bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study
Authors: Kähler Katharina C. , Gutzmer Ralf , Meier Friedegrund , Zimmer Lisa , Heppt Markus , Gesierich Anja , Thoms Kai-Martin , Utikal Jochen , Hassel Jessica C. , Loquai Carmen , Pföhler Claudia , Heinzerling Lucie , Kaatz Martin , Göppner Daniela , Pflugfelder Annette , Bohne Ann-Sophie , Satzger Imke , Reinhardt Lydia , Placke Jan-Malte , Schadendorf Dirk , Ugurel Selma 
Published: May 2021

BackgroundThe combination of BRAF and MEK inhibitors has become standard of care in the treatment of metastatic BRAF V600-mutated melanoma. Clinical factors for an early prediction of tumor response are rare. The present study investigated the association between the development of an early exanthema induced by vemurafenib or vemurafenib plus cobimetinib and therapy outcome.MethodsThis multicenter retrospective study included patients with BRAF V600-mutated irresectable AJCC-v8 stage IIIC/D to IV metastatic melanoma who received treatment with vemurafenib (VEM) or vemurafenib plus cobimetinib (COBIVEM). The development of an early exanthema within six weeks after therapy start and its grading according to CTCAEv4.0 criteria was correlated to therapy outcome in terms of best overall response, progression-free (PFS), and overall survival (OS).ResultsA total of 422 patients from 16 centers were included (VEM, n=299; COBIVEM, n=123). 20.4% of VEM and 43.1% of COBIVEM patients developed an early exanthema. In the VEM cohort, objective responders (CR/PR) more frequently presented with an early exanthema than non-responders (SD/PD); 59.0% versus 38.7%; p=0.0027. However, median PFS and OS did not differ between VEM patients with or without an early exanthema (PFS, 6.9 versus 6.0 months, p=0.65; OS, 11.0 versus 12.4 months, p=0.69). In the COBIVEM cohort, 66.0% of objective responders had an early exanthema compared to 54.3% of non-responders (p=0.031). Median survival times were significantly longer for patients who developed an early exanthema compared to patients who did not (PFS, 9.7 versus 5.6 months, p=0.013; OS, not reached versus 11.6 months, p=0.0061). COBIVEM patients with a mild early exanthema (CTCAEv4.0 grade 1-2) had a superior survival outcome as compared to COBIVEM patients with a severe (CTCAEv4.0 grade 3-4) or non early exanthema, respectively (p=0.047). This might be caused by the fact that 23.6% of patients with severe exanthema underwent a dose reduction or discontinuation of COBIVEM compared to only 8.9% of patients with mild exanthema.ConclusionsThe development of an early exanthema within 6 weeks after treatment start indicates a favorable therapy outcome upon vemurafenib plus cobimetinib. Patients presenting with an early exanthema should therefore be treated with adequate supportive measures to provide that patients can stay on treatment.
Central Nervous System Hemangioblastoma in a Pediatric Patient Associated With Von Hippel-Lindau Disease: A Case Report and Literature Review
Authors: Yang Bo , Li Zhenyu , Wang Yubo , Zhang Chaoling , Zhang Zhen , Zhang Xianfeng 
Published: May 2021

BackgroundHemangioblastoma is a benign tumor of the central nervous system and may appear as a component of von Hippel-Lindau (VHL) disease. At present, approximately 40 cases of optic nerve HGBs have been reported in the literature. VHL disease is a rare autosomal-dominant inherited cancer syndrome with different phenotypes caused by variants in the VHL gene. Herein, the authors describe a case of a pediatric patient with VHL disease and with optic nerve HGB, a rare phenotypic expression. The purpose of this study was to explore the genotype-phenotype, clinical features, treatment and follow-up of VHL-associated hemangioblastomas in pediatric patients.Case DescriptionA 12-year-old boy presented with vision loss, headache and dizziness at our hospital. Magnetic resonance imaging (MRI) revealed a large (19.8 mm*18.5 mm*23.5 mm) irregular mass located in the suprasellar region. The mass was successfully removed after craniotomy and microsurgical treatment. The pathological diagnosis was left optic nerve HGB. Genetic analyses showed p.Pro86Leu (c. 257C&gt;T) heterozygous missense mutations in the VHL gene.ConclusionThis is the first reported pediatric case of VHL-associated optic nerve HGB. The genotype-phenotype correlation of VHL disease may provide new evidences for predicting tumor penetrance and survival. Gross tumor resection combined with stereotactic radiosurgery might be the most beneficial treatment.
CT-Based Radiomics Signature With Machine Learning Predicts MYCN Amplification in Pediatric Abdominal Neuroblastoma
Authors: Chen Xin , Wang Haoru , Huang Kaiping , Liu Huan , Ding Hao , Zhang Li , Zhang Ting , Yu Wenqing , He Ling 
Published: May 2021

PurposeMYCN amplification plays a critical role in defining high-risk subgroup of patients with neuroblastoma. We aimed to develop and validate the CT-based machine learning models for predicting MYCN amplification in pediatric abdominal neuroblastoma.MethodsA total of 172 patients with MYCN amplified (n = 47) and non-amplified (n = 125) were enrolled. The cohort was randomly stratified sampling into training and testing groups. Clinicopathological parameters and radiographic features were selected to construct the clinical predictive model. The regions of interest (ROIs) were segmented on three-phrase CT images to extract first-, second- and higher-order radiomics features. The ICCs, mRMR and LASSO methods were used for dimensionality reduction. The selected features from the training group were used to establish radiomics models using Logistic regression, Support Vector Machine (SVM), Bayes and Random Forest methods. The performance of four different radiomics models was evaluated according to the area under the receiver operator characteristic (ROC) curve (AUC), and then compared by Delong test. The nomogram incorporated of clinicopathological parameters, radiographic features and radiomics signature was developed through multivariate logistic regression. Finally, the predictive performance of the clinical model, radiomics models, and nomogram was evaluated in both training and testing groups.ResultsIn total, 1,218 radiomics features were extracted from the ROIs on three-phrase CT images, and then 14 optimal features, including one original first-order feature and eight wavelet-transformed features and five LoG-transformed features, were identified and selected to construct the radiomics models. In the training group, the AUC of the Logistic, SVM, Bayes and Random Forest model was 0.940, 0.940, 0.780 and 0.927, respectively, and the corresponding AUC in the testing group was 0.909, 0.909, 0.729, 0.851, respectively. There was no significant difference among the Logistic, SVM and Random Forest model, but all better than the Bayes model (p &lt;0.005). The predictive performance of the Logistic radiomics model based on three-phrase is similar to nomogram, but both better than the clinical model and radiomics model based on single venous phase.ConclusionThe CT-based radiomics signature is able to predict MYCN amplification of pediatric abdominal NB with high accuracy based on SVM, Logistic and Random Forest classifiers, while Bayes classifier yields lower predictive performance. When combined with clinical and radiographic qualitative features, the clinics-radiomics nomogram can improve the performance of predicting MYCN amplification.
A Randomized Case Series Approach to Testing Efficacy of Interventions for Minimally Verbal Autistic Children
Authors: Saul Jo , Norbury Courtenay 
Published: May 2021

BackgroundRandomized Controlled Trials (RCTs) are the gold standard for assessing whether an intervention is effective; however, they require large sample sizes in order to detect small effects. For rare or complex populations, we advocate a case series approach as a more realistic and useful first step for intervention evaluation. We consider the importance of randomization to such designs, and advocate for the use of Randomization Tests and Between Case Effect Sizes to provide a robust and statistically powerful evaluation of outcomes. In this tutorial, we describe the method, procedures, and analysis code necessary to conduct robust single case series, using an empirical example with minimally verbal autistic children.MethodWe applied a pre-registered (https://osf.io/9gvbs) randomized baseline design with between-case effect size to a case series (n = 19), to test the efficacy of a novel, parent-mediated, app-based speech production intervention (BabbleBooster) for minimally verbal autistic children. Parent-rated probe scores were used to densely sample performance accuracy over time.ResultsParents were able to reliably code their children’s speech productions using BabbleBooster. A non-significant Randomization Test and small Between-Case Effect Size (d = 0.267), suggested there was no evidence that BabbleBooster improved speech production in minimally verbal autistic children, relative to baseline scores, during this brief period of intervention.ConclusionThe current analyses exemplify a more robust approach to examining treatment effects in rare or complex populations, where RCT may be difficult or premature to implement. To facilitate adoption of this method by researchers and practitioners, we provide analysis code that can be adapted using open source R packages. Future studies could use this case series design to evaluate interventions aiming to improve speech and language outcomes for minimally verbal autistic children, and other heterogeneous and hard to reach populations.
Validation and Psychometric Properties of the Persian Version of the 21-Item Game Addiction Scale With a Sample of Adolescents and Young Adults
Authors: Abdoli Nasrin , Farnia Vahid , Alikhani Mostafa , Sadeghi-Bahmani Dena , Dürsteler Kenneth M. , Esmaeili Maryam , Brühl Annette , Brand Serge 
Published: May 2021

Background: Excessive gaming has become a psychological health issue for both gamers and their social environments. This observation holds true for western but also non-western countries such as Iran. The aim of the present study was to translate and validate a Persian version of the Game Addiction Scale 21 (GAS 21) using a sample of adolescents and adults.Methods: A total of 412 participants (mean age: 22.16 years; 55.3% females) took part in the study. They completed questionnaires covering sociodemographic information and gaming-related information, as well as the Persian version of the GAS 21, the GAS 7, the Internet Addiction Test, and the Generalized Self-Efficacy Scale.Results: Of the initial 21 items of the Persian version of the GAS 21, five proved redundant and were eliminated. Factors analyses yielded four factors explaining 66.35% of the variance: 1. Withdrawal; 2. Feelings of guilt and addiction; 3. Mood modification; 4. Issues of time budget. Cronbach's alphas were satisfactory (alphas &gt; 0.87). To validate the results, scores on the translated version were compared with the well-established Young Internet Addiction test. Factors correlated positively (rs between 0.21 and 0.31) with overall score on this latter test but, against expectations, positively with the generalized self-efficacy scale.Conclusions: A Persian version of the Game Addiction Scale-21 proved to be a useful tool for assessing the risk of game addiction behavior. Further, the solution with 16 items loading on four factors appears respond to the ecological need of parsimony.
Determinants of Social Distancing Among South Africans From 12 Days Into the COVID-19 Lockdown: A Cross Sectional Study
Authors: Sewpaul Ronel , Mabaso Musawenkosi , Dukhi Natisha , Naidoo Inbarani , Vondo Noloyiso , Davids Adlai Steven , Mokhele Tholang , Reddy Sasiragha Priscilla 
Published: May 2021

Introduction: Social or physical distancing has been an effective measure for reducing the spread of COVID-19 infections. Investigating the determinants of adherence to social distancing can inform public health strategies to improve the behaviour. However, there is a lack of data in various populations. This study investigates the degree to which South Africans complied with social distancing during the country's COVID-19 lockdown and identifies the determinants associated with being in close contact with large numbers of people.Materials and Methods: Data was collected from a South African national online survey on a data free platform, supplemented with telephone interviews. The survey was conducted from 8 to 29 April 2020. The primary outcome was the number of people that participants came into close contact with (within a 2-metre distance) the last time they were outside their home during the COVID-19 lockdown. Multivariate multinomial regression investigated the socio-demographic, psychosocial and household environmental determinants associated with being in contact with 1–10, 11–50 and more than 50 people.Results: Of the 17,563 adult participants, 20.3% reported having not left home, 50.6% were in close physical distance with 1–10 people, 21.1% with 11–50 people, and 8.0% with &gt;50 people. Larger household size and incorrect knowledge about the importance of social distancing were associated with being in contact with &gt;50 people. Male gender, younger age and being in the White and Coloured population groups were significantly associated with being in contact with 1–10 people but not with larger numbers of people. Employment, at least secondary school education, lack of self-efficacy in being able to protect oneself from infection, and moderate or high risk perception of becoming infected, were all associated with increased odds of close contact with 1–10, 11–50, and &gt;50 people relative to remaining at home.Conclusion: The findings identify subgroups of individuals that are less likely to comply with social distancing regulations. Public health communication, interventions and policy can be tailored to address these determinants of social distancing.
Metaviromes Reveal the Dynamics of Pseudomonas Host-Specific Phages Cultured and Uncultured by Plaque Assay
Authors: Alanin Katrine Wacenius Skov , Junco Laura Milena Forero , Jørgensen Jacob Bruun , Nielsen Tue Kjærgaard , Rasmussen Morten Arendt , Kot Witold , Hansen Lars Hestbjerg 
Published: May 2021

Isolating single phages using plaque assays is a laborious and time-consuming process. Whether single isolated phages are the most lyse-effective, the most abundant in viromes, or those with the highest ability to make plaques in solid media is not well known. With the increasing accessibility of high-throughput sequencing, metaviromics is often used to describe viruses in environmental samples. By extracting and sequencing metaviromes from organic waste with and without exposure to a host-of-interest, we show a host-related phage community’s shift, as well as identify the most enriched phages. Moreover, we isolated plaque-forming single phages using the same virome–host matrix to observe how enrichments in liquid media correspond to the metaviromic data. In this study, we observed a significant shift (p = 0.015) of the 47 identified putative Pseudomonas phages with a minimum twofold change above zero in read abundance when adding a Pseudomonas syringae DC3000 host. Surprisingly, it appears that only two out of five plaque-forming phages from the same organic waste sample, targeting the Pseudomonas strain, were highly abundant in the metavirome, while the other three were almost absent despite host exposure. Lastly, our sequencing results highlight how long reads from Oxford Nanopore elevates the assembly quality of metaviromes, compared to short reads alone.
Promotion of the Development of Sentinel Species in the Water Column: Example Using Body Size and Fecundity of the Egg-Bearing Calanoid Copepod Eurytemora affinis
Authors: Souissi Sami , Souissi Anissa 
Published: May 2021

The development of sentinel species in aquatic ecosystems is mostly based on benthic organisms; however, organisms living in water column such as zooplankton have received less attention, except for some cladocerans. In this paper, a new ecological indicator based on simple measurements of the size and fecundity of egg-bearing calanoid copepods is developed. The well-studied estuarine copepod Eurytemora affinis is used to illustrate this new framework. A large database obtained from laboratory experiments developed under different conditions is used to define a reference regression line between clutch size (CS) and prosome length (PL). The same database allowed one to confirm that the coefficient of variation (CV) of CS is an adequate estimator of the accumulated stress at population level. The CV of PL shows very little variability in all experimental and field conditions. The values of CS and PL obtained from the Seine, Loire, Gironde, Scheldt and Elbe estuaries in Europe are compared to the reference regression line. A quality index (QI) is calculated as a percentage of difference between the observed and the predicted CS. The QI classified 19 samples collected in the Seine estuary between 2004 and 2010 into four classes according to the physiological condition of the copepod female. A single sampling from June 2004 (5.26%) showed a very good condition, whereas 57.9% of the sampling dates confirmed good conditions. On the other hand, four sampling dates were associated to very bad conditions and three sampling dates indicated bad conditions. Seven additional samples obtained from other European estuaries between 2006 and 2009 were also used. Females showing poor conditions were observed in the early spring of 2005 and 2008 as well as during the month of November. These years were characterized by very strong climatic anomalies with a very cold late winter in 2005 and a warm winter in 2008. Therefore, it seems that the QI perfectly reflected the strong stress caused by the sudden change in hydro-climatic conditions that have certainly affected the physiology of copepod females and probably the availability of food. The new indicator is very simple to calculate and can be generalised to several aquatic ecosystems (fresh water and brackish water) by targeting the dominating egg-bearing calanoid copepods. As in the case of E. affinis, the development of sentinel species based on copepods or cladocerans can enrich ecological and ecotoxicological studies given their capacity to integrate the variability of their habitats’ quality at the individual and population levels.
On the operation of blowers controlled by mechanical blades under extreme conditions
Authors: Овсейчук Б.В. , Гусейнова Е.С. , Адам Ф. 
Published: May 2021

Снижение затрат электроэнергии на подачу воздуха в системы аэрации очистных сооружений за счет применения регулируемых воздуходувок является актуальной задачей. Представлен комплексный анализ опыта эксплуатации одноступенчатых центробежных воздуходувок, регулируемых механическими поворотными лопатками, в условиях низких температур окружающей среды, характерных для России. В ходе проведенного мониторинга контролировались параметры работы воздуходувок (температура воздуха на входе в компрессор, избыточное давление на выходе из компрессора, уровень вибрации, температура смазочного масла, температура подшипников вала рабочего колеса, потребляемый приводным электродвигателем ток).
Reducing energy costs for air supply to aeration systems of the treatment facilities by using adjustable air blowers is an urgent task. A comprehensive analysis of operating single-stage centrifugal air blowers controlled by mechanical rotating blades under low ambient temperatures typical for Russia is presented. In the process of monitoring, the parameters of the air blowers were monitored (air temperature at the compressor inlet, excess pressure at the compressor outlet, vibration level, lubricating oil temperature, temperature of the impeller shaft bearings, input current consumed of the electric drive motor).
Meningkatkan Kompentensi Pengelola Wisata Desa melalui Penyuluhan Pelayanan Prima
Authors: Hermawan Hary 
Published: May 2021

Increasing Competency of Village Tourism Managers through Counseling Prime Services. Customer satisfaction is the key to winning business competition today, including the tourism business. But in the field, there are still many tourism people who still ignore this at this time. A phenomenon that is often encountered is cheating in business, attracting prices too high to achieve big profits in a short time. Therefore, it is very important to do counselling on how to manage good tourism services with a 5-dimensional approach to excellent service, especially for prospective tourism destinations that will develop. To find out the effectiveness of this program, a descriptive analysis has been carried out. The test results indicate there is an understanding of participants about excellent service after counselling.
OPTIMIZATION OF MOLECULAR DETECTION FOR Vibrio cholerae and PATHOGENIC Escherichia coli USING MULTIPLEX PCR
Authors: Waturangi Diana Elizabeth , Petrus Jason , Kosasih Rico , Roseline Felicia 
Published: May 2021

Vibrio cholerae and pathogenic Escherichia coli were considered as main causative agent foodborne diseases especially in many developing countries, such as Indonesia. Thereby, rapid detection of these pathogenic bacteria is necessary to treat food-borne related diseases causing by these bacteria. In this case, multiplex PCR allows multiple genes amplification in one reaction thereby enable to perform rapid detection of these pathogenic bacteria. The objective of this study is to optimize uniplex and multiples PCR of V. cholerae and pathogenic E. coli detection and determine the sensitivity and specificity of this assays. We used various virulence genes for each pathogenic bacterium as markers for uniplex and multiplex PCR detection. Based on this research, the optimum results of V. cholerae and pathogenic E. coli were obtained with a primer concentration of 16 µM for ctxA and ompU, 30 µM for ace, and 50 µM for zot, and toxR; 2 µM for elt and 5 µM for stx, respectively. Finally, based on the standardization method by ISO/TS 20836 these assays had 0% false positive, 0% false negative, 100% specificity, and 100% sensitivity; 0% false positive, 4% false negative, 100% specificity, and 96% sensitivity for V. cholerae and pathogenic E. coli respectively. The optimized method was qualified to be used as a molecular detection for V. cholerae as well as EHEC and ETEC detection according to ISO/TS 20836 (2017) from drinking water samples.