bluuebunny/crossref_metadata_2025_split huggingface dataset:
A computational pipeline to determine lobular electric field distribution during cerebellar transcranial direct current stimulation
Authors: Rezaee Zeynab , Dutta Anirban 
Published: January 2019

AbstractObjectiveCerebellar transcranial direct current stimulation (ctDCS) is challenging due to the complexity of the cerebellar structure. Therefore, our objective is to develop a freely available computational pipeline to perform cerebellar atlas-based electric field analysis using magnetic resonance imaging (MRI) guided subject-specific head modeling.MethodsWe present a freely available computational pipeline to determine subject-specific lobular electric field distribution during ctDCS. The computational pipeline can isolate subject-specific cerebellar lobules based on a spatially unbiased atlas (SUIT) for the cerebellum, and then calculates the lobular electric field distribution during ctDCS. The computational pipeline was tested in a case study using a subject-specific head model as well as using a Colin 27 Average Brain. The 5cmx5cm anode was placed 3 cm lateral to inion, and the same sized cathode was placed on the contralateral supraorbital area (called Manto montage) and buccinators muscle (called Celnik montage). A 4×1 HD-ctDCS electrode montage was also implemented for a comparison using analysis of variance (ANOVA).ResultsEta-squared effect size after three-way ANOVA for electric field strength was 0.05 for lobule, 0.00 for montage, 0.04 for head model, 0.01 for lobule*montage interaction, 0.01 for lobule* head model interaction, and 0.00 for montage*head model interaction in case of Enorm. Here, the electric field strength of both the Celnik and the Manto montages affected the lobules Crus II, VIIb, VIII, IX of the targeted cerebellar hemispheres while Manto montage had more bilateral effect. The HD-ctDCS montage primarily affected the lobules Crus I, Crus II, VIIb of the targeted cerebellar hemisphere. Our freely available computational modeling approach to analyze subject-specific lobular electric field distribution during ctDCS provided an insight into healthy human anodal ctDCS results
MOU-EC: model-based whole-brain effective connectivity to extract biomarkers for brain dynamics from fMRI data and study distributed cognition
Authors: Gilson M , Zamora-López G , Pallarés V , Adhikari MH , Senden M , Tauste Campo A , Mantini D , Corbetta M , Deco G , Insabato A 
Published: January 2019

AbstractNeuroimaging techniques are increasingly used to study brain cognition in humans. Beyond their individual activation, the functional associations between brain areas have become a standard proxy to describe how information is distributed across the brain network. Among the many analysis tools available, dynamic models of brain activity have been developed to overcome the limitations of original connectivity measures such as functional connectivity. In particular, much effort has been devoted to the assessment of directional interactions between brain areas from their observed activity. This paper summarizes our recent approach to analyze fMRI data based on our whole-brain effective connectivity referred to as MOU-EC, while discussing the pros and cons of its underlying assumptions with respect to other established approaches. Once tuned, the model provides a connectivity measure that reflects the dynamical state of BOLD activity obtained using fMRI, which can be used to explore the brain cognition. We focus on two important applications. First, as a connectivity measure, MOU-EC can be used to extract biomarkers for task-specific brain coordination, understood as the patterns of areas exchanging information. The multivariate nature of connectivity measures raises several challenges for whole-brain analysis, for which machine-learning tools presents some advantages over statistical testing. Second, we show how to interpret changes in MOU-EC connections in a collective and model-based manner, bridging with network analysis. To illustrate our framework, we use a dataset where subjects were recorded in two conditions, watching a movie and a black screen (referred to as rest). Our framework provides a comprehensive set of tools that open exciting perspectives for the study of distributed cognition, as well as neuropathologies.
Testing for batch effect through age predictors
Authors: Mamoshina Polina , Kochetov Kirill , Putin Evgeny , Aliper Alex , Zhavoronkov Alex 
Published: January 2019

AbstractTranscriptome profiling has been shown really useful in the understanding of the aging process. To date, transcriptomic data is the second most abundant omics data type following genomics. To deconvolute the relationship between transcriptomic changes and aging one needs to conduct an analysis on the comprehensive dataset. At the same time, biological aging clocks constructed for clinical use needs to robustly predict new data without any further retraining. In this paper, we develop a transcriptomic deep-learned age predictor. Deep neural networks (DNN) are trained and tested on more than 6 000 blood gene expression samples from 17 datasets. We apply methods based on output derivatives of DNN to rank input genes by their importance in age prediction and reduce the dimensional of the data. We also show that batch effect in transcriptome datasets of healthy humans is indeed significant, but the existing normalization techniques, while removing technical variation quite effectively, also remove age-associated changes. So robust methods of age prediction are needed.
Early Life Adversity, but not suicide, is associated with less prefrontal cortex gray matter in adulthood
Authors: Underwood Mark D. , Bakalian Mihran J. , Escobar Teresa , Kassir Suham , Mann J. John , Arango Victoria 
Published: January 2019

AbstractBackgroundSuicide and major depression (MDD) are more prevalent in individuals reporting early life adversity (ELA). Prefrontal cortex volume is reduced by stress acutely and progressively in vivo, and changes in neuron and glia density are reported in depressed suicide decedents. We previously found reduced levels of the neurotrophic factor BDNF in suicide decedents and with ELA, and in the present study we sought to determine whether cortex thickness, neuron density or glia density in the dorsolateral prefrontal (BA9) and anterior cingulate (BA24) cortex are associated with ELA or suicide.MethodsA total of 52 brains, constituting 13 quadruplets of nonpsychiatric nonsuicide controls and MDD suicide decedents with and without ELA (n=13/group), all with psychological autopsy, were matched for age, sex and postmortem interval. Brains were collected at autopsy and frozen and blocks containing BA9 and BA24 were later dissected, post-fixed and sectioned. Sections were immunostained for NeuN to label neurons and counterstained with thionin to stain glial cell nuclei. Cortex thickness, neuron and glial density and neuron volume were measured by stereology.ResultsCortical thickness was 6% less with an ELA history in BA9 and 12% less in BA24 (p<0.05), but not in depressed suicide decedents in either BA9 or BA24. Neuron density was not different in ELA or in suicide decedents, but glial density was 17% greater with ELA history in BA9 and 15% greater in BA24, but not in suicides. Neuron volume was not different with ELA or suicide.DiscussionReported ELA, but not the stress associated with suicide, is associated with thinner prefrontal cortex and greater glia density in adulthood. ELA may alter normal neurodevelopment and contribute to suicide risk.
The Impact of Uremia and Intestinal Dysbiosis on Hepatic Drug Metabolism in a Rat Model of Progressive Chronic Kidney Disease
Authors: Hartjes Emily D , Lim Yong Jin , Velenosi Thomas J , Al Kait F , Macklaim Jean M , Kucey Andrew S , Reid Gregor , Burton Jeremy P , Gloor Gregory B , Urquhart Bradley L 
Published: January 2019

AbstractNonrenal clearance pathways such as drug metabolism are decreased in chronic kidney disease (CKD). Although the mechanism remains elusive, uremic toxin retention and an altered gut microbiota are suspected to influence cytochrome P450s (CYPs) contributing to the unpredictable pharmacokinetics in patients with CKD. We characterized dysbiosis and uremia in CKD to elucidate associations between CYP expression and CKD progression. Rats fed control or CKD-inducing adenine diet were subsequently studied at five time points over 42 days. CYP expression and activity were compared to alterations in the 1) plasma and liver metabolome and 2) gut bacterial microbiota. CYP3A2 and CYP2C11 were downregulated in CKD by ≥76% (p<0.001) concurrently with or slightly prior to CKD onset as defined by serum creatinine. Metabolite profiles were altered prior to changes in the gut microbiota, and gut-derived uremic toxins including indoxyl sulfate, phenyl sulfate and 4-ethylphenyl sulfate correlated with CYP3A2 or CYP2C11 expression. Bacterial genera Turicibacter and Parabacteroides were identified as being characteristic of CKD. In conclusion, CYP3A2 and CYP2C11 are downregulated before dysbiosis and correlate with select uremic toxins.
Transfer of regulatory knowledge from human to mouse for functional genomic analysis
Authors: Holland Christian H. , Szalai Bence , Saez-Rodriguez Julio 
Published: January 2019

AbstractTranscriptome profiling followed by differential gene expression analysis often leads to unclear lists of genes which are hard to analyse and interpret. Functional genomic tools are powerful approaches for downstream analysis, as they summarize the large and noisy gene expression space in a smaller number of biological meaningful features. In particular, methods that estimate the activity of processes by mapping transcripts level to process members are popular. However, footprints of either a pathway or transcription factor (TF) on gene expression show superior performance over mapping-based gene sets. These footprints are largely developed for human and their usability in the broadly-used model organism Mus musculus is uncertain. Evolutionary conservation of the gene regulatory system suggests that footprints of human pathways and TFs can functionally characterize mice data. In this paper we analyze this hypothesis. We perform a comprehensive benchmark study exploiting two state-of-the-art footprint methods, DoRothEA and an extended version of PROGENy. These methods infer TF and pathway activity, respectively. Our results show that both can recover mouse perturbations, confirming our hypothesis that footprints are conserved between mice and humans. Subsequently, we illustrate the usability of PROGENy and DoRothEA by recovering pathway/TF-disease associations from newly generated disease sets. Additionally, we provide pathway and TF activity scores for a large collection of human and mouse perturbation and disease experiments (2,374). We believe that this resource, available for interactive exploration and download (https://saezlab.shinyapps.io/footprint_scores/), can have broad applications including the study of diseases and therapeutics.
Cognitive resonance: When information carry‐over constrains cognitive plasticity
Authors: Ferrari Maud C. O. , Horn Marianna E. , Chivers Douglas P. 
Published: January 2019

Abstract

When faced with a changing environment, some species appear to adapt quickly, while others seem unable to update the value of environmental cues on which they base their decisions, leading them to display seemingly maladaptive responses.

While behavioural and cognitive plasticity are two traits that should predict the ability of species to update the value of environmental cues, we argue that this flexibility may be constrained by ontogeny. While sensitive periods have been shown to exist for establishing an individual’s food, habitat and mate preference, no studies have established the existence of a cognitive sensitive period for predation‐related information.

In this study, we used wood frogs, Lithobates sylvaticus, to demonstrate the existence of a sensitive period for predation‐related information, with risk information learned as embryos maintained for more than 5 weeks, while the same information learned as tadpoles was unused after just 10 days. Next, we demonstrated that tadpoles that had learned a cue as safe as embryos were unable to update the cue as risky after three fear conditioning attempts, while tadpoles that learned the cue as safe a few days prior did successfully update the cue as risky after three conditionings.

We coined the term “cognitive resonance” to describe how information learned early in life can have marked cognitive consequence later in life, affecting not only the duration for which information learned is actively used in decision‐making, but how this information can interfere with the acquisition of up‐to‐date information about the environment.

Cognitive resonance might be beneficial in stable environments where the change in the value of a cue is relatively small through time, but it can quickly become costly in environments where the identity of potential threats changes quickly, as in the case of introduced species.

A plain language summary is available for this article.
Unraveling the scales of effect of landscape structure on primate species richness and density of titi monkeys (Callicebus nigrifrons)
Authors: Gestich Carla C. , Arroyo‐Rodríguez Víctor , Ribeiro Milton C. , da Cunha Rogério G. T. , Setz Eleonore Z. F. 
Published: January 2019

AbstractIn the Anthropocene, many animal populations are increasingly confined to human‐modified landscapes, in which different spatial variables describing landscape composition and configuration influence species persistence. Forest specialist species are particularly vulnerable to these landscape disturbances. Yet, landscape effects may be undetected if assessed at the wrong spatial scale. Thus, identifying the “scale of effect”, which is the optimal spatial scale for estimating ecological responses to each landscape variable, is needed to understand the impact of landscape structure modification on species. Here, we explored the scale of effect of two compositional (forest cover and anthropogenic cover) and two configurational landscape variables (forest patch density and forest edge density) on two ecological responses: primate species richness and group densities of titi monkeys (Callicebus nigrifrons). We sampled 16 study sites in northeastern São Paulo State, Brazil. For each site, we measured each landscape variable within 10 different‐sized landscapes ranging from 0.2 to 28.3 km2 to identify the scale of effect of each landscape variable. The strength of all the primate‐landscape relationships varied across spatial scales. Although both ecological responses were most strongly associated with forest cover at the largest scale, the scale of effect of the other landscape variables differed between the response variables. These results suggest that each response variable is shaped by landscape patterns and processes operating across different spatial scales. We highlight the importance of separately assessing the scale of effect of each landscape variable on each ecological response to better understand the impact of landscape structure on species persistence.
PentraSorb C‐Reactive Protein: Characterization of the Selective C‐Reactive Protein Adsorber Resin
Authors: Mattecka Stephan , Brunner Patrizia , Hähnel Britta , Kunze Rudolf , Vogt Birgit , Sheriff Ahmed 
Published: January 2019

AbstractC‐reactive protein (CRP) is well known as a general marker of inflammation. It furthermore represents a reliable risk factor for cardiac events and mediates tissue damage in acute myocardial infarction (AMI). It has been demonstrated that selective CRP depletion by extracorporeal apheresis in a porcine AMI model had beneficial effects on the infarcted area and the cardiac output. We therefore developed a novel adsorber for CRP apheresis from human plasma (PentraSorb CRP). It is intended for use in the clinic as therapy for patients suffering from AMI or other acute inflammatory diseases with elevated CRP plasma levels. The PentraSorb resin specifically bound CRP from human blood plasma and almost no other proteins as determined via Sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS‐PAGE). The resin further efficiently and selectively depleted CRP from plasma with low as well as high CRP concentrations (10–100 mg/L) at different flow rates, ranging from 17 to 40 mL/min. The resin was regenerable for up to 200 times without losing its CRP binding capacity or affecting biocompatibility. The depletion of CRP from plasma was comparable between the utilized small‐scale column (0.5 mL resin) and the PentraSorb CRP adsorber (20 mL resin volume). The established features can therefore be applied to the clinical setting. In summary, PentraSorb CRP provides a novel, specific, and efficient CRP‐binding resin that could be used in apheresis therapy for patients suffering from inflammatory diseases such as AMI, stroke, acute pancreatitis, and Crohn's disease.
Nutritional dual burden in Indigenous young adults: The geographical differential
Authors: Davison Belinda , Goodall Jennifer , Whalan Sarah , Montgomery‐Quin Kathleen , Howarth Timothy , Singh Gurmeet 
Published: January 2019

AbstractObjectiveNutritional dual burden is defined as the coexistence of underweight and overweight in the same population. We report the rates of nutritional dual burden in Indigenous young men and women in the Northern Territory. Additionally, we examine the impact geographical area has on these rates.DesignCross‐sectional data obtained from the longitudinal Aboriginal Birth Cohort Study.SettingParticipants residing in over 40 urban and remote communities across the Top End of the Northern Territory.ParticipantsYoung adults aged 23–28 years; urban (n = 99) and remote (n = 316).Main outcome measure(s)Anthropometric data was directly collected using standardised methods. Underweight was defined as BMI ≤ 18.5 kg/m2 and overweight/obese as body mass index ≥ 25 kg/m2. Remote residency was categorised by established shires/regions (Vic/Daly, Arnhem and Tiwi).ResultsSignificantly higher levels of underweight were seen in remote participants, compared to urban participants, irrespective of sex. Further differences were seen by regions, with the highest rates seen in Vic/Daly, compared to Arnhem and Tiwi. Higher rates of overweight/obesity were found in urban participants, compared to remote. The levels of overweight/obesity varied, depending on region of residence.ConclusionUnderweight and overweight patterns coexist in Indigenous young adults, with variation across geographical regions. Health programs need to take this dual nutritional burden into consideration to avoid worsening the severity of underweight, whilst reducing levels of overweight.
Ureteric implantation into the bowel portion of augmented bladders during kidney transplantation: a review of urological complications and outcomes
Authors: Tan Lynnette R. L. , Tiong Ho Yee 
Published: January 2019

BackgroundIn patients with bladder augmentation undergoing kidney transplantation, conventional technique recommends anastomosing the transplanted ureter to the bladder. We report our technique of ureteric implantation into the bowel portion of the enterocystoplasty, and review the urological outcomes of transplantation in these patients.MethodsSeven patients (mean age: 26 years (range 24–54 years), two females, five deceased donors) with augmented cystoplasty and subsequent kidney transplantation by a single surgeon from 2011 to 2015 were reviewed. Following standard vascular anastomosis and reperfusion of the transplanted kidney, ureteric implantation involved continuous 5/0 polydiaoxanone anastomosis between the spatulated ureter and full thickness bowel portion of the cystoplasty over a 6‐Fr double J stent. A second peri‐anastomosis layer of bowel plication was performed to prevent reflux using interrupted 3/0 vicryl sutures. Short‐term urological and kidney function outcomes were evaluated.ResultsCauses of renal failure included: posterior urethral valve with reflux nephropathy (two patients), bilateral vesicoureteric reflux (two patients), lumbosacral agenesis with neurogenic bladder (one patient), tuberculosis of the urinary tract with post‐infective ureteric stricture (one patient), and lupus nephritis (one patient). Bladder reconstruction was performed at median duration of 103 months (35–171 months) before transplantation. Gastrocystoplasty was performed in two patients while colon and/or ileum were used in the remaining six. After transplantation, all reconstructed bladders except one had a Mitrofanoff for clean intermittent self‐catheterization, 5–8 times per day. There were no post‐operative ureteric/surgical complications. Delayed graft function occurred in three of seven patients. 30‐day asymptomatic bacteriuria rate was three out of seven after stent removal. 1‐year post‐transplantation, patient and graft survival were 100%. Mean serum creatinine was 142.7 (standard deviation: 51.48). Median number of hospital admissions for urinary tract infections was 0.225 (range 0–0.40). Over a median follow‐up period of 4 years (2–7 years), one graft failed from acute T‐cell‐mediated rejection. This patient passed away from cardio‐respiratory collapse after a seizure, 35 months post‐transplantation. As of June 2018, the other six kidney grafts were functioning. No complications including calculi formation and/or malignancy were reported.ConclusionIn patients with previously augmented bladders now undergoing kidney transplantation, ureteric implantation into the bowel portion of the cystoplasty appears to be safe.
Collagenase injections for Dupuytren's contracture: prospective cohort study in a public health setting
Authors: Fletcher Jason , Tan Ezekiel S. L. , Thomas Michael , Taylor Fraser , Elliott Devlin , Bindra Randy 
Published: January 2019

BackgroundDupuytren's disease causes a flexion contracture of the hand that limits hand function and reduces quality of life. Traditional management is surgical excision which is associated with potentially serious complications. A viable alternative is collagenase Clostridium histolyticum (CCH) (Xiaflex®; Pfizer Australia) which is an effective, safe, outpatient treatment that to date has no published data in the Australian public health setting.MethodsA prospective cohort, single centre study, enrolling 54 patients to treat 81 joints with CCH. Patients received a single dose to the cord followed by joint manipulation 48 h later. Primary endpoint was reduction in contracture to 0 to 5° of full extension assessed 4 weeks after injection. Secondary endpoints included range of motion, patient satisfaction and function as measured by the Southampton Dupuytren's Scoring Scheme (SDSS).ResultsPrimary endpoint was achieved in 48% of joints (66% metacarpophalangeal and 19% proximal interphalangeal). Mean flexion contracture improved by 40o and 25o for metacarpophalangeal and proximal interphalangeal joints, respectively. Mean active range of motion improved by 39o and 18o, respectively. At 30 days and 12 months, SDSS score demonstrated sustained improvement versus baseline (1.88 versus 8.24 P ≤ 0.0005 and 1.59 versus 8.07 P ≤ 0.0005). Sixty‐eight percent of patients were either very satisfied or satisfied at 12‐month follow‐up. Side effects of treatment were minor; with oedema and bruising the most common (87% and 85%, respectively).ConclusionCCH injections are a viable treatment for Dupuytren's contracture in the Australian public health setting.