bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of CSPG4 as a promising target for translational combinatorial approaches in osteosarcoma
Authors: Riccardo Federica , Tarone Lidia , Iussich Selina , Giacobino Davide , Arigoni Maddalena , Sammartano Federica , Morello Emanuela , Martano Marina , Gattino Francesca , Maria Raffaella De , Ferrone Soldano , Buracco Paolo , Cavallo Federica 
Published: June 2019

Background: Osteosarcoma (OSA) is a highly metastatic pediatric bone tumor. Adjuvant chemotherapy and surgical resection represent standard treatments; however, the prognosis is still poor. Effective strategies are urgently needed. Chondroitin sulfate proteoglycan (CSPG)4 is a transmembrane proteoglycan with a low expression in normal tissues but high expression in several solid tumors, where it plays a central tumorigenic role. Therefore, it represents a promising therapeutic target. The high homology between human and canine CSPG4 and the recognized translational power of canine tumors as preclinical models for human malignancies prompted us to evaluate CSPG4 expression and the consequences of its immune-targeting for both human and canine OSA treatment. Methods: We analyzed CSPG4 overexpression in human and canine OSA samples and its significance for the survival of OSA patients. We exploited functional in vitro experiments to assess the antitumor potential of CSPG4 immune-targeting. Results: CSPG4 is overexpressed in OSA and has possible clinical implications as suggested by an evident correlation between CSPG4 overexpression and a shorter survival for both OSA-affected humans and dogs. The potential of CSPG4 immune-targeting for OSA treatment came from the ability of anti-CSPG4 monoclonal antibodies and sera, derived from human-CSPG4-DNA vaccinated canine patients, to significantly inhibit human and canine CSPG4-positive OSA cell proliferation, migration, and osteospheres generation. Moreover, CSPG4 immune-targeting has been shown to potentiate the effect of doxorubicin. Conclusions: Overall, these results provide the rationale to investigate the CSPG4 immune-targeting as a promising weapon for the treatment of CSPG4-positive OSA canine patients, to be successfully translated to a human setting.
Prostate abscess: A comprehensive review of the literature
Authors: Ridgway Alexander J , Luk Angus Chin-On , Pearce Ian 
Published: June 2019

Prostate abscess (PA) is a rare but serious infection of the prostate gland. Traditionally a complication of urethral gonococcal infection, the majority of PAs are now seen in the older or immunosuppressed populations, in men with existing prostatic disease, or those who have undergone recent instrumentation of the lower urinary tract. Aetiological organisms are diverse, often with non-specific presentations posing a diagnostic challenge. Multiple management options have been described, however no consensus exists on what is the best practice. This comprehensive review examines the literature surrounding this condition in detail, with a focus on diagnostic and surgical treatment options. Recommendations for practice are made where appropriate. This article aims to edge towards a national guideline for the management of PA and inspire more research in the field. Level of evidence - 3a
A systematic review of the accuracy of the digital rectal examination as a method of measuring prostate gland volume
Authors: Christie David RH , Windsor Jane , Sharpley Christopher F 
Published: June 2019

Objective: There are many important clinical scenarios in which estimates of the volume of the prostate gland can have an influence on clinical decisions. The digital rectal examination is the simplest and most readily available method for measuring it. It is commonly performed numerous times every day by practising urologists and radiation oncologists. The prostate gland volume is the most studied parameter arising from it. Although reported in many heterogeneous studies, the accuracy of the digital rectal examination in measuring the volume has never been reviewed. Our aim was to conduct the world’s first systematic review. Methods: Articles from the literature were included if they compared the digital rectal examination with more accurate measures including fluid displacement after radical prostatectomy and transrectal ultrasound measurements. Results: Nineteen articles describing 7891 patients were reviewed and summarised. Wide variations were noted but most studies provided correlation coefficients that lay between 0.3 and 0.7. For those studies that did not involve special training in volume estimation or were not conducted by a urologist with a special interest in the correlation, the coefficients were below 0.6. For eight studies that analysed the estimated volume as a categorical variable, concordance was described using a variety of statistical tests but was generally high. Conclusions: The reported correlations were weak to moderate strength indicating that the digital rectal examination may not be accurate enough when quantitative measurements are required. However, enlargement of the prostate was detectable with high levels of concordance, indicating that the digital rectal examination is effective for that purpose. Level of evidence: Not applicable for this multicentre audit.
Is the qSOFA more reliable than SIRS in detecting post-operative PCNL patients requiring escalation of care?
Authors: Small Robert P , Hendry Jane L , McKay Alastair C , McPhee Arthur S , Jones Gareth E 
Published: June 2019

Aims Percutaneous nephrolithotomy is known to have a significant risk of sepsis and traditionally the systemic inflammatory response score has been used to identify post-operative patients requiring higher levels of care. Recently, the quick Sepsis Related Organ Failure Assessment score has been developed as a rapid and easy tool to assess patients likely to deteriorate from sepsis. We aim to evaluate the quick Sepsis Related Organ Failure Assessment system against the established systemic inflammatory response score criteria in identifying patients at risk of intensive care unit admission following percutaneous nephrolithotomy. Patients and Methods A retrospective review of 157 patients undergoing percutaneous nephrolithotomy between May 2015 and November 2018 at our institution was performed. Patient demographics of age, sex and American Society of Anesthesiologists’ score were collected. Quick Sepsis Related Organ Failure Assessment and systemic inflammatory response scores were calculated at 24 hours and 7 days post-operatively. Primary outcome was admission to an intensive care unit. Specificity, sensitivity, positive and negative predictive values were calculated for the systemic inflammatory response and quick Sepsis Related Organ Failure Assessment scores. Results Of 157 patients undergoing percutaneous nephrolithotomy, eight (5.1%) and 52 (33.1%) scored positively for quick Sepsis Related Organ Failure Assessment and systemic inflammatory response score criteria within 24 hours. Quick Sepsis Related Organ Failure Assessment scoring had a higher specificity (98.7%: 95% confidence interval 98.6–98.7%) and positive predictive value (75.0: 95% confidence interval 74.0–75.0%) than systemic inflammatory response score criteria (69.5%: 95% confidence interval 69.3–69.7%), (11.5%; 95% confidence interval 1.2–11.8%) in predicting intensive care unit admission following percutaneous nephrolithotomy. Quick Sepsis Related Organ Failure Assessment correlated strongly with intensive care unit admission and overall length of stay, whereas systemic inflammatory response score correlated weakly with both parameters. Conclusion Quick Sepsis Related Organ Failure Assessment demonstrated a statistically significant improvement in predicting intensive care unit admission and overall length of stay versus systemic inflammatory response score criteria following percutaneous nephrolithotomy. Further multi-centre studies are required to validate these findings, which are the first to be published in a urology-specific patient population. Level of Evidence: 4
Avoiding antibiotics in the management of recurrent UTIs in women: What are our options?
Authors: Yang Bob , Blick Christopher , Foley Steve 
Published: June 2019

Urinary tract infections are one of the most common infections worldwide, accounting in the United Kingdom for 1–3% of all medical consultations. Fifty per cent of women will experience one episode of urinary tract infection in their lifetimes and of these, up to 30% will develop recurrent urinary tract infections. Such women often rely on long-term low dose antibiotics. Level of evidence: Not applicable for this multicentre audit.
Social Feedback Modulates Neural Response Associated With Cognitive Bias in Individuals Expressing Anxious Symptoms
Authors: Thompson Khalil , King Kendrick , Nahmias Eddy , Fani Negar , Kvaran Trevor , Tone Erin B. , Turner Jessica A. 
Published: June 2019

Background Social anxiety is characterized by a tendency to overestimate the likelihood of negative outcomes and consequences before, during, and after interpersonal interactions with social partners. Recent evidence suggests that a network of brain regions critical for perspective-taking, threat appraisal, and uncertainty resolution may function atypically in those prone to social anxiety. In this study, we used functional magnetic resonance imaging to examine neural activity in specific regions of interest in a sample of young adults who endorsed high or low levels of social anxiety. Methods We recruited 31 college student volunteers (age: 18–28 years), categorized as having high or low anxiety based on their Liebowitz Social Anxiety Scale-Self Report scores. These participants were each scanned while playing the iterated Prisoner’s Dilemma game with three computerized confederates, two of whom they were deceived to believe were human co-players. This study focuses on data collected during play with the presumed humans. Regions of interest were defined for the temporoparietal junction, anterior midcingulate, and dorsomedial prefrontal cortex. Average weighted mean blood-oxygen-level-dependent signals for each subject were extracted and analyzed using mixed design analyses of variance to detect group differences in activation during decision-making, anticipation, and appraisal of round outcomes during the game. Results Behavior analysis revealed that the high-anxiety group was more likely to defect than the low-anxiety group. Neuroimaging analysis showed that the high-anxiety group exhibited elevated blood-oxygen-level-dependent activity relative to the low-anxiety group in all three regions during the social feedback appraisal phase but not during decision-making or the anticipation of interaction outcomes. Conclusions These findings provide evidence that some behaviors linked to cognitive biases associated with social anxiety may be mediated by a network of regions involved in recognizing and processing directed social information. Future investigation of the neural basis of cognition and bias in social anxiety using the prisoner’s dilemma and other economic-exchange tasks is warranted. These tasks appear to be highly effective, functional magnetic resonance imaging-compatible methods of probing altered cognition and behavior associated with anxiety and related conditions.
Discovery and characterization of 2 novel subpopulations of aPS/PT antibodies in patients at high risk of thrombosis
Authors: Chinnaraj Mathivanan , Planer William , Pengo Vittorio , Pozzi Nicola 
Published: June 2019

AbstractAnti-phosphatidylserine/prothrombin (aPS/PT) antibodies are often detected in patients with antiphospholipid syndrome (APS), but how aPS/PT engage prothrombin at the molecular level remains unknown. Here, the antigenic determinants of immunoglobulin G aPS/PT were investigated in 24 triple-positive APS patients at high risk of thrombosis by using prothrombin mutants biochemically trapped in closed and open conformations, and relevant fragments spanning the entire length of prothrombin. Two novel unexpected findings emerged from these studies. First, we discovered that some aPS/PT are unique among other anti-prothrombin antibodies insofar as they efficiently recognize prothrombin in solution after a conformational change requiring exposure of fragment-1 to the solvent. Second, we identified and characterized 2 previously unknown subpopulations of aPS/PT, namely type I and type II, which engage fragment-1 of prothrombin at different epitopes and with different mechanisms. Type I target a discontinuous density-dependent epitope, whereas type II engage the C-terminal portion of the Gla-domain, which remains available for binding even when prothrombin is bound to the phospholipids. Based on these findings, APS patients positive for aPS/PT were classified into 2 groups, group A and group B, according to their autoantibody profile. Group A contains mostly type I antibodies whereas group B contains both type I and type II antibodies. In conclusion, this study offers a first encouraging step toward unveiling the heterogeneity of anti-prothrombin antibodies in correlation with thrombosis, shedding new light on the mechanisms of antigen–autoantibody recognition in APS.
Associations between readmission and patient-reported measures in acute psychiatric inpatients: a study protocol for a multicenter prospective longitudinal study (the ePOP-J study)
Authors: Yamaguchi Sosei , Ojio Yasutaka , Koike Junko , Matsunaga Asami , Ogawa Makoto , Tachimori Hisateru , Kikuchi Akiko , Kimura Hiroshi , Inagaki Ataru , Watanabe Hiroyuki , Kishi Yoshiki , Yoshida Koji , Hirooka Takaaki , Oishi Satoru , Matsuda Yasuhiro , Fujii Chiyo 
Published: June 2019

Abstract
Background
Several previous observational studies have reported the risk factors associated with readmission in people with mental illness. While patient-reported experiences and outcomes have become increasingly important in healthcare, only a few studies have examined these parameters in terms of their direct association with readmission in an acute psychiatric setting. This project will investigate multiple factors associated with readmission and community living in acute psychiatric patients in Japan. This study will primarily investigate whether patient-reported experiences at discharge, particularly quality of life (QoL), are associated with future readmission and whether readmission after the index hospitalization is associated with changes in patient-reported outcomes during the study period. Here, we describe the rationale and methods of this study.

Methods
This multicenter prospective cohort study is being conducted in 21 participating Japanese hospitals, with a target sample of approximately 600 participants admitted to the acute psychiatric ward. The study has four planned assessment points: time of index admission (T1), time of discharge (from the index admission) (T2), 6 months after discharge from the index admission (T3), and 12 months after discharge from the index admission (T4). Participants will complete self-reported measures including a QoL scale, a subjective disability scale, and an empowerment- and self-agency-related scale at each assessment point; additionally, service satisfaction, subjective view of need for services, and subjective relationships with family members will be assessed at T2 and T3. We will assess the participants’ hospitalization during the study period and evaluate several potential individual- and service-level factors associated with readmission and patient-reported experiences and outcomes. Multivariate analyses will be conducted to identify potential associations between readmission and patient-reported experiences and outcomes.

Discussion
The present study may produce evidence on how patient-reported experiences at discharge influence readmission and on the influence of readmission on the course of patient-reported outcomes from admission to community living after discharge. The study may contribute to improving care for both patients’ subjective views of their own health conditions and their community lives in an acute psychiatric setting.
Trial registration University Hospital Medical Information Network—Clinical Trials Registry (UMIN-CTR) UMIN000034220. Registered on September 20, 2018.
Extracellular lipid loading augments hypoxic paracrine signaling and promotes glioma angiogenesis and macrophage infiltration
Authors: Offer Svenja , Menard Julien A. , Pérez Julio Enríquez , de Oliveira Kelin G. , Indira Chandran Vineesh , Johansson Maria C. , Bång-Rudenstam Anna , Siesjö Peter , Ebbesson Anna , Hedenfalk Ingrid , Sundgren Pia C. , Darabi Anna , Belting Mattias 
Published: June 2019

AbstractBackgroundPrimary brain tumors, in particular glioblastoma (GBM), remain among the most challenging cancers. Like most malignant tumors, GBM is characterized by hypoxic stress that triggers paracrine, adaptive responses, such as angiogenesis and macrophage recruitment, rescuing cancer cells from metabolic catastrophe and conventional oncological treatments. The unmet need of strategies to efficiently target tumor “stressness” represents a strong clinical motivation to better understand the underlying mechanisms of stress adaptation. Here, we have investigated how lipid loading may be involved in the paracrine crosstalk between cancer cells and the stromal compartment of the hypoxic tumor microenvironment.MethodsRegions from patient GBM tumors with or without the lipid loaded phenotype were isolated by laser capture microdissection and subjected to comparative gene expression analysis in parallel with cultured GBM cells with or without lipid loading. The potential involvement of extracellular lipids in the paracrine crosstalk with stromal cells was studied by immunoprofiling of the secretome and functional studies in vitro as well as in various orthotopic GBM mouse models, including hyperlipidemic ApoE−/− mice. Statistical analyses of quantitative experimental methodologies were performed using unpaired Student’s T test. For survival analyses of mouse experiments, log-rank test was used, whereas Kaplan-Meier was performed to analyze patient survival.ResultsWe show that the lipid loaded niche of GBM patient tumors exhibits an amplified hypoxic response and that the acquisition of extracellular lipids by GBM cells can reinforce paracrine activation of stromal cells and immune cells. At the functional level, we show that lipid loading augments the secretion of e.g. VEGF and HGF, and may potentiate the cross-activation of endothelial cells and macrophages. In line with these data, in vivo studies suggest that combined local tumor lipid loading and systemic hyperlipidemia of ApoE−/− mice receiving a high fat diet induces tumor vascularization and macrophage recruitment, and was shown to significantly decrease animal survival.ConclusionsTogether, these data identify extracellular lipid loading as a potentially targetable modulator of the paracrine adaptive response in the hypoxic tumor niche and suggest the contribution of the distinct lipid loaded phenotype in shaping the glioma microenvironment.
Evidence that DNA repair genes, a family of tumor suppressor genes, are associated with evolution rate and size of genomes
Authors: Voskarides Konstantinos , Dweep Harsh , Chrysostomou Charalambos 
Published: June 2019

AbstractAdaptive radiation and evolutionary stasis are characterized by very different evolution rates. The main aim of this study was to investigate if any genes have a special role to a high or low evolution rate. The availability of animal genomes permitted comparison of gene content of genomes of 24 vertebrate species that evolved through adaptive radiation (representing high evolutionary rate) and of 20 vertebrate species that are considered as living fossils (representing a slow evolutionary rate or evolutionary stasis). Mammals, birds, reptiles, and bony fishes were included in the analysis. Pathway analysis was performed for genes found to be specific in adaptive radiation or evolutionary stasis respectively. Pathway analysis revealed that DNA repair and cellular response to DNA damage are important (false discovery rate = 8.35 × 10−5; 7.15 × 10−6, respectively) for species evolved through adaptive radiation. This was confirmed by further genetic in silico analysis (p = 5.30 × 10−3). Nucleotide excision repair and base excision repair were the most significant pathways. Additionally, the number of DNA repair genes was found to be linearly related to the genome size and the protein number (proteome) of the 44 animals analyzed (p < 1.00 × 10−4), this being compatible with Drake’s rule. This is the first study where radiated and living fossil species have been genetically compared. Evidence has been found that cancer-related genes have a special role in radiated species. Linear association of the number of DNA repair genes with the species genome size has also been revealed. These comparative genetics results can support the idea of punctuated equilibrium evolution.
The Variable Sampling Interval EWMA X¯ Chart with Estimated Process Parameters
Authors: Teoh Wei Lin , Ong L. V. , Khoo Michael B. C. , Castagliola Philippe , Chong Z. L. 
Published: June 2019

Abstract
The exponentially weighted moving average (EWMA) X¯ chart with the variable-sampling-interval (VSI) feature is usually scrutinized under the assumption of known process parameters. However, in practice, process parameters are usually unknown, and they need to be estimated from the in-control Phase-I data set. With this in mind, this article proposes the VSI EWMA X¯ chart in which the process parameters are estimated. A Markov Chain approach is adopted to derive the run-length properties of the VSI EWMA X¯ chart with estimated process parameters. The standard deviation of the average time to signal (SDATS) is employed to measure the practitioner-to-practitioner variation in the control chart’s performance. This variation occurs because different Phase-I datasets are used among practitioners to estimate the process parameters. Based on the SDATS criterion, this article provides recommendations regarding the minimum number of required Phase-I samples. For an optimum implementation, this article develops two optimization algorithms for the VSI EWMA X¯ chart with estimated process parameters, i.e., by minimizing the (i) out-of-control expected value of the average time to signal (AATS) and (ii) out-of-control expected value of the AATS (EAATS) for the cases of deterministic and unknown shift sizes, respectively. With the implementation of these new design procedures, the VSI EWMA X¯ chart with estimated process parameters is not only able to achieve a desirable in-control performance, but it is also able to quickly detect changes in the process.
An Innovative Approach to Simulate Biocorrosion in Concrete Pipes
Authors: Roghanian Negar , Banthia Nemkumar 
Published: June 2019

Abstract
Concrete corrosion in wastewater concrete pipes is mainly caused by the diffusion of aggressive solutions and in situ production of sulfuric acid by sulfur oxidizing microorganisms, which affect the physicochemical properties of concrete. In this study, a novel pilot-scale experimental setup was designed to replicate conditions in sewage systems as well as the bacterial-induced corrosion process in concrete pipes. The reliability of this test was evaluated by conducting a flexural strength test on arch-shaped cement mortar specimens over a 6-month period. Quantitative assessments of the properties were carried out over the 6-month period, and the average corrosion rate of 3 mm/y with 73 % reduction in bending strength (of the initial strength) and an average weight loss of 15 % was observed in cement-based mortar specimens. The proposed methodology and the results provide a better understanding of the biocorrosion process and quantitative information on the performance and effectiveness of different pipe/coating materials, which is necessary in evaluating concrete pipe’s durability.