bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microdialysis for chronic exertional compartment syndrome: a pilot study
Authors: Lohrer Heinz , Klein Jochen , Nauck Tanja , Schönberg Tobias 
Published: March 2021

Abstract
Background
Diagnosing chronic exertional compartment syndrome (CECS) is still a challenge. An increase in intramuscular pressure during and following exercise is accepted as the diagnostic standard. However, neither the methods used nor the interpretation of the obtained results are sufficiently standardized.

Methods
In the present pilot study, the metabolic state of CECS patients was investigated using microdialysis. We hypothesized that there was no difference in intramuscular concentrations of glucose, lactate, glutamate, and glycerol before and after exercise (H10) or between patients suffering from CECS and healthy control subjects (H20). This study was designed as an explorative case-control study (level of evidence III). Twelve patients suffering from CECS of the lower leg and six matched asymptomatic control subjects underwent microdialysis in the anterior (n = 7) or deep posterior compartment (n = 11) of the leg. Following ultrasound-guided insertion of the microdialysis catheters, 10-minute fractions of the dialysates were collected first during rest and then following fatigue- or pain-induced discontinuation of exercise. Dialysates were analysed for lactate, glucose, glutamate, and glycerol concentrations 6 × 10 min before and 6 × 10 min after exercise.

Results
Exercise-induced increases in lactate, glutamate, and glycerol concentrations were detected in both CECS patients and control subjects (all p < 0.001). No differences between CECS patients and control subjects were found by comparing the intramuscular glucose, lactate, glutamate, and glycerol concentrations at rest and following exercise (all p > 0.05).

Conclusions
We found exercise-induced increases in the lactate, glutamate, and glycerol levels in skeletal muscle. However, the metabolic changes did not differentiate CECS patients from healthy subjects.

Trial registration
The registration trial number is DRKS00021589 on DRKS. ‘Retrospectively registered’. Date of registration: April 4, 2020.
Atezolizumab in combination with intrathecal chemotherapy and radiation for treatment of isolated cerebral nervous system relapse in a patient with extranodal NK/T cell lymphoma: a case report
Authors: Lipsitt Amanda E. , Hung Jaclyn Y. , Langevin Anne-Marie 
Published: March 2021

Abstract
Background
Extranodal NK/T cell lymphoma (ENKTL) is an aggressive form of Epstein-Barr virus (EBV)-associated non-Hodgkin’s lymphoma which historically has a poor prognosis. When relapse occurs, particularly in the cerebral nervous system (CNS), survival is rare. The immune checkpoint pathway family of proteins is highly expressed in many human tumors, especially in EBV-related malignancies. To the best of our knowledge, there are no reports of immune checkpoint inhibitors used either alone or in combination for the treatment of ENTKL CNS relapse, yet there are promising results in metastatic CNS involvement of other malignancies.

Case presentation
This is the case of a 29-year-old Hispanic male with ENKTL who was treated at first relapse with 24 doses of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor, atezolizumab, over a 17-month period. He remained in remission for 18 months until he experienced an isolated CNS relapse and on-going evidence of chronic EBV infection. Salvage therapy was provided as a combination of triple intrathecal (TIT) chemotherapy, radiation, and atezolizumab. He continues on maintenance atezolizumab and remains alive 1-year post CNS relapse.

Conclusions
The results from this case suggest that atezolizumab should be considered as part of the treatment regimen for relapsed ENKTL. They also demonstrate the benefit of using atezolizumab in combination with TIT chemotherapy and radiation as a viable treatment option for ENKTL CNS relapse and indicate that atezolizumab is an option for long-term maintenance therapy for patients with ENKTL.
A proposed modulatory role of the endocannabinoid system on adipose tissue metabolism and appetite in periparturient dairy cows
Authors: Myers Madison N. , Zachut Maya , Tam Joseph , Contreras G. Andres 
Published: March 2021

AbstractTo sustain the nutrient demands of rapid fetal growth, parturition, and milk synthesis, periparturient dairy cows mobilize adipose tissue fatty acid stores through lipolysis. This process induces an inflammatory response within AT that is resolved as lactation progresses; however, excessive and protracted lipolysis compounds the risk for metabolic and inflammatory diseases. The suppression of lipolytic action and inflammation, along with amplification of adipogenesis and lipogenesis, serve as prospective therapeutic targets for improving the health of periparturient dairy cows. Generally, the activation of cannabinoid receptors by endocannabinoids enhances adipogenesis and lipogenesis, suppresses lipolysis, and increases appetite in mammals. These biological effects of activating the endocannabinoid system open the possibility of harnessing the endocannabinoid system through nutritional intervention in dairy herds as a potential tool to improve dairy cows’ health, although much is still to be revealed in this context. This review summarizes the current knowledge surrounding the components of the endocannabinoid system, elaborates on the metabolic effects of its activation, and explores the potential to modulate its activity in periparturient dairy cows.
Multivariate distributions of correlated binary variables generated by pair-copulas
Authors: Lin Huihui , Chaganty N. Rao 
Published: March 2021

AbstractCorrelated binary data are prevalent in a wide range of scientific disciplines, including healthcare and medicine. The generalized estimating equations (GEEs) and the multivariate probit (MP) model are two of the popular methods for analyzing such data. However, both methods have some significant drawbacks. The GEEs may not have an underlying likelihood and the MP model may fail to generate a multivariate binary distribution with specified marginals and bivariate correlations. In this paper, we study multivariate binary distributions that are based on D-vine pair-copula models as a superior alternative to these methods. We elucidate the construction of these binary distributions in two and three dimensions with numerical examples. For higher dimensions, we provide a method of constructing a multidimensional binary distribution with specified marginals and equicorrelated correlation matrix. We present a real-life data analysis to illustrate the application of our results.
Pan-cancer chromatin analysis of the human vtRNA genes uncovers their association with cancer biology
Authors: Fort Rafael Sebastián , Duhagon María Ana 
Published: March 2021

Background: The vault RNAs (vtRNAs) are a class of 84-141-nt eukaryotic non-coding RNAs transcribed by RNA polymerase III, associated to the ribonucleoprotein complex known as vault particle. Of the four human vtRNA genes, vtRNA1-1, vtRNA1-2 and vtRNA1-3, clustered at locus 1, are integral components of the vault particle, while vtRNA2-1 is a more divergent homologue located in a second locus. Gene expression studies of vtRNAs in large cohorts have been hindered by their unsuccessful sequencing using conventional transcriptomic approaches. Methods: VtRNA expression in The Cancer Genome Atlas (TCGA) Pan-Cancer cohort was estimated using the genome-wide DNA methylation and chromatin accessibility data (ATAC-seq) of their genes as surrogate variables. The association between vtRNA expression and patient clinical outcome, immune subtypes and transcriptionally co-regulated gene programs was analyzed in the dataset. Results: VtRNA1-1 has the most accessible chromatin, followed by vtRNA1-2, vtRNA2-1 and vtRNA1-3. Although the vtRNAs are co-regulated by transcription factors related to viral infection, vtRNA2-1 is the most independently regulated homologue. VtRNA1-1 and vtRNA1-3 chromatin status does not significantly change in cancer tissues. Meanwhile, vtRNA2-1 and vtRNA1-2 expression is widely deregulated in neoplastic tissues and its alteration is compatible with a broad oncogenic role for vtRNA1-2, and both tumor suppressor and oncogenic functions for vtRNA2-1. Yet, vtRNA1-1, vtRNA1-2 and vtRNA2-1 promoter DNA methylation predicts a shorter patient overall survival cancer-wide. In addition, gene ontology analyses of vtRNAs co-regulated genes identify a chromosome regulatory domain, epithelial differentiation, immune and thyroid cancer gene sets for specific vtRNAs. Furthermore, vtRNA expression patterns are associated with cancer immune subtypes and vtRNA1-2 expression is positively associated with cell proliferation and wound healing. Conclusions: Our study presents the landscape of vtRNA expression cancer-wide, identifying co-regulated gene networks and ontological pathways associated with the different vtRNA genes that may account for their diverse roles in cancer.
Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab
Authors: Caetano Rosângela , Cordeiro Dias Villela Correa Marilena , Villardi Pedro , Almeida Rodrigues Paulo Henrique , Garcia Serpa Osorio-de-Castro Claudia 
Published: March 2021

Background
This study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization.

Methods
A retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc., and its financialized business model; and examine global eculizumab sales revenues since its first marketing authorization.

Results
Our search yielded 32 patent families divided into 98 applications. The first patent granted was filed in 1995 by Alexion Pharmaceuticals, Inc. in the US. Eculizumab has always been as an orphan drug, except in the Brazilian regulatory agency. All clinical indications approved thus far refer to rare diseases (e.g., paroxysmal nocturnal hemoglobinuria syndrome, atypical hemolytic-uremic syndrome, refractory and generalized myasthenia gravis, and neuromyelitis optica spectrum disorder). Alexion’s revenues amounted to more than US$25 billion between 2007 and 2019, showing a growing trend. Eculizumab led sales from the beginning, being the only product in the company’s portfolio until 2015. In 2019, the drug accounted for 79.1% of all revenues.

Discussion
Our findings show that a strategy focused on obtaining orphan drug designation, expanding therapeutic indications and the geographic range of marketing approvals, extending monopoly periods, and prioritizing public procurement niches has enhanced revenues and helped the company achieve leadership in a highly specific and profitable market.
Piscirickettsia salmonis shedding and tissue burden, and hematological responses during cohabitation infections in chum Oncorhynchus keta, pink O. gorbuscha and Atlantic salmon Salmo salar
Authors: Long Amy , Jones Simon R. M. 
Published: March 2021

Background
Salmonid rickettsial septicemia is an emergent and geographically widespread disease of marine-farmed salmonids caused by infection with the water-borne bacterium Piscirickettsia salmonis. Very little is known about the route, timing, or magnitude of bacterial shedding from infected fish.

Methodology/principal findings
A cohabitation challenge model was used to assess shedding from chum Oncorhynchus keta, pink O. gorbuscha and Atlantic salmon Salmo salar. Infections in donor fish were established by intraperitoneal injection of P. salmonis. Naïve recipients were cohabitated with donor fish after which cumulative percent morbidity and mortality (CMM) was monitored, and bacterial burdens in kidney and in tank water were measured by qPCR. All donor fish died with mean days-to-death (MDD) among species ranging from 17.5 to 23.9. Among recipients, CMM ranged from 42.7% to 77.8% and MDD ranged from 49.7 to 56.4. In each trial, two peaks of bacterial DNA concentrations in tank water closely aligned with the MDD values of donor and recipient fish. Bacterial tissue burden and shedding rate, and plasma physiological parameters were obtained from individual donors and recipients. Statistically significant positive correlations between the shedding rate and P. salmonis kidney burden were measured in donor pink and in donor and recipient chum salmon, but not in donor or recipient Atlantic salmon. In Atlantic salmon, there was a negative correlation between kidney bacterial burden and hematocrit, plasma Ca++ and Mg++ values, whereas in infected chum salmon the correlation was positive for Na+ and Cl- and negative for glucose.

Conclusions
A dependency of bacterial shedding on species-specific patterns of pathogenesis was suggested. The coincidence of bacterial shedding with mortality will inform pathogen transmission models.
Socio-demographic factors impact disabilities caused by perinatal asphyxia among Chinese children
Authors: Ao Deng , Guo Shuai , Yun Chunfeng , Zheng Xiaoying 
Published: March 2021

BackgroundDisabilities caused by perinatal asphyxia will burden child health and well-being. To date, our understanding about the situation and risk factors of perinatal asphyxia-induced disabilities among Chinese children is still limited.ObjectivesTo evaluate the prevalence and socio-demographic risk factors of disabilities caused by perinatal asphyxia among Chinese children in 2006 and compare disability trajectories across different socio-demographic status.MethodsCross-sectional data came from the 2006 China National Survey on Disability which includes a total of 616,940 children aged 0–17 years old was employed in the investigation. Perinatal asphyxia-induced disabilities were identified by following the guidance in consensus manuals. Population-weighted numbers and prevalence rates were investigated, and multivariable logistic regression was performed to evaluate associations between disabilities and socio-demographic factors. Adjusted predictions at representative values were computed to compare the disability trajectories relative to significant socio-demographic variables.ResultsThe prevalence rate of disabilities caused by perinatal asphyxia was 7.70 per 10,000 children (95% CI: 7.01–8.39). Male (OR 1.81, 95% CI: 1.47–2.23) and low family income (OR: 1.73, 95% CI: 1.21–2.49) have higher and the increase of per additional year of age (OR: 0.89, 95% CI: 0.88–0.91) has lower probability of being disabilities caused by perinatal asphyxia. Further disability trajectories showed that differences in probability between gender and family income group were more evident before age 7 and weakened with increasing age.ConclusionsOur results showed that both demographic and socioeconomic characteristics are risk factors for disabilities caused by perinatal asphyxia. Of these, gender and family income have much higher impact than other factors on the prevalence rate of disabilities caused by perinatal asphyxia at infants and young children. Multiple society sectors should increase their effort to bring about fundamental social change to prevent disabilities caused by perinatal asphyxia, especially concerning younger children and their families.
Las pandemias en el cine: argumentos que se han hecho virales
Authors: Juanes Méndez Juan A. 
Published: March 2021

Las pandemias siempre han sido una de las grandes preocupaciones de la humanidad dado que en algún momento de la historia han azotado a la población mundial.
La situación actual generada por el coronavirus, ha hecho que las películas sobre infecciones, epidemias, pandemias, etc., hayan sido las más visionadas en diferentes plataformas de streaming, debido al confinamiento que hemos tenido que padecer. Este trabajo pretende hacer una visión general de las principales y más llamativas películas que tratan sobre distintos aspectos de patologías por contagios virales. Este tipo de películas siempre ha mostrado gran interés en la población, siendo por lo general muy rentables económicamente para las productoras cinematográficas. Con la visualización de estas películas se busca contribuir, a una sensibilización de la población mundial y poder difundir y promover medidas higiénico-sanitarias.
DIVERSIDADE DE METODOLOGIAS E DE ABORDAGENS NA EDUCAÇÃO: QUANDO O TODO É MAIOR QUE A SOMA DAS PARTES
Authors: Castro Paulo Alexandre de , Barros Victor F. A. , Leão Celina P. , Masa Juan Arias 
Published: March 2021

Neste número especial do periódico cientÃ­fico â€œBrazilian Journal of Education, Technology and Societyâ€ (BRAJETS), que foi produzido em parceria com o 8Âº Congresso Ibero-Americano em Investigação Qualitativa (CIAIQ2019) tem como tema/fio condutor a â€œDiversidade de metodologias e de abordagens na Educação: Quando o TODO é maior que a SOMA das PARTES.â€. Os dez artigos, em suas versões estendidas (em relação as versões do CIAIQ2019) dos trabalhos selecionados e convidados, por uma comissão cientÃ­fica/organizadora do CIAIQ2019 discorrem/debatem sobre diversidade, metodologias, abordagens e visões diferenciadas na Educação. Como a história da parceria entre o CIAIQ e o BRAJETS tem mostrado, buscamos de forma contÃ­nua, e com alta nÃ­vel de qualidade dos trabalhos, a divulgação da investigação qualitativa junto Ã comunidade cientÃ­fica nas áreas alvos da Revista que são: educação, tecnologia, medicina, sociedade e internacionalização de programas de pós-graduação. Lembrando sempre que, temos como foco, objetivo maior, proporcionar representatividade e qualidade dos artigos publicados neste periódico, para isso nos certificamos de que todos eles passassem por um processo de revisão double-blind, por meio de análise criteriosa de uma comissão cientÃ­fica composta de pesquisadores de excelência, extremamente qualificados e ativos em suas respectivas áreas de atuação. Feita esse preâmbulo, convidamos a todos vocês da comunidade acadêmica a aproveitar a leitura deste número especial, e nós da comissão cientÃ­fica/organizadora da BRAJETS e do CIAIQ desejamos a todas(o) as(os) leitoras(es) que essa compilação de artigos lhes possam ser úteis e inspiradores de futuros trabalhos.
Sustainable Development and the United Nations Dialogues
Authors: Riley Sophie 
Published: March 2021

The Earth Summit (1992) heralded what was anticipated to be a new era in environmental regulation with the advent of sustainable development. The concept was based on integrating environmental protection with economic development, supported by specific objectives, such as protection of biodiversity and achievement of intergenerational equity. By the early part of the 21st-century it was apparent that sustainable development had become equated with continuous economic growth, human domination and commodification of nature. This article argues that shortcomings in sustainable development, apparent over the past 25 years, are partly due to the concept’s initial formulation and also attributable to the way the concept has been interpreted and implemented. This validates calls for reconfiguring society’s value systems by better integrating law and policy with Earth-centric principles. The discussion argues that this involves more than tinkering with the key tenets of sustainable development, instead of necessitating their reconceptualisation in accordance with philosophies of Earth jurisprudence.
Investigation of the Adequacy of Bridge Design Loads in Pakistan
Authors: Shahid I , Noman A. K. , Farooq S. H. , Arshad Ali 
Published: March 2021

Weight, configuration, and volume of traffic vary from country to country. But, in developing countries like Pakistan, bridges are designed based on codes of developed countries. Hence, these bridges may not have desired safety level. In this study, safety levels of three sample bridges has been investigated in terms of structural reliability index. Live load effects (shear and moments) in girders were determined using weigh-in-motion data (WIM) and were extrapolated to 75 years using non-parametric fit. Two live load models and two strengths, required by 1967 Pakistan Code of Practice for Highway Bridges (PHB Design-Case) and that required by the 2012 AASHTO LRFD Bridge Design Specifications (AASHTO Design-Case) were used in reliability analysis. It is found that actual trucks produce moment and shear in girders 11 to 45 percent higher than live load models of PHB and AASHTO design cases. Values of structural reliability indices vary from 1.25 to 2.50 and from 2.45 to 3.15 for PHB and AASHTO design cases, respectively, and are less than the target reliability index value of 3.50 used in the design codes as benchmark. It is revealed after the research that bridges in Pakistan may not have desired safety level, and current live load models may not be the true representation of service-level truck traffic.
Application of Artificial Neural Network to Predict Biodiesel Yield from Waste Frying Oil Transesterification
Authors: Haryanto Agus , Saputra Tri Wahyu , Telaumbanua Mareli , Gita Amiera Citra 
Published: March 2021

Used frying oil (UFO) has a great potential as feedstock for biodiesel production. This study aims to develop an artificial neural network (ANN) model to predict biodiesel yield produced from base-catalyzed transesterification of UFO. The experiment was performed with 100 mL of UFO at three different molar ratios (oil:methanol) (namely 1:4, 1:5, and 1:6), conducted with reaction temperatures of 30 to 55oC (raised by 5oC), and reaction time of 0.25, 0.5, 1, 2, 3, 6, 8, and 10 minutes. Prediction model was based on ANN model consisting of three layers with 27 combinations of three activation functions (tansig, logsig, purelin). All activation function architectures were trained using Levenberg- Marquardt train type with 126 data set (87.5%) and learning rate of 0.001. Model validation used 18 data set (12.5%) measured at reaction time of 8 min. Results showed that two ANN models with activation function of logsig-purelin-logsig and purelin-logsig-tansig be the best with RRMSE of 2.41% and 2.44% with R2 of 0.9355 and 0.9391, respectively. Predictions of biodiesel yield using ANN models are significantly better than those of first-order kinetics.