bluuebunny/crossref_metadata_2025_split huggingface dataset:
Online interventions geared toward increasing resilience and reducing distress in family caregivers
Authors: Shin Ji Youn , Choi Sung Won 
Published: December 2019

Purpose of review
Family caregivers of patients with cancer often spend a great deal of effort on physically and emotionally demanding work while taking care of patients. However, the majority of caregivers are not properly equipped for their role as caregivers, which may lead to increased distress in both caregivers and patients. Herein, we reviewed the recent literature (last 3 years) examining online interventions that seek to support caregiver resilience and decrease distress.

Recent findings
Our search identified interventions involving three main themes: informational support, positive activities, and social support. These are mostly in the form of web-based tools and mobile apps targeting both usability and quality of life. Social network services are also considered in this review as a new environment for caregivers to connect with other individuals with lived experience in similar circumstances.

Summary
Existing studies on online interventions to support caregivers is still at a formative development stage and pilot tests of feasibility, rather than a substantive body of randomized controlled trials to assess the impact in different user populations, or to determine specific factors that impact caregiver distress level or resilience. More research is needed to further assess the long-term effects of online interventions on caregiver stress and resilience. Also, the role of different types of social network services and new forms of interaction, such as conversational agents, has not yet been fully investigated in caregiver populations. Future research should strive to seek new modes of providing services that may present novel opportunities to enhance caregiver resilience and reduce distress.
Tensors and compositionality in neural systems
Authors: Martin Andrea E. , Doumas Leonidas A. A. 
Published: December 2019

Neither neurobiological nor process models of meaning composition specify the operator through which constituent parts are bound together into compositional structures. In this paper, we argue that a neurophysiological computation system cannot achieve the compositionality exhibited in human thought and language if it were to rely on a multiplicative operator to perform binding, as the tensor product (TP)-based systems that have been widely adopted in cognitive science, neuroscience and artificial intelligence do. We show via simulation and two behavioural experiments that TPs violate variable-value independence, but human behaviour does not. Specifically, TPs fail to capture that in the statementsfuzzy cactusandfuzzy penguin, both cactus and penguin are predicated byfuzzy(x) and belong to the set of fuzzy things, rendering these arguments similar to each other. Consistent with that thesis, people judged arguments that shared the same role to be similar, even when those arguments themselves (e.g., cacti and penguins) were judged to be dissimilar when in isolation. By contrast, the similarity of the TPs representingfuzzy(cactus) andfuzzy(penguin) was determined by the similarity of the arguments, which in this case approaches zero. Based on these results, we argue that neural systems that use TPs for binding cannot approximate how the human mind and brain represent compositional information during processing. We describe a contrasting binding mechanism that any physiological or artificial neural system could use to maintain independence between a role and its argument, a prerequisite for compositionality and, thus, for instantiating the expressive power of human thought and language in a neural system.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
Tools and Resources: Remote, automated and MRI-compatible administration of interoceptive inspiratory resistive loading
Authors: Rieger Sebastian W , Stephan Klaas Enno , Faull Olivia K. 
Published: December 2019

AbstractResearch on how humans perceive sensory inputs from their bodies (‘interoception’) has been rapidly gaining momentum, with interest across a host of disciplines from physiology through to psychiatry. However, studying interoceptive processes is not without significant challenges, and many methods utilised to access internal states have been largely devoted to capturing and relating naturally-occurring variations in interoceptive signals (such as heartbeats) to measures of how the brain processes these signals. An alternative procedure involves the controlled perturbation of specific interoceptive axes. This is challenging because it requires non-invasive interventions that can be repeated many times within a subject and that are potent but safe. Here we present an effective methodology for instigating these perturbations within the breathing domain. We describe a custom-built circuitry that is capable of delivering inspiratory resistive loads automatically and precisely. Importantly, our approach is compatible with magnetic resonance imaging environments, allowing for the administration of complicated experimental designs in neuroimaging as increasingly required within developing fields such as computational psychiatry/psychosomatics. We describe the experimental setup for both the control and monitoring of the inspiratory resistive loads, and demonstrate its possible utilities within different study designs. This methodology represents an important step forward from the previously utilised, manually-controlled resistive loading setups, which present significant experimental burdens with prolonged and/or complicated sequences of breathing stimuli.
Ontario Neurodegenerative Disease Research Initiative (ONDRI): Structural MRI methods & outcome measures
Authors: Ramirez Joel , Holmes Melissa F. , Scott Christopher J.M. , Ozzoude Miracle , Adamo Sabrina , Szilagyi Gregory M. , Goubran Maged , Gao Fuqiang , Arnott Stephen R. , Lawrence-Dewar Jane M. , Beaton Derek , Strother Stephen C. , Munoz Douglas P. , Masellis Mario , Swartz Richard H. , Bartha Robert , Symons Sean , Black Sandra E. ,   the ONDRI Investigators
Published: December 2019

ABSTRACTThe Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 year multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, and cerebrovascular disease patients. This heterogeneous cross-section of patients with complex neurodegenerative and neurovascular pathologies pose significant challenges for standard neuroimaging tools. To effectively quantify regional measures of normal and pathological brain tissue volumes, the ONDRI neuroimaging platform implemented a semi-automated MRI processing pipeline that was able to address many of the challenges resulting from this heterogeneity. This paper describes the comprehensive neuroimaging pipeline methods used to generate regional brain tissue volumes & neurovascular markers.
Anti-inflammatory treatment with FTY720 starting after onset of symptoms reverses synaptic and memory deficits in an AD mouse model
Authors: Kartalou Georgia-Ioanna , Pereira Ana Rita Salgueiro , Endres Thomas , Lesnikova Angelina , Casarotto Plinio , Pousinha Paula , Delanoe Kevin , Edelmann Elke , Castrén Eero , Gottmann Kurt , Marie Helene , Lessmann Volkmar 
Published: December 2019

AbstractTherapeutical approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Repurposing FDA approved drugs like fingolimod (FTY720) for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms. Here, we addressed whether the FDA approved drug fingolimod rescues AD related synaptic deficits and memory dysfunction in an APP/PS1 AD mouse model when medication starts after onset of symptoms (at 5 months). Male mice received intraperitoneal injections of fingolimod for 1-2 months starting at 5-6 months. This treatment rescued spine density as well as long-term potentiation in hippocampal CA1 pyramidal neurons, and ameliorated dysfunctional hippocampus-dependent memory that was observed in untreated APP/PS1 animals at 6-7 months of age. Immunohistochemical analysis with markers of microgliosis (Iba1) and astrogliosis (GFAP) revealed that our fingolimod treatment regime strongly down regulated neuro-inflammation in the hippocampus and cortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and cortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology and related memory performance deficits observed in untreated AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.
Towards a Chimeric Vaccine against Multiple Isolates ofMycobacteroides- An Integrative Approach
Authors: Satyam Rohit , Bhardwaj Tulika , Jha Niraj Kumar 
Published: December 2019

AbstractNontuberculous mycobacterial infection (NTM) such as endophthalmitis, dacryocystitis, canaliculitis are pervasive across the globe and are currently managed by antibiotics such as cefoxitin/imipenem and azithromycin/clarithromycin. However, the recent cases of Mycobacteroides developing drug resistance reported along with the improper practice of medicine intrigued us to explore its genomic and proteomic canvas at a global scale. A timely developed vaccine against Mycobacteroides is, therefore, a much requirement. Consequently, we carried out a vivid Genomic study on five recently sequenced strains of Mycobacteroides and explored their Pan-Core genome/ proteome. The promiscuous antigenic proteins were identified via a subtractive proteomics approach that qualified for virulence causation, resistance and essentiality factors for this notorious bacterium. An integrated pipeline was developed for the identification of B Cell, MHC class I, II epitopes. Our final vaccine construct, V6 qualified for all tests such as absence for allergenicity, presence of antigenicity, etc. and contains β defensin adjuvant, linkers, LAMP1 signal peptide, and PADRE (Pan HLA-DR epitopes) amino acid sequence. The vaccine construct, V6 also interacts with a maximum number of MHC molecules, and the TLR4/MD2 complex confirmed by docking and molecular dynamics simulation studies. The knowledge harnessed from the current study can help improve the current treatment regimens and propel further related studies.
Susceptibility to auditory closed-loop stimulation of sleep slow oscillations changes with age
Authors: Schneider Jules , Lewis Penelope A. , Koester Dominik , Born Jan , Ngo Hong-Viet V. 
Published: December 2019

AbstractBackgroundCortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate sleep-dependent memory consolidation. Experiments utilising auditory closed-loop stimulation to enhance these oscillations have shown great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups.ObjectiveWe examined the possibility of enhancing SOs and performance on different memory tasks in a healthy older population using auditory closed-loop stimulation and contrast effects to a young adult cohort.MethodsIn a within-subject design, subjects (n = 17, 55.7 ± 1.0 years, 9 female) received auditory click stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to those reported previously in a younger cohort (n = 11, 24.2 ± 0.9 years, 8 female).ResultsOvernight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups.ConclusionsOur findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations.HighlightsAuditory closed-loop stimulation induced SOs and sleep spindles in older subjectsStimulation effects were reduced and overall susceptibility diminished with ageSlow oscillation and sleep spindle dynamics deviated from those in younger subjectsStimulation shows no evidence for memory effect in older subjects
In vivostudies of glucagon secretion by human islets transplanted in mice
Authors: Tellez Krissie , Hang Yan , Gu Xueying , Stein Roland W. , Kim Seung K. 
Published: December 2019

AbstractRelatively little is known about regulated glucagon secretion by human islet α cells compared to insulin secretion from β cells, despite conclusive evidence of dysfunction in both cell types in diabetes mellitus. Distinct insulin sequences in humans and mice permitin vivostudies of β cell regulation after human islet transplantation in immunocompromised mice, whereas identical glucagon sequences prevent analogousin vivomeasures of glucagon output from human α cells. We used CRISPR/Cas9 genome editing to remove glucagon-encoding codons 2-29 in immunocompromised (NSG) mice, preserving production of other proglucagon-derived hormones, like Glucagon-like-peptide 1. TheseNSG-Glucagon knockout (NSG-GKO) mice had phenotypes associated with glucagon signaling deficits, including hypoglycemia, hyperaminoacidemia, hypoinsulinemia, and islet α cell hyperplasia.NSG-GKOhost metabolic and islet phenotypes reverted after human islet transplantation, and human islets retained regulated glucagon and insulin secretion.NSG-GKOmice provide an unprecedented resource to investigate unique, species-specific human α cell regulationin vivo.
Effect of EBV-Transformation on Oxidative Phosphorylation Physiology in Human Cell lines
Authors: Weinstein Rachel N. , Crawford Douglas L. 
Published: December 2019

AbstractDo the immortalized and cryopreserved white blood cells that are part of the 1,000 Human Genomes Project represent a valuable cellular physiological resource to investigate the importance of genome wide sequence variation? While much research exists on the nucleotide variation in the 1,000 Human Genomes, there are few quantitative measures of these humans’ physiologies. Fortunately, physiological measures can be done on the immortalized and preserved cells from each of the more than 1,000 individuals that are part of Human Genome project. However, these human white blood cells were immortalized by transforming them with the Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines (LCL)). This transformation integrates the viral genome into the human genome and potentially affects important biological differences among individuals. The questions we address here are whether EBV transformations significantly alters the cellular physiology so that 1) replicate transformations within an individual are significantly different, and 2) whether the variance among replicates obscures the variation among individuals. To address these questions, we quantified oxidative phosphorylation (OxPhos) metabolism in LCLs from six individuals with 4 separate and independent EBV-transformations. We examined OxPhos because it is critical for energy production, and mutations in this pathway are responsible for most inborn metabolic diseases. The data presented here demonstrate that there are small but significant effects of EBV-transformations on some OxPhos parameters. In spite of significant variation due to transformations, there is greater and significant variation among individuals in their OxPhos metabolism. Thus, the LCLs from the 1,000 Human Genome project could provide valuable insights into the natural variation of cellular physiology because there is statistically significant variation among individuals when using these EBV-transformed cells.
The transformation effect of R&D subsidies on firm performance
Authors: Wang Fengrong , Li Yafei , Sun Jinping 
Published: December 2019

Purpose
The purpose of this paper studies the transformation effect of research and development (R&D) subsidies on firm performance in emerging economies from the perspective of capital and product markets. It also studies the mechanisms behind R&D subsidies’ transformation effect.

Design/methodology/approach
This study mainly explores the transformation effect of government R&D subsidies on corporate performance and its non-linear characteristics using Chinese A-share listed companies’ data from 2008 to 2016. The authors use the instrumental variable method to reduce endogenous problems and conduct a series of robustness tests to support the conclusions. The mechanisms of the transformation effect are explored via mediation effect models. The impact of firm heterogeneities on the transformation effect is also addressed.

Findings
Results indicate that R&D subsidies promote firm performance and experience obvious transformation effects only within a “moderate interval.” R&D subsidies play a vital role in enhancing firm performance mainly via two mechanisms, namely, signal financing and innovation incentives. Further, the transformation effect is much greater in non-state-owned, young and large enterprises.

Originality/value
This paper contributes to understanding how R&D subsidies affect corporate performance from the perspective of capital and product markets by applying the linear and non-linear techniques that can clarify the relationship between the selected variables under study. The findings of this study might be helpful to identify the right directions for the government to implement and promote the R&D subsidy policies more effectively.
Fault-tolerant redundant repairable system with different failures and delays
Authors: Shekhar Chandra , Kumar Amit , Varshney Shreekant , Ammar Sherif I. 
Published: December 2019

Purpose
The internet of things and just-in-time are the embryonic model of innovation for the state-of-the-art design of the service system. This paper aims to develop a fault-tolerant machining system with active and standby redundancy. The availability of the fault-tolerant redundant repairable system is a key concern in the successful deployment of the service system.

Design/methodology/approach
In this paper, the authors cogitate a fault-tolerant redundant repairable system of finite working units along with warm standby unit provisioning. Working unit and standby unit are susceptible to random failures, which interrupt the quality-of-service. The system is also prone to common cause failure, which tends its catastrophe. The instantaneous repair of failed unit guarantees the increase in the availability of the unit/system. The time-to-repair by the single service facility for the failed unit follows the arbitrary distribution. For increasing the practicability of the studied model, the authors have also incorporated real-time machining practices such as imperfect coverage of the failure of units, switching failure of standby unit, common cause failure, reboot delay, switch over delay, etc.

Findings
For deriving the explicit expression for steady-state probabilities of the system, the authors use a supplementary variable technique for which the only required input is the Laplace–Stieltjes transform (LST) of the repair time distribution.

Research limitations/implications
For complex and multi-parameters distribution of repair time, derivation of performance measures is not possible. The authors prefer numerical simulation because of its importance in the application for real-time uses.

Practical implications
The stepwise recursive procedure, illustrative examples, and numerical results have been presented for the diverse category of repair time distribution: exponential (M), n-stage Erlang (Ern), deterministic (D), uniform (U(a,b)), n-stage generalized Erlang (GE[n]) and hyperexponential (HE[n]).

Social implications
Concluding remarks and future scopes have also been included. The studied fault-tolerant redundant repairable system is suitable for reliability analysis of a computer system, communication system, manufacturing system, software reliability, service system, etc.

Originality/value
As per the survey in literature, no previous published paper is presented with so wide range of repair time distribution in the machine repair problem. This paper is valuable for system design for reliability analysis of the fault-tolerant redundant repairable.
An empirical study on the online learning experience of MOOCs: Indian students’ perspective
Authors: Pillai Rajasshrie , Sivathanu Brijesh 
Published: December 2019

PurposeThe purpose of this paper is to investigate the online learning experience (LE) of massive open online courses (MOOCs) among the students in India using the lens of community of inquiry (CoI) model and two additional contextual factors.Design/methodology/approachThe study conducted a survey using a structured questionnaire among the undergraduate and postgraduate students to examine the LE of MOOCs using the CoI framework and contextual variables – technical barrier (TB) and hedonic motivation (HD). The primary data were analyzed with the partial least squares structural equation modeling technique.FindingsThe results show that teaching presence (TP) influences cognitive presence (CP) and social presence (SP). SP influences CP. It is also found that TP, SP and CP influence the LE of MOOCs. It is found that TB negatively influences LE but is not significant and HD significantly influences LE positively for MOOCs.Research limitations/implicationsThis study has a few limitations as it is a cross-sectional study in India, which surveyed undergraduate and postgraduate MOOCs learners, and caution needs to be taken while generalizing the outcomes. Further studies can be conducted across other countries considering demographic factors like age, gender, income groups, education and profession.Practical implicationsThis research highlights the antecedents influencing the LE of MOOC learners using the CoI framework which will help the MOOC designers and marketers to apprehend the factors influencing LE. The results of this research will help them formulate suitable strategies in the design and delivery of MOOCs to improve the LE of learners.Originality/valueThis unique research investigates and empirically validates the CoI framework to understand LE of MOOC learners in India. This research extends the CoI framework by adding contextual factors – TB and HD in the context of a developing country.