bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of NF1 and non-NF1 congenital pseudarthrosis of the tibia based on germline NF1 variants: genetic and clinical analysis of 75 patients
Authors: Zhu Guanghui , Zheng Yu , Liu Yaoxi , Yan An , Hu Zhengmao , Yang Yongjia , Xiang Shiting , Li Liping , Chen Weijian , Peng Yu , Zhong Nanbert , Mei Haibo 
Published: September 2019

Abstract

Background
Congenital pseudarthrosis of the tibia (CPT) is a rare disease. Some patients present neurofibromatosis type 1 (NF1), while some others do not manifest NF1 (non-NF1). The etiology of CPT, particularly non-NF1 CPT, is not well understood. Here we screened germline variants of 75 CPT cases, including 55 NF1 and 20 non-NF1. Clinical data were classified and analyzed based on NF1 gene variations to investigate the genotype-phenotype relations of the two types of patients.

Results
Using whole-exome sequencing and Multiplex Ligation-Dependent Probe Amplification, 44 out of 55 NF1 CPT patients (80.0%) were identified as carrying pathogenic variants of the NF1 gene. Twenty-five variants were novel; 53.5% of variants were de novo, and a higher proportion of their carriers presented bone fractures compared to inherited variant carriers. No NF1 pathogenic variants were found in all 20 non-NF1 patients. Clinical features comparing NF1 CPT to non-NF1 CPT did not show significant differences in bowing or fracture onset, lateralization, tissue pathogenical results, abnormality of the proximal tibial epiphysis, and follow-up tibial union after surgery. A considerably higher proportion of non-NF1 patients have cystic lesion (Crawford type III) and used braces after surgery.

Conclusions
We analyzed a large cohort of non-NF1 and NF1 CPT patients and provided a new perspective for genotype-phenotype features related to germline NF1 variants. Non-NF1 CPT in general had similar clinical features of the tibia as NF1 CPT. Germline NF1 pathogenic variants could differentiate NF1 from non-NF1 CPT but could not explain the CPT heterogeneity of NF1 patients. Our results suggested that non-NF1 CPT was probably not caused by germline NF1 pathogenic variants. In addition to NF1, other genetic variants could also contribute to CPT pathogenesis. Our findings would facilitate the interpretation of NF1 pathogenic variants in CPT genetic counseling.
A correlation study of BK Polyoma Virus infection and prostate Cancer among Sudanese patients - immunofluorescence and molecular based case-control study
Authors: Gorish Babbiker Mohammed Taher , Ournasseir Mohammed Elfatih Hussein , Shammat Iman Mohammed 
Published: September 2019

Abstract

Background
Polyomavirus hominis1, also called BK virus (BKV) is a well-known etiological agent of renal transplant nephropathy and cystitis. Recently, it got great attention from the researcher as a principal predisposing factor for different kinds of cancers including prostate cancer (PCa). Thus, this study aims to determine the correlation between BKV infection and PCa through a descriptive case-control based study.

Methods
A total of 55 paraffin-embedded tissue blocks of patients with PCa and another 55 tissue blocks from BPH patients were obtained. In parallel, respective urine samples were collected from all the cases and controls. The existence of BKV large T antigen (LTAg) was analyzed by Direct Immunofluorescence assay. Only BKV LTAg positive specimens were further analyzed for the presence of viral DNA by using a conventional PCR then subjected to viral load quantitation by using Q-PCR.

Result
BKV LTAg was identified in 30% (17/55) of cases tissue specimens and only in 7% (4/55) of the controls tissue specimens with P-value 0.002 and Odd ratio 5.7. The conventional PCR detects the BKV DNA in 16 out of 17 cases specimens while only two out of four controls specimens were identified with a viral DNA. The mean of the BKV DNA load was higher significantly among cases 6733 ± 6745 copies/ml when compared to controls 509.0 ± 792.9 copies/m with a p-value of 0.002.

Conclusion
More BKV prevalence with high viral load was observed in PCa patients tissue compared to BPH specimens. PCa Gleason scores 9 and 7 were the most cancer grades identified with the presence of BKV DNA. Our findings are thus consistent with a significant link between the BKV infection and the PCa risk. Prostate or seminal fluids should be selected as principal specimens for future studies and can, therefore, be designated as screening samples to find early virus evidence in the prostate tissue. Detection of early virus evidence may help to reduce the risk of PCa cancer due to BKV.
Computational analysis of viable parameter regions in models of synthetic biological systems
Authors: Pušnik Žiga , Mraz Miha , Zimic Nikolaj , Moškon Miha 
Published: September 2019

AbstractBackgroundGene regulatory networks with different topological and/or dynamical properties might exhibit similar behavior. System that is less perceptive for the perturbations of its internal and external factors should be preferred. Methods for sensitivity and robustness assessment have already been developed and can be roughly divided into local and global approaches. Local methods focus only on the local area around nominal parameter values. This can be problematic when parameters exhibits the desired behavior over a large range of parameter perturbations or when parameter values are unknown. Global methods, on the other hand, investigate the whole space of parameter values and mostly rely on different sampling techniques. This can be computationally inefficient. To address these shortcomings ’glocal’ approaches were developed that apply global and local approaches in an effective and rigorous manner.ResultsHerein, we present a computational approach for ’glocal’ analysis of viable parameter regions in biological models. The methodology is based on the exploration of high-dimensional viable parameter spaces with global and local sampling, clustering and dimensionality reduction techniques. The proposed methodology allows us to efficiently investigate the viable parameter space regions, evaluate the regions which exhibit the largest robustness, and to gather new insights regarding the size and connectivity of the viable parameter regions. We evaluate the proposed methodology on three different synthetic gene regulatory network models, i.e. the repressilator model, the model of the AC-DC circuit and the model of the edge-triggered master-slave D flip-flop.ConclusionsThe proposed methodology provides a rigorous assessment of the shape and size of viable parameter regions based on (1) the mathematical description of the biological system of interest, (2) constraints that define feasible parameter regions and (3) cost function that defines the desired or observed behavior of the system. These insights can be used to assess the robustness of biological systems, even in the case when parameter values are unknown and more importantly, even when there are multiple poorly connected viable parameter regions in the solution space. Moreover, the methodology can be efficiently applied to the analysis of biological systems that exhibit multiple modes of the targeted behavior.
miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2
Authors: Xiao Xiao , Jiang Youjing , Liang Weibo , Wang Yanyun , Cao Shuqiang , Yan He , Gao Linbo , Zhang Lin 
Published: September 2019

AbstractFerroptosis, a newly discovered form of iron-dependent regulated cell death, has been implicated in traumatic brain injury (TBI). MiR-212-5p has previously been reported to be downregulated in extracellular vesicles following TBI. To investigate whether miR-212-5p is involved in the ferroptotic neuronal death in TBI mice, we first examined the accumulation of malondialdehyde (MDA) and ferrous ion, and the expression of ferroptosis-related molecules at 6 h, 12 h, 24 h, 48 h and 72 h following controlled cortical impact (CCI) in mice. There was a significant upregulation in the expression ofGpx4andAcsl4at 6 h,Slc7a11from 12 h to 72 h, andNox2andSat1from 6 h to 72 h post injury. Similarly, an upregulation in the expression of Gpx4 at 6 h, Nox2 from 6 h to 72 h, xCT from 12 h to 72 h, and Sat1 at 72 h after CCI was observed at the protein level. Interestingly, MDA and ferrous ion were increased whereas miR-212-5p was decreased in the CCI group compared to the sham group. Furthermore, we found that overexpression of miR-212-5p attenuated ferroptosis while downregulation of miR-212-5p promoted ferroptotic cell death partially by targeting prostaglandin-endoperoxide synthase-2 (Ptgs2) in HT-22 and Neuro-2a cell lines. In addition, administration of miR-212-5p in CCI mice significantly improved learning and spatial memory. Collectively, these findings indicate that miR-212-5p may protect against ferroptotic neuronal death in CCI mice partially by targeting Ptgs2.
Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4
Authors: Zhu Meng-Xuan , Wei Chuan-Yuan , Zhang Peng-Fei , Gao Dong-Mei , Chen Jie , Zhao Yan , Dong Shuang-Shuang , Liu Bin-Bin 
Published: September 2019

AbstractBackgroundATPase associated with a variety of cellular activities (AAA ATPase) family members are closely linked to tumor formation and progression. However, their roles in hepatocellular carcinoma (HCC) largely remain unclear.MethodsBioinformatic analyses of public databases were used to excavate the potential AAA ATPases that may contribute to HCC, and thyroid hormone receptor interactor 13 (TRIP13) was selected to following researches because of its most prominently differential expression. Western blot, qRT-PCR and immunohistochemistry were used to detect the expression of TRIP13 in HCC tissues, and then the relationship between TRIP13 expression and clinicopathological parameters were evaluated. Finally, its functions and potential mechanisms were investigated through a series gain- and loss-of-function strategies both in vitro and in vivo.ResultsTRIP13 was significantly overexpressed in HCC tissues and high level of TRIP13 was closely correlated with a worse clinical outcome. Functionally, elevated TRIP13 facilitated cell proliferation, migration, invasion, and promoted cellular epithelial–mesenchymal transition (EMT) in vitro, while promote tumor growth and lung metastasis in vivo. Mechanistically, TRIP13 interacted with ACTN4 and positively regulated its expression, thus activating the AKT/mTOR pathway to drive tumor progression. Moreover, miR-192-5p served as an upstream regulator of TRIP13 by directly binding to TRIP13 mRNA 3′ UTR, which may partially explain the high expression of TRIP13 in HCC.ConclusionOur findings identified TRIP13 as a promising candidate oncogene in HCC, and TRIP13 induced cell migration, invasion and metastasis of HCC through the AKT/mTOR signaling via interacting with ACTN4.
Reliability of a two‐probe ultrasound imaging procedure to measure strain in the Achilles tendon
Authors: Molyneux Prue , Ellis Richard F. , Carroll Matthew 
Published: September 2019

AbstractBackgroundAlteration in the strain properties of the Achilles tendon may lead to adaptations such as pathological stiffening. Stiff tendons have reduced adaptive ability, which may increase the risk for developing tendinopathy. Strain can be measured using musculoskeletal ultrasound imaging. A two‐probe ultrasound procedure may reduce the measurement error associated with a one‐probe procedure. However, the reliability of the two‐probe procedure has not been established. This study aimed to determine the within‐session intra‐ and inter‐rater reliability and between‐session reliability of a two‐probe ultrasound procedure to measure Achilles tendon strain.MethodsParticipants were 29 healthy individuals (19 females, 10 males; mean age 33.6 years). Achilles tendon images were acquired with a two‐probe ultrasound procedure as the ankle moved through a standardised range of motion (20° plantarflexion to 10° dorsiflexion). Both probes were positioned longitudinally, one over the musculotendinous junction and the second over the calcaneal insertion of the Achilles tendon. Repeat measurements were taken for all participants at the initial study visit, and for 10 participants in a second measurement session 4 weeks later. Strain measures were calculated from pre‐captured images using Motion Analysis 2014v1 software by two independent raters. Within‐session intra‐ and inter‐rater reliability and between‐session intra‐rater reliability were calculated using intraclass correlation coefficients (ICC) with 95% confidence intervals. The standard error of measurement was also calculated.ResultsThe two‐probe procedure to measure Achilles tendon strain showed excellent within‐session intra‐rater (ICC = 0.84, p < 0.001) and inter‐rater reliability (ICC = 0.88, p = 0.003), but poor between‐session intra‐rater reliability (ICC = 0.18, p = 0.397).ConclusionThe two‐probe procedure to measure Achilles tendon strain is reliable for repeated measurements on the same day. However, measurement error increased when strain was measured on different days, which may be attributable to a combination of examiner error and participant factors. Measurement of Achilles tendon strain offers an additional tool for evaluating the tendon's mechanical characteristics. The ability to reliably quantify strain may allow clinicians to identify those at risk for Achilles tendinopathy and formulate more effective management plans.
Palliative care in the emergency department as seen by providers and users: a qualitative study
Authors: Di Leo Silvia , Alquati Sara , Autelitano Cristina , Costantini Massimo , Martucci Gianfranco , De Vincenzo Francesco , Kuczynska Beata , Morini Alessandra , Trabucco Laura , Ursicelli Raffaella , Catania Gianluca , Ghirotto Luca 
Published: September 2019

Abstract

Background
Much effort has been made to explore how patients with advanced chronic illness and their families experience care when they attend the Emergency Department, and many studies have investigated how healthcare professionals perceive Palliative Care provision in the Emergency Department. Various models exist, but nonetheless incorporating palliative care into the Emergency Department remains challenging. Considering both healthcare professionals’ and users’ perspective on problems encountered in delivering and receiving appropriate palliative care within this context may provide important insight into meaningful targets for improvements in quality of care. Accordingly, this study aims at exploring issues in delivering palliative care in the Emergency Department from the perspective of both providers and users, as part of a larger project on the development and implementation of a quality improvement program in Italian Emergency Departments.

Methods
A qualitative study involving focus group interviews with Emergency Department professionals and semi-structured interviews with patients with palliative care needs in the Emergency Department and their relatives was conducted. Both datasets were analyzed using Thematic Analysis.

Results
Twenty-one healthcare professionals, 6 patients and 5 relatives participated in this study. Five themes were identified: 1) shared priorities in Emergency Department among healthcare professionals and patients, 2) the information provided by healthcare professionals and that desired by relatives, 3) perception of environment and time, 4) limitations and barriers to the continuity of care, and 5) the contrasting interpretations of giving and receiving palliative care.

Conclusions
This study provides insights into targets for changes in Italian Emergency Departments. Room for improvement relates to training for healthcare professionals on palliative care, the development of a shared care pathway for patients with palliative care needs, and the optimization of Emergency Department environment. These targets will be the basis for the development of a quality improvement program in Italian Emergency Departments.
Metabolic support in the critically ill: a consensus of 19
Authors: Wernerman Jan , Christopher Kenneth B. , Annane Djillali , Casaer Michael P. , Coopersmith Craig M. , Deane Adam M. , De Waele Elisabeth , Elke Gunnar , Ichai Carole , Karvellas Constantine J. , McClave Stephen A. , Oudemans-van Straaten Heleen M. , Rooyackers Olav , Stapleton Renee D. , Takala Jukka , van Zanten Arthur R. H. , Wischmeyer Paul E. , Preiser Jean-Charles , Vincent Jean-Louis 
Published: September 2019

Abstract
Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.
Epinephrine, inodilator, or no inotrope in venoarterial extracorporeal membrane oxygenation implantation: a single-center experience
Authors: Zotzmann Viviane , Rilinger Jonathan , Lang Corinna N. , Kaier Klaus , Benk Christoph , Duerschmied Daniel , Biever Paul M. , Bode Christoph , Wengenmayer Tobias , Staudacher Dawid L. 
Published: September 2019

AbstractBackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) can be a rescue therapy for patients in cardiogenic shock or in refractory cardiac arrest. After cannulation, vasoplegia and cardiac depression are frequent. In literature, there are conflicting data on inotropic therapy in these patients.MethodsAnalysis of a retrospective registry of all patients treated with VA-ECMO in a university hospital center between October 2010 and December 2018 for cardiogenic shock or extracorporeal cardiopulmonary resuscitation (eCPR) with a focus on individual early inotropic therapy.ResultsA total of 231 patients (age 58.6 ± 14.3, 29.9% female, 58% eCPR, in-house survival 43.7%) were analyzed. Of these, 41.6% received no inotrope therapy within the first 24 h (survival 47.9%), 29.0% received an inodilator (survival 52.2%), and 29.0% received epinephrine (survival 25.0%). Survival of patients with epinephrine was significantly worse compared to other patient groups when evaluating 30-day survival (p = 0.034/p = 0.005) and cumulative incidence of in-hospital death (p = 0.001). In a multivariate logistic regression analysis, treatment with epinephrine was associated with mortality in the whole cohort (OR 0.38,p = 0.011) as well as after propensity score matching (OR 0.24,p = 0.037). We found no significant differences between patients with inodilator treatment and those without.ConclusionEarly epinephrine therapy within the first 24 h after cannulation for VA-ECMO was associated with poor survival compared to patients with or without any inodilator therapy. Until randomized data are available, epinephrine should be avoided in patients on VA-ECMO.
A review of current practice in the design and assessment of internal pilots in UK NIHR clinical trials
Authors: Rosala-Hallas Anna , Gamble Carrol , Blazeby Jane , Williamson Paula R. 
Published: September 2019

Abstract

Background
Internal pilots provide useful information which can help to optimise the running of the main trial. Although some recommendations exist in the literature for the design of internal pilots, little is known about current practice in terms of the specification and also the assessment of progression criteria. The aim of the review is to provide an overview of current practice.

Methods
A cohort of clinical trials with an internal pilot, funded by the National Institute for Health Research (NIHR), Health Technology Assessment programme (HTA), extracted in 2017 was reviewed. Data were extracted from: project descriptions; summary of changes from the first stage; feedback about the full application; monitoring notes; progress report history and protocols, for information about the design and assessment of internal pilots.

Results
Fifty-seven studies were reviewed. An internal pilot was first proposed in the early stages of the trial in the majority of cases. Target number for recruitment, rate of randomisation, retention/primary outcome ascertainment rate, rate of treatment adherence and consent rate were included as progression criteria. All but one study was permitted to continue to the main trial; however, 25% did not strictly meet the progression criteria. Changes were made to the design of the main trial for 25% of studies, mainly in terms of conduct of recruitment.

Conclusions
This review provides insight into the process of designing and assessing internal pilots. Progression criteria are sometimes not met; however, committees involved in the reviewing process will recommend continuation to the main trial, usually accompanied by a second review or close monitoring. Recommendations are made to optimise the process.