bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTK7-Targeting CAR T-cells for the Treatment of Lung Cancer and other Malignancies
Authors: Jie Yamin , Liu Guijun , Feng Lina , Li Ying , E Mingyan , Wu Liangliang , Rong Guanghua , Li Yongwu , Wei Huafeng , Gu Anxin 
Published: July 2020

Abstract
Background: In spite of impressive success in treating hematologic malignancies, adoptive therapy with chimeric antigen receptor modified T cells (CAR T) has not yet been effective in solid tumors, where identification of suitable tumor-specific antigens remains a major obstacle for CAR T-cell therapy due to the “on target off tumor” toxicity. Protein tyrosine kinase 7 (PTK7) is a member of the Wnt-related pseudokinases and identified as a highly expressed antigen enriched in cancer stem cells (CSCs) from multiple solid tumors, including but not limited to triple-negative breast cancer, non-small cell lung cancer, and ovarian cancer, suggesting it may serve as a promising tumor-specific target for CAR T-cell therapy. Methods: In this study, we constructed 3 different PTK7-specific CAR (PTK7-CAR1/2/3) each comprising a humanized PTK7-specific single chain variable fragment (scFv), hinge and transmembrane (TM) regions of the human CD8α molecule, 4-1BB intracellular co-stimulatory domain (BB-ICD), and CD3ζ intracellular domain (CD3ζ-ICD) sequence, and then prepared the CAR T cells by lentivirus mediated transduction of human activated T cells accordingly, and sequentially evaluated their antigen-specific recognition and killing activity in vitro and in vivo.Results: T cells transduced with all 3 PTK7-CAR candidates exhibited antigen-specific cytokine production and potent cytotoxicity against naturally expressing PTK7-positive tumor cells of multiple cancer types without mediating cytotoxicity of a panel of normal primary human cells; meanwhile, in vitro recursive cytotoxicity assays demonstrated that only PTK7-CAR2 modified T cells retained effective through multiple rounds of tumor challenge. Using in vivo xenograft models of lung cancers with different expression level of PTK7, systemic delivery of PTK7-CAR2 modified T cells significantly prevented tumor growth and prolonged overall survival of mice. Conclusion: Altogether, our results support PTK7 as a therapeutic target suitable for CAR T-cell therapy that could be applied for lung cancers and many other solid cancers with PTK7 overexpression.
The molecular basis of socially-mediated phenotypic plasticity in a eusocial paper wasp
Authors: Taylor Benjamin , Cini Alessandro , Wyatt Christopher , Reuter Max , Sumner Seirian 
Published: July 2020

Abstract
Phenotypic plasticity, the ability to produce multiple phenotypes from a single genotype, represents an excellent model with which to examine the relationship between gene expression and phenotypes. Despite this, analyses of the molecular bases of plasticity have been limited by the challenges of linking individual phenotypes with individual-level gene expression profiles, especially in the case of complex social phenotypes. Here, we tackle this challenge by analysing the individual-level gene expression profiles of Polistes dominula paper wasps following the loss of a queen, a perturbation that induces some individuals to undergo a significant phenotypic shift and become replacement reproductives. Using a machine learning approach, we find a strong response of caste-associated gene expression to queen loss, wherein individuals’ expression profiles become intermediate between queen and worker states. Importantly, this change occurs even in individuals that appear phenotypically unaffected. Part of this response is explained by individual attributes, most prominently age. These results demonstrate that large changes in gene expression may occur in the absence of detectable phenotypic changes, resulting here in a socially mediated de-differentiation of individuals at the transcriptomic but not the phenotypic level. Our findings also highlight the complexity of the relationship between gene expression and phenotype, where transcriptomes are neither a direct reflection of the genotype nor a proxy for the molecular underpinnings of the external phenotype.
Hybrid memristor-CMOS neurons for in situ learning in fully hardware memristive spiking neural networks
Authors: Zhang Xumeng , Lu Jian , Wang Rui , Wei Jinsong , Shi Tuo , Dou Chunmeng , Wu zuheng , Shang Dashan , Xing Guozhong , Liu Qi , Liu Ming 
Published: July 2020

Abstract
Spiking neural network, consisting of spiking neurons and plastic synapses, is a promising but relatively underdeveloped neural network for neuromorphic computing. Inspired by the human brain, it provides a unique solution for highly efficient data processing. Recently, memristor-based neurons and synapses are becoming intriguing candidates to build spiking neural networks in hardware, owing to the close resemblance between their device dynamics and the biological counterparts. However, the functionalities of memristor-based neurons are currently very limited, and a hardware demonstration of fully memristor-based spiking neural networks supporting in situ learning is very challenging. Here, a hybrid spiking neuron by combining the memristor with simple digital circuits is designed and implemented in hardware to enhance the neuron functions. The hybrid neuron with memristive dynamics not only realizes the basic leaky integrate-and-fire neuron function but also enables the in situ tuning of the connected synaptic weights. Finally, a fully hardware spiking neural network with the hybrid neurons and memristive synapses is experimentally demonstrated for the first time, with which in situ Hebbian learning is achieved. This work opens up a way towards the implementation of spiking neurons, supporting in situ learning for future neuromorphic computing systems.
Evaluation of the effects of an interdisciplinary lifestyle and health program for adolescents and its benefits for maintaining health.
Authors: Schuster Anja , Schwenoha Karin , Oberkofler Edith , Lirk Gerald , Ardelt-Gattinger Elisabeth , Weghuber Daniel , Ring-Dimitriou Susanne , Freudenthaler Thomas , Oostingh Gertie J. , Bogner Barbara 
Published: July 2020

Abstract
Background

Obesity numbers have doubled worldwide since 1980, leading to individual life-quality threatening issues and a socioeconomic challenge. A number of school programs have been initiated to prevent the epidemic-like spreading of obesity.
Methods

109 adolescents (42 females and 67 males aged 15.0 ± 0.7 years) were included into this six-month interdisciplinary school-based study. The aim was to assess various implementation outcomes based on the effect of health education, including the promotion of healthy eating patterns and a limitation of sugar-containing beverage consumption via the feedback of analysed anthropometric data, biomedical parameters, physical fitness tests and an eating and physical activity behaviour questionnaire.
Results

Overall, the results demonstrated a positive effect on body fat content and physical activity. In addition, a trend towards a benefit on parameters of muscle and fat metabolism was detected.
Conclusions

An interdisciplinary life-style program integrated into the school curriculum is suited to have a positive impact on health outcomes. By enhancing the awareness for healthy nutrition and the importance of physical activity, self-empowerment was increased, resulting in an improvement of health-associated parameters.
Evolutionary and genomic analysis of four SARS-CoV-2 isolates circulating in March 2020 in Sri Lanka; Additional evidence on multiple introduction and further transmission
Authors: Satharasinghe Dilan Amila , Parakatawella Parakatawella Mudiyanselage Shalini Daupadi Kumari , Premarathne Jayasekara Mudiyanselage Krishanthi Jayarukshi Kumari , Jayasooriya L. J.P. Anura P. , Prathapasinghe Gamika A. , Yeap Swee Keong 
Published: July 2020

Abstract
The molecular epidemiology of the virus, and mapping help to understand the evolution of the epidemics and apply quick control measures. The study genomic evidence of multiple SARS-CoV-2 introductions into Sri Lanka and virus evolution during circulation. Whole-genome sequences of four SARS-CoV-2 strains obtained from COVID-19 positive patients reported in Sri Lanka during March 2020 were compared with sequences from Europe and elsewhere. The phylogenetic analysis revealed that the sequence of the sample of first local patient collected on 10th March, who contacted tourists from Italy, was clustered with SARS-CoV-2 strains collected from Italy, Germany, France and Mexico. Subsequently, the sequence of the isolate obtained on 19th March also clustered in the same group with the samples collected in March and April from Belgium, France, India, and South Africa. The other two strains of SARS-CoV-2 were segregated from the main cluster, and the sample collected from 16th March clustered with England and the sample collected on 30th March showed the highest genetic divergent to the isolate of Wuhan, China. Here we report the first molecular epidemiological study conducted on circulating SARS-CoV-2 in Sri Lanka. The finding provides the robustness of molecular epidemiological tools and its application in tracing possible exposure in disease transmission during the pandemic.
The effect and mechanism of Dufulin in controlling tomato yellow leaf curl virus on tomato plants
Authors: Huang Liping , Wang Shuaixin , Zhang Zhuo , Zhou Xuguo , Zhang Zhanhong , Zheng Limin , Gao Yang , Hu Fang , Zhang Deyong , Tan Xinqiu , Shi Xiaobin , Liu Yong 
Published: July 2020

Abstract
Background: Tomato yellow leaf curl virus (TYLCV) causes critical production loss in tomato cultivation. The control of TYLCV in tomato is done mainly by using pesticide which is difficult and expensive, making it essential to find an environmentally friendly chemical agent to control TYLCV. Dufulin has been widely used to prevent and control viral diseases in tobacco and rice in recent years. In this study, we investigated the effect and mechanism of Dufulin on TYLCV on tomato plants.Methods: The control effect of Dufulin on TYLCV was evaluated by field experiments. The expression level of PI II and NPR1 in healthy and TYLCV-infected tomato after treatments were determined by Real-time fluorescent quantitative PCR (qRT-PCR). Handheld chlorophyll meter was applied to compare the content of chlorophyll and nitrogen in healthy and TYLCV-infected tomato after treatments.Results: It showed that the relative control effect of 20% Dufulin on TYLCV reached above 68% in 2018 to 2020. Jasmonic acid (JA) level was higher on healthy tomato, but lower on TYLCV-infected tomato plants treated with Dufulin compared to control. Salicylic acid (SA) level was higher on healthy and TYLCV-infected tomato plants treated with Dufulin compared to control. Chlorophyll content on healthy and TYLCV-infected tomato plants was higher after treatment with Dufulin compared to control. Nitrogen content on tomato plants showed no significant difference after spraying Dufulin compared to control.Conclusions: We found the first evidence of control effects TYLCV using Dufulin. It induced plant defense and increased plant chlorophyll content to help plants resist infection which is helpful for future control of TYLCV in tomato.
Establishment of a clinical nomogram model to predict the progression of COVID-19 to severe disease
Authors: tu changli , Wang Guojie , Tan Cuiyan , Chen Meizhu , Xiang Zijun , Peng Hu , Wang Ying , Liang Yingjian , Huang Yiying , Wang Zhenguo , Wu Jian , Cao Qizhen , Han Qiang , Xu Lin , Huang Jin , Zheng Xiaobin , Chen Qiuyue , Geng Yayuan , Guo Na , Zhou Xiaorong , Liu Xinran , Cui Ning , Liu Jing , Shan Hong 
Published: July 2020

Abstract
Background

Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aimed to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely, efficient manner.
Methods

This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed with the discrimination curve.
Results

Risk factors, including demographics data, symptoms, laboratory and image findings were recorded for the 202 patients. Eight of the 52 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model; they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. Sensitivity, specificity and AUC were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset.
Conclusions

We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.
Informing the real-world implementation of a home-based physical activity program for mothers at risk of postnatal depression: Perspectives from key stakeholders.
Authors: Teychenne Megan , Apostolopoulos Maria , Ball Kylie , Olander Ellinor K , Opie Rachelle S , Rosenbaum Simon , Laws Rachel 
Published: July 2020

Abstract
Background Physical activity (PA) is a modifiable risk factor for postnatal depression (PND) and programs are needed to enhance PA amongst women at risk of PND. Key stakeholder involvement in informing development and implementation of such programs is vital. However, little research demonstrates key stakeholder insights to inform development and implementation of PA programs for improving PND. The aim of this study was to explore key stakeholder perspectives on the design and delivery of a home-based PA program for mothers with PND symptoms to inform future real-world implementation and scale-up.Methods In September to November 2019, representatives from various key stakeholder organisations involved in postnatal PA and/or mental health, public health and policy in Australia (n = 11) participated in semi-structured interviews exploring their perceptions on the design and delivery of a home-based PA program for mothers with PND symptoms. The interview schedule was informed by both the Consolidated Framework for Implementation Research (CFIR) and the PRACTical planning for Implementation and Scale-up (PRACTIS) guide. Thematic analyses were used for qualitative data.Results The relative priority of PND and PA was high for most organisations involved, although none implemented PA programs supporting women at risk of PND. Most stakeholders perceived the program as appealing due to addressing barriers to postnatal PA, although identified some feasibility issues regarding funding and delivery mechanisms. Suggestions for program adaptations included an equity focus (e.g. providing socioeconomically disadvantaged women with a greater program dose; translating web-app based content into various languages). Planned components of the program were suggested to align (i.e. relative advantage) with existing initiatives (e.g. equipment hire for nurseries scheme) and screening systems for PND (timing of referral). Perceived barriers to scale-up included logistics/cost of equipment, organisational capacity demands and safety risks/liability. Perceived enablers to scale-up included linking the program with ‘adjunct’ programs and services.Conclusions While the program was appealing and most organisations could see a role in endorsing and/or referring to the program, funding and delivery mechanisms still need to be identified.
The prevalence of low health literacy and its socio-demographic risk factors in Hebei: a provincially cross-sectional survey
Authors: Yang Qiuxia , Yu Shuli , Wang Changhong , Gu Guoxiao , Yang Ziwen , Liu Huihui , Lin Linghui , Qiao Yu , Yu Lijing , Feng Qiang , Niu Guangxu 
Published: July 2020

Abstract
Background: This study aimed to evaluate the prevalence of low health literacy in Hebei Province of China, and to investigate its socio-demographic risk factors.Methods: This study was a community-based, cross-sectional questionnaire survey with a multiple-stage randomization design and a sample size of 10560. Participants’ health literacy status was evaluated by a questionnaire based on the 2012 Chinese Resident Health Literacy Scale. Meanwhile, participants’ socio-demographic characteristics were also collected by the questionnaire.Results: A total of 9952 participants provided valid questionnaires and were included in the final analyses. The mean health literacy score was 63.1±17.1 points; for its subscales, the mean basic knowledge and concepts score, lifestyle score, health-related skills score were 31.7±9.0, 17.2±4.8, 14.3±4.1, respectively. Meanwhile, low health literacy prevalence was 81.0%; for its subscales, low basic knowledge and concepts prevalence (70.6%) was numerically reduced compared to low lifestyle prevalence (87.4%) and low health-related skills prevalence (86.1%). Further analyses showed that age, male and rural area were positively associated, but education level and annual household income were negatively associated with low health literacy prevalence. Further multivariate logistic regression analyses showed that higher age, male, lower education level, lower annual household income and rural area were closely correlated with the risks of low total health literacy or low health literacy in subscales in Hebei Province.Conclusion: The prevalence of low health literacy is 81.0% in Hebei Province. Meanwhile, higher age, male, lower education level, lower annual household income and rural area closely associate with low health literacy risk.
N2-3 Stage Nasopharyngeal Carcinoma Patients With Cervical Node Necrosis And Extracapsular Spread Benefit From Capecitabine Maintenance Chemotherapy
Authors: Liu Ting , Liu Siwen , Gu Yuting , Wen Xuehua 
Published: July 2020

Abstract
Purpose: The purpose of this study was to analyze the efficacy and toxicities of concurrent chemoradiotherapy plus capecitabine maintenance chemotherapy for N2-3 stage nasopharyngeal carcinoma (NPC) with cervical node necrosis (CNN) and extracapsular spread(ECS).Patients and methods: This study included 283 N2-3 stage NPC patients with CNN and extracapsular spread who were treated with concurrent chemoradiotherapy. The prescribed doses delivered to the planning target volumes (PTVs), PTVnx, PTVnd, PTV1, and PTV2, were 68–72, 66–70, 60–64, and 52–56 Gy, respectively, in 30–32 fractions. All patients received induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin alone (80–100 mg/m2, day 1, every 21 days is a cycle).Two weeks after completion of concurrent chemoradiotherapy, oral capecitabine (twice daily after meals for 14 consecutive days every 3 weeks) was administered to maintenance chemotherapy patients. Maintenance chemotherapy was administered for 6 months.Results: The 5-year overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 84.8%, 95.4%, and 86.6%, respectively, for all patients. The 5-year OS rates for patients who accepted capecitabine maintenance chemotherapy (group 1) and patients without maintenance chemotherapy (group 2) were 93.8% and 82.1% (P=0.021), respectively. The 5-year LRFS rates for groups 1 and 2 were 96.9% and 95.0% (P=0.467), respectively. The 5-year DMFS rates for groups 1 and 2 were 93.8% and 84.4% (P=0.044), respectively. Hand-Foot syndrome, myelotoxic effects, fatigue, and gastrointestinal symptoms were the common but not severe (grades 1–2) toxicities of the capecitabine maintenance chemotherapy.Conclusion: Capecitabine maintenance chemotherapy improves the outcome and reduces the occurrence of distant failure in N2-3 stage NPC patients with CNN and extracapsular spread. The side effects of treatment were generally tolerated. More clinical trials are required to evaluate the efficacy and toxicity of it.
Unimproved water sources in Ethiopia: Spatial variation and household point-of-use treatment practice based on 2016 Demographic and Health Survey
Authors: Tefera Yohannes , Geremew Abraham 
Published: July 2020

Abstract
Background

Improved water sources are not equally available in all geographical regions. Populations dependent on unsafe water sources are recommended to treat their water at point-of-use using adequate methods to reduce associated health problems. In Ethiopia, the spatial distribution of households using unimproved water sources have been incomplete or ignored in most of the studies. Moreover, evidence on the point-of-use water treatment practice of households dependent on such water sources is scarce. Therefore, the current study is intended to analyse the spatial distribution of unimproved water sources by wealth quintiles at country level and point-of-use treatment practices using nationally representative data.
Method:

The data of 2016 Ethiopian Demographic and health survey (EDHS) conducted on 16650 households from 643 clusters were used for the analysis. For spatial analysis, the raw and spatially smoothed coverage data was joined to the geographic coordinates based on DHS cluster identification code. Global spatial autocorrelation was performed to analyse whether the pattern of unimproved water coverage is clustered, dispersed, or random across the study areas. Once a positive global autocorrelation was confirmed, a local spatial autocorrelation analysis was applied to detect local clusters. The point-of-use water treatment is analysed based on reported use of either boiling, bleach, filtration or SODIS.
Result

There were 5005 households using unimproved water sources for drinking purpose. Spatial variation of unimproved water coverage was observed with high coverage observed at Amhara, Afar, Southern Nations Nationalities and People and Somalia regions. Disparity in unimproved water coverage between wealth quintiles was also observed. The reported point-of-use water treatment practices among these households is only 6.24%. The odds of point-of-use water treatment among household heads with higher education status is 2.5 times high (95%CI = 1.43–4.36) compared to those who did not attend education.
Conclusion

An apparent clustering trend with high unimproved water coverage was observed between regions and among wealth quintiles hence indicates priority areas for future resource allocation and the need for regional and national policies to address the issue. Promoting households to treat water prior to drinking is essential to reduce health problems.