bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating human services and criminal justice data with claims data to predict risk of opioid overdose among Medicaid beneficiaries: A machine-learning approach
Authors: Lo-Ciganic Wei-Hsuan , Donohue Julie M. , Hulsey Eric G. , Barnes Susan , Li Yuan , Kuza Courtney C. , Yang Qingnan , Buchanich Jeanine , Huang James L. , Mair Christina , Wilson Debbie L. , Gellad Walid F.
Published: March 2021

Health system data incompletely capture the social risk factors for drug overdose. This study aimed to improve the accuracy of a machine-learning algorithm to predict opioid overdose risk by integrating human services and criminal justice data with health claims data to capture the social determinants of overdose risk. This prognostic study included Medicaid beneficiaries (n = 237,259) in Allegheny County, Pennsylvania enrolled between 2015 and 2018, randomly divided into training, testing, and validation samples. We measured 290 potential predictors (239 derived from Medicaid claims data) in 30-day periods, beginning with the first observed Medicaid enrollment date during the study period. Using a gradient boosting machine, we predicted a composite outcome (i.e., fatal or nonfatal opioid overdose constructed using medical examiner and claims data) in the subsequent month. We compared prediction performance between a Medicaid claims only model to one integrating human services and criminal justice data with Medicaid claims (i.e., integrated model) using several metrics (e.g., C-statistic, number needed to evaluate [NNE] to identify one overdose). Beneficiaries were stratified into risk-score decile subgroups. The samples (training = 79,087, testing = 79,086, validation = 79,086) had similar characteristics (age = 38±18 years, female = 56%, white = 48%, having at least one overdose = 1.7% during study period). Using the validation sample, the integrated model slightly improved on the Medicaid claims only model (C-statistic = 0.885; 95%CI = 0.877–0.892 vs. C-statistic = 0.871; 95%CI = 0.863–0.878), with small corresponding improvements in the NNE and positive predictive value. Nine of the top 30 most important predictors in the integrated model were human services and criminal justice variables. Using the integrated model, approximately 70% of individuals with overdoses were members of the top risk decile (overdose rates in the subsequent month = 47/10,000 beneficiaries). Few individuals in the bottom 9 deciles had overdose episodes (0-12/10,000). Machine-learning algorithms integrating claims and social service and criminal justice data modestly improved opioid overdose prediction among Medicaid beneficiaries for a large U.S. county heavily affected by the opioid crisis.
Aging steepens the slope of power spectrum density of 30-minute continuous blood pressure recording in healthy human subjects
Authors: Mano Jumpei , Saku Keita , Kinoshita Hiroyuki , Mannoji Hiroshi , Kanaya Shigehiko , Sunagawa Kenji
Published: March 2021

Background

The increase of blood pressure (BP) variability (BPV) is recognized as an important additional cardiovascular risk factor in both normotensive subjects and hypertensive patients. Aging-induced atherosclerosis and autonomic dysfunction impair the baroreflex and, in turn, augment 24-hour BPV. In small and large animal experiments, impaired baroreflex steepens the slope of the power spectrum density (PSD) of continuous BP in the frequency range of 0.01 to 0.1 Hz. Although the repeated oscillometric BP recording over 24 hours or longer is a prerequisite to quantify BPV in humans, how the very short-term continuous BP recording reflects BPV remains unknown. This study aimed to evaluate the impact of aging on the very short-term (30-min) BPV in healthy human subjects by frequency analysis.

Methods

We recorded continuous BP tonometrically for 30 min in 56 healthy subjects aged between 28 and 85 years. Considering the frequency-dependence of the baroreflex dynamic function, we estimated the PSD of BP in the frequency range of 0.01 to 0.1 Hz, and compared the characteristics of PSD among four age groups (26–40, 41–55, 56–70 and 71–85 years).

Results

Aging did not significantly alter mean and standard deviation (SD) of BP among four age groups. PSD was nearly flat around 0.01 Hz and decreased gradually as the frequency increased. The slope of PSD between 0.01 and 0.1 Hz was steeper in older subjects (71 years or older) than in younger subjects (55 years or younger) (p < 0.05).

Conclusions

Aging steepened the slope of PSD of BP between 0.01 and 0.1 Hz. This phenomenon may partly be related to the deterioration of the baroreflex in older subjects. Our proposed method to evaluate very short-term continuous BP recordings may contribute to the stratification of BPV.
Assembly assay identifies a critical region of human fibrillin-1 required for 10–12 nm diameter microfibril biogenesis
Authors: Jensen Sacha A. , Atwa Ondine , Handford Penny A.
Published: March 2021

The human FBN1 gene encodes fibrillin-1 (FBN1); the main component of the 10–12 nm diameter extracellular matrix microfibrils. Marfan syndrome (MFS) is a common inherited connective tissue disorder, caused by FBN1 mutations. It features a wide spectrum of disease severity, from mild cases to the lethal neonatal form (nMFS), that is yet to be explained at the molecular level. Mutations associated with nMFS generally affect a region of FBN1 between domains TB3-cbEGF18—the "neonatal region". To gain insight into the process of fibril assembly and increase our understanding of the mechanisms determining disease severity in MFS, we compared the secretion and assembly properties of FBN1 variants containing nMFS-associated substitutions with variants associated with milder, classical MFS (cMFS). In the majority of cases, both nMFS- and cMFS-associated neonatal region variants were secreted at levels comparable to wild type. Microfibril incorporation by the nMFS variants was greatly reduced or absent compared to the cMFS forms, however, suggesting that nMFS substitutions disrupt a previously undefined site of microfibril assembly. Additional analysis of a domain deletion variant caused by exon skipping also indicates that register in the neonatal region is likely to be critical for assembly. These data demonstrate for the first time new requirements for microfibril biogenesis and identify at least two distinct molecular mechanisms associated with disease substitutions in the TB3-cbEGF18 region; incorporation of mutant FBN1 into microfibrils changing their integral properties (cMFS) or the blocking of wild type FBN1 assembly by mutant molecules that prevents late-stage lateral assembly (nMFS).
Virological failure and antiretroviral resistance among HIV-infected children after five years follow-up in the ANRS 12225-PEDIACAM cohort in Cameroon
Authors: Tagnouokam-Ngoupo Paul Alain , Penda Ida Calixte , Tchatchueng Mbougua Jules Brice , Tetang Ndiang Suzie , Yuya Septoh Francis , Kenne Angeladine , Ngallè Jeannine Eboumbou , Jakpou Sorel , Ateba Ndongo Francis , Warszawski Josiane , Faye Albert , Tejiokem Mathurin Cyrille ,   The ANRS-Pediacam Study Group
Published: March 2021

Objective

In the present study, we aimed to evaluate the virological failure (VF) and drug resistance among treated HIV-infected children after five years follow-up in the ANRS-Pediacam cohort in Cameroon.

Methods

From November 2007 to October 2011, HIV-infected children born to HIV-infected mothers were included in the ANRS-PEDIACAM study and followed-up for more than 5 years. Plasma viral load (VL) was measured at each visit (every three months until month 24 and every 6 months thereafter). VF was the main outcome and HIV drug resistance test was performed using the ANRS procedures and algorithm.

Results

Data from 155 children were analyzed. The median age at combination antiretroviral therapy (cART) initiation was 4.2 months (interquartile range (IQR): 3.2–5.8), with 103 (66.5%) children taking LPV/r-containing regimen and 51 (32.9%) children taking NVP. After five years follow-up, 63 (40.6%; CI: 32.9–48.8) children experienced VF. The median duration between cART initiation and VF was 22.1 months (IQR: 11.9–37.1) with a median VL of 4.8 log10 (IQR: 4.0–5.5). Among the 57 children with HIV drug resistance results, 40 (70.2%) had at least one drug resistance mutation. The highest resistance rates (30.4–66.1%) were obtained with Lamivudine; Efavirenz; Nevirapine and Rilpivirine.

Conclusions

These results show high resistance to NNRTI and emphasize the need of VL and resistance tests for optimal follow-up of HIV-infected people especially children.
Perceptions of the parents of deceased children and of healthcare providers about end-of-life communication and breaking bad news at a tertiary care public hospital in India: A qualitative exploratory study
Authors: Das Manoja Kumar , Arora Narendra Kumar , Chellani Harish Kumar , Debata Pradeep Kumar , Meena K. R. , Rasaily Reeta , Kaur Gurkirat , Malik Prikanksha , Joshi Shipra , Kumari Manisha
Published: March 2021

Background

Parents of dying children face unique challenge and expect compassionate support from health care providers (HCPs). This study explored the experiences of the parents and HCPs about the end-of-life care and breaking bad news and related positive and negative factors in Indian context.

Methods

This qualitative exploratory study was conducted at paediatrics department of a tertiary care hospital in Delhi. In-depth interviews with the parents (n = 49) and family members (n = 21) of the children died at the hospital and HCPs (6 doctors, 6 nurses and 4 support staffs) were conducted. Also events and communication around death of eight children were observed. Data were inductively analysed using thematic content analysis method to identify emerging themes and codes.

Results

Doctors were the lead communicators. Majority of parents perceived the attitude, communication and language used as by resident doctors as brief, insensitive and sometimes inappropriate or negative. They perceived that the attitude and communication by senior doctor’s as empathetic, positive and complete. Parents recalled the death declaration by resident doctors as non-empathetic, blunt and cold. Most parents received no emotional support from HCPs during and after death of their child. All doctors expressed that death of their patients affected them and their emotions, which they coped through different activities. The overcrowded wards, high workload, infrastructural limitation and no formal communication training added to the emotional stress of the HCPs.

Conclusions

Majority of the communication by the HCPs during the hospitalisation and end-of-life period were perceived as suboptimal by the parents. The HCPs were emotionally affected and faced end-of-life communication challenges. The study highlights the communication by HCPs and support for parents during the end-of-life communication and breaking bad news. It suggests adoption of context specific communication protocol and materials and training of HCPs in communication to improve the quality of care.
Mobile health technologies supporting colonoscopy preparation: A systematic review and meta-analysis of randomized controlled trials
Authors: El Bizri Maria , El Sheikh Mariam , Lee Ga Eun , Sewitch Maida J.
Published: March 2021

Background

Mobile health (mHealth) technologies are innovative solutions for delivering instructions to patients preparing for colonoscopy.

Objective

To systematically review the literature evaluating the effectiveness of mHealth technologies supporting colonoscopy preparation on patient and clinical outcomes.

Methods

MEDLINE, EMBASE, CINAHL and CENTRAL were searched for randomized controlled trials (RCTs) that evaluated the effectiveness of mHealth technologies for colonoscopy preparation on patient and clinical outcomes. Two reviewers independently assessed study eligibility, extracted data, and appraised methodological quality using the Cochrane Risk-of-Bias tool. Data were pooled using random effects models and when heterogeneity, assessed using I2, was statistically significant, a qualitative synthesis of the data was performed. Publication bias was assessed using a funnel plot.

Results

Ten RCTs (3,383 participants) met inclusion criteria. MHealth interventions included smartphone apps, SMS text messages, videos, camera apps, and a social media app. Outcomes were bowel cleanliness quality, user satisfaction, colonoscopy quality indicators (cecal intubation time, withdrawal time, adenoma detection rate), adherence to diet, and cancellation/no-show rates. MHealth interventions were associated with better bowel cleanliness scores on the Boston Bowel Preparation Scale [standardized mean difference (SMD) 0.57, 95%CI 0.37–0.77, I2 = 60%, p = 0.08] and the Ottawa Bowel Preparation Scale [SMD -0.39, 95%CI -0.59–0.19, I2 = 45%, p = 0.16], but they were not associated with rates of willingness to repeat the colonoscopy using the same regimen [odds ratio (OR) 1.88, 95%CI 0.85–4.15, I2 = 48%, p = 0.12] or cancellations/no-shows [OR 0.96, 95%CI 0.68–1.35, I2 = 0%]. Most studies showed that adequate bowel preparation, user satisfaction and adherence to diet were better in the intervention groups compared to the control groups, while inconsistent findings were observed for the colonoscopy quality indicators. All trials were at high risk of bias for lack of participant blinding. Visual inspection of a funnel plot revealed publication bias.

Conclusions

MHealth technologies show promise as a way to improve bowel cleanliness, but trials to date were of low methodological quality. High-quality research is required to understand the effectiveness of mHealth technologies on colonoscopy outcomes.
Farming System for Nutrition-a pathway to dietary diversity: Evidence from India
Authors: Pradhan Aliza , S. Raju , D. J. Nithya , Panda Akshaya Kumar , Wagh Rupal D. , Maske Mahesh R. , R. V. Bhavani
Published: March 2021

Farming is the main livelihood of a majority of people in India. The country is also home to a large population of undernourished people. This indicates potential for mainstreaming the nutrition dimension in the farming system to impact on nutrition outcomes. A Farming System for Nutrition (FSN) study was conducted in two agro-ecologically different locations from 2013–2018, to explore the feasibility of nutrition-sensitive agricultural interventions. The baseline survey in 2013–2014 revealed that the population in the study area was largely undernourished and that household diets were cereal-dominated. The FSN model was designed in consultation with community members, to increase availability of nutrient-dense cereals and pulses, by enhancing production and crop diversification at the farm level, promoting cultivation of nutrient-rich fruits and vegetables in nutrition gardens and supporting interventions to promote access to animal foods. Nutrition awareness initiatives were undertaken to build capacity at the local level and translate production diversity to consumption diversity. An endline survey was conducted in 2017 (July-October), following three years of intervention. Crop, vegetable and animal food production and food consumption was compared with the baseline data. There was evidence of higher production and consumption of nutrient rich foods, improved household dietary diversity; and understanding and acceptance of nutrition-sensitive agriculture. The number of items consumed under each food group, frequency of consumption of food and average per capita intake of nutrient-rich foods were found to have improved. The results provide evidence regarding feasibility of location-specific FSN models to promote sustainable and healthy diets, using locally available plant and animal food resources, to address nutrition deficiencies in farm families.
Evaluating the state-of-the-art in mapping research spaces: A Brazilian case study
Authors: Galuppo Azevedo Francisco , Murai Fabricio
Published: March 2021

Scientific knowledge cannot be seen as a set of isolated fields, but as a highly connected network. Understanding how research areas are connected is of paramount importance for adequately allocating funding and human resources (e.g., assembling teams to tackle multidisciplinary problems). The relationship between disciplines can be drawn from data on the trajectory of individual scientists, as researchers often make contributions in a small set of interrelated areas. Two recent works propose methods for creating research maps from scientists’ publication records: by using a frequentist approach to create a transition probability matrix; and by learning embeddings (vector representations). Surprisingly, these models were evaluated on different datasets and have never been compared in the literature. In this work, we compare both models in a systematic way, using a large dataset of publication records from Brazilian researchers. We evaluate these models’ ability to predict whether a given entity (scientist, institution or region) will enter a new field w.r.t. the area under the ROC curve. Moreover, we analyze how sensitive each method is to the number of publications and the number of fields associated to one entity. Last, we conduct a case study to showcase how these models can be used to characterize science dynamics in the context of Brazil.
Cost-effectiveness of financial incentives to improve glycemic control in adults with diabetes: A pilot randomized controlled trial
Authors: Egede Leonard E. , Walker Rebekah J. , Dismuke-Greer Clara E. , Pyzyk Sarah , Dawson Aprill Z. , Williams Joni S. , Campbell Jennifer A.
Published: March 2021

Purpose

Determine the cost-effectiveness of three financial incentive structures in obtaining a 1% within group drop in HbA1c among adults with diabetes.

Methods

60 African Americans with type 2 diabetes were randomized to one of three financial incentive structures and followed for 3-months. Group 1 (low frequency) received a single incentive for absolute HbA1c reduction, Group 2 (moderate frequency) received a two-part incentive for home testing of glucose and absolute HbA1c reduction and Group 3 (high frequency) received a multiple component incentive for home testing, attendance of weekly telephone education classes and absolute HbA1c reduction. The primary clinical outcome was HbA1c reduction within each arm at 3-months. Cost for each arm was calculated based on the cost of the intervention, cost of health care visits during the 3-month time frame, and cost of workdays missed from illness. Incremental cost effectiveness ratios (ICER) were calculated based on achieving a 1% within group drop in HbA1c and were bootstrapped with 1,000 replications.

Results

The ICER to decrease HbA1c by 1% was $1,100 for all three arms, however, bootstrapped standard errors differed with Group 1 having twice the variation around the ICER coefficient as Groups 2 and 3. ICERs were statistically significant for Groups 2 and 3 (p<0.001) indicating they are cost effective interventions.

Conclusions

Given ICERs of prior diabetes interventions range from $1,000-$4,000, a cost of $1,100 per 1% within group decrease in HbA1c is a promising intervention. Multi-component incentive structures seem to have the least variation in cost-effectiveness.
Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder
Authors: Zolkipli-Cunningham Zarazuela , Naviaux Jane C. , Nakayama Tomohiro , Hirsch Charlotte M. , Monk Jonathan M. , Li Kefeng , Wang Lin , Le Thuy P. , Meinardi Simone , Blake Donald R. , Naviaux Robert K.
Published: March 2021

Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Responses were studied in C57BL/6J mice in the maternal immune activation (MIA) model and controls. Basal metabolic rates and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Intraperitoneal eATP dropped basal metabolic rate measured by whole body oxygen consumption by 74% ± 6% (mean ± SEM) and rectal temperature by 6.2˚ ± 0.3˚C in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. Breathomics showed an increase in exhaled carbon monoxide, dimethylsulfide, and isoprene. Metabolomics revealed an acute increase in lactate, citrate, purines, urea, dopamine, eicosanoids, microbiome metabolites, oxidized glutathione, thiamine, niacinamide, and pyridoxic acid, and decreased folate-methylation-1-carbon intermediates, amino acids, short and medium chain acyl-carnitines, phospholipids, ceramides, sphingomyelins, cholesterol, bile acids, and vitamin D similar to some children with ASD. MIA animals were hypersensitive to postnatal exposure to eATP or poly(IC), which produced a rebound increase in body temperature that lasted several weeks before returning to baseline. Acute hyperpurinergia produced metabolic and behavioral changes in mice. The behaviors and metabolic changes produced by ATP injection were associated with mitochondrial functional changes that were profound but reversible.
Genetic analysis of a potato (Solanum tuberosum L.) breeding collection for southern Colombia using Single Nucleotide Polymorphism (SNP) markers
Authors: Berdugo-Cely Jhon A. , Martínez-Moncayo Carolina , Lagos-Burbano Tulio César
Published: March 2021

Detailed knowledge on genetic parameters such as diversity, structure, and linkage disequilibrium (LD) and identification of duplicates in a germplasm bank and/or breeding collection are essential to conservation and breeding strategies in any crop. Therefore, the potato genetic breeding collection at the Universidad de Nariño in Colombia, which is made up of diploid and tetraploid genotypes in two of the more diverse genebanks in the world, was analyzed with 8303 single nucleotide polymorphisms (SNP) from SolCAP version 1. In total, 144 genotypes from this collection were analyzed identifying an 57.2% of the polymorphic markers that allowed establishing two and three subpopulations that differentiated the diploid genotypes from the tetraploids. These subpopulations had high levels of heterozygosity and linkage disequilibrium. The diversity levels were higher in the tetraploid genotypes, while the LD levels were higher in the diploid genotypes. For the tetraploids, the genotypes from Peru had greater diversity and lower linkage disequilibrium than those from Colombia, which had slightly lower diversity and higher degrees of LD. The genetic analysis identified, adjusted and/or selected diploid and tetraploid genotypes under the following characteristics: 1) errors in classification associated with the level of ploidy; 2) presence of duplicates; and 3) genotypes with broad genetic distances and potential use in controlled hybridization processes. These analyses suggested that the potato genetic breeding collection at the Universidad de Nariño has a genetic base with a potential use in breeding programs for this crop in the Department of Nariño, in southern Colombia.
Structural basis of Blastomyces Endoglucanase-2 adjuvancy in anti-fungal and -viral immunity
Authors: dos Santos Dias Lucas , Dobson Hannah E. , Bakke Brock Kingstad , Kujoth Gregory C. , Huang Junfeng , Kohn Elaine M. , Taira Cleison Ledesma , Wang Huafeng , Supekar Nitin T. , Fites J. Scott , Gates Daisy , Gomez Christina L. , Specht Charles A. , Levitz Stuart M. , Azadi Parastoo , Li Lingjun , Suresh Marulasiddappa , Klein Bruce S. , Wüthrich Marcel
Published: March 2021

The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.
The granuloma in cryptococcal disease
Authors: Ristow Laura C. , Davis J. Muse
Published: March 2021

Although we have recognized cryptococcosis as a disease entity for well over 100 years, there are many details about its pathogenesis which remain unknown. A major barrier to better understanding is the very broad range of clinical and pathological forms cryptococcal infections can take. One such form has been historically called the cryptococcal granuloma, or the cryptococcoma. These words have been used to describe essentially any mass lesion associated with infection, due to their presumed similarity to the quintessential granuloma, the tubercle in tuberculosis. Although clear distinctions between tuberculosis and cryptococcal disease have been discovered, cellular and molecular studies still confirm some important parallels between these 2 diseases and what we now call granulomatous inflammation. In this review, we shall sketch out some of the history behind the term “granuloma” as it pertains to cryptococcal disease, explore our current understanding of the biology of granuloma formation, and try to place that understanding in the context of the myriad pathological presentations of this infection. Finally, we shall summarize the role of the granuloma in cryptococcal latency and present opportunities for future investigations.
Adenovirus-vectored T cell vaccine for hepacivirus shows reduced effectiveness against a CD8 T cell escape variant in rats
Authors: Hartlage Alex S. , Dravid Piyush , Walker Christopher M. , Kapoor Amit
Published: March 2021

There is an urgent need for a vaccine to prevent chronic infection by hepatitis C virus (HCV) and its many genetic variants. The first human vaccine trial, using recombinant viral vectors that stimulate pan-genotypic T cell responses against HCV non-structural proteins, failed to demonstrate efficacy despite significant preclinical promise. Understanding the factors that govern HCV T cell vaccine success is necessary for design of improved immunization strategies. Using a rat model of chronic rodent hepacivirus (RHV) infection, we assessed the impact of antigenic variation and immune escape upon success of a conceptually analogous RHV T cell vaccine. Naïve Lewis rats were vaccinated with a recombinant human adenovirus expressing RHV non-structural proteins (NS)3-5B and later challenged with a viral variant containing immune escape mutations within major histocompatibility complex (MHC) class I-restricted epitopes (escape virus). Whereas 7 of 11 (64%) rats cleared infection caused by wild-type RHV, only 3 of 12 (25%) were protected against heterologous challenge with escape virus. Uncontrolled replication of escape virus was associated with durable CD8 T cell responses targeting escaped epitopes alone. In contrast, clearance of escape virus correlated with CD4 T cell helper immunity and maintenance of CD8 T cell responses against intact viral epitopes. Interestingly, clearance of wild-type RHV infection after vaccination conferred enhanced protection against secondary challenge with escape virus. These results demonstrate that the efficacy of an RHV T cell vaccine is reduced when challenge virus contains escape mutations within MHC class I-restricted epitopes and that failure to sustain CD8 T cell responses against intact epitopes likely underlies immune failure in this setting. Further investigation of the immune responses that yield protection against diverse RHV challenges in this model may facilitate design of broadly effective HCV vaccines.
A swine arterivirus deubiquitinase stabilizes two major envelope proteins and promotes production of viral progeny
Authors: Guo Rui , Yan Xingyu , Li Yanhua , Cui Jin , Misra Saurav , Firth Andrew E. , Snijder Eric J. , Fang Ying
Published: March 2021

Arteriviruses are enveloped positive-strand RNA viruses that assemble and egress using the host cell’s exocytic pathway. In previous studies, we demonstrated that most arteriviruses use a unique -2 ribosomal frameshifting mechanism to produce a C-terminally modified variant of their nonstructural protein 2 (nsp2). Like full-length nsp2, the N-terminal domain of this frameshift product, nsp2TF, contains a papain-like protease (PLP2) that has deubiquitinating (DUB) activity, in addition to its role in proteolytic processing of replicase polyproteins. In cells infected with porcine reproductive and respiratory syndrome virus (PRRSV), nsp2TF localizes to compartments of the exocytic pathway, specifically endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi complex. Here, we show that nsp2TF interacts with the two major viral envelope proteins, the GP5 glycoprotein and membrane (M) protein, which drive the key process of arterivirus assembly and budding. The PRRSV GP5 and M proteins were found to be poly-ubiquitinated, both in an expression system and in cells infected with an nsp2TF-deficient mutant virus. In contrast, ubiquitinated GP5 and M proteins did not accumulate in cells infected with the wild-type, nsp2TF-expressing virus. Further analysis implicated the DUB activity of the nsp2TF PLP2 domain in deconjugation of ubiquitin from GP5/M proteins, thus antagonizing proteasomal degradation of these key viral structural proteins. Our findings suggest that nsp2TF is targeted to the exocytic pathway to reduce proteasome-driven turnover of GP5/M proteins, thus promoting the formation of GP5-M dimers that are critical for arterivirus assembly.
Efecto de la sincronización rítmica en pacientes con Trastorno del Espectro Autista
Authors: Díaz Abrahan Verónika , Gentili Sebastian , Justel Nadia
Published: March 2021

Las investigaciones realizadas en los últimos años ponen el énfasis en la relación existente entre las alteraciones sensoriales y del movimiento en los trastornos del espectro autista, adjudicando el déficit a una alteración a nivel cortical y a una disfunción cerebelosa temprana. Desde el campo de la musicoterapia, se ha abordado el déficit sensorio-motor a través de técnicas para la compensación y/o rehabilitación de funciones cognitivas. El propósito de este trabajo es presentar un abordaje destinado apacientes con Trastorno del Espectro Autista (TEA), basado en el beneficio potencial de la sincronicidad rítmica sobre la regulación sensoriomotriz y sus consecuencias posteriores en las áreas deficitarias propias del cuadro. Para ello se seleccionaron 18 pacientes, entre 10 y 25 años, diagnosticados con TEA, quienes realizaron dos experiencias musicales, con y sin acompañamiento musicoterapeutico, de tres fragmentos musicales correspondientes a los géneros jazz, clásico y folclore. Los resultados indican que el acompañamiento por parte del musicoterapeuta, de ciertos fragmentos musicales, mejora el rendimiento de la sincronicidad rítmica así como también el contacto visual que el paciente realiza hacia al profesional, lo que podría brindar una posible intervención para el abordaje de los aspectos en déficit en el TEA.
Eficacia de la estimulación magnética transcraneal en el Trastorno Obsesivo Compulsivo: Revisión sistemática
Authors: Arroyo Delgado Carmen
Published: March 2021

Los últimos avances en neurociencia han permitido conocer mejor la neurobiología del trastorno obsesivo compulsivo (TOC) y, de esta forma, plantear nuevos tratamientos, como la estimulación magnética transcraneal (EMT), que, al inducir cambios funcionales en la actividad cerebral a nivel cortical, se propone como una alternativa válida para el tratamiento de pacientes con TOC refractario a otros tratamientos previos, evitando de esta forma la neurocirugía. Este artículo revisa la eficacia de la EMT en ensayos clínicos para el TOC, mostrando como posibles dianas terapéuticas el área motora suplementaria (AMS), la corteza prefrontal dorsolateral (CPFdl) y la orbitofrontal (COF). No obstante, se pone de manifiesto también que se necesita nuevos estudios con mayor tamaño muestral y poder de generalización para poder llegar a una conclusión certera.
Tratamiento Neuropsicológico en la Enfermedad de Huntington: Una revisión sistemática
Authors: Vidal Marín Cristina
Published: March 2021

La enfermedad de Huntington (EH) es una enfermedad neurodegenerativa, crónica, progresiva y deteriorante que presenta alteraciones físicas, cognitivas y psiquiátricas. Actualmente no existe un tratamiento efectivo para esta enfermedad, por lo que los fármacos disponibles actúan para aliviar los síntomas físicos y psiquiátricos. Existen evidencias de que las déficits cognitivos pueden aparecer hasta 10 años antes de los síntomas nucleares de la enfermedad, por lo que resulta clave el tratamiento neuropsicológico en la EH. El objetivo de este estudio es realizar una revisión sobre el tratamiento neuropsicológico en la enfermedad de Huntington. Para ello se ha realizado una búsqueda exhaustiva electrónica y manual, donde se han encontrado 8 artículos que cumplían los criterios de inclusión y exclusión. En los estudios incluidos en esta revisión no se han encontrado resultados significativos sobre el tratamiento neuropsicológico en la EH, pero sí evidencias de que puede ser beneficioso un programa multidisciplinar con rehabilitación cognitiva incluida, ya que se han encontrado mejorías mínimas en las evaluaciones cognitivas y ningún retroceso en las puntuaciones. Estos resultados en una enfermedad donde los síntomas se agravan con el paso del tiempo puede ser un indicador de la efectividad de los tratamientos neuropsicológicos.
Rehabilitación de los miembros inferiores tras un ictus: Intervención desde terapia ocupacional en caso único
Authors: Cerdán Diez Davinia , Pastor Zaplana José Ángel , Rivera-Riquelme María
Published: March 2021

Una de las principales manifestaciones tras sufrir daño cerebral es una disfunción en la deambulación, por ello la rehabilitación de la misma es una de las demandas primordiales de las personas que han sufrido una lesión cerebral. Este estudio pretende constatar la eficacia de la combinación de los métodos Bobath y Perfetti en el tratamiento de la marcha y su inclusión en las actividades de la vida diaria (AVD) en un adulto tras sufrir un ictus, con el objetivo de demostrar la cabida de la Terapia Ocupacional en la rehabilitación de los miembros inferiores (MMII). El estudio muestra la intervención en un varón con hemiparesia y patología de pie equino durante tres meses, con 5 sesiones semanales. Se evaluó con Escala Tinetti (marcha), Escala Daniels (fuerza), Índice de Barthel, Escala de Lawton y Brody (AVD) y una escala de sensibilidad creada ad hoc. Los resultados muestran mejora en equilibrio, distribución de peso en MMII y en las AVD tras la intervención. En conclusión, la aplicación de dichos métodos sobre el pie equino, favorecen la adquisición de una marcha más estable y funcional que influye directamente en una realización más independiente de las AVD.
Evaluación neurocognitivo-emocional en la enfermedad de Pelizaeus-Merzbacher (PMD)
Authors: López-Sánchez María
Published: March 2021

Pelizaeus-Merzbacher (en adelante PMD) es una enfermedad crónica, minoritaria y neurodegenerativa que pertenece a las leucodistrofias hipomielinizanes. El objetivo de este estudio es proporcionar una base científica de los aspectos cognitivos, ya que en la actualidad se carece de bibliografía enfocada en esto, y así enfatizar en la necesidad de intervención desde la estimulación y la neuropsicología. Los resultados del estudio sugieren que un mayor número síntomas iniciales, fundamentalmente el bajo tono muscular y los problemas de motricidad, correlaciona con una mayor gravedad a nivel motriz en el momento presente. Además, el tiempo medio para llegar a un diagnóstico (4 años y 2 meses), correlaciona positivamente con el número de terapias que reciben los cuidadores, si bien es cierto que parece que este tiempo se está acortando en los últimos años. El estado emocional de los cuidadores muestra una leve sintomatología ansioso-depresiva, correlacionando positivamente la Ansiedad Estado con el número de manifestaciones iniciales y negativamente con las habilidades motrices de la persona con PMD. Entre las terapias de elección para personas con PMD destaca la fisioterapia y la logopedia, no encontrándose la rehabilitación neuropsicológica entre las terapias que reciben este colectivo. Por último, existe una correlación negativa entre la Salud física y las Habilidades del lenguaje.
Rehabilitación de las Funciones Ejecutivas en la Esquizofrenia: Una revisión sistemática
Authors: Wolnik Lena
Published: March 2021

Varios estudios señalan una relación entre el limitado rendimiento funcional de las personas afectadas por la esquizofrenia y el funcionamiento cognitivo deficitario, concretamente de las funciones ejecutivas. Se han desarrollado diversos programas de rehabilitación cognitiva para mejorar el rendimiento funcional de estos pacientes. Este articulo revisa la eficacia de los diferentes programas de rehabilitación y de los diferentes enfoques de entrenamiento sobre el rendimiento cognitivo, especialmente de las funciones ejecutivas y el rendimiento funcional de los pacientes. Los artículos revisados apoyan la evidencia de que la rehabilitación cognitiva supone un método prometedor en la terapia de esquizofrenia. A pesar de ello, algunos resultados obtenidos desafían el papel mediador de las funciones ejecutivas sobre el rendimiento funcional de las personas. Sin embargo, se detecta una falta de estudios con un mayor tamaño muestral y una metodología unificada, que posibilite la generalización y la comparación de los resultados obtenidos.
Motivating for Reading through Transmedia Storytelling: A Case Study with Students from a Middle School in the Médio Tejo Region
Authors: Faria-Ferreira Ana Paula , Faria Ferreira Patrícia Alexandra , Marques Célio Gonçalo
Published: March 2021

The evolution of information and communication technologies has changed the way we relate to each other and how we build our knowledge. This creates challenges for education systems, as school must provide all students with the educational experiences that will enable them to develop the skills reflected in the profile of the 21st-century student on com  pletion of compulsory schooling. It is up to teachers to find new ways of teaching, making the most of the resources and digital tools made available by mobile technologies. Technology can make a significant contribution to increasing students' motivation because it is closer to what they like and use in their daily lives. And this introduction of technology into the classroom can promote student-oriented teaching, which contributes to the development of skills such as autonomy, critical thinking and self-esteem.

One of the areas that can contribute to this paradigm shift is the creation of experiences in immersive learning environments such as Transmedia Storytelling. Immersive learning environments can favour the creation and implementation of projects that promote reading skills in schools. This is the focus of this article.

The aim of this study is to evaluate the impact of transmedia storytelling on the level of motivation of students and on the improvement of pedagogical practices implemented by the teachers involved. This case study was carried out in the subject of Portuguese in three 7th-grade classes of a school from the Médio Tejo region.

The results obtained suggest a high level of motivation of students and teachers. The latter recognise that pedagogical routes using Transmedia Storytelling contribute to the motivation, autonomy and improvement of students' learning.
Bacteriological quality of raw milk marketed in and around Guwahati city, Assam, India
Authors: Kakati Smita , Talukdar Archana , Hazarika Razibuddin Ahmed , Raquib Masuk , Laskar Saurabh Kumar , Saikia Girindra Kumar , Hussein Zakir
Published: March 2021

Background and Aim: Milk is a highly perishable commodity, which is subjected to various types of contamination right from the farm level to the consumers' table. This study aimed to assess the quality of raw milk sold in and around Guwahati city based on the microbial load. Materials and Methods: A total of 200 raw pooled milk samples collected from 25 different locations in and around Guwahati city were subjected to quality evaluation based on the methylene blue reduction test (MBRT), standard plate count, and coliform count as per the standard procedure. Results: Out of the 200 samples evaluated, more than 50% of them were graded as poor to very poor quality based on the MBRT results. None of the samples could be graded as excellent quality and only 14.5% were graded as good quality. The standard plate count and coliform count of all the raw milk samples were found to be significantly higher than the legal standard. A highly significant (p<0.01) difference was observed for standard plate count and coliform count among the different locations in and around Guwahati city. Conclusion: From the present study, it could be inferred that raw milk sold in most parts of Guwahati city do not confer to the legal microbiological standard and may pose a high risk of milk-borne illness among consumers of the city, which needs a systematic series of actions to be implemented properly.
Microbiome structure in a recirculating aquaculture system and its connection to infections in sturgeon fish
Authors: Sergaliev Nurlan Khabibullovich , Kakishev Murat Galikhanovich , Ginayatov Nurbek Satkanuly , Nurzhanova Farida Khamidullievna , Andronov Evgeny Evgenievich
Published: March 2021

Aim: This study aimed to determine the bacterial composition at various stages of the temperature regime in a recirculating aquaculture system (RAS) to assess the pathological risk of a group of opportunistic pathogenic microflora. Materials and Methods: Water temperature, incidences of illnesses, and fish mortality were monitored, during the research period to identify the causes of pathogens in sturgeons. Analysis of the nucleotide sequences was performed using the quantitative insights into microbial ecology module. Sequence alignment in the analysis of the distribution of gene libraries was performed using the Unclust method. The RDP database was used for the taxonomic identification of operational taxonomic units. Results: The pattern of the contraction of infection among sturgeons bred in the RAS was established. A detailed analysis of the microbiome structure's taxonomic features showed dominant taxa during the "artificial wintering" period and at a temperature optimum in industrial aquaculture. It was found that the main outbreaks of pseudomonosis occurred during this period in the RAS. With a decrease in temperature of the aquatic environment, the incidence of illness increased by 75% compared with the optimum temperature period. Pseudomonas, Cetobacterium, and Lactococcus were specific taxa characteristic for the "artificial wintering" period. Xanthomonadaceae and Flavobacterium were specific taxa characteristic for the optimum temperature. Conclusion: Consequently, the microbial structure was determined at different temperature regimes in a RAS, and the dominant communities were identified. The pattern of the contraction of infection caused by an opportunistic microflora (pseudomonosis) among sturgeons was established, allowing for the development and correction of treatment and preventive measures.
Adaptation of a Refactoring DSL for the Object-Oriented Paradigm
Authors: Németh Dávid J. , Horpácsi Dániel , Tejfel Máté
Published: March 2021

Many development environments offer refactorings aimed at improving non-functional properties of software, but we have no guarantees that these transformations indeed preserve the observable behavior of the source code they are applied on. An existing domain-specific language makes it possible to formalize automatically verifiable refactorings via instantiating predefined transformation schemes with conditional term rewrite rules.
We present a proposal for adapting this language from the functional to the object-oriented programming paradigm, using Java instead of Erlang as a representative. The behavior-preserving property of discussed refactorings is characterized with a multilayered definition of equivalence for Java programs, including the conformity relation of class hierarchies. Based on the decomposition of a complex refactoring rule, we show how new transformation schemes can be identified, along with modifications and extensions of the description language required to accommodate them. Finally, we formally define the chosen base refactoring as a composition of scheme instances.
Áldás vagy átok? A magántőke-befektetések hatása a gazdaságra
Authors: Karsai Judit
Published: March 2021

A gazdasági és politikai élet szereplői körében már régóta világszerte vita folyik arról, hogy a magántőke- befektetések milyen hatást gyakorolnak a gazdaságra. A vita fókuszában a magántőke-befektetéseknek csak egy szűkebb csoportja áll, nevezetesen a hitel igénybevételéből történő kivásárlások (Leveraged Buyout, LBO) hatása. Miközben a cégek fejlődésének korai fázisában történő kockázatitőke-befektetések pozitív hatását senki sem kérdőjelezi meg, a válság közepette különös élességgel vetődik fel egy kérdés. Vajon a magántőke valóban olyan tulajdonosi modell, amely képes a megvásárolt cégek fenntartható javulását előidézni, avagy csupán egy egyszerű pénzügyi konstrukció, esetleg mindkettő. A kérdés tehát valójában az, hogy a magántőke a kivásárlásra kerülő cégek részvényeire tett, hitellel kiegészített ajánlata révén, a cégeket szakszerűen kiválasztva és menedzselve jut-e a tőzsdei befektetésekhez képest magasabb hozamokhoz, avagy csupán egy pénzügyi trükkről van szó, amely az adókedvezmények kihasználásával és a cégekben lévő vagyon kiszivattyúzásával csak a jövedelmeket rendezi át.