bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting rational antibiotic prescribing for non-complicated infections: Understanding social influence in primary care networks in Germany
Authors: Poss-Doering Regina , Kamradt Martina , Glassen Katharina , Andres Edith , Kaufmann-Kolle Petra , Wensing Michel
Published: February 2020

Background Primary care networks in Germany are formalized regional collaborations of physicians and other healthcare providers. Common goals are optimized healthcare processes and services for patients, enhanced communication, agency for professional concerns and strengthened economic power. In the ARena study (Sustainable reduction of antibiotic-induced antimicrobial resistance), 14 primary care networks in two federal German states aimed to promote appropriate antibiotics use for acute non-complicated infections by fostering awareness and understanding. Factors related to the role of primary care networks were to be identified.
Methods
For this study, audio-recorded telephone interviews were conducted with physicians, non-physician health professionals and stakeholder representatives. Pseudonymized verbatim transcripts were coded using thematic analysis. In-depth analysis was based on the inductive categories ‘social support’, ‘social learning’, ‘social normative pressures’ and ‘social contagion’ to reflect social influence processes. Data generated through a survey with physicians and non-physician health professionals were analyzed descriptively to foster understanding of the networks’ potential impact on antibiotic prescribing.
Results

Social influence processes proved to be relevant regarding knowledge transfer, manifestation of best-practice care and self-reflection. Peer communication was seen as great asset, main reason for membership and affirmative for own perspectives. All interviewed physicians (n=27) considered their network to be a strong support factor for daily routines, introduction of new routines, and continuity of care. They utilized network-offered training programs focusing on best practice guideline-oriented use of antibiotics and considered their networks supportive in dealing with patient expectations. A shared attitude combined with ARena intervention components facilitated reflected management of antibiotic prescribing. Non-physician health professionals (n=11) also valued network peer exchange. They assumed their employers joined networks to offer improved and continuous care. Stakeholders (n=7) expected networks and their members to be drivers for care optimization.
Conclusion

Primary care networks play a crucial role in providing a platform for professional peer exchange, social support and reassurance. With regards to their impact on antibiotic prescribing for acute non-complicated infections, networks seem to facilitate and amplify quality improvement programs by providing a platform for refreshing awareness, knowledge and self-reflection among care providers. They are well suited to promote a rational use of antibiotics.
Long-term Outcomes of Conservative Treatment and Endovascular Treatment in Patients with Symptomatic Spontaneous Isolated Superior Mesenteric Artery Dissection: A Single-center Experience
Authors: Xu Leyin , Shao Jiang , Zhang Daming , Qiu Chenyang , Wang Jingjing , Li Kang , Fang Lijing , Zhang Xin , Lei Jinsong , Lai Zhichao , Ma Jiangyu , Yu Yanying , Yu Xiaoxi , Du Fenghe , Qi Wanting , Chen Junye , Liu Bao
Published: February 2020

Background: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder, and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD.
Methods: Forty-two consecutive SISMAD patients who were admitted to a single center between October 2009 and May 2018 were enrolled in this study. Based on their symptoms, 15 had conservative treatment, and 27 had endovascular treatment. The baseline characteristics, treatments, and follow-up results of the conservative group and endovascular group were analysed.
Results: The rates of symptom relief were 93.3% in the conservative group and 96.3% in the endovascular group. The procedure-related complications in the endovascular group included one case of pseudoaneurysm formation in the left brachial artery. During the follow-up period (median 28.5 months), a higher proportion of patients in the conservative group had symptom recurrence (42.9% in the conservative group versus 4.8% in the endovascular group, p < 0.001). Four patients in the conservative group and one patient in the endovascular group had additional endovascular intervention during follow-up. Compared with the conservative group, patients in the endovascular group had statistically significantly longer symptom-free survival ( p = 0.014) and a higher rate of superior mesenteric artery (SMA) remodeling ( p < 0.001).
Conclusions: For symptomatic SISMAD, endovascularly treated patients had a lower rate of symptom recurrence and a higher rate of SMA remodeling in the long term. Prospective, multi-center studies are needed to confirm the long-term outcomes of both treatments.
Reversed paired-gRNA plasmid cloning strategy for efficient genome editing in Escherichia coli.
Authors: Ding Tingting , Huang Chaoyong , Liang Zeyu , Ma Xiaoyan , Wang Ning , Huo Yi-Xin
Published: February 2020

Background: Co-expression of two distinct guide RNAs (gRNAs) has been used to facilitate the application of CRISPR/Cas9 system in fields such as large genomic deletion. The paired gRNAs are often placed adjacently in the same direction and expressed individually by two identical promoters, constituting direct repeats (DRs) which are susceptible to self-homologous recombination. As a result, the paired-gRNA plasmids cannot remain stable, which greatly prevents scalable application of the CRISPR/Cas9 system. Results: To address this limitation, different DRs-involved paired-gRNA plasmids were designed and the events of recombination were characterized. Deletion between DRs occurred with high frequencies during plasmid construction and subsequent plasmid propagation. This recombination event was RecA-independent, which agreed with the replication slippage model. To increase plasmid stability, a reversed paired-gRNA plasmids (RPGPs) cloning strategy was developed by converting DRs to the more stable invert repeats (IRs), which completely eliminated DRs-induced recombination. Using RPGPs, rapid deletion of chromosome fragments up to 100 kb with an efficiency of 83.33% was achieved in Escherichia coli. Conclusions: The RPGPs cloning strategy serves as a general solution to avoid plasmid RecA-independent recombination. It can be adapted to applications that rely on paired gRNAs or repeated genetic parts.
Addressing the quality and scope of paediatric primary care in South Africa: Evaluating contextual impacts of the introduction of the Practical Approach to Care Kit for children (PACK Child)
Authors: Murdoch Jamie , Curran Robyn , Cornick Ruth , Picken Sandy , Bachmann Max , Bateman Eric , Simelane Makhosazana Lungile , Fairall Lara
Published: February 2020

Background: Despite significant reductions in mortality, preventable and treatable conditions remain leading causes of death and illness in children in South Africa. The PACK Child intervention, comprising clinical decision support tool (guide), training strategy and health systems strengthening components, was developed to expand on WHO’s Integrated Management of Childhood Illness programme, extending care of children under 5 years to those aged 0-13 years, those with chronic conditions needing regular follow-up, integration of curative and preventive measures and routine care of the well child. In 2017-2018, PACK Child was piloted in 10 primary healthcare facilities in the Western Cape Province. Here we report findings from an investigation into the contextual features of South African primary care that shaped how clinicians delivered the PACK Child intervention within clinical consultations.
Methods: Process evaluation using linguistic ethnographic methodology which provides analytical tools for investigating human behaviour, and the shifting meaning of talk and text within context. Methods included semi-structured interviews, focus groups, ethnographic observation, audio-recorded consultations and documentary analysis. Analysis focused on how mapped contextual features structured clinician-caregiver interactions.
Results: Primary healthcare facilities demonstrated an institutionalised orientation to minimising risk upheld by provincial documentation, providing curative episodic care to children presenting with acute symptoms, and preventive care including immunisations, feeding and growth monitoring, all in children 5 years or younger. Children with chronic illnesses such as asthma rarely receive routine care. These contextual features constrained the ability of clinicians to use the PACK Child guide to facilitate diagnosis of long-term conditions, elicit and manage psychosocial issues, and navigate use of the guide alongside provincial documentation.
Conclusion: Our findings provide evidence that PACK Child is catalysing a transition to an approach that strikes a balance between assessing and minimising risk on the day of acute presentation and a larger remit of care for children over time. However, optimising success of the intervention requires reviewing priorities for paediatric care which will facilitate enhanced skills, knowledge and deployment of clinical staff to better address acute illnesses and long-term health conditions of children of all ages, as well as complex psychosocial issues surrounding the child.
One-step RT-qPCR assay for ZIKV RNA detection in Aedes aegypti samples: A protocol to study infection & gene expression during ZIKV infection
Authors: Araujo Ricardo Vieira , Feitosa-Suntheimer Fabiana , Gold Alexander S. , Londono-Renteria Berlin , Colpitts Tonya Michelle
Published: February 2020

Background : Zika virus (ZIKV) is transmitted to humans during the bite of an infected mosquito. In a scenario of globalization and climate change, the frequency of outbreaks has and will increase in areas with competent vectors, revealing a need for continuous improvement of ZIKV detection tools in vector populations. A simple, rapid and sensitive assay for viral detection is qRT-PCR, yet oligos optimized for ZIKV detection in mammalian cells and samples have repeatedly shown high background when used on mosquito RNA. In this work we present a one-step qRT-PCR protocol that allows for the detection of ZIKV in mosquitoes and for the evaluation of gene expression from the same mosquito sample and RNA. This assay is a less expensive qRT-PCR approach than that most frequently used in the literature and has a much lower background, allowing for confident detection. Methods : Our new oligo design to detect ZIKV RNA included in silico analysis of both viral and mosquito ( Ae. aegypti and Ae. albopictus )genomes, targeting sequences conserved between Asian and African ZIKV lineages, but not matching Aedes genomes. This assay will allow researchers to avoid nonspecific amplification in insect samples due to viral integration into the mosquito genome, a phenomenon known to happen in wild and colonized populations of mosquitoes. Standard curves constructed with in vitro transcribed ZIKV RNA were used to optimize the sensitivity, efficiency and reproducibility of the assay. Results: Finally, the assay was used with success to detect both ZIKV RNA in infected mosquitoes and to detect expression of the Defensin A gene, an antimicrobial peptide (AMP) involved in Aedes aegypti immune response to virus infection. Conclusions : The experimental approach to detect ZIKV RNA in Aedes aegypti presented here has demonstrated to be specific, sensitive and reliable, and additionally it allows for the analysis of mosquito gene expression during ZIKV infection.
Five Novel PRNP Gene Polymorphisms and Their Potential Effect on Scrapie Susceptibility in Three Native Ethiopian Sheep Breeds
Authors: Teferedegn Eden Yitna , Yaman Yalcin , Un Cemal
Published: February 2020

Background Classical scrapie susceptibility in sheep has been linked to three polymorphisms at codon 136, 154, and 171 in the prion protein gene ( PRNP) whereas atypical scrapie susceptibility is related to polymorphisms at position 141. Many other variants over the length of the PRNP have been reported. Some of the variants may play crucial roles in fighting against the emergence of a new form of scrapie disease. Scrapie surveillance, scrapie associated genotyping and PRNP characterization studies have been conducted across the globe. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breed’s PRNP gene has socioeconomic and scientific merits. This study aimed to identify PRNP variants in three native Ethiopian sheep breeds and their potential effect on scrapie susceptibility. Results Five novel variants were identified in the PRNP gene of three native Ethiopian sheep breeds. Four non-synonymous heterozygous substitutions i.e. H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA) and one synonymous N103N (AAC-->AAT) were detected. In addition to the novel variants, polymorphisms at codon 126,127,138,142,146,231 and 237 were also identified. The haplotype ARR was observed in Menz and Afar breeds at frequencies of 0.02 and 0.05 respectively. Neither ARR/ARR nor VRQ/VRQ genotypes were identified in the population under study. Conclusion Two of the novel variants at codon 99 and 103 that are placed closer to the proteinase K cleavage site and the variant at codon 116 in the palindrome region along with variants at codon 127 in glycine repeat domain may influence the conformational flexibility of prion protein. The rarity of ARR haplotype and the abundance of 141L variant demonstrated that the present study population was less resistant to classical scrapie and less predisposed to genotype associated atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies during interbreeding, crossbreeding and help to take precautionary measures against scrapie. Keywords: Ethiopian sheep; Novel Variations; Polymorphism; Prion gene; Scrapie Susceptibility
A Randomized Controlled 24-week Trial to Evaluate the Efficacy and Safety of Bi Qi Capsule for the Treatment of Knee Osteoarthritis
Authors: Xia Xuan , Wang Huanrui , Liu Zehao , Cai Xiao , Chen Xianghong , Lv Yuan , Chen Xiumin , Huang Qingchun , Huang Runyue
Published: February 2020

Objective: To evaluate the efficacy and tolerability of Bi Qi capsule in knee osteoarthritis. Patients and methods: An open-label, 24-week, parallel randomized controlled trial conducted between October 2016 to October 2018. Patients with knee osteoarthritis were randomly assigned 1:1 to receive Bi Qi capsule (1.2g, twice a day) and Calcitriol capsule (0.25ug, once a day). Western Ontario and McMaster Universities Osteoarthritis (WOMAC) was the primary outcome, including pain, stiffness, and function subscale scores. Secondary outcome measures were visual analogue scale (VAS) score for the patients assessment of pain, bone mineral density (BMD), patient’s assessment of function using the Health Assessment Questionnaire (HAQ). Safety was assessed by recording adverse events (AEs). Results: 100 patients were included in the study. 15(15%) patients discontinued the study because of lack of efficacy, adverse events and loss of follow up. At the end of the treatment ,the decrease in WOMAC total score was -8.7(4.9) and -5.4(5.6) and improvement of WOMAC function was -4.88(3.6) and -2.70(3.86) in the Bi Qi group and the controlled group, respectively (p＜0.01). The improvement in BMD of left femoral neck was 0.05(0.2) and -0.01(0.04) , improvement in T score of left femoral neck was 0.15(0.5) and -0.05(0.3) in the Bi Qi group and the controlled group, respectively (p＜0.01). No significant difference was observed between treatment groups for changes in WOMAC pain, WOMAC stiffness, VAS, BMD of lumbar spine, T score of lumber spine and HAQ over 24 weeks. Two adverse events were reported in Bi Qi group: facial edema (n=1), nausea (n=1) and one adverse events was reported in controlled group: lip swelling (n=1). All these adverse events were mild and could be alleviated after withdrawing treatment. Conclusion: It can be concluded that Bi Qi capsule was found to be effective and safe in reducing WOMAC total score, improving WOMAC function and BMD in individuals suffering from KOA.
Epidemiological analysis of Porcine Viral Diarrhea Pathogens in Local Area
Authors: Shi Ying , Li Benqiang , Tao Jie , Cheng Jinghua , liu Huili
Published: February 2020

Background Porcine viral diarrhea can cause great damage to the pig industry and high mortality to piglets. Furthermore, multiple pathogen infections and synergistic infections commonly existed in clinic. This has resulted in great difficulties in determining the main pathogenic factors, which would delay the prevention and control of diseases. Methods A total of 518 porcine stool specimens were collected from 9 pig herds in Shanghai, China from 2015 to 2017 and used for pathogen detection. A Luminex xTAG multiplex detection method was developed for the detection of 11 viral diarrhea pathogens, which allows for the simultaneous qualitative and quantitative detection of viral diarrhea pathogens in clinical samples. Results The minimum detection rate of the Luminex xTAG multiplex detection method was at least 10 times higher than the traditional PCR method. As a result, 209 (40.3%) were positive for porcine kobuvirus (PKoV), 138 (26.6%) for porcine astrovirus (PAstV), 91 (17.6%) for porcine epidemic diarrhea virus (PEDV), 78 (15.1%) for porcine sapelovirus (PSV), 68 (13.1%) for porcine sapovirus (PoSaV), 27 (5.2%) for porcine teschovirus (PTV), 25 (4.8%) for porcine deltacoronavirus (PDCoV), 17 (3.3%) for porcine rotavirus (PoRV), 16 (3.1%) for transmissible gastroenteritis virus (TGEV), 10 (1.9%) for porcine torovirus (PToV), and 9 (1.7%) for bovine viral diarrhea virus (BVDV), respectively. Furthermore, multiple infection rate of diarrhea sample was 17.57% for dual-infection, 11.58%for triple-infection, 4.63% for quadruple-infection, 0.77% for quintuple-infection, 0.58% for sextuple-infection and septuple-infection, respectively. Infection pattern of the viral diarrheal pathogens was changing, and different farm had the various diarrhea infection patterns, which proved the great importance of epidemiological surveillance and the guidance effect to clinical production. PoSaV, PoRV, PAstV, PToV and PEDV were indicated as the predominant viruses of clinical samples collected in 2017 by the quantitative analysis. Conclusions Here we provide a Luminex xTAG multiple detection method for viral diarrhea pathogen infection in clinical,which was more sensitive and specific than general multiplex PCR method. Furthermore, the surveillance confirmed the complicated infection status in China, which demonstrated the need for continuous surveillance and provided data for the prevention and control of viral diarrhea.
An ATP-free packaging of T4 DNA
Authors: Hara Seiko , Koike Isao
Published: February 2020

Packaging of viral DNA into a capsid with the liquid crystalline density is a crucial step of the viral reproduction. The DNA packaging with the ATP fueled molecular motor is an established packaging system of viral DNA. However, the velocity and the efficiency are not well match with the in vivo processes. On the other hand, DNA compacts with the conformational change by multivalent cations exclusively of the valences higher than three. The conformational change of DNA was not considered as the vehicle of DNA packaging of viruses. Here, T4 DNA, ejected from a capsid in the ambient concentration of phosphate corresponding to the intra-cell concentration, is packaged into the capsid when the ambient concentration of phosphate decreases to the extra-cell concentration in the coexistence with divalent cations, Ca2+ and Mg2+. The compaction and packaging process coincide with the conformational change of DNA. Divalent cations can compact T4 DNA when the counter anion is phosphate. The DNA-packaged and re-generated virions showed equivalent infective ability with the original populations. The conformational changes of DNA between compact forms and coil forms were differentiated by the fluorescent microscopy. Identification between packaged- or unpackaged-DNA was confirmed by enzymatically. The infectious ability of the re-generated virions was confirmed by pfu. The concentration of ATP in the packaging process was measured by luminometric method. The packaging is proceeded in pM or lower concentration of ATP. This is a new packaging process of viral DNA practically free from ATP into which conformational change of DNA is incorporated. The conventional and new packaging processes may cooperate to accomplish the DNA packaging process of T4. The results may provide new interpretations of the life cycle of T4.
Infrared and Visible Image Fusion Based on Nonlinear Enhancement and NSST Decomposition
Authors: XING Xiaoxue , LIU Cheng , LUO Cong , XU Tingfa
Published: February 2020

In Multi-scale Geometric Analysis (MGA)-based fusion methods for infrared and visible images, adopting the same representation for the two types of the images will result in the non-obvious thermal radiation target in the fused image, which can hardly be distinguished from the background. To solve the problem, a novel fusion algorithm based on nonlinear enhancement and Non-Subsampled Shearlet Transform (NSST) decomposition is proposed. Firstly, NSST is used to decompose the two source images into low- and high-frequency sub-bands. Then, the wavelet transform(WT) is used to decompose high-frequency sub-bands into obtain approximate sub-bands and directional detail sub-bands. The “average” fusion rule is performed for fusion for approximate sub-bands. And the “max-absolute” fusion rule is performed for fusion for directional detail sub-bands. The inverse WT is used to reconstruct the high-frequency sub-bands. To highlight the thermal radiation target, we construct a non-linear transform function to determine the fusion weight of low-frequency sub-bands, and whose parameters can be further adjusted to meet different fusion requirements. Finally, the inverse NSST is used to reconstruct the fused image. The experimental results show that the proposed method can simultaneously enhance the thermal target in infrared images and preserve the texture details in visible images, and which is competitive with or even superior to the state-of-the-art fusion methods in terms of both visual and quantitative evaluations.
An Easy-to-use Clinical Nomogram for Predicting the Prognosis of Patients with Hepatocellular Carcinoma Concomitantly Suffer from Severe Fibrosis or Cirrhosis: A Population-based Analysis.
Authors: Hanyue Wang , Shiye Ruan , Yiping Zou , Liang Jin , Haosheng Jin , Chaofeng Hu
Published: February 2020

Background Patients with hepatocellular carcinoma (HCC) concomitantly suffer from liver cirrhosis may have worse prognosis. Based on Surveillance, Epidemiology, and End Results (SEER) database, we evaluated the overall survival (OS) and cancer-specific survival (CSS) of these patients. Methods A total of 2,369 patients were selected from the SEER database. They were classified into F0 (n=691) and F1 (n=1,678) groups by different Ishak fibrosis score. Propensity score matching (PSM) and Kaplan-Meier method were performed to evaluate the OS and CSS. The F1 group were randomized into training sub-set (n = 1,176, 70%) and validation sub-set (n = 502, 30%) for further construction and validation of nomogram . Results After matched, there were statistically significant worse outcome for F1 group patients compared with F0 group (n=587, OS: P<0.001, CSS: P<0.001). Six independent predictors for both OS and CSS were identified to construct the nomograms by COX regression analyses. The nomogram performed well concerning its ability of discrimination and calibration and its net benefits compared with the conventional staging system. Conclusions Patients with HCC concomitantly suffer from severe fibrosis or cirrhosis has a significant worse survival compared with none or moderate fibrosis patients. The validated nomograms provided useful prediction of survival.
Possible therapeutic effects of berberine on bone damage in high-fat diet-induced obese rats
Authors: Wang Yan , Chen Fulian , Wang Hongwei , Wang Yan , Zhang Mengqi , Huan Zhikun , Li Jiaxuan , Shao Shanshan , Yu Chunxiao , Xu Jin
Published: February 2020

Background Obesity has a negative impact on bone health; thus far, no specific pharmacotherapy has been approved. Berberine has shown improvements in osteoporosis in some animal models. However, it remains unknown whether berberine ameliorates obesity-induced bone damage. This study aims to evaluate the effect of berberine on bone damage in high-fat diet (HFD)-induced obese rats. Methods Male Sprague-Dawley rats were randomly assigned to a normal control diet (ND) group or HFD group. After the HFD induced obesity, the models were successfully established. Then, these rats were randomly divided into the HFD + berberine (HB) group or HFD group and were intraperitoneally administered berberine or an equivalent volume of DMSO, respectively, once a day for another 10 weeks. Micro-CT and three-point bending tests were conducted to evaluate bone microstructure and biomechanics. Serum was collected for the detection of P1NP, CTX-1, calcium (Ca) and phosphorus (P), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). HE staining was performed to observe the number of trabecular and bone marrow adipocytes. Results HFD-induced obese rats displayed decreased biomechanical properties, such as maximum load, maximum fracture load, ultimate tensile strength, stiffness, and energy absorption, compared with the ND rats (p<0.05). However, berberine attenuated bone damage, including maximum load, maximum fracture load, and stiffness, in the HB group compared with the HFD group (p<0.05). Trabecular bone markers were decreased in the HFD group compared with the ND group (p<0.05). All parameters were improved, as shown by micro-CT and HE staining, in the HB group compared to the HFD group. Cortical bone markers were not significantly different among all groups. Moreover, CTX-1, TNF-α, IL-1β and the number of adipocytes in bone marrow were significantly increased in HFD-induced obese rats. After treatment with berberine, TNF-α, IL-1β and the number of adipocytes in bone marrow were significantly decreased, and P1NP levels were higher in the HB group than in the HFD group. Conclusions Berberine might be a potential therapeutic agent for treating bone damage in HFD-induced obese rats by inhibiting inflammatory factors, reducing bone marrow adiposity and improving bone formation.
DeepSeqPanII: an interpretable recurrent neural network model with attention mechanism for peptide-HLA class II binding prediction
Authors: LIU ZHONGHAO , Jin Jing , Cui Yuxin , Xiong Zheng , Nasiri Alireza , Zhao Yong , Hu Jianjun
Published: February 2020

Background: Human leukocyte antigen (HLA) complex molecules play an essential role in immune interactions by presenting peptides on the cell surface to T cells. With significant progress in deep learning, a series of neural network based models have been proposed and demonstrated with their good performances for peptide-HLA class I binding prediction. However, there still lack effective binding prediction models for HLA class II protein binding with peptides due to its inherent challenges. In this work, we present a novel sequence-based pan-specific neural network structure, DeepSeaPanII, for peptide-HLA class II binding prediction. Compared with existing pan-specific models, our model is an end-to-end neural network model without the need for pre- or post-processing on input samples. Results: The leave-one-allele-out cross validation and benchmark evaluation results show that our proposed network model achieved state-of-the-art performance in HLA-II peptide binding. Besides state-of-the-art performance in binding affinity prediction, DeepSeqPanII can also extract biological insight on the binding mechanism over the peptide and HLA sequences by its attention mechanism based binding core prediction capability. Conclusions: In this work, we present a novel neural network structure for peptide-HLA class II binding prediction. It has state-of-the-art performance and could display insightful information it learned benefiting from attention module we carefully designed. Without requiring additional data, this structure could be applied to other related sequence problems. The source code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPanII.
Propionic acid induces dendritic spine loss by MAPK/ERK signaling and dysregulation of autophagic flux
Authors: Choi Hyosun , Mun Ji Young
Published: February 2020

Propionic acid (PPA) is a short-chain fatty acid that is an important mediator of cellular metabolism. It is also a by-product of human gut enterobacteria and a common food preservative. A recent study found that rats administered with PPA showed autistic-like behaviors like restricted interest, impaired social behavior, and impaired reversal in a T-maze task. This study aimed to identify a link between PPA and autism phenotypes facilitated by signaling mechanisms in hippocampal neurons. Findings indicated autism-like pathogenesis associated with reduced dendritic spines in PPA-treated hippocampal neurons. To uncover the mechanisms underlying this loss, we evaluated autophagic flux, a functional readout of autophagy, using relevant biomedical markers. Results indicated that autophagic flux is impaired in PPA-treated hippocampal neurons. At a molecular level, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway was activated and autophagic activity was impaired. We also observed that a MAPK inhibitor rescued dendritic spine loss in PPA-treated hippocampal neurons. Taken together, these results suggest a previously unknown link between PPA and autophagy in spine formation regulation in hippocampal neurons via MAPK/ERK signaling. Our results indicate that MAPK/ERK signaling participates in autism pathogenesis by autophagy disruption affecting dendritic spine density. This study may help to elucidate other mechanisms underlying autism and provide a potential strategy for treating ASD-associated pathology.
Comparison of senescence-related changes between three- and two-dimensional cultured adipose-derived mesenchymal stem cells
Authors: Yin Qiliang , Xu Na , Xu Dong sheng , Dong Ming xin , Shi Xiu min , Wang Yan , Hao Zhuo , Zhu Shuang shuang , Zhao Dong hai , Jin Hao fan , Liu Wen sen
Published: February 2020

Background: Adipose-derived mesenchymal stem cells ( ADMSCs ) have attracted widespread interest as cell-based tissue repair systems. To obtain adequate quantities of ADMSCs for therapeutic applications, extensive in vitro expansion is required. However, under current two-dimensional (2D) approaches , ADMSCs rapidly undergo replicative senescence , and cell growth is impeded and stem cell properties are eliminated by mechanisms that are poorly understood . These issues limit the extensive applications of ADMSCs . In this study, we investigated senescence-related changes in mesenchymal stem cells (MSCs) isolated from human adipose tissue in 2D and three-dimensional (3D) cultures. Methods: We studied cell growth over a given period (21 days) to determine if modes of culture were associated with ADMSCs senescence. ADMSCs were isolated from healthy females by liposuction surgery and then were grew in 2D and 3D cultures. The cell morphology was observed during cell culture. Every other time of culture, senescence-associated β-galactosidase (SA-β-gal) expression, cell viability, and differentiation potential of ADMSCs from 2D and 3D cultures were detected. Also, senescence and stemness related genes expression, telomere length, telomerase activity, and energy metabolism of ADMSCs for different culture time were evaluated. Results: With long-term propagation, we observed significant changes in cell morphology, proliferation, differentiation abilities and energy metabolism, which were associated with increases in SA-β-gal activity, and decreases in telomere length and activity . Notably, when cultured in 3D, these changes were improved. Conclusions: Our results indicate that 3D culture is able to ameliorate senescence-related changes in ADMSCs.
“Moving forward with life’: Perceived acceptability and benefits of a brief alcohol-focused intervention for people receiving antiretroviral therapy in South Africa.
Authors: Myers Bronwyn , Parry Charles , Morojele Neo , Nkosi Sebenzile , Shuper Paul , Kekwaletswe Connie , Sorsdahl Katherine
Published: February 2020

Background: In South Africa, like other low-and middle-income countries, interventions are needed to address the impact of hazardous drinking on adherence to antiretroviral therapy among people living with HIV (PLWH). Participant feedback about these interventions can identify ways to enhance their acceptability and potential impact. As part of a randomized controlled trial of a brief motivational interviewing and problem-solving therapy (MI-PST) intervention among PLWH who report hazardous drinking, we interviewed participants about their perceptions of this alcohol-reduction intervention.Methods: The trial was conducted in HIV treatment clinics operating from 6 hospitals in the Tshwane region of South Africa. In the trial, 305 participants were randomly assigned to the intervention comprising four modules of MI-PST delivered over two sessions. We conducted qualitative in-depth interviews of participants’ views about the acceptability and usefulness of the intervention for facilitating behaviour change on completion of the last intervention session and at the six-month study end-point. Twenty-four participants were interviewed after the final intervention session and 25 at the six-month follow up. Data were analysed using the framework approach. Results: Three themes emerged from the interviews that reflect participants’ perceptions of the acceptability and usefulness of this intervention. The first theme describes participants’ perceptions of the acceptability of screening and brief alcohol-focused interventions for PLWH. The second theme describes participants’ views of the usefulness of the intervention for reducing alcohol use and addressing life stressors. The third theme reflects participants’ views on how the intervention could be modified for greater reach and impact.Conclusion: Findings suggest that participants considered this intervention to be acceptable and useful for facilitating reductions in alcohol consumption. This study is the first to describe how PLWH applied the skills taught in the MI-PST intervention to manage and cope with daily problems instead of drinking heavily.
Identification of grade-specific diagnostic and prognostic biomarkers of key candidate genes and pathways in breast cancer by integrated bioinformatics analysis
Authors: Zhang HanYu , Zhou XiuLing , Zhang XiaoMing , Yu ZhongYu , Wang JianTao , Guo XinYu , Hu Yue , GUO JingChun , Tao YingHong , Zhou HouGuang
Published: February 2020

Purpose: Breast cancer (BC) is the most common malignant tumor in women. Due to the mechanism of BC has not yet been completely clear, we aim to identify the key pathway and genes in BC based on bioinformatics method. Methods: Samples were obtained from NCBI-GEO website. Then, GEO2R tools and Venn diagram software were used to identify the differentially expressed genes (DEGs). Next, analyze Kyoto Encyclopedia of Gene and Genome (KEGG) pathway and gene ontology (GO) were analyzed by Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction (PPI) network was drew by Search Tool for the Retrieval of Interacting Genes (STRING). Afterwards, we selected the core genes from PPI network by Molecular Complex Detection (MCODE) plug-in. And we performed Kaplan-Meier analysis to assess the overall survival of the core genes. Last Gene Expression Profiling Interactive Analysis (GEPIA) was used to discover highly expressed genes in BC. Results: DEGs contained 23 up-regulated and 32 down-regulated genes. GO described molecular function (MF), cellular component (CC), and biological process (BP). KEGG pathway showed DEGs were mainly involved in ECM-receptor interaction, p53 signaling pathway, PPAR signaling pathway, signaling pathways regulating pluripotency of stem cells, cGMP-PKG signaling pathway and Tyrosine metabolism. Finally, we screened 15 core genes, 14 of which had adverse prognosis and high expression in BC. Conclusions: In the current study, 14 core genes of BC were identified based on bioinformatics method, which could useful to provide essential information for early diagnosis and treatment of BC.
Whole transcriptome analyis of human lung tissue to identify COPD-associated gene
Authors: Zhu Yizhang , Li Qiuyu , Zhou Aiyuan , Racanelli Alexandra C. , Choi Augustine M.K. , Yin Yuxin
Published: February 2020

Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent respiratory symptoms and airflow restriction. The mechanisms underlying pathogenesis in COPD are still poorly understood. Identification of the dysfunctional genes in human lung from patients with Chronic obstructive pulmonary disease (COPD) will help up to understand the pathology of this disease. To identify the dysfunctional genes in human lung from patients with Chronic obstructive pulmonary disease (COPD). We used transcriptomic data of lung tissue for 91 COPD cases and 182 matched healthy controls from the Genotype-Tissue Expression (GTEx) database. We employed a stringent model controlling for known covariates and hidden confounders. DESeq2 R package (v1.20.0) was used to test for differential expression.Results: We identified 1,359 significant differentially expressed genes (DEG) with 707 upregulated and 602 downregulated respectively. We evaluated the identified DEGs in an independent microarray cohort of 219 COPD and 108 controls, demonstrating the robustness of our result. Functional annotation of COPD-associated genes highlighted the activation of complement cascade, dysregulation of inflammatory response and extracellular matrix organization in the COPD patients. In addition, we identified several novel key-hub genes involved in the COPD pathogenesis using a network analysis method.Conclusion: In summary, our study represents the comprehensive analysis of gene expression on COPD with the largest sample size, providing great resource for the molecular research in the COPD community.
Identification of Potential Crucial Genes in Atrial Fibrillation: A Bioinformatic Analysis
Authors: Zhang Junguo , Huang Xin , Wang Xiaojie , Gao Yanhui , Liu Li , Li Ziyi , Chen Xuejiao , Zeng Jie , Ye Zebing , Li Guowei
Published: February 2020

Background Atrial fibrillation (AF) is clearly heritable, affecting 2-3% of the population in Europe and the USA. However, a substantial proportion of heritability is still lacking. In the present study, we aim to identify potential crucial genes associated with AF through bioinformatic analyses of public datasets.Methods Microarray data sets of GSE115574, GSE31821, GSE79768, GSE41177 and GSE14975 from the Gene Expression Omnibus (GEO) database were enrolled. After merging all microarray data and adjusted batch effect, differentially expressed genes (DEGs) were identified. Functional enrichment analyses based on Gene Ontology (GO) resource, Kyoto Encyclopedia of Genes and Genomes (KEGG) resource, Gene Set Enrichment Analysis (GSEA), Reactome Pathway Database and Disease Ontology (DO) were carried out for DEGs. Protein-protein interaction (PPI) network was constructed using the STRING database. Combined with aforementioned significant bioinformatics information, potential crucial genes were subsequently selected. The potential crucial genes coupled with corresponding predicted microRNAs involved in AF were then assessed.Result We identified 27 of DEGs with gene expression fold change (FC) ≥ 1.5 and 5 with FC ≥ 2 of AF patients compared with sinus rhythm controls. The most significantly enriched pathway was regulation of insulin-like growth factor transport and uptake by insulin-like growth factor binding proteins. IGFBP2, C1orf105, FHL2, CHGB, ATP1B4, IGFBP3, SLC26A9, CXCR4 and HTR2B were considered the potential crucial genes. Sixteen corresponding predicted microRNAs, of which 5 targeting IGFBP3 and 8 FHL2, might be associated with AF. The comparative toxicogenomics database (CTD) database showed CXCR4, IGFBP2, IGFBP3 and FHL2 had higher scores with AF.Conclusions The 9 potential crucial genes, especially CXCR4, IGFBP2, IGFBP3 and FHL2, may be associated with risk of AF. MicroRNAs targeting IGFBP3 and FHL2 may be potential biomarkers or therapeutic targets for AF. Our study provided new insights of AF into genetics, molecular pathogenesis and new therapeutic targets.
Identification of bipolar disorder using a combination of multimodality magnetic resonance imaging and machine learning techniques
Authors: Li Hao , Cui Liqian , Cao Liping , Zhang Yizhi , Liu Yueheng , Deng Wenhao , Zhou Wenjin
Published: February 2020

Background Bipolar disorder (BPD) is a common mood disorder that is often goes misdiagnosed or undiagnosed. Recently, machine learning techniques have been combined with neuroimaging methods to aid in the diagnosis of BPD. However, most studies have focused on the construction of classifiers based on single-modality MRI. Hence, in this study, we aimed to construct a support vector machine (SVM) model using a combination of structural and functional MRI, which could be used to accurately identify patients with BPD. Methods In total, 44 patients with BPD and 36 healthy controls were enrolled in the study. Clinical evaluation and MRI scans were performed for each subject. Next, image pre-processing, voxel-based morphometry (VBM), and ReHo analyses were performed. The grey matter volumes or ReHo values of the clusters showed significant differences as discriminant features in the SVM classification model. Based on extracted features, the SVM model was established, and discriminant analysis was performed. Results After using the two-sample t-test with multiple comparisons, 12 clusters with significant differences were extracted from the data. Next, we used both VBM and ReHo data to construct the new SVM classifier, which could effectively identify patients with BPD at an accuracy of 90% in the test data (p=0.0014). Limitations The sample size was small, and we were unable to eliminate the potential effects of medications. Conclusions A combination of structural and functional MRI can be of added value in the construction of SVM classifiers to aid in the accurate identification of BPD in the clinic.
Effect of atorvastatin on AGEs-induced injury of cerebral cortex via inhibiting NADPH oxidase -NF-κB pathway in ApoE-/- mice
Authors: li zhenhan , Yang Peiye , Feng Bo
Published: February 2020

Background There is close association between type 2 diabetes and cognitive impairment. AGEs-RAGE pathway plays critical role to induce neurodegenerative encephalopathy. Statins can reduce the expression of AGEs-induced RAGE in aorta. It is not clear whether statins have potential benefits on AGEs-induced cognitive impairment. In this study, the effects of atorvastatin on inflammation and oxidation stress in cerebral cortex were investigated and the underlying mechanisms were explored. Methods 40 male ApoE-/- mice were randomly divided into four groups: control, AGEs (30mg/kg/day), AGEs (30mg/kg/day) + ALT711 (1mg/kg/day) and AGEs (30mg/kg/day) + ATV (10mg/kg/day). Aβ formation in cerebral cortex was assessed through Congo red staining and the functional state of neurons were evaluated by Nissl's staining. Immunostaining was performed to assess the accumulation of AGEs in the cerebral cortex. The expressions of mRNA and protein of RAGE, NF-κB p65 and NADPH oxidase p47phox were detected by Real-time PCR and Western blot. Results There were significant increases in AGE deposit, Aβ formation and the expressions of RAGE, NF-κB p65 and NADPH oxidase p47phox and decrease in Nissl body in AGEs group compared with control group. ALT711 recovered above change compared with AGEs group. Atorvastatin reduced Aβ formation and suppressed AGEs-induced expressions of NF-κB p65 and NADPH oxidase p47phox. Atorvastatin has little effects on AGE deposit and RAGE expressions. Conclusions Atorvastatin alleviates AGEs-induced neuronal impairment via inhibiting NADPH oxidase-NF-κB pathway and is of benefit in preventing the progression of degenerative encephalopathy.
Long noncoding RNA TTN-AS1 promotes breast cancer cell migration and invasion via sponging miR-140-5p
Authors: Li Yusheng , Wang Fan
Published: February 2020

Objectives Breast cancer (BC) is one of the most ordinary fatal cancers. Recent studies have identified the vital role of long noncoding RNAs (lncRNAs) in the development and progression of BC. In this research, lncRNA TTN-AS1 was studied to identify how it functioned in the metastasis of BC.Methods TTN-AS1 expression of tissues was detected by RT-qPCR in 56 BC patients. Wound healing assay and transwell assay were used to observe the biological behavior changes of BC cells through gain or loss of TTN-AS1. In addition, luciferase assays and RNA immunoprecipitation (RIP) assay were performed to discover the potential targets of TTN-AS1 in BC cells.Results TTN-AS1 expression level in BC samples was higher than that of adjacent ones. Besides, cell migrated ability and cell invaded ability of BC cells were inhibited after TTN-AS1 was silenced. Cell migrated ability and cell invaded ability of BC cells were promoted after TTN-AS1 was overexpressed. In addition, miR-140-5p was upregulated after silence of TTN-AS1 in BC cells, while miR-140-5p was downregulated after overexpression of TTN-AS1 in BC cells. Furthermore, luciferase assays and RNA immunoprecipitation assay (RIP) showed that miR-140-5p was a direct target of TTN-AS1 in BC.Conclusion Our study uncovers a new oncogene in BC and suggests that TTN-AS1 could enhance BC cell migration and invasion via sponging miR-140-5p, which provides a novel therapeutic target for BC patients.
Quality of life in older people with dementia: using nursing staff and family members as proxies
Authors: Schneider Daniel , Winter Vera , Konnopka Alexander
Published: February 2020

Background To assess health-related quality of life (QoL) of nursing home residents with dementia using the nursing staff and the residents’ family members as proxy raters, to determine the level of agreement between both groups, and to analyze how functional independence, the number of challenging behaviors, nursing home suitability, and the rater group influence QoL assessments.Methods Nursing staff and family members assessed residents’ QoL using the short version of the Quality of Life in Dementia (QUALIDEM) instrument. The nursing staff also assessed functional independence and the number of challenging behaviors, while nursing home suitability was assessed by the nursing staff and family members. Multiple linear regressions were run with each QoL dimension as the dependent variable.Results The agreement between nursing staff and family members on the QoL dimensions, for n=53 residents with dementia, was relatively poor, and for each QoL dimension, the reported scores were higher among the nursing staff. Residents’ functional independence and the nursing home suitability were associated with a higher QoL, and more challenging behaviors were associated with a lower QoL, particularly according to the assessments of the nursing staff.Conclusion Including family members as an additional rater group is recommended as a valuable way to discuss and possibly improve quality of care and QoL. Keywords: nursing homes, health-related quality of life, proxy ratings