bluuebunny/crossref_metadata_2025_split huggingface dataset:
Checkpoint: An Innovative Programme to Navigate People Away from the Cycle of Reoffending: Implementation Phase Evaluation
Authors: Weir Kevin , Routledge Gillian , Kilili Stephanie 
Published: February 2019

AbstractThis study develops an evidence base for the use of deferred prosecution schemes within a police setting. Checkpoint is a voluntary adult offender deferred prosecution scheme operating in Durham Constabulary, UK. Checkpoint targets low-level offenders entering the Criminal Justice System by providing an alternative to a criminal prosecution. It offers a tailored, 4-month programme agreed through a contract. The scheme targets the reasons why offenders commit crime by assessing their individual needs in order to provide interventions. Applying theories of deterrence and desistance, we describe the process of the Checkpoint intervention and the implementation findings of the 519 offenders in the programme. The results indicate that the Checkpoint Implementation phase cohort achieved a lower re-arrest and reoffending rate in comparison to a typical Durham Out Of Court Disposal sample, at reduced harm and cost. The initial conclusions presented here establish the foundations for further research in this policy area.
A Person-Centered Prehabilitation Program Based on Cognitive-Behavioral Physical Therapy for Patients Scheduled for Lumbar Fusion Surgery: A Randomized Controlled Trial
Authors: Lotzke Hanna , Brisby Helena , Gutke Annelie , Hägg Olle , Jakobsson Max , Smeets Rob , Lundberg Mari 
Published: February 2019

Abstract

Background
Prehabilitation programs have led to improved postoperative outcomes in several surgical contexts, but there are presently no guidelines for the prehabilitation phase before lumbar fusion surgery.

Objective
The objective was to investigate whether a person-centered physical therapy prehabilitation program, based on a cognitive-behavioral approach, is more effective than conventional care in reducing disability and improving functioning after lumbar fusion surgery in patients with degenerative disk disease.

Design
This study was a randomized controlled trial.

Setting
The study took place at 2 private spine clinics and 1 university hospital.

Patients
We prospectively enrolled 118 patients scheduled for lumbar fusion surgery.

Intervention
The active intervention used a person-centered perspective and focused on promoting physical activity and targeting psychological risk factors before surgery. The control group received conventional preoperative care.

Measurements
The primary outcome was the Oswestry Disability Index score. Secondary outcomes were back and leg pain intensity, catastrophizing, kinesiophobia, self-efficacy, anxiety, depression, health-related quality of life, and patient-specific functioning, physical activity, and physical capacity. Data were collected on 6 occasions up to 6 months postoperatively. A linear mixed model was used to analyze the change scores of each outcome.

Results
No statistically significant between-group difference was found on the primary outcome (disability) over time (baseline to 6 months). Among secondary outcome measures, a statistically significant interaction effect (“Group × Time”) was seen for the European Quality of Life 5 Dimensions Questionnaire. The largest between-group difference on the European Quality of Life 5 Dimensions Questionnaire index was seen 1 week prior to surgery and favored the active intervention. The largest between-group effect sizes at the 6-month follow-up favored the active intervention, and were seen for physical activity intensity, steps per day, and the One Leg Stand Test. Both groups reached the minimal important change for the primary outcome and, in several secondary outcomes (pain intensity, back and leg; pain catastrophizing; anxiety; health-related quality of life [EQ5D VAS]), already at 8-week follow-up.

Limitations
The participants’ preoperative level of disability was lower than normative values, which suggests selection bias.

Conclusions
Both interventions led to clinically important changes, but it is not clear what kind of prehabilitation program is the most effective.
Twinkle is not the mitochondrial DNA replicative helicase in C. elegans, but may have alternate mitochondrial functions
Authors: Henderson Hope R. , Euro Liliya , Suomalainen Anu , Dillin Andrew 
Published: February 2019

ABSTRACTDysfunction of mitochondrial DNA replication machinery is a common cause of mitochondrial diseases. The minimal mammalian replisome is made up of DNA polymerase gamma, replicative helicase Twinkle, and single-stranded DNA binding protein. The replisome is localized to the inner mitochondrial membrane and serves as the site of mitochondrial DNA replication and mitochondrial fission. Recently, a sequence homolog of Twinkle was uncovered in the nematode Caenorhabditis elegans. Here, we characterized this homolog, twnk-1, and report that twnk-1 does not function as the primary mitochondrial DNA replicative helicase in this species, as loss of twnk-1 does not result in reduce mitochondrial DNA levels, or result in other expected mitochondrial dysfunctions such as reduced oxygen consumption rates, increased sensitivity to metabolic perturbations, or reduced muscle function. Instead, twnk-1 mutants have increased mitochondrial DNA as they age, and exhibit phenotypes associated with mitochondrial stress, including reduced fecundity, an activation of the mitochondrial unfolded protein response, and mitochondrial fragmentation. Our results suggest in Caenorhabditis elegans, twnk-1 does not function as the mitochondrial DNA replicative helicase, but has an alternative function in regulating mitochondrial function.
SURF1 mutations causative of Leigh syndrome impair human neurogenesis
Authors: Inak Gizem , Rybak-Wolf Agnieszka , Lisowski Pawel , Jüttner René , Zink Annika , Mlody Barbara , Glažar Petar , Secker Christopher , Ciptasari Ummi H. , Stenzel Werner , Hahn Tobias , Diecke Sebastian , Priller Josef , Gotthardt Michael , Kühn Ralf , Wanker Erich E. , Rajewsky Nikolaus , Schülke Markus , Prigione Alessandro 
Published: February 2019

AbstractMutations in the mitochondrial complex IV assembly factor SURF1 represent a major cause of Leigh syndrome (LS), a rare fatal neurological disorder. SURF1-deficient animals have failed to recapitulate the neuronal pathology of human LS, hindering our understanding of the disease mechanisms. We generated induced pluripotent stem cells from LS patients carrying homozygous SURF1 mutations (SURF1 iPS) and performed biallelic correction via CRISPR/Cas9. In contrast to corrected cells, SURF1 iPS showed impaired neuronal differentiation. Aberrant bioenergetics in SURF1 iPS occurred already in neural progenitor cells (NPCs), disrupting their neurogenic potency. Cerebral organoids from SURF1 iPS were smaller and recapitulated the neurogenesis defects. Our data imply that SURF1 mutations cause a failure in the development of maturing neurons. Using NPC function as an interventional target, we identified SURF1 gene augmentation as a potential strategy for restoring neurogenesis in LS patients carrying SURF1 mutations.
Inbreeding depression causes reduced fecundity in Golden Retrievers
Authors: Chu Erin T. , Simpson Missy J. , Diehl Kelly , Page Rodney L. , Sams Aaron J. , Boyko Adam R. 
Published: February 2019

ABSTRACTInbreeding depression has been demonstrated to impact vital rates, productivity, and performance in many domestic species. Many in the field have demonstrated the value of genomic measures of inbreeding compared to pedigree-based estimates of inbreeding; further, standardized, high-quality phenotype data on all individuals is invaluable for longitudinal analyses of a study cohort. We compared measures of reproductive fitness in a small cohort of Golden Retrievers enrolled in the Golden Retriever Lifetime Study (GRLS) to a genomic measurement of inbreeding, FROH. We demonstrate a statistically significant negative correlation between fecundity and FROH.This work sets the stage for larger scale analyses to investigate genomic regions associated with fecundity and other measures of fitness.
An oligarchy of NO-producing interneurons controls basal and evoked blood flow in the cortex
Authors: Echagarruga Christina T. , Gheres Kyle , Drew Patrick J. 
Published: February 2019

AbstractChanges in cortical neural activity are coupled to changes in local arterial diameter and blood flow. However, the neuronal types and the signaling mechanisms that control the basal diameter of cerebral arteries or their evoked dilations are not well understood. Using chronic two-photon microscopy, electrophysiology, chemogenetics, and pharmacology in awake, head-fixed mice, we dissected the cellular mechanisms controlling the basal diameter and evoked dilation in cortical arteries. We found that modulation of overall neural activity up or down caused corresponding increases or decreases in basal arterial diameter. Surprisingly, modulation of pyramidal neuron activity had minimal effects on basal or evoked arterial dilation. Instead, the neurally-mediated component of arterial dilation was largely regulated through nitric oxide released by neuronal nitric oxide synthase (nNOS)-expressing neurons, whose activity was not reflected in electrophysiological measures of population activity. Our results show that cortical hemodynamic signals are not controlled by the average activity of the neural population, but rather the activity of a small ‘oligarchy’ of neurons.
Exact p-values for large-scale single step genome-wide association, with an application for birth weight in American Angus
Authors: Aguilar Ignacio , Legarra Andres , Cardoso Fernando , Masuda Yutaka , Lourenco Daniela , Misztal Ignacy 
Published: February 2019

ABSTRACTBACKGROUNDSingle Step GBLUP (SSGBLUP) is the most comprehensive method for genomic prediction. Point estimates of marker effects from SSGBLUP are often used for Genome Wide Association Studies (GWAS) without a formal framework of hypothesis testing. Our objective was to implement p-values for GWAS studies in the ssGBLUP framework, showing algorithms, computational procedures, and an application to a large beef cattle population.METHODSP-values were obtained based on the prediction error (co)variance for SNP, which uses the inverse of the coefficient matrix and formulas to compute SNP effects.RESULTSComputation of p-values took a negligible time for a dataset with almost 2 million animals in the pedigree and 1424 genotyped sires, and no inflation was observed. The SNP passing the Bonferroni threshold of 5.9 in the −log10 scale were the same as those that explained the highest proportion of additive genetic variance, but the latter was penalized (as GWAS signal) by low allele frequency.CONCLUSIONThe exact p-value for SSGWAS is a very general and efficient strategy for QTL detection and testing. It can be used in complex data sets such as used in animal breeding, where only a proportion of pedigreed animals are genotyped.
Chromatin compartment dynamics in a haploinsufficient model of cardiac laminopathy
Authors: Bertero Alessandro , Fields Paul A. , Smith Alec S. T. , Leonard Andrea , Beussman Kevin , Sniadecki Nathan J. , Kim Deok-Ho , Tse Hung-Fat , Pabon Lil , Shendure Jay , Noble William S. , Murry Charles E. 
Published: February 2019

AbstractPathogenic mutations in A-type nuclear lamins cause dilated cardiomyopathy, which is postulated to result from dysregulated gene expression due to changes in chromatin organization into active and inactive compartments. To test this, we performed genome-wide chromosome conformation analyses (Hi-C) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with a haploinsufficient mutation for lamin A/C. Compared to gene-corrected cells, mutant hiPSC-CMs have marked electrophysiological and contractile alterations, with modest gene expression changes. While large-scale changes in chromosomal topology are evident, differences in chromatin compartmentalization are limited to a few hotspots that escape inactivation during cardiogenesis. These regions exhibit upregulation of multiple non-cardiac genes includingCACNA1A, encoding for neuronal P/Q-type calcium channels. Pharmacological inhibition of the resulting current partially mitigates the electrical alterations. On the other hand, A/B compartment changes do not explain most gene expression alterations in mutant hiPSC-CMs. We conclude that global errors in chromosomal compartmentation are not the primary pathogenic mechanism in heart failure due to lamin A/C haploinsufficiency.SummaryBertero et al. observe that lamin A/C haploinsufficiency in human cardiomyocytes markedly alters electrophysiology, contractility, gene expression, and chromosomal topology. Contrary to expectations, however, changes in chromatin compartments involve just few regions, and most dysregulated genes lie outside these hotspots.Condensed titleGenomic effects of lamin A/C haploinsufficiency
Dynamically Linking Influenza Virus Infection Kinetics, Lung Injury, Inflammation, and Disease Severity
Authors: Myers Margaret A. , Smith Amanda P. , Lane Lindey C. , Moquin David J. , Aogo Rosemary , Woolard Stacie , Thomas Paul G. , Vogel Peter , Smith Amber M. 
Published: February 2019

AbstractInfluenza viruses cause a significant amount of morbidity and mortality. Understanding host immune control efficacy and how different factors influence lung injury and disease severity are critical. Here, we established dynamical connections between viral loads, infected cells, CD8+T cell-mediated clearance, lung injury, inflammation, and disease severity using an integrative model-experiment exchange. The model was validated through CD8 depletion and whole lung histomorphometry, which showed that the infected area matched the model-predicted infected cell dynamics and that the resolved area paralleled the relative CD8 dynamics. Inflammation could further be predicted by the infected cell dynamics, and additional analyses revealed nonlinear relations between lung injury, inflammation, and disease severity. These links between important pathogen kinetics and host pathology enhance our ability to forecast disease progression, potential complications, and therapeutic efficacy.
Responses of bats to landscape transformation in an Andean agricultural landscape
Authors: Vélez-Orozco Mariana , Romero Laura M. , Castaño John H. , Carranza-Quiceno Jaime A. , Pérez-Torres Jairo , Torres Diego A. 
Published: February 2019

AbstractThe current debate on the future of biodiversity gives rise to the need to integrate agricultural landscapes into conservation strategies. Bats are an important component of vertebrate diversity in many terrestrial landscapes where they provide invaluable and important ecosystem services to human societies such as insect pest control, pollination and seed dispersal. Here we study bat diversity and abundance in three landscapes representing a transformational gradient (continuous forests, forest fragments and crops) in an Andean agricultural scenario known as Colombia’s “Coffee Cultural Landscape”. We captured 1146 bats from 32 species and 4 families. The bat diversity and abundance in this landscape were high, especially for frugivorous bats, but there were no differences among the three transformational landscapes. However, some species were captured differentially between landscapes, suggesting that these landscapes have characteristics that influence the relative abundance of bats. Additionally, body weight and sex affect the abundance of some species in forest fragments and crops.
Reward prediction error modulates saccade vigor
Authors: Sedaghat-Nejad Ehsan , Herzfeld David J. , Shadmehr Reza 
Published: February 2019

AbstractMovements toward rewarding stimuli exhibit greater vigor, i.e., increased velocity and reduced reaction-times. This invigoration may be due to release of dopamine before movement onset. Dopamine release is strongly modulated by reward prediction error (RPE). Here, we generated an RPE event in the milliseconds before movement onset and tested whether there was a causal relationship between RPE and vigor. Human subjects made saccades toward an image. During the execution of their primary saccade, we probabilistically changed the position and content of the image. This led to a secondary saccade following completion of the primary saccade. We focused on properties of this secondary saccade. On some trials, the content of the secondary image was more valuable than the first image, resulting in a +RPE event that preceded the secondary saccade. On other trials, this content was less valuable, resulting in a -RPE event. We found that reaction-time and velocity of the secondary saccade were affected in an orderly fashion by the magnitude and direction of the preceding RPE event: the most vigorous saccades followed the largest +RPE, whereas the least vigorous saccades followed the largest -RPE. Presence of the secondary saccade indicated that the primary saccade had experienced a movement error, inducing trial-to-trial adaptation: the subsequent primary saccade was changed in the direction of the movement error in the previous trial. However, motor learning from error was not affected by the RPE event. Therefore, reward prediction error, and not reward per se, modulated vigor of saccades.Author summaryDoes dopamine release before onset of a movement modulate vigor of the ensuing movement? To test this hypothesis, we relied on the fact that RPE is a strong modulator of dopamine. Our innovation was a task in which an RPE event occurred precisely before onset of a movement. We probabilistically produced a combination of large or small, negative or positive RPE events before onset of a saccade, and observed that the vigor of the saccade that followed carried a robust signature of the preceding RPE event: high vigor saccades followed +RPE events, while low vigor saccades followed -RPE events. This suggests that control of vigor is partly through release of dopamine in the moments before onset of the movement.
Evaluation of the psychometric properties of the HIV Disability Questionnaire among adults living with HIV in the United Kingdom
Authors: Brown Darren , Simmons Bryony , Boffito Marta , Aubry Rachel , Nwokolo Nneka , Harding Richard , O’Brien Kelly 
Published: February 2019

AbstractObjectiveTo evaluate the psychometric properties of the HIV Disability Questionnaire (HDQ) among adults living with HIV in London, United Kingdom (UK).MethodsThis is a cross-sectional measurement study. We recruited and administered the self-reported HDQ, seven criterion measures, and a demographic questionnaire with adults living with HIV accessing HIV care. We determined median and interquartile ranges (IQR) for disability presence, severity and episodic scores (range 0-100). We calculated Cronbach’s alpha (α) Kuder-Richardson-20 (KR-20) statistics for disability and episodic scores respectively (internal consistency reliability), smallest detectable change (SDC) for each HDQ severity item and domain (precision), and tested 36 a priori hypotheses assessing correlations between HDQ and criterion scores (construct validity).ResultsOf N=243 participants, all were male, median age 40 years, 94% currently taking antiretroviral therapy, and 22% living with ≥2 concurrent health conditions. Median HDQ domain scores ranged from 0 (IQR: 0,7) (difficulties with day-to-day activities domain) to 27 (IQR: 14, 41) (uncertainty domain). Cronbach’s alpha for the HDQ severity scale ranged from 0.85 (95% Confidence Interval (CI): 0.80-0.90) in the cognitive domain to 0.93 (95%CI: 0.91-0.94) in the mental-emotional domain. The KR-20 statistic for the HDQ episodic scale ranged from 0.74 (95%CI: 0.66-0.83) in the cognitive domain to 0.91 (95%CI: 0.89-0.94) in the uncertainty domain. SDC ranged from 7.3-15.0 points on the HDQ severity scale for difficulties with day-to-day activities and cognitive symptoms domains, respectively. The majority of the construct validity hypotheses (n=30/36, 83%) were confirmed.ConclusionsThe HDQ possesses internal consistency reliability and construct validity with varied precision when administered to males living with HIV in London, UK. Clinicians and researchers may use the HDQ to measure the nature and extent of disability experienced by PLHIV in the UK, and to inform HIV service provision to address the health-related challenges among PLHIV.
AI: from rational agents to socially responsible agents
Authors: Vetrò Antonio , Santangelo Antonio , Beretta Elena , De Martin Juan Carlos 
Published: February 2019

Purpose
This paper aims to analyze the limitations of the mainstream definition of artificial intelligence (AI) as a rational agent, which currently drives the development of most AI systems. The authors advocate the need of a wider range of driving ethical principles for designing more socially responsible AI agents.

Design/methodology/approach
The authors follow an experience-based line of reasoning by argument to identify the limitations of the mainstream definition of AI, which is based on the concept of rational agents that select, among their designed actions, those which produce the maximum expected utility in the environment in which they operate. The problem of biases in the data used by AI is taken as example, and a small proof of concept with real datasets is provided.

Findings
The authors observe that biases measurements on the datasets are sufficient to demonstrate potential risks of discriminations when using those data in AI rational agents. Starting from this example, the authors discuss other open issues connected to AI rational agents and provide a few general ethical principles derived from the White Paper AI at the service of the citizen, recently published by Agid, the agency of the Italian Government which designs and monitors the evolution of the IT systems of the Public Administration.

Originality/value
The paper contributes to the scientific debate on the governance and the ethics of AI with a critical analysis of the mainstream definition of AI.