bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate cancer tumour control probability modelling for external beam radiotherapy based on multi-parametric MRI-GTV definition
Authors: Sachpazidis Ilias , Mavroidis Panayiotis , Zamboglou Constantinos , Klein Christina Marie , Grosu Anca-Ligia , Baltas Dimos 
Published: May 2020

Abstract
Purpose: To evaluate the applicability and estimate the radiobiological parameters of linear-quadratic Poisson tumour control probability (TCP) model for primary prostate cancer patients for two relevant target structures (prostate gland and GTV). The TCP describes the dose–response of prostate after definitive radiotherapy (RT). Also, to analyse and identify possible significant correlations between clinical and treatment factors such as planned dose to prostate gland, dose to GTV, volume of prostate and mpMRI-GTV based on multivariate logistic regression model.Methods: The study included 129 intermediate and high-risk prostate cancer patients (cN0 and cM0), who were treated with image-guided intensity modulated radiotherapy (IMRT) +/- androgen deprivation therapy with a median follow-up period of 81.4 months (range: 42.0 - 149.0) months. Tumour control was defined as biochemical relapse free survival according to the Phoenix definition (BRFS). MpMRI-GTV was delineated retrospectively based on a pre-treatment multi-parametric MR imaging (mpMRI), which was co-registered to the planning CT. The clinical treatment planning procedure was based on prostate gland, delineated on CT imaging modality.Results: Our results indicated an appropriate α/β = 1.3 Gy for prostate gland and α/β = 2.9 Gy for mpMRI-GTV. Only for prostate gland, EQD2 and gEUD 2Gy were significantly lower in the biochemical relapse (BR) group compared to the biochemical control (BC) group. Fitting results to the linear-quadratic Poisson TCP model for prostate gland and α/β = 1.3 Gy were D 50 = 66.8 Gy with 95%CI [64.6 Gy, 69.0 Gy], and γ = 3.81 with 95%CI [2.58, 5.20]. For mpMRI-GTV and α/β = 2.9 Gy, D 50 was 68.1 Gy with 95%CI [66.1 Gy, 70.0 Gy], and γ = 4.45 with 95%CI [3.00, 6.12]. The fitness of the model was better for prostate gland. For the multivariate logistic model, the gEUD 2Gy for prostate gland showed a very high significant predictive value ( p = 0.001), whereas regarding mpMRI-GTV only its volume showed a significance ( p = 0.01).Conclusion: The linear-quadratic Poisson TCP model was better fit when the prostate gland was considered as responsible target than with mpMRI-GTV. This is compatible with the results of the comparison of the dose distributions among BR and BC groups and with the results achieved with the multivariate logistic model regarding gEUD 2Gy . Probably limitations of mpMRI in defining the GTV explain these results. Another explanation could be the relatively homogeneous dose prescription and the relatively low number of recurrences.
Joint Destructive Role of Mast Cells in Rheumatoid Arthritis
Authors: Kim Kyoung-Woon , Kim Bo-Mi , Won Ji-Yeon , Min Hong-Ki , Lee Kyung-Ann , Lee Sang-Heon , KIM HAE-RIM 
Published: May 2020

Abstract
Background: We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods: Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results: The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FceR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase- and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions: Mast cells and their mediators such as tryptase, chymase, and histamine were increased in RA synovial tissues and fluid. Mast cells stimulated osteoclast differentiation in monocytes. The inhibition of mast cells could be a new therapeutic option for reducing joint destruction in RA.
Reliability of Dopamine Transporter PET Measurements with [18F]FE-PE2I in patients with Parkinson's Disease
Authors: Kerstens Vera S. , Fazio Patrik , Sundgren Mathias , Matheson Granville J. , Franzén Erika , Halldin Christer , Cervenka Simon , Svenningsson Per , Varrone Andrea 
Published: May 2020

Abstract
Background. Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson’s disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [18F]FE-PE2I-PET in PD patients. Methods. Nine patients with PD (Hoehn & Yahr stage < 3) were included (men/women: 6/3; mean age 65.2±6.8y). Each patient underwent two [18F]FE-PE2I-PET measurements within 7–28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less-affected side. Results. [18F]FE-PE2I showed absolute variability estimates of 5.3–7.6% in striatal regions and 11% in substantia nigra, and ICCs of 0.74—0.97 (median: 0.91). The absolute variability for functional striatal subdivisions was 6.0–9.6% and ICCs of 0.76–0.91 (median: 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5–11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p<0.0125).Conclusion. DAT-PET measurements with [18F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [18F]FE-PE2I PET of DAT is a suitable disease progression marker in PD. Trial registration number: EudraCT 2017-003327-29 Keywords: reliability, test-retest, [18F]FE-PE2I, dopamine transporter, Parkinson’s disease
Pleiotropic Effects of RsmA and RsmE Proteins in Pseudomonas Fluorescens 2P24
Authors: Zhang Yang , Zhang Bo , Wu Haiyan , Wu Xiaogang , Yan Qing , Zhang Li-qun 
Published: May 2020

Abstract
Background: Pseudomonas fluorescens 2P24 is a rhizosphere bacterium that produces 2,4-diacetyphloroglucinol (2,4-DAPG) as the decisive secondary metabolite to suppress soilborne plant diseases. The biosynthesis of 2,4-DAPG is strictly regulated by the RsmA family proteins RsmA and RsmE. However, mutation of both of rsmA and rsmE genes results in reduced bacterial growth.Results: In this study, we showed that overproduction of 2,4-DAPG in the rsmA rsmE double mutant influenced the growth of strain 2P24. This delay of growth could be partially reversal when the phlD gene was deleted or overexpression of the phlG gene encoding the 2,4-DAPG hydrolase in the rsmA rsmE double mutant. RNA-seq analysis of the rsmA rsmE double mutant revealed that a substantial portion of the P. fluorescens genome was regulated by RsmA family proteins. These genes are involved in the regulation of 2,4-DAPG production, cell motility, carbon metabolism, and type six secretion system.Conclusions: These results suggest that RsmA and RsmE are the important regulators of genes involved in the plant-associated strain 2P24 ecologic fitness and operate a sophisticated mechanism for fine-tuning the concentration of 2,4-DAPG in the cells.
Age-Related Decrease of Expression of GDF9 and BMP15 Genes in Follicle Fluid and Granulosa Cells from Poor Ovarian Responders
Authors: Gong Yan , Li-Ling Jesse , Xiong Dongsheng , Wei Jiajing , Zhong Taiqing , Tan Hao 
Published: May 2020

Abstract
Background: Growth differentiation factor 9 ( GDF9 ) and bone morphogenetic protein 15 ( BMP15 ) genes play important roles in folliculogenesis. Altered expression of the GDF9 and BMP15 genes have been found among patients with poor ovarian response (POR). In this prospective cohort study, we determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods: A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed based on the Bologna criteria and sub-divided into different age groups: group A (< 35 year old), group B (35 ~ 40 year old) and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of GDF9 and BMP15 in the FF and GCs was determined with enzyme linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. Results: Compared with group C, groups A and B had significantly more transplantable embryos and higher rates of implantation and clinical pregnancy ( P < 0.05). Group A also had significantly more two pronuclei (2PN) oocytes ( P < 0.05). The expression level of GDF9 and BMP15 in the FF and GCs differed significantly among the three groups ( P < 0.05), showing a trend of decline with age. Conclusion: For poor ovarian responders, the expression of GDF9 and BMP15 is declined with increased age in accompany with poorer oocyte quality and IVF outcome, particularly for those over 40.
Vascular Function and Cardiovascular Risk in a HIV Infected and HIV Free Cohort of African Ancestry: Baseline Profile, Rationale and Methods of the Longitudinal EndoAfrica-NWU Study
Authors: Fourie Carla Maria Theresia , Roux Shani Botha-Le , Smith Wayne , Schutte Aletta E , Breet Yolandi , Mels Carina MC , Gafane-Matemane Lebo F , Lammertyn Leandi , Uys Lisa , Burger Adele , Joseph Jitcy S , Goswami Nandu , De Boever Patrick , Strijdom Hans 
Published: May 2020

Abstract
Background: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world’s largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. Methods: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. Results: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m 2 ) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p=0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p<0.047) in PLHIV. Conclusion: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.
Structural and functional modelling of SARS-CoV-2 entry in animal models
Authors: Brooke Greg N. , Prischi Filippo 
Published: May 2020

Abstract
SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 13 May 2020, has infected over 4 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor and TMPRSS2 protease usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret and mouse. Here we showed that ACE2, but not TMPRSS2, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Comparison of SARS-CoV and SARS-CoV-2 S proteins bound the ACE2 receptors showed that the SARS-CoV-2 Spike glycoprotein has adapted to bind the human, but not rodents, ACE2 with high affinity. In contrast, we did not detect species-specific adaptation for TMPRSS2. Analysis of binding modes and protein contacts indicates that ferrets are the most suitable model for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 is similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the K18-hACE2 mouse, are also likely to be useful models for studies investigating viral entry.
Sewage Pooling Test for SARS-CoV-2
Authors: Guha Ritam , Sengupta Anik , Dutta Ankan 
Published: May 2020

Abstract
CoVID-19 is currently one of the biggest threats to mankind. To date, it is the reason for infections of over 35 lakhs and death of over 2 lakh human beings. We propose a procedure to detect CoVID-19 affected localities using a sewage mass testing and pooling mechanism which has gained ground in recent times. The proposed method named Sewage Pooling Algorithm tests wastewater samples from sewage systems to pinpoint the regions which are affected by maximum chances of the virus spread. The algorithm also uses a priority-based backtracking procedure to perform testing in sewage links depending on the probability of infection in the sub-areas. For places with very rare CoVID cases, we present a gradient-based search method to prune those areas. The proposed method has less human intervention and increases the effective tests/million people overcurrent in-place methods.
Early Oral Protein-Containing Diets Following Elective Lower Gastrointestinal Tract Surgery in Adults: A Meta-Analysis of Randomized Clinical Trials.
Authors: PU Hong , Heighes Philippa T. , Simpson Fiona , WANG Yaoli , LIANG Zeping , Wischmeyer Paul , Hugh Thomas J. , Doig Gordon S. 
Published: May 2020

Abstract
Background: Although current guidelines make consensus recommendations for the early resumption of oral intake after surgery, a recent comprehensive meta-analysis failed to identify any patient-centred benefits. We hypothesized this finding was attributable to pooling studies providing effective protein-containing diets with ineffective non-protein liquid diets. Therefore, the aim of this paper was to investigate the safety and efficacy of early oral protein-containing diets versus later (traditional) feeding after elective lower gastrointestinal tract surgery in adults. Methods: PubMed, Embase and the China National Knowledge Infrastructure databases were searched from inception until 1 August 2019. Reference lists of retrieved studies were hand searched to identify randomized clinical trials reporting mortality. No language restrictions were applied. Study selection, risk of bias appraisal and data abstraction were undertaken independently by two authors. Disagreements were settled by obtaining an opinion of a third author. Majority decisions prevailed. After assessment of underlying assumptions, a fixed-effects method was used for analysis. The primary outcome was mortality. Secondary outcomes included surgical site infections, postoperative nausea and vomiting, serious postoperative complications and other key measures of safety and efficacy . Results: Eight randomized clinical trials recruiting 657 patients were included. Compared with later (traditional) feeding, commencing an early oral protein-containing diet resulted in a statistically significant reduction in mortality (Odds Ratio [OR] 0.31, P =0.02, I 2 =0%). An early oral protein-containing diet also significantly reduced surgical site infections (OR 0.39, P =0.002, I 2 =32%), postoperative nausea and vomiting (OR 0.62, P =0.04, I 2 =37%), serious postoperative complications (OR 0.60, P =0.01, I 2 =25%) and significantly improved other major outcomes. No harms attributable to an early oral protein-containing diet were identified. Conclusions: The results of this systematic review can be used to upgrade current guideline statements to a Grade A recommendation supporting an oral protein-containing diet commenced before the end of postoperative day 1 after elective lower gastrointestinal surgery in adults.
Knowledge and Utilization of Family Planning Methods Among People Living With Hiv In Kathmandu Valley
Authors: Bhoosal Anshu , Karki Namrata , Parajuli Riya 
Published: May 2020

Abstract
Background HIV is a major global health issue, targeting the immune system and making the body prone to diseases. People living with HIV mostly face societal stigma and fear of disclosure resulting in discrimination of accessing health facilities leading to multiple sex partners, increased sexual activity and less use of condoms. HIV positive women are at risk of transmitting HIV to their infants and their partners. Thus, the family planning services if provided to PLHIV can help to improve their and families health. In addition to, it reduces the risk of mother-to-child transmission (PMTCT). The facts related to PLHIV with respect to pregnancy and childbearing are not available. The purpose of this study is to focus on the status of the use of family planning methods and explore factors affecting the utilization among people living with HIV and AIDS in Kathmandu valley of Nepal. The study is expected to contribute in enhancing the present understanding of PLHIV towards family planning.Methods The cross sectional descriptive method was used for the research. The study followed Population proportion to size method for the calculation of the respondents from four ART sites of Kathmandu Valley. Structured questionnaire used previously in similar research has been adopted with necessary question related to dual contraceptive use.Results The mean age group of the respondents was (39.16 ± 6.969) years. More than two third respondents (69.5%) were Hindu. 34.8% respondents were married at the less than 20 years of age. Almost three- fourth of the PLHIV (74.4%) were literate where more than three fourth (79.3%) their spouses were literate and educated. About half of the respondents (43.9%) were found to be involved in professional/ technical/ managerial. More than half of the respondent’s spouses (63.4%) were HIV positive. All the respondents (100%) respondents had disclosed their status to their partners. Neither the respondents nor their partner had fertility desire. 28% of neither respondents nor their partners had used the family planning methods before HIV diagnosis. More than half (60.4%) of the respondents had sexual intercourse prior to last 6 months. 15.9% of the respondents positively responded to use of dual protection. Only 11% either respondents or their partners had used the emergency contraceptive pill. 17.7% respondents did not use any family planning. This study revealed that almost half of the respondents (48.8%) had the good knowledge on the use of contraception.Conclusion The use of dual protection is much less than the half of the respondents. Therefore, counseling and health education towards motivating PLHIV on using dual FP methods to avoid the risk of HIV, STIs and unplanned pregnancy is encouraged.