bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Assembly Study of Type I Collagen Extracted from Male Wistar Hannover Rat Tail Tendons
Authors: González-Masís Jeimmy C. , Cubero-Sesin Jorge M. , Corrales-Ureña Yendry Regina , Guerrero Simón , González-Camacho Sara , Mora-Ugalde Nohelia , Vega-Baudrit José Roberto , Gonzalez-Paz Rodolfo J.
Published: July 2020

Background: Collagen is the main structural protein in the extracellular matrix in the numerous connective tissues in the body. As the main component of connective tissue, it is the most abundant protein in mammals. Method: Collagen Type I from Wistar Hannover rat tail was obtained and it allowed to describe the thermodynamic profile during self-assembly by isothermal titration calorimetry (Nano ITC) as a novel technique. Results: The enthalpy of self-assembly of the 0,01035 moles of collagen was 33,89 mJ; relevant data in tissue engineering and 3D collagen fibrils bio-impressions organs, with a periodicity of 65 nm were obtained and characterized. Conclusions: Calorimetric analysis shows higher energy release event at the isoelectric point of the protein, suggesting an overall exothermic process due to self-assembly of the collagen and an endothermic process due to aggregation of denatured collagen.
Capsid-like particles decorated with the SARS2-CoV-2 receptor-binding domain elicit strong virus neutralization activity
Authors: Fougeoux Cyrielle , Goksøyr Louise , Idorn Manja , Soroka Vladislav , Myeni Sebenzile K. , Dagil Robert , Janitzek Christoph M. , Søgaard Teit , Aves Kara-Lee , Horsted Emma W. , Erdoğan Sayit Mahmut , Gustavsson Tobias , Dorosz Jerzy , Clemmensen Stine , Larsen Laurits , Thrane Susan , Vidal-Calvo Elena E. , Khalifé Paul , Hulen Thomas M. , Choudhary Swati , Theisen Michael , Singh Susheel , Garcia-Senosiain Asier , Oosten Linda Van , Pijlman Gorben , Hierzberger Bettina , Domeyer Tanja , Nalewajek Blanka W. , Strøbæk Anette , Skrzypczak Magdalena , Andersson Laura F. , Dalebout Tim , Iversen Kasper , Harritshøj Lene H. , Mordmüller Benjamin , Ullum Henrik , Reinert Line , de Jongh Willem Adriaan , Kikkert Marjolein , Paludan Soren , Theander Thor , Nielsen Morten , Salanti Ali , Sander Adam
Published: July 2020

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we developed two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens were displayed on AP205 CLPs through a novel split-protein Tag/Catcher ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD, and RBD displayed on CLPs bound the ACE2 receptor with nanomolar affinity. Mice were vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induced higher levels of serum anti-RBD antibodies, than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicited virus neutralization antibody titers comparable to those found in patients which had recovered from Covid-19. Following booster vaccinations, the virus neutralization titers exceeded those measured after natural infection, at serum dilutions above 1:10.000. Thus, the RBD-CLP vaccine is highly promising candidates for preventing COVID-19 disease.
Simultaneous CK2/TNIK/Dyrk1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease
Authors: Sato Katsutoshi , Padgaonkar Amol , Baker Stacey , Cosenza Stephen , Rechkoblit Olga , Subbaiah DRC Venkata , Domingo-Domenech Josep , Port Elisa , Reddy M.V. Ramana , Aggarwal Aneel , Irie Hanna , Reddy E. Premkumar
Published: July 2020

Triple negative breast cancer (TNBC) remains clinically challenging as patients have heterogeneous responses to current standard of care therapies. Chemotherapy sensitivity is a strong predictor of long-term outcomes for patients, and incomplete response of early stage disease to chemotherapy treatment is associated with a much higher risk of disease relapse and metastatic progression, often occurring within a short time from initial diagnosis. Therefore, treatment strategies that target chemotherapy-resistant TNBC and/or enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSC) have been proposed to represent a chemotherapy-resistant subpopulation within the tumor which are also responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. We have identified a novel multi-kinase inhibitor 108600 from a screen for inhibitors of this TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of the BCSC population. Treatment with 108600 induces G2M arrest and eventual apoptosis of TNBC cells in vitro and of TNBC xenografts in vivo, and overcomes chemotherapy (paclitaxel) resistance of triple negative patient-derived xenografts (PDX). Finally, treatment with 108600 and chemotherapy suppressed the growth of already established TNBC metastases, providing additional support for the clinical translation of this agent to clinical trials.
Slowing Down DNA Translocation through Solid-State Nanopores by Edge-Field Leakage
Authors: Wang Ceming , Sensale Sebastian , Pan Zehao , Senapati Satyajyoti , Chang Hsueh-Chia
Published: July 2020

Solid-state nanopores allow high-throughput single-molecule detection but identifying and even registering all translocating small molecules remain key challenges due to their high translocation speeds. We show here the same electric field that drives the molecules into the pore can selectively pin and delay their transport. A thin high-permittivity dielectric coating on slender bullet-shaped polymer nanopores permits electric field leakage at the pore tip to produce a voltage-dependent surface field on the upper periphery of the pore that can reversibly edge-pin entering molecules that can absorb conformally to the tip corner. This localized tip field renders molecular entry an activated process with sensitive exponential dependence on the bias voltage and molecular rigidity. The exponential sensitivity allows us to selectively prolong the translocation time of short single-stranded DNA molecules by up to 5 orders of magnitude, allowing discrimination against their double-stranded duplexes with 97% confidence. We show evidence that the leak-field pinned single-stranded DNA actually absorbs onto the edge before entering the pore, yielding translocation times as long as minutes.
Halomonas Venusta Mediated Detoxification and Biotransformation of Selenite Into Selenium Nanoparticles Exhibiting Various Biomedical Applications
Authors: Vaigankar Diviya Chandrakant , Dubey Santosh Kumar , Mujawar Sajiya Yusuf , Mohanty Ajeet Kumar
Published: July 2020

Marine environment is in constant threat due to anthropogenic activities which are involved in disturbing the aquatic flora and fauna due to accumulation of toxic metals and metalloids. The current study involves the use of microbial remediation strategy for reduction of toxic sodium selenite (Na2SeO3) into less toxic elemental Se (Se0) with concurrent synthesis of Se nanoparticles (SeNPs) possessing several biomedical potential. Selenite reducing bacterial strain isolated from Mandovi estuary of Goa, India was identified as Halomonas venusta based on 16S rRNA gene sequence analysis and designated as strain GUSDM4. It's maximum tolerance level for Na2SeO3 was 100 mM. The 2, 3-diaminonaphthalene based spectroscopic analysis clearly demonstrated 93% reduction of 4 mM Na2SeO3 to Se0 during late stationary growth phase of Halomonas venusta. Biosynthesis of SeNPs commenced within 4 h during log phase which was clearly evident from red colour in the growth medium and a characteristic peak at 265 nm revealed by UV-Vis spectrophotometry. The intracellular synthesis of SeNPs was confirmed by transmission electron microscopy (TEM) of these bacterial cells. Characterization of SeNPs by X-ray crystallography, TEM and energy dispersive X-ray analysis clearly demonstrated spherical SeNPs of 20-80 nm diameter with hexagonal crystal lattice. These SeNPs at 50 µg/mL exhibited 90% free radical scavenging activity and also demonstrated anti-biofilm activity at 20 µg/mL against common human pathogens which was evident by SEM analysis. These SeNPs interestingly revealed excellent dose-dependent and selective anti-proliferative activity against A549 cancer cell line and mosquito larvicidal activity against Aedes aegypti, Culex quinquefasciatus and Anopheles stephensi. Therefore, these studies have demonstrated amazing potential of marine bacterium, Halomonas venusta in bioremediation along with biosynthesis of SeNPs and their applications as free radical scavenger, anti-biofilm, chemo-therapeutic and larvicidal agents which is the first report of its kind.
Characteristics of the community-structure of A2O processes under different temperature conditions in plateau areas
Authors: Zong Yongchen , Li Yuanwei , Huang Decai , Hao Kaiyue , Lu Guanghua
Published: July 2020

Background: In this study, laboratory-scale A2O wastewater treatment was performed in Linzhi at an altitude of 3000 meters. Water temperatures were maintained at four operating conditions (25°C, 20°C, 15°C, and 10°C). Sludge in the aerobic tank was assessed by 16SrRNA sequencing and composition analysis. The Phylum, Class, Order, Family, Genus, and Species of the sludge were also confirmed.Results: The bacteria within the sludge showed significant differences at varying temperatures (P<0.05). A significant correlation between the bacteria numbers in anaerobic tanks and anoxic tanks also occurred. Indicators of community richness, community uniformity, community diversity and other areas showed differences. Significant differences in bacteria abundance were also observed and differed to those of previously reported superior community categories and proportions. T-tests were used to identify temperature-sensitive community at each level. Correlation analysis of environmental factors and colony structure further confirmed the association between temperature and colony structure (P<0.05). The removal rates of TP, TN, NH3-N, and COD were all affected by the sample community structure. The variety of colony structure include nitrifying bacteria, denitrifying bacteria, phosphorus accumulating bacteria and other bacterial differed, but their proportions were relatively low. Heatmaps were used to identify species sensitive to temperature, TP, TN, NH3-N, COD at the species level.Conclusions: Amongst the common dominant bacteria at the species level, Bacteroidetes_bacterium_OLB10 was significantly related to temperature. Other common dominant bacteria that were related to temperature metagenome_g__Gordonia, unclassified_f__Burkholderiaceae, uncultured_bacterium_g__norank_f__Saprospiraceae.
Depressive, Anxiety, and Burnout Symptoms on Health Care Personnel at a Month After COVID-19 Outbreak in Indonesia: A Documentary Research Using Rasch Model Analysis
Authors: Sunjaya Deni Kurniadi , Herawati Dewi Marhaeni Diah , Siregar Adiatma YM
Published: July 2020

Background: Health personnel who demonstrated close contact with patients with COVID-19, might experience a higher risk of infection and psychological problems. This study aims to explore depressive, anxiety, and burnout symptoms among health care personnel with a higher risk for psychological trauma.Methods: This study was a cross-sectional study using secondary data from an online assessment, which was conducted one month after the COVID-19 outbreak. A total of 544 respondents from 21 provinces in Indonesia were included. Data on depressive, anxiety, and burnout symptoms were transformed using the Rasch model. Data from health professionals in the higher risk group and the lower risk group were analyzed.Results: A higher percentage of health professionals experiencing depressive symptoms (22.8%), anxiety (28.1%), and burnout (26.8%) are found in the higher risk group. The chance for the higher risk group’s personnel to present with moderate and severe depressive symptoms, anxiety, and burnout are 5.3 (p < 0.05), 1.36 (p > 0.05), and 3.92 (p < 0.05) times higher, respectively. The probability for patient-induced burnout is 2.13 (p < 0.05) times higher and highest among the other burn out dimensions. The depressive symptoms complained were similar between groups: loneliness, sleep disturbances, difficulty concentrating, and inability to initiate activities. Loneliness demonstrates the highest logit value among the symptoms.Conclusions: Health professionals with direct contact and responsibility to treat COVID-19 patients exhibit a higher risk to experience depressive symptoms and burnout. Communication with peers and staying in contact with family needs to be encouraged. Physiological well-being should be considered for high-risk health personnel. Incentive or insurance guaranteed by the government or institution is essential as a reward and compensation during this period.
Molecular Characterization of G6PD Mutations Reveals the High Frequency of G6PD Aures in the Mon-Khmer Population
Authors: Sanephonasa Amkha , Cheepsunthorn Chalisa Louicharoen , Khaminsou Naly , Savongsy Onekham , Nuchprayoon Issarang , Leecharoenkiat Kamonlak
Published: July 2020

Background
The prevalence and genotypes of G6PD deficiency vary worldwide, with higher prevalence in malaria endemic areas. The first time assessment of G6PD deficiency prevalence and molecular characterization of G6PD mutations in the Mon-Khmer population were performed in this study.
Methods
A total of 252 unrelated Mon-Khmer participants residing in the Lao People's Democratic Republic (PDR) were recruited. All participant samples were tested for G6PD enzyme activity and G6PD gene mutations. The amplification refractory mutation system (ARMS)-PCR for detecting G6PD Aures was developed in this study.
Results
The G6PD mutations were detected in 11.51% (29/252) of the participants. The mutation pattern was homogenous, predominantly involving the G6PD Aures mutation (6.75%), followed by 1.19% G6PD Union and 0.79% each G6PD Jammu, G6PD Mahidol and G6PD Kaiping. One subject (0.4%) each carried G6PD Viangchan and G6PD Canton. Interestingly, one case of coinheritance of G6PD Aures and Quing Yan was detected in this cohort.
Conclusion
The G6PD Aures mutation is highly prevalent in Mon-Khmer ethnic group. The common G6PD variants in continental Southeast Asian populations, G6PD Viangchan, Canton, Kaiping, Union and Mahidol, were not prevalent in this ethnic group. The technical simplicity of the developed ARMS-PCR will facilitate the final diagnosis of the G6PD Aures.
Performance Analysis for Cooperative Jamming and Artificial Noise Aided Secure Transmission Scheme in Vehicular Communication Network
Authors: Qiu Bin , Jing Chao
Published: July 2020

Vehicular communication has emerged as a supporting technique for improving road traffic safety and efficiency in the intelligent transportation system (ITS). However, the wireless vehicular communication links may suffer from an eavesdropping threat due to the wireless broadcasting nature and high-mobility of vehicles. In practice, artificial noise (AN) assisted beamforming scheme can be utilized for fighting against multiple malicious eavesdroppers. Unfortunately, channel estimation errors caused by the high mobility of vehicles may lead to noise leakage at the legitimate receiver, thus resulting significant loss in the secrecy performance. In this paper, a joint cooperative jamming and AN aided secure transmission scheme is proposed in vehicular communication network by considering the imperfect channel state information(CSI). In this scheme, cooperative jammers are utilized for further enhancing physical layer security. We derive the closed-form expressions of the connection and secrecy outage probabilities in the presence of AN leakage and signal offset using a stochastic geometry approach. Furthermore, the proposed scheme is capable of maximizing the secrecy throughput in terms of relative vehicular velocity for balancing both the reliability and security of the legitimate link. We further comprehensively analyze the effect of key system parameters on secrecy performance through asymptotic analysis. Finally, the effectiveness of the proposed scheme is validated by numerical results.
Proposing A Reliable Method of Securing and Verifying the Credentials of Graduates through Blockchain
Authors: T Rama Reddy , Rayudu Srinivas , V Raghavendran Ch , R.V.S. Lalitha , B Annapurna
Published: July 2020

Education acts as a soul in the overall societal development, in one way or the other. Aspirants, who gain their degrees genuinely, will help society with their knowledge and skills. But the other side of the coin, the problem of fake certificates, is alarming and worrying. It has been prevalent in different forms from paper-based dummy certificates to replicas backed with database tampering and has increased to astronomic levels in this digital era. In this regard, an overlay mechanism using Blockchain technology is proposed to store the genuine certificates in digital form and verify them firmly whenever needed without delay. The proposed system makes sure that the certificates, once verified, can be present online in an immutable form for further reference and provides a tamper-proof concealment to the existing certification system. To confirm the credibility of the proposed method, a prototype of blockchain-based credential securing and verification system is developed in ethereum test network. The implementation and test results show that it is a secure and feasible solution to online credential management system.
Identification of IFITM1 with prognostic value in pancreatic cancer using network module-based analysis
Authors: Wu Lingyun , Zhu Xinli , Tang Mengmeng , Wang Lihong , Ma Chiyuan , Liang Tingbo , Yan Senxiang
Published: July 2020

Background: Despite improvements reported in diagnosis and treatments in recent decades, pancreatic cancer still characterized with poor prognosis and low survival rate among solid tumors. Intensive interests have grown in exploring novel predictive biomarkers, aiming to enhance the efficiency in early detection and treatment prognosis.Methods: In this study, we identified the differentially expressed genes (DEGs) in pancreatic cancer through analyzed five gene expression profiles, and established the functional modules according to the functional interaction (FI) network between DEGs.Results: Significant upregulation of the selected DEG, IFITM1, was evaluated in several bioinformatics online tools and verified with immunohistochemistry staining from 90 pancreatic cancer patients’ samples. Prognostic data showed that high expression of IFITM1 associated with poor survival and multivariate Cox regression analysis showed that IFITM1 was one of independent prognostic factor for the overall survival. Meanwhile, significant correlations of the expression of IFITM1 and the infiltration of immune cells were found by TIMER. Furthermore, higher level of IFITM1 was assessed in pancreatic cancer cell lines compared to normal human pancreatic duct epithelial cell and silencing IFITM1 in tumor cells remarkedly inhibited the cancer tumorigenicity.Conclusion: Collectively, our findings suggested that IFITM1 might have promising clinical utility for pancreatic cancer.
Overhydration and low serum prealbumin predict peritoneal dialysis-related peritonitis in continuous ambulatory peritoneal dialysis patients
Authors: Quy Quyen Dao Bui , Huy Tuan Pham Ngoc , Duc Loc Nguyen , Van My Pham , Huu Dung Nguyen , Duy Toan Nguyen , Viet Tien Tran , Do Quyet , Viet Thang Le
Published: July 2020

Background In this study, we focused on the role of overhydration (OH) and low serum prealbumin concentration in predicting 3-year peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patientsMethods We measured serum prealbumin concentration and OH by body composition monitor on 278 CAPD patients (159 males and 119 females) to predict 3-year peritonitis. We created the baseline demographics of all patients with the mean age of 46 years and the median peritoneal dialysis (PD) duration of 21 months.Results After the 3-year follow-up, 44 patients diagnosed PD-related peritonitis (15.8%). Low education, serum albumin, prealbumin, high CRP-hs and OH were independent risk factors for predicting peritonitis during 36 months in CAPD patients. Based on the Kaplan–Meier analysis, we realized that patients with low prealbumin and high OH were the good predictors of 3-year peritonitis in CAPD patients (Prealbumin: AUC = 0.838, cut-off value = 32.5 mg/dL, Se = 90.9%, OH: AUC = 0.851, cut-off value = 1.33 L, Se = 79.5%, Sp = 85.5%), (Log-rank test p < 0.001).Conclusion Overhydration and low serum prealbumin level were the good predictors of PD-related peritonitis in CAPD patients.
Perinatal Outcomes in Cystic Fibrosis Women: Data From the Italian Cystic Fibrosis Registry.
Authors: Padoan Rita , Quattrucci Serena , Amato Annalisa , Salvatore Marco , Giordani Barbara , Salvatore Donatello , Campagna Giuseppe
Published: July 2020

Data from the Italian Cystic Fibrosis Registry (ICFR) concerning pregnancies in the period 2010-2015 were used to investigate the association between the pre-conception clinical status and perinatal outcomes of women with CF.

The assessed clinical variables were genotype, pre-conception age, the body mass index (BMI), and the percentage of predicted forced expiratory volume in one second (ppFEV1); the analysed outcomes were gestational age, birth weight (BW), and the frequency of caesarean deliveries.

Complete information concerning mother and child was available for 56 pregnanciesthat came to term. The median pre-conception age was 30.8 years (18.7-42.3); median BMI was 21.5 kg/m2(16.5-26.8); and median ppFEV1was 73.9% (30-128%).Twenty-four women (42.8%) carried class I-III mutations, and 25 (44.8%) at least one mutation conferring residual CFTR function or having variable clinical consequences.
The median duration of pregnancy was 37 weeks (31-41), and the frequency of prematurity was 28.30%. Median BW was 2,910 g (1,300-3,650). There was a positive correlation between BMI and ppFEV1 in comparison with BW (r=0.29 andr=0.31 by p=0.048 and p=0.032, respectively), but no correlation between age and BW. The overall frequency of caesarean sections was 63.64%, but it was 77.27% among the women with severe genotypes. A lower ppFEV1 corresponded to a lower BW (p=0.047). Respiratory function had no effect on the percentage of caesarean deliveries.

The nutritional status and respiratory function of CF mothers correlate with their newborn’s BW. Caesarean sections are very frequent, even in young women with normal lung function.
Prognostic models for predicting overall and cancer-specific survival in hepatocellular carcinoma: A competing risk analysis
Authors: Lin Kongying , Huang Qizhen , Ding Zongren , Zeng Yongyi , Liu Jingfeng
Published: July 2020

Objectives

This study was conducted to estimate the probability of cancer-specific survival (CSS) of HCC and establish a competing risk nomogram for predicting the CSS of HCC using a large population-based cohort.
Methods

Patients diagnosed with HCC between 2004 and 2015 were identified from the Surveillance Epidemiology and End Results Program. The CSS and overall survival (OS) were the endpoints of the study. A competing risk nomogram for predicting CSS was built with Fine and Gray’s competing risk model, and the nomogram for predicting OS was constructed with Cox proportional hazard regression models. The predictive performance of the model was tested in terms of discrimination and calibration.
Results

A total of 34,957 patients were included in the study and randomly divided into a training set and validation set at a ratio of 9:1. Multivariate analysis identified age, race, sex, surgical therapy, chemotherapy, radiotherapy, tumour diameter, and tumour staging as independent predictive factors of CSS. Additionally, marital status was identified as an independent predictive factor of OS. Using these factors, corresponding nomograms were constructed for CSS and OS. In the validation set, the concordance-index of the two nomogram models reached 0.810 and 0.750, respectively. Calibration curves revealed good consistency between the prediction of models and observed outcome. Furthermore, cumulative incidence function analysis and Kaplan-Meier analysis divided patients into four distinct risk subgroups, supporting the predictive performance of the models.
Conclusions

In this population-based analysis, we developed and validated nomograms for individualized prediction of CSS and OS in patients with HCC.
Liposomes Embedded in Layer by Layer Constructs as Simplistic Exosome Transfer Model
Authors: Prieto Gerardo , Domínguez-Arca Vicente , Costa Rui R. , Carvalho Ana M. , Taboada Pablo , Reis Rui L. , Pashkuleva Iva
Published: July 2020

Background. Exosomes are extracellular vesicles originating from the exfoliation of the cellular membrane. They are involved in cell-to-cell and cell-to-matrix signaling, exchange of bioactive molecules, tumorigenesis and metastasis, among others. To mitigate the limited understanding of exosome transfer phenomena, we developed a simplistic model that mimics exosomes and their interactions with cells and the extracellular matrix. The proposed model is a layer-by-layer (LbL) film built from the polycationic poly-L-lysine (PLL) and the glycosaminoglycan hyaluronic acid (HA) to provide ECM mimicry. Positively charged 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and N1,N1,N14,N14-tetramethyl-N1,N14-ditetradecyltetradecane-1,14-diaminium dibromide (GS14) liposomes were embedded in this construct to act as exosome analogs.Results. To simulate exosomes carrying substances, Nile Red was loaded as a model of lipophilic cargo molecules. The integration of each component was followed by quartz-crystal microbalance measurements, which confirmed the immobilization of intact liposomes on the underlying (PLL/HA)3 soft film. The release of Nile Red from liposomes either embedded in the LbL construct or exposed at its surface revealed a fast first order release. This system was validated as a model for exosome/cell interactions by incubation with breast cancer cells MDA-MB-231. We observed higher internalization for embedded liposomes when compared with surface-exposed ones, showcasing that the ECM mimic layers do not constitute a barrier to liposome/cell interactions but favor them.Conclusions. Our findings indicate that the developed model enhances the structural stability of liposomes and induces endocytosis from breast cancer cells. We envisage that the internalization can be tuned by exploring different levels of embedment to achieve a cellular uptake modulated in a spatiotemporal dependent manner. The versatility provided by the LbL technique will allow incorporating additional specialized biomaterials to better mimic the structure and composition of exosomes and their role in cell-to-cell communications.
Dendritic cells matured with recombinant human sperm associated antigen 9 (rhSPAG9) induce CD4+, CD8+ T cells and activate NK cells: A potential candidate molecule for immunotherapy in cervical cancer
Authors: Dhandapani Hemavathi , Jayakumar Hascitha , Seetharaman Abirami , Ganeshrajah Selvaluxmy , Singh Shirley Sunder , Jagadish Nirmala , Suri Anil , Thangarajan Rajkumar , Ramanathan Priya
Published: July 2020

Background
Dendritic cell (DC)-based immunotherapy is capable of activating the immune system, and in particular tumour-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumour. However, major limitations are the availability of autologous tumour cells as antigenic source and the selection of antigen that may have potential to activate both CD8 + and CD4 + T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4 + and CD8 + T cell responses for future DCs-based vaccine trials in cervical cancer patients.
Methods
Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. Subsequently, the efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumour lysate (TLDCs), to induce CD4+, CD8 + T cells and activating NK cells. In addition, we investigated the effect of the chemotherapeutic drug cisplatin on phenotypic and functional potential of SPDCs.
Results
Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic CD4 + and CD8 + T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83 p = 0.4; for migration p = 0.2). In contrast, TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, but this was also not statistically significant (IL12p40, p = 0.06). We also found that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3+Tregs in autologous co-cultures.
Conclusions
This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumour burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention. This strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer.
Mapping the PHQ-8 to EQ-5D, HUI3 and SF6D in Patients with Depression
Authors: Abdin Edimansyah , Chong Siow Ann , Seow Esmond , Tan Kelvin Bryan , Subramaniam Mythily
Published: July 2020

There is limited evidence of mapping the clinical instrument to a generic preference-based instrument in an Asian patient population. The current study aims to map the eight-item Patient Health Questionnaire depression scale (PHQ) onto the EuroQol five-dimensional (EQ-5D), the Health Utilities Index Mark 3 (HUI3) and the Short Form-6D SF-36 to inform future in cost-utility analyses for treatment in depression sample. A total of 249 participants who have completed PHQ-8, EQ5D, SF6D and HUI-3 questionnaires were included in the analyses. A beta regression mixture model was used to map the utility scores. The results were compared against two common regression methods including Ordinary Least Square (OLS) and Tobit regression models. The mean age of the sample was 36.2 years (SD=11.1). The mean EQ-5D-3L, EQ-5D-5L, HUI3 and SF-6D utility scores were 0.615, 0.709, 0.461 and 0.607, respectively. The EQ-5D-3L, EQ-5D-5L and SF-6D utility scores were best predicted by the beta mixture regression model consisting of PHQ total sores, PHQ-squared, and covariates including age and gender. The HUI3 was best predicted by the OLS model. The current study provides important evidence to clinicians and researchers about the mapping algorithms that can be used in economics evaluation among patients with depression.
Identification of DNA repair-related genes predicting pathogenesis and prognosis for liver cancer
Authors: Zhu Wenjing , Zhang Qiliang , Liu Min , Yan Meixing , Chu Xiao , Li Yongchun
Published: July 2020

Background: Liver cancer (LC) is one of the most fatal cancers throughout the world. More efficient and sensitive gene signatures that could accurately predict survival in LC patients are vitally needed to promote a better individualized and effective treatment. Material/Methods: 422 LC patients with both RNA-Seq and clinical data in TCGA were embedded in our study. Gene set enrichment analysis (GSEA) was applied to identify genes and hallmark gene sets that are more valuable for liver cancer therapy. Cox regression analysis was used to identify genes related to overall survival (OS) and build the prediction model. cBioPortal database was used to examine the alterations of the panel mRNA signature. ROC curves and Kaplan–Meier curves were used to validate the prediction model. Besides, the expression of the genes in the model were validated using quantitative real-time PCR in clinical tissue specimens. Results: The panel of DNA repair-related mRNA signature consisted of seven mRNAs: RFC4, ZWINT, UPF3B, NCBP2, ADA, SF3A3, and GTF2H1. On-line analysis of cBioPortal database found that the expression of the panel mRNA has a wide variation ranging from 7% to 10%. All the mRNAs were significantly upregulated in LC tissues compared to normal tissues (P < 0.05). The risk model is closely related to the OS of LC patients. The hazard ratio (HR) is 2.184 (95%CI [confidence interval]:1.523-3.132) and log-rank P-value<0.0001. For clinical specimen validation, we found that all of the genes in the model upregulated in liver cancer tissues versus normal liver tissues, which was consistent with the results predicted. Conclusions: Our study demonstrated a mRNA signature including seven mRNA for prognosis prediction of LC. This panel gene signature provides a new criterion for accurate diagnosis and therapeutic target of LC.
Evaluating an Institutional health Partnership using the ESTHER EFFECt tool: A Case Study of an Evaluation of the Institutional Health Partnership Between Nigeria CDC and Public Health England
Authors: Razavi Ahmed , Erondu Ngozi , Haddock Katie , Johal Gurnam , Oyebanji Oyeronke , Ihekweazu Chikwe , Okereke Ebere
Published: July 2020

Background: Bilateral Institutional Health Partnerships (IHPs) are a means of strengthening health systems and are becoming increasing prevalent in global health. Nigeria Centre for Disease Control (NCDC) and Public Health England (PHE) have engaged in one such IHP as part of Public Health England’s International Health Regulations Strengthening project. Presently, there have been limited evaluations of IHPs resulting in limited evidence of their effectiveness in strengthening health systems despite the concept being used across the world.Methods: The ESTHER EFFECt tool was used to evaluate the IHP between NCDC and PHE. Senior leadership from both organisations participated in a two-day workshop where their perceptions of various elements of the partnership were evaluated. This was done through an initial quantitative survey followed by a facilitated discussion to further explore any arising issues.Results: This evaluation is the first published evaluation of a bilateral global health partnership undertaken by NCDC and PHE. NCDC scores were consistently higher than PHE scores. Key strengths and weaknesses of the partnership were identified such as having wide ranging institutional engagement, however needing to improve dissemination mechanisms following key learning activity.Conclusions: There is a dearth of evidence measuring the effectiveness of international health partnerships; of the studies that exist, many are lacking in academic rigour. We used the ESTHER EFFECt tool as it is an established method of evaluating the progress of the partnership, with multiple previous peer-reviewed publications. This will hopefully encourage more organisations to publish evaluations of their international health partnerships and build the evidence base.
Facilely Reducing Recalcitrance of Lignocellulosic Biomass by a Newly Developed Ethylamine Based Deep Eutectic Solvent for Biobutanol Fermentation
Authors: Xu Guochao , Li Hao , Xing Wanru , Gong Lei , Dong Jinjun , Ni Ye
Published: July 2020

Background: Biobutanol is promising and renewable alternative to traditional fossil fuels and could be produced by Clostridium species from lignocellulosic biomass. However, biomass is recalcitrant to be hydrolyzed into fermentable sugars attributed to the densely packed structure by layers of lignin. Development of pretreatment reagents and processes for increasing surface area, removing hemicellulose and lignin, and enhancing the relative content of cellulose is currently an area of great interest. Deep eutectic solvents (DESs), a new class of green solvents, are effective in the pretreatment of lignocellulosic biomass. However, it remains challenging to achieve high titers of total sugars and usually requires combinatorial pretreatment with other reagents. In this study, we aim to develop novel DESs with high application potential in biomass pretreatment and high biocompatibility for biobutanol fermentation.Results: Several DESs with betaine chloride and ethylamine chloride (EaCl) as hydrogen bond acceptors were synthesized. Among them, EaCl:LAC with lactic acid as hydrogen bond donor displayed the best performance in the pretreatment of corncob. Only by single pretreatment with EaCl:LAC, total sugars of as high as 53.5 g·L–1 could be reached. Consecutive batches for pretreatment of corncob were performed using gradiently decreased cellulase by 5 FPU·g–1. At the end of the sixth batch, the concentration and specific yield of total sugars were 58.8 g·L–1 and 706 g·kg–1 pretreated corncob, saving a total of 50% cellulase. Utilizing hydrolysate as carbon source, butanol titer of 10.4 g·L–1 was achieved with butanol yield of 137 g·kg–1 pretreated corncob by Clostridium saccharobutylicum DSM13864.Conclusions: Ethylamine and lactic acid based deep eutectic solvent is promising in pretreatment of corncob with high total sugar concentrations and compatible for biobutanol fermentation. This study provides an efficient pretreatment reagent for facilely reducing recalcitrance of lignocellulosic materials and a promising process for biobutanol fermentation from renewable biomass.
Physiological and Transcriptional Response to Drought Stress Among Bioenergy Grass Miscanthus Species
Authors: De Vega Jose J. , Teshome Abel , Klaas Manfred , Grant Jim , Finnan John , Barth Susanne
Published: July 2020

Background: Miscanthus is a commercial lignocellulosic biomass crop owing to its high biomass productivity, particularly in the temperate regions. This study was conducted to elucidate physiological and molecular responses of four Miscanthus species subjected to well-watered and droughted greenhouse conditions. Results: A significant biomass loss was observed under drought conditions for all genotypes. A sterile M. x giganteus showed a lower reduction in biomass yield under drought conditions compared to the control than the other species. Under well-watered conditions, biomass yield was as good as or better than control conditions in all species tested. M. sinensis was more tolerant than M. sacchariflorus to both water stress conditions. 4,389 of the 67,789 genes (6.4%) in the reference genome were differentially expressed among four Miscanthus species. Most of the genes were differentially expressed in a single species, but the enrichment analysis of gene ontology (GO) terms revealed that the same biological processes were regulated in all the species during stress conditions. Namely, upregulated differentially expressed genes were significantly involved in sucrose and starch metabolism, redox, and water and glycerol homeostasis and channel activity. Multiple copies of starch metabolic enzymes BAM and waxy GBSS-I were strongly up-regulated in drought stress in all Miscanthus genotypes. Twelve aquaporins (PIP1, PIP2 and NIP2) were also up-regulated in drought stress across genotypes. On the other hand, downregulated differentially expressed genes were significantly involved in protein kinase activity, cell receptor signalling and phosphorylation. Conclusions: Findings in the present study can assist in implementing molecular breeding approaches of drought resistant Miscanthus and its domestication.
Whole Exome Sequencing Aids The Diagnosis of Fetal Skeletal Dysplasia
Authors: Tang Hui , Zhang Qin , Yin Linliang , Xiang Jingjing , Wang Jing , Wang Ting
Published: July 2020

Background: Skeletal dysplasia is a complex group of bone and cartilage disorders with strong clinical and genetical heterogeneousity. Several types have prenatal phenotypes. And it is difficult to make a molecular diagnosis rapidly due to lacking family history and non-specific and limited clinical symptoms in utero. This study aims to diagnose 16 Chinese fetuses with skeletal dysplasia.Methods: Single nucleotide polymorphism-array (SNP-array) was performed in 12 of 16 samples. If no microdeletions or microreplications related to skeletal dysplasia were detected, whole-exome sequencing (WES) was adopted. And the last four cases only got whole-exome sequencing for analyzing copy number variants and single nucleotide variations at the same time.Results: Among the 16 cases, 12 patients received definitive diagnosis and we detected one deletion in DMD gene by SNP-array and 15 variants of 6 genes including FGFR3, COL1A1, COL1A2, ALPL, HSPG2 and DYNC2H1. 8 variants of COL1A1, COL1A2, ALPL and HSPG2 are novel. And somatic mosaicism in asymptomatic parent with mutations in COL1A1 or COL1A2 was observed.Conclusions: In general, our study expanded the prenatal phenotypes in Duchenne muscular dystrophy (DMD)/ Becker muscular dystrophy (BMD), found 8 novel variants and elucidated that the utilization of whole-exome sequencing improved the diagnosis yield of skeletal dysplasia and provided useful genetic counseling guidance for parents.
MRI background parenchymal enhancement, breast density and breast cancer risk factors: A cross-sectional study in pre- and post-menopausal women.
Authors: Brooks Jennifer D , Christensen Rebecca A G , Sung Janice S , Pike Malcolm C , Orlow Irene , Bernstein Jonine L , Morris Elizabeth A
Published: July 2020

Background: Histologically normal breast fibroglandular tissue (FGT) enhances on contrast MRI and is called background parenchymal enhancement (BPE). Having high BPE is associated with an increased risk of breast cancer. We examined the relationship between MRI-FGT (a volumetric assessment of breast density) and BPE and breast cancer risk factors.Methods: This was a cross-sectional study of 419 women without breast cancer undergoing contrast-enhanced breast MRI. All women completed a questionnaire at the time of MRI. Prevalence ratios (PR) and 95% confidence intervals (CI) describing the relationship between breast cancer risk factors and BPE and MRI-FGT were generated using modified Poisson regression. Results: In multivariable adjusted models a positive association between BMI and BPE was observed, with a 5-unit increase in BMI associated with a 16% and 38% increase in prevalence of high BPE in pre- and post-menopausal women respectively. Conversely, a strong inverse relationship between BMI and MRI-FGT was observed in both pre- (PR=0.65, 95% CI 0.57, 0.76 per 5-unit increase of BMI) and post-menopausal (PR=0.67, 95% CI 0.57, 0.79, per 5-unit increase in BMI) women. Current use of oral contraceptives was associated with high BPE while use of preventive medication (e.g., tamoxifen) was associated with low BPE. Conclusion: This study identifies patient characteristics and exposures associated with BPE and MRI-FGT. BPE is a new imaging marker of breast cancer risk. The results of this study provide further support for the role of hormonal exposures on BPE.
Design and analysis of a spatially shaped laser beam used for temperature field simulation
Authors: Nie Shuzhen , Zhao Tianzhuo , Xiao Hong , Fan Zhongwei
Published: July 2020

Laser has controllable space-time characteristics and can be loaded on materials as a heat source in laser manufacturing, laser medical and other fields. In the thermal fatigue test of engine parts, thermal load can also be considered by laser beam. In this paper, a large aperture spatially shaped laser beam with complex and uneven intensity distribution is selected as the heat source for temperature field simulation. Using the method of key nodes selection, the temperature distribution of a few key nodes can reflect the desired temperature field of the whole nodes. Based on finite element model (FEM), through the numerical simulation of the temperature field, optimized intensity distribution of the shaped laser beam is calculated, and a diffractive optics element (DOE) is designed to achieve the shaping effect. The results show that a spatially shaped laser beam can be used for temperature field simulation.
Early initiation of breastfeeding and its association with peer counseling and membership in breastfeeding support groups in the Philippines
Authors: Saniel Ofelia P , Pepito Veincent Christian F , Amit Arianna Maever L
Published: July 2020

Background: Early initiation of breastfeeding (EIBF), defined as initiation of breastfeeding within one hour after giving birth, is one of the recommended optimal breastfeeding practices. We aimed to determine whether being visited by a peer counselor during pregnancy and if mother’s membership in a breastfeeding support group are associated with EIBF. We also aimed to examine the interaction between the two main exposure variables to assess their joint effects on EIBF.Methods: We used data from the endline survey of a program implemented in the Philippines, which contained socioeconomic data from the household of the mother-newborn dyads, demographic characteristics of the mothers, and their infant and young child feeding practices. We used logistic regression methods for survey data to study these associations.Results: Out of the 2,343 newborns, only 1,500 (63.1%) had EIBF. Upon controlling for confounders, those who were visited by a peer counselor during the prenatal period had 1.18 times greater odds of EIBF (95%CI: 0.88-1.57; p=0.26) compared to those who were not visited. On the other hand, members of breastfeeding support groups had 1.33 times higher odds of EIBF (95% CI: 0.99-1.79; p=0.06) compared to those who were not members of breastfeeding support groups. There is no interaction between the two exposure variables on their effect on EIBF. Conclusions: The lack of association between a visit by a peer counselor during pregnancy or mother’s membership in breastfeeding support groups and EIBF highlights the need for new strategies to enhance the role of peer counselors and breastfeeding support groups in promoting breastfeeding.
Gender differences in externalizing and internalizing problems in Singaporean children and adolescents with attention-deficit/ hyperactivity disorder
Authors: Lau Tsz Wing Ivy , Lim Choon Guan , Acharryya Sanchalika , Lim-Ashworth Nikki , Tan Yi Ren , Fung Daniel
Published: July 2020

Background : Studies on gender differences in attention-deficit/ hyperactivity disorder (ADHD) comorbidities in the Asian populations have been limited and previous studies have shown inconclusive findings. Singapore is a city-state country in Southeast Asia with a population of 5.7 million. This study examined gender differences in internalizing and externalizing problems in Singaporean children and adolescents with ADHD. The plausible social factors underlying the gender differences were discussed. Methods : A total of 773 participants (aged 6 to 18, 88% males) newly diagnosed with ADHD were recruited from the only public child and adolescent psychiatric center in Singapore. Their internalizing and externalizing problems were assessed using the Child Behavioral Checklist and Teacher’s Report Form by parents and teachers respectively. Demographics and relevant social factors were collected using parent questionnaires. Results : Females with ADHD were reported to have less delinquent and aggressive behavior but more depressive symptoms than their male counterparts, similar to findings in the Western literature. Older age, lower socioeconomic status and parental use of physical punishment were associated with higher internalizing and externalizing problems after controlling for other factors. Conclusions: Gender differences in ADHD comorbidities do exist in the Asian clinical population. This suggests a need for gender-specific assessment of ADHD as females do not present with much externalizing problem which makes identification more difficult.