bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a myoelectric upper limb orthosis for rehabilitation of the upper limb in traumatic brain injury: A case report
Authors: Pundik Svetlana , McCabe Jessica , Kesner Samuel , Skelly Margaret , Fatone Stefania 
Published: June 2020

Background Upper limb motor deficits following traumatic brain injury are prevalent and effective therapies are needed. The purpose of this case report was to illustrate response to a novel therapy using a myoelectric orthosis in a person with TBI. Case description: A 42-year-old female, 29.5 years post-traumatic brain injury with diminished motor control/coordination, and learned nonuse of the right arm. She also had cognitive deficits and did not spontaneously use her right arm functionally. Intervention Study included three phases: baseline data collection/device fabrication (five weeks); in-clinic training (2×/week for nine weeks); and home-use phase (nine weeks). The orthosis was incorporated into motor learning-based therapy. Outcomes: During in-clinic training, active range of motion, tone, muscle power, Fugl-Meyer, box and blocks test, and Chedoke assessment score improved. During the home-use phase, decrease in tone was maintained and all other outcomes declined but were still better upon study completion than baseline. The participant trained with the orthosis 70.12 h, logging over 13,000 repetitions of elbow flexion/extension and hand open/close. Discussion Despite long-standing traumatic brain injury, meaningful improvements in motor function were observed and were likely the results of high repetition practice of functional movement delivered over a long duration. Further assessment in a larger cohort is warranted.
The effectiveness of R&D subsidies in fostering firm innovation: The role of knowledge-sourcing activities
Authors: Afcha Sergio , Lucena Abel 
Published: June 2020

This article presents a novel conceptual framework that uses the notion of knowledge sourcing to explain how firms realize benefits from R&D subsidies in terms of innovations. The study considers two dimensions of the firm’s knowledge sourcing: its R&D effort and level of openness to technology markets. This article proposes that the policy-induced effects of R&D subsidies on the knowledge-sourcing process increase firms’ innovation outcomes, thus making this policy intervention effective in promoting innovation. By using panel data from Spanish manufacturing firms, this article presents evidence consistent with the hypothesis that by changing the knowledge sourcing of firms, National R&D subsidy programs in Spain also favor more firm innovation, measured by patent applications and new product launches. It is also documented that the granting of R&D subsidies does not affect firm innovation directly but rather through inducing changes in the firm’s R&D effort and openness to technology markets. JEL CLASSIFICATION: O32, O36, O38
Transition Experiences of Caregivers of Older Adults With Dementia and Multiple Chronic Conditions: An Interpretive Description Study
Authors: Lam Annie , Ploeg Jenny , Carroll Sandra L. , Duggleby Wendy , McAiney Carrie , Julian Patricia 
Published: June 2020

Introduction Family caregivers provide most of the care for older persons living with dementia (PLWD) and multiple chronic conditions (MCCs) in the community. Caregivers experience transitions, such as changes to their health, roles, and responsibilities, during the process of caring. Transitions encompass a time when caregivers undergo stressful responses to change. However, we know little about the transition experiences of caregivers of persons living with both dementia and MCCs. Objective This qualitative study explored the transition experiences of caregivers of PLWD within the context of MCCs, from the perspective of both caregivers and practitioners. The research question was the following: What are the transition experiences of family caregivers in providing care to older PLWD and MCCs living in the community? Methods This study was conducted using an interpretive description approach. Semistructured interviews were conducted with 19 caregivers of older community-dwelling PLWD and MCCs and 7 health-care providers working with caregivers in Ontario, Canada. Concurrent data collection and inductive data analysis were used. Results Caregivers of older PLWD and MCCs experienced four key transitions: (a) taking on responsibility for managing multiple complex conditions, (b) my health is getting worse, (c) caregiving now defines my social life, and (d) expecting that things will change. Findings highlight how the coexistence of MCCs with dementia complicates caregiver transitions and the importance of social networks for facilitating transitions. Conclusion The study provided insight on the transition experiences of caregivers of older PLWD and MCCs. MCCs increased the care load and further complicated caregivers’ transition experiences. Health-care providers, such as nurses, can play important roles in supporting caregivers during these transitions and engage them as partners in care.
Line-selective macrophage activation with an anti-CD40 antibody drives a hemophagocytic syndrome in mice
Authors: Ingoglia Giada , Yalamanoglu Ayla , Pfefferlé Marc , Dubach Irina L. , Schaer Christian A. , Valkova Kristyna , Hansen Kerstin , Schulthess Nadja , Humar Rok , Schaer Dominik J. , Vallelian Florence 
Published: June 2020

Abstract
Hemophagocytic syndromes comprise a cluster of hyperinflammatory disorders, including hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Overwhelming macrophage activation has long been considered a final common pathway in the pathophysiology of hemophagocytic syndromes leading to the characteristic cytokine storm, laboratory abnormalities, and organ injuries that define the clinical spectrum of the disease. So far, it is unknown whether primary macrophage activation alone can induce the disease phenotype. In this study, we established a novel mouse model of a hemophagocytic syndrome by treating mice with an agonistic anti-CD40 antibody (Ab). The response in wild-type mice is characterized by a cytokine storm, associated with hyperferritinemia, high soluble CD25, erythrophagocytosis, secondary endothelial activation with multiple organ vaso-occlusion, necrotizing hepatitis, and variable cytopenias. The disease is dependent on a tumor necrosis factor-α–interferon-γ–driven amplification loop. After macrophage depletion with clodronate liposomes or in mice with a macrophage-selective deletion of the CD40 gene (CD40flox/flox/LysMCre), the disease was abolished. These data provide a new preclinical model of a hemophagocytic syndrome and reinforce the key pathophysiological role of macrophages.
American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain
Authors: Brandow Amanda M. , Carroll C. Patrick , Creary Susan , Edwards-Elliott Ronisha , Glassberg Jeffrey , Hurley Robert W. , Kutlar Abdullah , Seisa Mohamed , Stinson Jennifer , Strouse John J. , Yusuf Fouza , Zempsky William , Lang Eddy 
Published: June 2020

Background:The management of acute and chronic pain for individuals living with sickle cell disease (SCD) is a clinical challenge. This reflects the paucity of clinical SCD pain research and limited understanding of the complex biological differences between acute and chronic pain. These issues collectively create barriers to effective, targeted interventions. Optimal pain management requires interdisciplinary care.Objective:These evidence-based guidelines developed by the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in pain management decisions for children and adults with SCD.Methods:ASH formed a multidisciplinary panel, including 2 patient representatives, that was thoroughly vetted to minimize bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic reviews. Clinical questions and outcomes were prioritized according to importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment.Results:The panel reached consensus on 18 recommendations specific to acute and chronic pain. The recommendations reflect a broad pain management approach, encompassing pharmacological and nonpharmacological interventions and analgesic delivery.Conclusions:Because of low-certainty evidence and closely balanced benefits and harms, most recommendations are conditional. Patient preferences should drive clinical decisions. Policymaking, including that by payers, will require substantial debate and input from stakeholders. Randomized controlled trials and comparative-effectiveness studies are needed for chronic opioid therapy, nonopioid therapies, and nonpharmacological interventions.
CRISPR/Cas9-targeted mutagenesis of the tomato susceptibility gene PMR4 for resistance against powdery mildew
Authors: Santillán Martínez Miguel I. , Bracuto Valentina , Koseoglou Eleni , Appiano Michela , Jacobsen Evert , Visser Richard G. F. , Wolters Anne-Marie A. , Bai Yuling 
Published: June 2020

Abstract
Background
The development of CRISPR/Cas9 technology has facilitated targeted mutagenesis in an efficient and precise way. Previously, RNAi silencing of the susceptibility (S) gene PowderyMildewResistance 4 (PMR4) in tomato has been shown to enhance resistance against the powdery mildew pathogen Oidium neolycopersici (On).

Results
To study whether full knock-out of the tomato PMR4 gene would result in a higher level of resistance than in the RNAi-silenced transgenic plants we generated tomato PMR4 CRISPR mutants. We used a CRISPR/Cas9 construct containing four single-guide RNAs (sgRNAs) targeting the tomato PMR4 gene to increase the possibility of large deletions in the mutants. After PCR-based selection and sequencing of transformants, we identified five different mutation events, including deletions from 4 to 900-bp, a 1-bp insertion and a 892-bp inversion. These mutants all showed reduced susceptibility to On based on visual scoring of disease symptoms and quantification of relative fungal biomass. Histological observations revealed a significantly higher occurrence of hypersensitive response-like cell death at sites of fungal infection in the pmr4 mutants compared to wild-type plants. Both haustorial formation and hyphal growth were diminished but not completely inhibited in the mutants.

Conclusion
CRISPR/Cas-9 targeted mutagenesis of the tomato PMR4 gene resulted in mutants with reduced but not complete loss of susceptibility to the PM pathogen On. Our study demonstrates the efficiency and versatility of the CRISPR/Cas9 system as a powerful tool to study and characterize S-genes by generating different types of mutations.
Development and application of a triplex real-time PCR assay for simultaneous detection of avian influenza virus, Newcastle disease virus, and duck Tembusu virus
Authors: Zhang Xiyu , Yao Ming , Tang Zhihui , Xu Daning , Luo Yan , Gao Yunfei , Yan Liping 
Published: June 2020

Abstract
Background
Pathogens including duck-origin avian influenza virus (AIV), duck-origin Newcastle disease virus (NDV) and duck Tembusu virus (DTMUV) posed great harm to ducks and caused great economic losses to the duck industry. In this study, we aim to develop a triplex real-time polymerase chain reaction (PCR) assay to detect these three viruses as early as possible in the suspicious duck flocks.

Results
The detection limit of the triplex real-time PCR for AIV, NDV, and DTMUV was 1 × 101 copies/μL, which was at least 10 times higher than the conventional PCR. In addition, the triplex assay was highly specific, and won’t cross-react with other duck pathogens. Besides, the intra-day relative standard deviation and inter-day relative standard deviation were lower than 4.44% for these viruses at three different concentrations. Finally, a total of 120 clinical samples were evaluated by the triplex real-time PCR, the conventional PCR and virus isolation, and the positive rates for these three methods were 20.83, 21.67, 19.17%, respectively. Taking virus isolation as the gold standard, the diagnostic specificity and positive predictive value of the three viruses were all above 85%, while the diagnostic sensitivity and negative predictive value of the three viruses were all 100%.

Conclusion
The developed triplex real-time PCR is fast, specific and sensitive, and is feasible and effective for the simultaneous detection of AIV, NDV, and DTMUV in ducks.
Impact of dietary Mannan-oligosaccharide and β-Glucan supplementation on growth, histopathology, E-coli colonization and hepatic transcripts of TNF-α and NF- ϰB of broiler challenged with E. coli O78
Authors: Fadl Sabreen Ezzat , El-Gammal Ghada Ahmed , Sakr Osama Atia , Salah Aly A. B. S. , Atia Ayman Ali , Prince Abdelbary Mohammed , Hegazy Abdelhaleem Mohamed 
Published: June 2020

Abstract
Background
Using probiotics have become popular. They are considered an alternative to Antibiotic Growth Promoters (AGP). Probiotics are supplemented into animal feed for improving growth performance along with preventing and controlling enteric pathogens. The aim of this work was to study the impact of dietary supplementation of Mannan-oligosaccharide and β-Glucan (Agrimos®) on broiler challenged with Escherichia coli O78 (E. coli O78 - marked with an antibiotic (320 μg ciprofloxacin/ml broth) on growth performance, serum biochemistry, immune organs-histopathology, E-coli colonization, and hepatic transcripts of Tumor necrosis factor-alpha (TNF-α) and Nuclear factor-kappa B (NF-ϰB). A total of 125 one-day-old chicks were used for conducting the experiment. Five one-day-old chicks were slaughtered for measuring the initial weight of the lymphoid tissue. The remaining chicks (120) were allotted into four groups according to Mannan-oligosaccharide and β-Glucan supplementation, and E. coli infection. The data were analyzed using SPSS version 16.

Results
Results indicated significant alteration of growth performance, serum biochemistry, and selected liver gene expression with pathological lesions, especially in the lymphoid organs due to E. coli infection. These alterations were mitigated by Mannan-oligosaccharide and β-Glucan supplementation.

Conclusion
It could be concluded, Mannan-oligosaccharide and β-Glucan supplementation in broiler’s diet improved the immune response of broilers and mitigated pathological lesion resulted from E. coli infection.
A systematic review of school meal nudge interventions to improve youth food behaviors
Authors: Metcalfe Jessica Jarick , Ellison Brenna , Hamdi Nader , Richardson Rachel , Prescott Melissa Pflugh 
Published: June 2020

AbstractBackgroundSchool meal programs have a large reach and thus are ideal environments in which to implement interventions targeting improved youth eating behaviors and reduced food waste. This systematic review summarizes the evidence on the effectiveness of school meal nudge interventions on influencing children’s eating and waste behaviors.MethodsInclusion criteria required studies have participants in primary or secondary school (grades K-12) with interventions that occurred during school lunch or breakfast in the cafeteria and included at least one of the following outcomes: selection, consumption, waste, or school meal participation. Analyses of intervention outcomes were restricted to studies of strong and moderate quality.ResultsTwenty-nine studies were included in the quality assessment. Included interventions fell into three categories: 1) placement/convenience, 2) marketing/promotion, or 3) variety/portions. The 20 strong and moderate quality studies included in outcome analyses generally used strong data collection methods and study designs, but were limited by an overall lack of intervention fidelity checks. Multi-component interventions often did not use methods that allowed for separate analyses of outcomes for different intervention components.ConclusionsSchool meal nudge interventions were positively associated with food selection, and had an inconsistent relationship with food consumption. There were few studies evaluating the impact of nudge interventions on meal participation or food waste. The limited evidence available links nudges to improved meal participation, as well as undesirable increases in food waste. Future research in this area should use methods that incorporate implementation metrics, attend to systems factors, and allow the outcomes of individual intervention components to be isolated.
RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human laryngeal squamous cell carcinoma
Authors: Shi Xinli , Li Shenghao , Wang Li , Li Hui , Li Zhen , Wang Weiyi , Bai Jing , Sun Yajing , Li Jianchun , Li Xiaoming 
Published: June 2020

Abstract
Background
Interferon-inducible 16 (IFI16)/caspase-1 inflammasome activates and secretes IL-1β. However, it is still unclear whether the IFI16 inflammasome is involved in human laryngeal squamous cell carcinoma. Autophagy directly removed inflammasome components and limited early IL-1β production. RalB is required for the crosstalk between inflammasome and autophagy in macrophages. Dihydroartemisinin (DHA), the main derived ingredient of artemisinin, has a variety of biological activities. The mechanism of DHA in regulating the crosstalk between IFI16 inflammasome and autophagy by inhibiting RalB expression was analyzed in order to provide clues for new therapeutic methods in laryngeal cancer.

Methods
The expression of IFI16 was analyzed by Oncomine and GEPIA databases and detected by Western blot and immunohistochemistry. The relationship between IFI16 inflammasome and autophagy was investigated by transmission electron microscopy, immunofluorescence assay, etc. in Hep-2, Cal-27 and HeLa cells treated with DHA. The xenograft tumor of hep-2 cell in nude mice were used to assess the effect of DHA on laryngeal cancer.

Results
It was reported for the first time in this study that IFI16 was overexpressed and positively correlated with caspase-1 in laryngeal carcinoma tissues. DHA significantly inhibited the activation of inflammasome and reduced IL-1β production in the microenvironment of Hep-2 cell xenograft tumor in nude mice. Mechanistically, we found that DHA degraded RalB, inhibited USP33 expression, and triggered autophagy. Meanwhile, enhanced autophagy can reduce the expression of RalB and USP33. Furthermore, DHA promotes autophagy, which suppresses the activation of IFI16/caspase-1 inflammasome and IL-1β production.

Conclusions
Therefore, our findings demonstrate that DHA may act as a RalB inhibitor to regulate the crosstalk between autophagy and IFI16/caspase-1 inflammasome, which inhibits IL-1β production in tumor microenvironment.
Factors influencing in-hospital death for pediatric patients with isolated methylmalonic acidemia: a nationwide inpatient database analysis
Authors: Jiang Yi-Zhou , Shi Yu , Shi Ying , Gan Lan-Xia , Kong Yuan-Yuan , Sun Li-Ying , Wang Hai-Bo , Zhu Zhi-Jun 
Published: June 2020

Abstract
Background
Patients with isolated methylmalonic acidemia (MMA) usually experience recurrent episodes of acute metabolic decompensation or metabolic stroke, require frequent hospitalization, and have a relatively high mortality rate. The aim of our study was to assess factors predicting the in-hospital death of pediatric patients with isolated MMA. We performed a retrospective study using data from the Hospital Quality Monitoring System, a national inpatient database in China collected from 2013 to 2017. All patients under 18 years old with a diagnosis of isolated MMA were included. Demographic, hospital-related, and clinical features were collected. Poisson regression was performed to identify potential influencing variables associated with in-hospital death.

Results
From 2013 to 2017, among 2317 admissions for pediatric patients diagnosed with isolated MMA, 1.77% had the outcome of death. In the univariate analysis, patients aged under 1 year had a higher risk of death than did those aged 1 year or older (odds ratio [OR] = 2.63, 95% confidence interval [CI]: 1.36–5.07). There was a higher risk of in-hospital death for patients admitted through emergency departments or via referrals than for those admitted through other routes (OR = 3.76, 95% CI: 1.84–7.67). Deaths were higher in hospitals with volumes of less than 50 patients with isolated MMA during the five study years (OR = 2.92, 95% CI: 1.46–5.83). Moreover, the risk of in-hospital death gradually decreased over time (OR = 0.72, 95% CI: 0.57–0.90). In the multivariate analysis, the abovementioned associations with the risk of in-hospital death remained statistically significant. However, no significant associations were observed between specific clinical signs and in-hospital death in either the univariate or the multivariate analysis.

Conclusions
Younger age, admission to hospitals with low patient volumes, and admission through emergency departments or referrals are associated with higher risk of in-hospital death. The co-existence of specific clinical signs appears to have no effect on in-hospital death.