the prepared organic fertilizer may mainly be inherited from the animal manure. The results also showed that the pathogens in the prepared organic fertilizer would significantly reduce, but would still cause partial pathogen proliferation.
Coupling Alkaline Conversion Zn Anode with Acidic Proton-insertion MoO3 Cathode for High-voltage Aqueous Rechargeable Hybrid Battery
Authors: Cai Pingwei , Ding Yichun , Liu Yangjie , Wen Zhenhai
Published: July 2020

Hydrogen ions (H+) and hydroxide ions (OH-) are regarded as ideal charge carriers for rechargeable batteries thanks to their small size, high ion mobility, low cost, and wide flexibility compared to the metal ions. However, the implementation of storage of both H+ and OH- in one electrochemical energy device face grand challenge due to incompatibility between H+ and OH-. Herein, we report an alkali-acid Zn-MoO3 hybrid battery that employ H+ and OH- as charge carriers of cathode and anode, respectively, in which the insertion/deinsertion of H+ take place on layer structured MoO3 cathode in acid while OH- are involved in alkaline conversion Zn anode, which offers a promising route to well address the incompatible issues of H+ and OH- in one electrolyte. The as-built hybrid battery can deliver a high open-circuit voltage of 1.85 V, a high rate capability, a high capacity of 158 mAh g-1 at a current density of 5 A g-1, and excellent capacity retention of above 90% over 200 cycles. This work sheds light on the development of aqueous energy devices with high voltage and energy density through materials engineering and device optimization.
Imaging features of hepatocellular carcinoma with bile duct tumor thrombus：a multicenter study
Authors: Huang Li-Ming , Wu Jun-Yi , Bai Yan-Nan , Wu Jia-Yi , Wei Yong-Gang , Zhang Zhi-Bo , Yan Mao-Lin
Published: July 2020

Background: There are still difficult and challenging problems in diagnosis of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) before operation. This study aimed to analyze the imaging features of HCC with B1-B3 BDTT. Methods: The clinicopathological data and imaging findings of 30 HCC patients with B1-B3 BDTT from three high-volume institutions were retrospectively reviewed. Eighteen patients underwent computed tomography (CT) scans and twelve patients underwent magnetic resonance imaging (MRI) scans before operation, respectively. The diagnosis of HCC with BDTT was conﬁrmed by postoperative pathologic examination.Results: According to Japanese classification, 5 patients were classified as B1 BDTT, 12 B2, 13 B3, and 82 B4, respectively. The HCC lesions were detected in all patients, and the localized bile duct dilation were detected in 28 (93.3%) patients. The BDTT was observed in all B3 patients and 3 B2 patients, but it was not observed in all B1 patients on CT or MRI. The BDTT showed relatively hypoattenuation on plain CT scans and T1W images, relatively hyperattenuation signals on T2W. The BDTT showed hyperattenuation at hepatic arterial phase with washout at portal venous phase. The localized biliary dilation showed no enhancement at hepatic arterial phase and no progressively delayed enhancement at portal venous phase, but it was more obvious at portal venous phase on CT.Conclusions: The HCC lesions and the localized bile duct dilatation on CT or MRI scans are imaging features of HCC with BDTT, which might facilitate the early diagnosis for B1-B3 BDTT.
The caliber of segmental and subsegmental vessels in COVID-19 pneumonia is enlarged: a distinctive feature in comparison with other forms of inflammatory and thromboembolic disease
Authors: Ambrosetti Maria Chiara , Battocchio Giulia , Fava Cristiano , Bejko Tatjana , Tacconelli Evelina , Minuz Pietro , Crisafulli Ernesto , Mansueto Giancarlo
Published: July 2020

Objective: to compare COVID-19 patients’ vessel caliber with that of normal lungs and lungs interested by other inflammatory and thromboembolic processes. Methods: between March and April 2020, 42 patients affected by COVID-19 pneumonia [COV-P] underwent a CT scan of the lung at Verona University Hospital for clinical indications. Lung images were compared to 4 different groups of patients (normal lung [NL], distal thromboembolism [DTE], bacterial and fungal pneumonia [Bact-P, Fung-P]) by a 4-year-experienced radiologist. Results: COV-P patients’ segmental and subsegmental vessels, as evaluated as the ratio with the corresponding bronchial branch (V/B ratio) were larger with respect to NL, DTE in the apparently healthy parenchyma, a result confirmed in the zones of opacification with respect to Bact-P and Fung-P. Conclusions: This is the first study to comparatively showing that segmental and subsegmental COVID-19 patients’ vessel caliber is significantly enlarged. This is a distinctive feature of COVID-19 pneumonia suggesting distinct pathophysiology as compared to other inflammatory and thromboembolic diseases and alerting radiologists to consider it when evaluating CT scan of suspected patients.
Salvianolate lyophilized injection induced autophagy against neuronal apoptosis through the Akt/mTOR pathway in Neuro-2a cells
Authors: Li Dongna , Ma Mengmeng , Zhang Wenqi , Xu Yangyang , Wang Shaoxia , Chai Lijuan , Guo Hong , Hu Limin
Published: July 2020

Background: Stroke remains a worldwide health problem. Salvianolate lyophilized injection (SLI) is one of the most widely-used in clinics in China for treating stroke. Our previous research found that SLI protects against stroke by inhibiting oxidative stress and inflammation. Whether SLI has other biological effects on stroke remains unknown. Methods: Neuro-2a (N2a) cells were treated with SLI (10, 25, 50μg/ml) and exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) as an in vitro model of ischemic stroke. Then, cell apoptosis was assessed using flow cytometry, apoptosis and autophagy related proteins were investigated by western blotting. Autophagy inhibitor 3-methyladenine (3-MA) pretreatment was used to detect the apoptosis effect of SLI on N2a cells. Results: In this work, we verified that SLI promoted cell proliferation, inhibited cell injury and apoptosis in OGD/R-induced N2a cells. The increase the expression of autophagy markers LC3 and Beclin-1, and decrease autophagy substrate protein p62 demonstrated the induction of autophagy by SLI. Additionally, we found that SLI activation of autophagy significantly preceded inhibition of apoptosis in N2a. Pretreatment with autophagy inhibitor 3-MA could antagonize the protective effect of SLI on inhibiting apoptosis, which may be related to the Akt/mTOR signalling pathway. Conclusions: The present study indicated that SLI has potential as a novel therapy for ischemic stroke, and its possible mechanism is to induced autophagy and inhibit apoptosis through blocking Akt/mTOR signaling pathway in OGD/R-induced N2a cells, providing new insights into the mechanism of SLI in the treatment of stroke.
Perinatal exposure to diesel exhaust origin secondary organic aerosol induces autism-like behavior in rats
Authors: Shwe Tin Tin Win , Thu Chaw Kyi Tha , Fujitani Yuji , Tsukahara Shinji , Hirano Seishiro
Published: July 2020

Background

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, social interactions and repetitive behaviors. The etiology of autism remains unknown and its molecular basis is not well understood. Both genetic and environmental factors may contribute ASD. In this study, we used diesel exhaust origin secondary organic aerosol (DE-SOA) as environmental pollutants. The aim of present study is to examine autism-like behaviors and related gene expressions in rats exposed to DE-SOA perinatally. Sprague-Dawley pregnant rats were exposed to clean air (control), diesel exhaust (DE) and DE-SOA in the exposure chamber for 5 h per day, 5days a week from gestational day 8 to postnatal day 21. At postnatal day 21, the male and female offspring rats were allocated into three different groups as follows: 1) rats exposed to clean filtered air; 2) rats exposed to DE; 3) rats exposed to DE-SOA. Social behaviors were investigated at 10 ~ 13-weeks-old rats using a 3-chambered social behavior test, social dominance tube test and marble burying test. Prefrontal cortex was collected under deep anesthesia to examine neurological and immunological markers, glutamate concentration, mast cell and microglia activation using real-time RT-PCR method, ELISA method and immunohistochemical analysis.
Results

DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior and increased repetitive behavior compared with the control rats. The mRNA expression levels of serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) were down-regulated whereas interleukin 1 β (IL-β), and heme oxygenase 1 (HO-1) were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA compared to the control rats. In addition, the expression of mast cells and microglia marker ionized calcium-binding adapter molecule (Iba)1 were increased in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was increased significantly in the prefrontal cortex of both male and female rats exposed to DE-SOA.
Conclusion

Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior in rats by modulating neurological and immunological markers in the prefrontal cortex.
Identification of prognostic-associated genes in colorectal cancer based on genome-wide expression profiles
Authors: Hou Siyu , Zhang Jinfeng , Chen Yanbo , Ning Shipeng , Li Guozheng , Zhang Xingda , Pang Da
Published: July 2020

Background: Colorectal cancer (CRC), a severe disease in the world. The dysregulation of genes plays a significant role in cancer. Method: In the present study, we first identified differentially expressed genes (DEGs) of CRC in the GSE71187 data set from the Gene Expression Omnibus (GEO) database. And through GO terminology and Gene and Genome (KEGG) pathway, the up-regulated DEG and down-regulated genes were enriched. Then, we selected hub genes and studied their related prognostic value through protein-protein interaction (PPI) network and integrated bioinformatics analysis. Finally, 7 genes with prognostic value were obtained by survival analysis and multivariate Cox proportional hazards regression models, as well as verified in the Oncomine and UALCAN database.Result: A total of 3,588 DEGs were identified with 1,474 upregulated and 3,114 downregulated. Then, GO terms and Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs and down-regulated genes were mainly involved in important GO terms and KEGG pathway, for example, defense response to other organism, leukocyte differentiation and epidermis developmen. In the PP network analysis, 6 hub modules and 86 module genes were identified. In the end, 7 genes with prognostic value were obtained through survival and multi-factor analysis. They have significant differences in varying degrees at the level of DNA, mRNA and protein.Conclusion: The results of the study may provide novel insight into the genes and associated pathways involved in CRC, and aid the identifcation of novel therapeutic targets and prognostic marker of CRC.
The heterologous expression and characterization of a novel chitinase with dual catalytic domains discovered from a wetland soil metagenome
Authors: Dai Yumei , Yang Feng , Liu Xiao , Wang Hongling , Yan Zhiying
Published: July 2020

Background: Microbial chitinases have attracted a lot of attention because of their great potential in many applications. Metagenome-based approach obtains the target genes from the environment directly without culturing the microbes and is becoming a powerful tool to discover the novel chitinases.Results: Gene P1724 was found in a chitin-enriched microbial community from a wetland on the Qinghai-Tibetan plateau using the metagenomic approach. The translated protein sequence of P1724 was predicted to have two GH18 catalytic domains and showed very low similarities with any known and hypothetical chitinases. The gene sequence of P1724 , its N-terminal GH18 domain ( P1724nGH18 ), or C-terminal GH18 domain ( P1724cGH18 ) was cloned and expressed in Escherichia coli BL21 (DE3). Using colloid chitin as substrate, these purified recombinant chitinases showed maximum hydrolytic activities at 40 °C, pH 5.0-6.0 and 0-0.5 M NaCl, and were cold adaptive since they were still active at 4 °C; the activities of three chitinases were decreased with the presence of Cu 2+ and EDTA, but increased with Ba 2+ and Ca 3+ ; all three chitinases showed both chitotiosidase and endochitinase activities, and could hydrolyze chitosan as well. Other than these common characteristics, P1724 and P1724nGH18 shared more similarity in temperature and pH stabilities, NaCl tolerance and substrate affinity, suggesting the N-terminal GH18 domain contributed more than the C-terminal GH18 did in biochemical characteristics of P1724. k cat / K m value (catalytic efficiency) of P1724 was significantly higher than the sum values of P1724nGH18 and P1724cGH18, which indicated that two GH18 domains of P1724 worked cooperatively in degrading chitin.Conclusion: Compared to most microbial chitinases that contain only one catalytic domain, P1724 contains two and was firstly discovered by the metagenomic approach. P1724, its N-terminal and C-terminal catalytic domains were heterologously expressed and characterized. These three recombinant chitinases are phylogenetically distant to any chitinases studied so far, have unique hydrolytic mode, high catalytic efficiency and so new promising candidates for chitinases in applications. In addition, this study broadens the knowledge of unknown chitinases in nature and shows a natural strategy for enzyme engineering by adding other catalytic domain(s).
Measuring Equity of Access to Health Services in Practice: Example of Eye Health Outreach Camps in Rural Malawi
Authors: Trotignon Guillaume , Jones Iain , Ali Shaneez Saeed , Mugwang’a Ziporah , Engels Thomas , Bechange Stevens , Kamwendo Effie , Schmidt Elena
Published: July 2020

Introduction

Equity in the access and use of health services is critical if countries are to make progress towards universal health coverage and address the systematic exclusion of the most vulnerable groups. The purpose of this study was to assess if the Co-ordinated Approach To Community Health programme implemented by Sightsavers was successful in reaching the poorest population and people living with disabilities in Kasungu district, Malawi. Outreach camps were organized to provide a range of integrated eye care services.
Methods

Between April and September 2017, data on socio-economic status, household characteristics and functional disability were collected from patients attending at eye camps in Kasungu district, Malawi. Results were compared to Demographic Health Surveys and Integrated Household Surveys data. Using asset-based questions on household characteristics (EquityTool© and Simple Poverty Scorecard©) and the Washington Group Short Set of Questions, individuals were categorized by wealth quintiles, poverty status, and functional disability status.
Results

A total of 1,358 participants participated in the study. The study shows that self-reported data on household characteristics and assets are reliable and can be collected in clinical settings (instead of relying on direct observations).Individuals attending outreach camps were poorer in terms of relative wealth and absolute poverty rates compared to the rest of the population in Kasungu. It was estimated that 9% of the participants belonged to the poorest quintile compared to 4% for the population in Kasungu (DHS 2015–2016). The ultra-poverty rate was also lower among respondents (13%) compared to 15% for Kasungu district (IHS 2017). The functional disability rate was 27.5% for study participants, and statistically higher among women and relatively poorer household dwellers.
Conclusions

Our study shows that existing tools can be reliably used and combined to assess equity of access to health services for vulnerable groups of the population. The findings suggest that the programme was successful in reaching the poorest people of the Kasungu district population as well as those with non-visual disabilities through outreach camps. However, it is essential to use sub-national data (district or regional level) from recent surveys for the purpose of benchmarking in order to produce accurate results.
Drug Repositioning Study in Search of Potent Inhibitors Blocking Multiple Pathways for the Treatment of Breast Cancer
Authors: Kashaw Sushil Kumar , Agarwal Shivangi , Dixit Anshuman
Published: July 2020

Breast cancer is most malignant cancer in women worldwide. The efforts are going on for improvement in patient’s survival and treatment strategies. The goal of the present work is to find out connections among drugs-genes-breast cancer and to re-purpose approved drugs for the treatment of breast cancer. In this context, the gene expression data of breast cancer samples was analyzed to identify the upregulated/downregulated genes in different clinical stages of breast cancer. A large number of genes were found to be upregulated/downregulated in different clinical stages of breast cancer. Some of the genes were found to be stage specific and some were common to all stages. The biological pathways were studied in early and late stages of breast cancer, which indicated that pathways as Methylglyoxal Degradation I, Catecholamine biosynthesis and Serotonin/Melatonin biosynthesis were enriched in early stage and pathways as Matrix metalloproteases, Airway pathology in COPD, Glycogen degradation II and Glycogen degradation III were enriched in late stages of breast cancer. The drug repurposing analysis revealed that the different classes of drugs as enzyme inhibitors, CNS agents, Glucocorticoids, insulin sensitizers, tubulin inhibitors, adhesion inhibitors showed strong connections with MCF7 cell line. Further, it was found that the drugs as Nortriptyline, AZD-6482, Acitretin and GW-507 were found to target multiple genes in interleukin pathway, enzymatic pathway and GPCR signaling pathway and drugs as Caffeine, Canertinib and Triciribine was found to target multiple genes which were dysregulated and involved in interleukin pathway, enzymatic pathway, GPCR signaling pathway and metabolic pathways.
Screening for GARS Variants in A Cohort of Chinese Patients With Inherited Peripheral Neuropathy
Authors: Sun Bo , He Zheng-Qing , Li Yan-Ran , Wang Hong-Fen , Cui Fang , Yang Fei , Huang Xu-Sheng
Published: July 2020

Background CMT2D is a rare subtype of axonal CMT, caused by the mutation of glycyl-tRNA synthetase (GARS) gene which is also a disease-causing gene of distal spinal muscular atrophy type V (dSMA-V) or hereditary motor neuropathy 5A (HMN5A). There were only several case reports in China, and no epidemiological study of CMT2D/ HMN5A yet.Methods We recruited the patients of Chinese Han descent clinically diagnosed with inherited peripheral neuropathy (IPN) from the Department of Neurology at Chinese PLA General Hospital (Beijing, China) from December 20, 2012 to July 31, 2019. All patients underwent a detailed medical history, neurological examination, laboratory examination, electrophysiological studies, and genetic testing.Results A total of 206 unrelated patients underwent genetic analysis, and we found four mutations of GARS from four different families, including c.794C>T (p.S265F), c.374A>G (p.E125G), c.1000A>T (p.I334F) and c.781T>G (p.Y261D), the first three of them were considered pathogenic. As for the three pathogenic mutation carriers, one patient was diagnosed as CMT2D, two patients were diagnosed as HMN5A.Conclusion GARS mutation is a rare cause of inherited peripheral neuropathy and the phenotype tends to be CMT2D or HMN5A. There might be a relatively higher mutation frequency in Asian population compared with Caucasians. Combination of clinical phenotype, auxiliary tests and genetic evidence to assess the pathogenicity of genetic variants in patients suspected as IPN is of vital importance.
Development and Validation of an Instrument to Measure Parental Factors Related to Substance Use Prevention in Adolescents
Authors: Mehri Seyed Mohsen , Rohban Alireza , Hashemian Masoumeh , Joveini Hamid , Mehri Ali , Rakhshani Mohammad Hassan , Shahrabadi Reza
Published: July 2020

Background:

The average age of using illicit drugs for the first time in adolescents has decreased in Iran over the past years. Studies show that family and environment play a notable role in keeping adolescents away from substances.

Aims:

The present study is an attempt to develop and validate a model-based questionnaire to measure parental factors related to substance use prevention in adolescents.

Methods:

This methodological study was carried out on 336 parents of high school students in Sabzevar- Iran, in 2018. The first draft of the questionnaire, including 136 items, was developed based on the constructs of the Health Promotion Model (HPM) using similar questionnaires, literature review, and interviewing 9 qualified experts. The validity of the questionnaire was measured through face validity (qualitative and quantitative), content validity (qualitative and quantitative), and construct validity (confirmatory factor analysis). The reliability of the questionnaire was measured by internal consistency and test-retest reliability. SPSS ver. 16 and LISREL ver. 8.2 software was used for statistical analysis.

Results:

Throughout the validation process, 35 items were omitted, and the final version of the questionnaire consisting of 101 items was developed. The overall content validity ratio was 0.81, which indicates the proper and understandable content of the items. The overall content validity index was 0.96, which indicates excellent expert validity. The Cronbach’s alpha coefficient of the questionnaire was 0.85 (constructs range= 0.73-0.96), and the intraclass correlation coefficient of the questionnaire was 0.78 (constructs range= 0.46-0.91), which indicates that the questionnaire has good internal consistency and test-retest reliability. Further, the confirmatory factor analysis yielded an appropriate fit for the model (RMSEA= 0.069, χ2/df= 2.77, GFI= 0.60, AGFI= 0.83, CFI= 0.83, NNFI= 0.83).

Conclusion:

The validity and reliability of the HPM-based questionnaire were supported. Therefore, the questionnaire can be used by health educators and health policymakers in empowerment programs for parents to improve their behavioral skills concerning the prevention of substance use in their adolescents.
Predictive ability of the Computer-Based Cognitive Assessment Tool for mild cognitive impairment in community-dwelling older adults: a 2-Year Longitudinal Study (Preprint)
Authors: Takahashi Junta , Kawai Hisashi , Suzuki Hiroyuki , Fujiwara Yoshinori , Watanabe Yutaka , Hirano Hirohiko , Kim Hunkyung , Ihara Kazushige , Miki Akiko , Obuchi Shuichi
Published: July 2020

BACKGROUND

The Computer-Based Cognitive Assessment Tool (CompBased-CAT) has been reported to have concurrent validity with the Mini-Mental State Examination (MMSE) and discriminating ability for dementia, but it was not clear whether it could predict incidence of cognitive impairment.

OBJECTIVE

This study examined the ability of the CompBased-CAT to predict mild cognitive impairment (MCI) after 2 years among community-dwelling older adults.

METHODS

A longitudinal study was conducted, involving 455 older adults (median age 72 years, range 65-89 years, 62.0% female) dwelling in communities. Cognitive function was assessed using the MMSE. MCI was defined as an MMSE score <27. The CompBased-CAT was conducted at baseline, and each sub-test score was converted to a Z-score, the sum of which became the total Z-score. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the predictive ability of the CompBased-CAT for incidence of MCI. Logistic regression analysis was conducted with the dependent variable (the incidence of MCI), and with the total Z-score as the independent variable, adjusted for all other covariates.

RESULTS

After 2 years, 32 (7.0%) of participants developed MCI. ROC curve analysis showed an area under the curve of 0.79, a sensitivity of 0.76, and a specificity of 0.75. Logistic regression analysis showed that total Z-score was significantly associated with prevention of MCI. The odds ratio (OR) was 1.34 (95% confidence interval 1.18-1.52, p<.001).

CONCLUSIONS

The present study showed that CompBased-CAT has sufficient predictive ability for MCI 2 years later and that it is useful for identifying dementia at an early stage.
Mobile Health Strategies to Tackle Skin Neglected Tropical Diseases With Recommendations From Innovative Experiences: Systematic Review (Preprint)
Authors: Carrion Carme , Robles Noemí , Sola-Morales Oriol , Aymerich Marta , Ruiz Postigo Jose Antonio
Published: July 2020

BACKGROUND

Neglected tropical diseases (NTDs) represent a diverse group of 20 communicable diseases that occur in tropical and subtropical areas in 149 countries, affecting over 1 billion people and costing developing economies billions of dollars every year. Within these diseases, those that present lesions on the skin surface are classified as skin NTDs (sNTDs). Mobile health interventions are currently being used worldwide to manage skin diseases and can be a good strategy in the epidemiological and clinical management of sNTDs.

OBJECTIVE

We aimed to analyze existing evidence about mobile health interventions to control and manage sNTDs in low- and middle-income countries (LMICs) and make recommendations for what should be considered in future interventions.

METHODS

A systematic review was conducted of the MEDLINE, Embase, and Scopus databases over 10 years up to April 30, 2020. All types of clinical studies were considered. Data were synthesized into evidence tables. Apps were selected through a comprehensive systematic search in the Google Play Store and Apple App Store conducted between March 20 and April 15, 2020.

RESULTS

From 133 potentially relevant publications, 13 studies met our criteria (9.8%). These analyzed eight different interventions (three SMS text messaging interventions and five app interventions). Six of the 13 (46%) studies were community-based cross-sectional studies intended to epidemiologically map a specific disease, mainly lymphatic filariasis, but also cutaneous leishmaniasis, leprosy, and NTDs, as well as sNTDs in general. Most of the studies were considered to have a high (5/13, 39%) or moderate (4/13, 31%) risk of bias. Fifteen apps were identified in the Google Play Store, of which three were also in the Apple App Store. Most of the apps (11/15, 73%) were targeted at health care professionals, with only four targeted at patients. The apps focused on scabies (3/15, 20%), lymphatic filariasis (3/15, 20%), cutaneous leishmaniasis (1/15, 7%), leprosy (1/15, 7%), yaws and Buruli ulcer (1/15, 7%), tropical diseases including more than one sNTDs (3/15, 20%), and NTDs including sNTDs (2/15, 13%). Only 1 (7%) app focused on the clinical management of sNTDs.

CONCLUSIONS

All mobile health interventions that were identified face technological, legal, final user, and organizational issues. There was a remarkable heterogeneity among studies, and the majority had methodological limitations that leave considerable room for improvement. Based on existing evidence, eight recommendations have been made for future interventions.
Impacts of Internet Use on Senior Citizens’ Depressive Symptoms in China: Urban-Rural Differences (Preprint)
Authors: Sun Kai , Zhao Yuxiang Chris , Tao Xiaofeng , Zhou Junjie , Liu Qianqian
Published: July 2020

BACKGROUND

Although existing studies report that Internet use can help senior citizens coping with depressive symptoms, so far limited studies have explored the impacts of Internet use on urban and rural senior citizens’ depression symptoms.

OBJECTIVE

This study aims to address the above gap and explore the impacts of Internet use on urban and rural senior citizens’ depressive symptoms in China.

METHODS

We use the data from the China Health and Retirement Longitudinal Study (CHARLS). We use the panel-data regression to examine the relationship between Internet use and depression. In order to obtain robust evidence, we built a treatment group by selecting senior citizens who did not use the Internet in 2013 (Wave 2) but did use it in 2015 (Wave 4), and a control group by selecting senior citizens who did not use the Internet in either Wave based on the propensity score matching (PSM) approach. We then examined the impacts of Internet use with linear regression analysis based on the difference-in-difference (DID) approach.

RESULTS

The empirical results indicate that Internet use could significantly alleviate rural senior citizens’ depression (β=-2.187, P=.006). The Frequency of Online have consistent effect on depression (β= -1.091, P=.001). In addition, the impacts of Internet use on rural senior citizens’ three specific depressive symptoms are significant (“I had trouble keeping my mind on what I was doing”, β= -0.537, P=.008; “I felt depressed”, β= -0.315, P=.014; “I felt everything I did was an effort”, β= -0.355, P=.021). The propensity score matching and difference-in-difference analysis is consistent with the results of panel date regression analysis.

CONCLUSIONS

Urban-rural differences exist in the impacts of Internet use on senior citizens’ depressive symptoms. Rural senior citizens’ depressive symptoms can be alleviated by Internet use and the frequency of Internet use. Policy makers should provide rural senior citizens more opportunities to access the Internet and more Internet-skill trainings to enable them to better utilize the Internet.
ОСОБЕННОСТИ ПОСТРОЕНИЯ СИСТЕМЫ СПЕЦИАЛЬНЫХ ОПЕРАТИВНО-РОЗЫСКНЫХ МЕРОПРИЯТИЙ В СЕТЯХ 5G
Authors: Тихвинский В.
Published: July 2020

Обеспечение законного перехвата сообщений в сетях пятого поколения становится насущной проблемой не только для отражения криминальных и террористических угроз, но и технологической проблемой в условиях изменения парадигмы услуг 5G и появления инновационных технологий передачи данных. В статье анализируется модель и архитектура системы технических средств обеспечения функций оперативно-розыскных мероприятий в сетях 5G, обоснованная Партнерским проектом 3GPP, и проблемные вопросы ее создания.
ПРОПУСКНАЯ СПОСОБНОСТЬ СЕТЕЙ ДОСТУПА И ОЦЕНКА СОЗДАВАЕМОГО ТРАФИКА
Authors: Зайцев В. , Соколов Н.
Published: July 2020

Обсуждаются тенденция продолжающегося роста пропускной способности в процессе модернизации сетей доступа и задача оценки трафика, создаваемого пользователями. Соотношение между величиной создаваемого трафика и необходимой пропускной способностью элементов телекоммуникационной системы, которая обеспечивает заданные показатели качества предоставления услуг, было хорошо изучено в эпоху доминирования телеграфии и телефонии. По мере включения данных и видео в состав нагрузки телекоммуникационных сетей, поддерживающих диалоговые услуги, возник ряд новых задач, которые потребовали пересмотра ряда положений теории телетрафика. В статье анализируются тенденции эволюции сетей доступа с точки зрения роста ее пропускной способности и приводятся результаты исследований, направленных на оценку параметров пакетного трафика.