bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated With Low Viral Reservoir in European Perinatally HIV-Infected Children
Authors: Tagarro Alfredo , Chan Man , Zangari Paola , Ferns Bridget , Foster Caroline , De Rossi Anita , Nastouli Eleni , Muñoz-Fernández María A. , Gibb Diana , Rossi Paolo , Giaquinto Carlo , Babiker Abdel , Fortuny Claudia , Freguja Riccardo , Cotugno Nicola , Judd Ali , Noguera-Julian Antoni , Navarro María Luisa , Mellado María José , Klein Nigel , Palma Paolo , Rojo Pablo ,   on behalf of the EPIICAL Consortium
Published: June 2018

Background:
Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size.

Setting:
We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting antiretroviral therapy (ART) <6 months of age.

Methods:
Total HIV-1 DNA was measured from 51 long-term suppressed children aged 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression.

Results:
At ART initiation, children were aged median [IQR] 2.3 [1.2–4.1] months, CD4% 37 [24–45] %, CD8% 28 [18–36] %, log10 plasma viral load (VL) 5.4 [4.4–5.9] copies per milliliter. Time to viral suppression was 7.98 [4.6–19.3] months. After suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL 50–400 followed by VL <50] and/or experienced periods of virological failure [≥2 consecutive VL ≥400 followed by VL <50]. Median total HIV-1 DNA was 43 [6195] copies/106 PBMC. Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, P = 0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, P = 0.0022) and the absence of viral failure/suboptimal response (AC 0.34 for those with fail/suboptimal response, P = 0.0483) were associated with lower total HIV-1 DNA.

Conclusions:
Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1–infected children minimize the size of viral reservoir.
Cognitive Performance and Frailty in Older HIV-Positive Adults
Authors: Paul Robert H. , Cooley Sarah A. , Garcia-Egan Paola M. , Ances Beau M. 
Published: June 2018

Objective:
This study examined the relative contribution of cognitive status to frailty among older individuals infected with HIV+.

Design:
Participants included 122 HIV+ individuals [mean age = 57.5 (6.6)] with a median CD4 cell count of 546. Undetectable viral load (<50 copies per mL) was observed in 94% of the sample. The sample was defined as frail (n = 21) and nonfrail (n = 101) according to the Fried phenotype criteria. Cognitive tests included measures of executive function, motor/psychomotor, language, learning, and memory. Performances were converted to standardized scores and averaged to calculate individual domain scores and a global index of cognitive function.

Methods:
Logistic and hierarchical regressions were completed to separately determine the associations between clinical, demographic, and cognitive variables with regards to frailty status.

Results:
Results of the logistic regressions revealed that lower executive function, female sex, and higher symptoms of depression were associated with frailty. The hierarchical analysis revealed no significant contribution of executive function to frailty status after accounting for female sex and symptoms of depression (Nagelkerke R2 = 0.15).

Conclusions:
These results emphasize the importance of sex distribution and mental health in explanatory models of frailty in HIV. Further, interventions targeting symptoms of depression may increase resilience in older HIV+ individuals.
Next-Generation Cancer Rehabilitation: A Giant Step Forward for Patient Care
Authors: Alfano Catherine M. , Pergolotti Mackenzi 
Published: June 2018

Abstract

Purpose
The aim of the study was to review the current state of cancer rehabilitation evidence and practice and delineate an agenda for building the future of cancer rehabilitation care.

Findings
Despite the benefits of cancer rehabilitation interventions and the unmet needs among patients with cancer, very few patients receive these services.

Conclusions
Interdisciplinary cancer rehabilitation should be implemented from diagnosis forward. Building this care involves coordinating efforts in four critical areas: innovating cancer rehabilitation care delivery, expanding the team of providers, creating precision medicine cancer rehabilitation, and demonstrating the value of cancer rehabilitation to drive referrals and reimbursement.

Clinical Relevance
Creating next-generation cancer rehabilitation care has the potential to improve the lives of the growing population of cancer survivors.
Diagnosis and Treatment of Edema and Lymphedema in the Cancer Patient
Authors: Hutchison Nancy A. 
Published: June 2018

Abstract

Background
Lymphedema occurs commonly in cancer survivors. It is crucial to properly assess cancer patients in order to distinguish lymphedema from general edema and to initiate evidence based treatment.

Purpose
To provide evidence based recommendations for screening, evaluating, and treating lymphedema and to establish the role of the nurse in the care of patients with lymphedema.

Methodology
Comprehensive overview with narrative literature review of evidence based lymphedema diagnosis and treatment.

Findings
Cancer-related edema represents numerous complex conditions. A variety of interventions are needed to address prevention, early detection, patient education, and effective treatment.

Conclusion
Lymphedema treatment is complex and multimodal, and is provided by an interdisciplinary team of properly trained professionals. Nurses play a major role in evaluating, treating and educating patients on the signs and symptoms of cancer-related edema and patient self-management.

Clinical Implications
Evidence-based assessment and treatment should be initiated early to improve outcomes and quality of life in patients with cancer-related lymphedema.
Exploring Mechanisms of Inhibition of Amyloid Seeding of Transthyretin
Authors: Saelices Lorena , Chung Kevin , Lee Ji H. , Coelho Teresa , Bijzet Johan , Benson Merrill D. , Eisenberg David S. 
Published: June 2018

AbstractAmyloid deposition of the hormone transporter transthyretin causes familial and sporadic amyloidoses. The current treatment for familial cases is gene-therapy by liver transplantation. However, this procedure is often insufficient to stop subsequent cardiac deposition. Our recent work has shown that preformed amyloid fibrils present in the heart by the time of surgery can template or seed further polymerization of native transthyretin. No drugs have been approved to stop or slow this seeding process; the only treatment option is heart transplantation. Here we explore two potential inhibitory mechanisms. Of clinical significance, we found that tetramer stabilization does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex-vivo fibrils efficiently inhibits amyloid seeding in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach to be further explored.
Improving Children’s and Their Visitors’ Hand Hygiene Compliance
Authors: Lary D. , Calvert A. , Nerlich B. , Segal J. , Vaughan N. , Randle J. , Hardie K. R. 
Published: June 2018

AbstractBackgroundNumerous interventions have tried to improve healthcare workers’ hand hygiene compliance, however little attention has been paid to children’s and their visitors’ compliance.AimTo increase children’s and visitors’ compliance using interactive educational interventions.MethodsThis was an observational study of hand hygiene compliance before and after the introduction of educational interventions. Qualitative data in the form of Questionnaires and interviews was obtained.FindingsHand hygiene compliance increased by 21.4% (P <0.001) following the educational interventions, with children’s compliance reaching 40.8% and visitors’ being 50.8%. Compliance varied depending on which of the ﬁve moments of hygiene was observed (P<0.001), with the highest compliance after body ﬂuid exposure (96%). Responses from questionnaires showed educational interventions raised awareness of the importance of hand hygiene (69%, 57%) compared to those who had not experienced the educational intervention (50%).ConclusionEducational interventions may result in a significant increase in children’s and visitors’ hand hygiene (P <0.001).
Leveraging mutational burden for complex trait prediction in sorghum
Authors: Valluru Ravi , Gazave Elodie E. , Fernandes Samuel B. , Ferguson John N. , Lozano Roberto , Hirannaiah Pradeep , Zuo Tao , Brown Patrick J. , Leakey Andrew D.B. , Gore Michael A. , Buckler Edward S. , Bandillo Nonoy 
Published: June 2018

ABSTRACTSorghum (Sorghum bicolor(L.) Moench) is a major staple food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. Though selection keeps deleterious mutations rare, their complete removal from the genome is impeded due to lack of recombination, drift, and their coupling with favorable loci. To study how deleterious mutations impact agronomic phenotypes, we identified putative deleterious mutations among ~5.5M segregating variants of 229 diverse sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that about 33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups; thecaudatumshows higher mutation burden while theguineahas lower burden. Across racial groups, the mutation burden correlated negatively with biomass, plant height, Specific Leaf Area (SLA), and tissue starch content, suggesting deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (5.2%). There is no advantage in total heritable variance for SLA and starch. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, our results suggest that including putatively deleterious variants in models do not significantly improve breeding accuracy because of extensive linkage. However, knowledge of deleterious variants could be leveraged for sorghum breeding through genome editing.
Mapping Mouse Brain Slice Sequence to a Reference Brain Without 3D Reconstruction
Authors: Xiong Jing , Ren Jing , Luo Liqun , Horowitz Mark 
Published: June 2018

AbstractHistological brain slices are widely used in neuroscience to study anatomical organization of neural circuits. Since data from many brains are collected, mapping the slices to a reference atlas is often the first step in interpreting results. Most existing methods rely on an initial reconstruction of the volume before registering it to a reference atlas. Because these slices are prone to distortion during sectioning process and often sectioned with nonstandard angles, reconstruction is challenging and often inaccurate. We propose a framework that maps each slice to its corresponding plane in the atlas to build a plane-wise mapping and then perform 2D nonrigid registration to build pixel-wise mapping. We use the L2 norm of the Histogram of Oriented Gradients (HOG) of two patches as the similarity metric for both steps, and a Markov Random Field formulation that incorporates tissue coherency to compute the nonrigid registration. To fix significantly distorted regions that are misshaped or much smaller than the control grids, we trained a context-aggregation network to segment and warp them to their corresponding regions with thin plate spline. We have shown that our method generates results comparable to an expert neuroscientist and is significantly better than reconstruction-first approaches.
N-Cadherin Provides a Cis and Trans Ligand for Astrotactin that Functions in Glial-Guided Neuronal Migration
Authors: Horn Zachi , Behesti Hourinaz , Hatten Mary E. 
Published: June 2018

AbstractPrior studies demonstrate that Astrotactin (ASTN1) provides a neuronal receptor for glial-guided CNS migration. Here we report that ASTN1 binds N-cadherin (CDH2) and that the ASTN1:CDH2 interaction supports cell-cell adhesion. To test the function of ASTN1:CDH2 binding in glial-guided neuronal migration, we generated a conditional loss ofCdh2in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronalCdh2, and more severe migration defects occurred after a conditional loss of glialCdh2. Expression of a mutant form of ASTN1 that does not bind CDH2, in granule cells, also slowed migration. Moreover,in vitrochimeras of granule cells and glia showed impaired neuron-glia attachment in the absence of glial, but not neuronal,Cdh2. Thus,cisandtransbindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron-glial bridge complex that promotes glial-guided neuronal migration.
Antagonistic paralogs control a switch between growth and pathogen resistance inC. elegans
Authors: Reddy Kirthi C. , Dror Tal , Underwood Ryan S. , Osman Guled A. , Desjardins Christopher A. , Cuomo Christina A. , Barkoulas Michalis , Troemel Emily R. 
Published: June 2018

AbstractImmune genes are under intense pressure from pathogens, which cause these genes to diversify over evolutionary time and become species-specific. Through a forward genetic screen we recently described aC. elegans-specific gene calledpals-22to be a repressor of “Intracellular Pathogen Response” or IPR genes. Here we describepals-25, which, likepals-22, is a species-specific gene of unknown biochemical function. We identifiedpals-25in a screen for suppression ofpals-22mutant phenotypes and found that mutations inpals-25suppress all known phenotypes caused by mutations inpals-22. These phenotypes include increased IPR gene expression, thermotolerance, and immunity against natural pathogens. Mutations inpals-25also reverse the reduced lifespan and slowed growth ofpals-22mutants. Transcriptome analysis indicates thatpals-22andpals-25control expression of genes induced not only by natural pathogens of the intestine, but also by natural pathogens of the epidermis. Indeed, in an independent forward genetic screen we identifiedpals-22as a repressor andpals-25as an activator of epidermal defense gene expression. These phenotypic and evolutionary features ofpals-22andpals-25are strikingly similar to species-specific R gene pairs in plants that control immunity against co-evolved pathogens.
blockCV: an R package for generating spatially or environmentally separated folds for k-fold cross-validation of species distribution models
Authors: Valavi Roozbeh , Elith Jane , Lahoz-Monfort José J. , Guillera-Arroita Gurutzeta 
Published: June 2018

SummaryWhen applied to structured data, conventional random cross-validation techniques can lead to underestimation of prediction error, and may result in inappropriate model selection.We present the R package blockCV, a new toolbox for cross-validation of species distribution modelling.The package can generate spatially or environmentally separated folds. It includes tools to measure spatial autocorrelation ranges in candidate covariates, providing the user with insights into the spatial structure in these data. It also offers interactive graphical capabilities for creating spatial blocks and exploring data folds.Package blockCV enables modellers to more easily implement a range of evaluation approaches. It will help the modelling community learn more about the impacts of evaluation approaches on our understanding of predictive performance of species distribution models.
Grey matter biomarker identification in Schizophrenia: detecting regional alterations and their underlying substrates
Authors: Chatzi V. , Teixeira R.P. , Shawe-Taylor J. , Altmann A. , O’Daly O. , Christiaens D. , Schrouff J. , Tournier J.-D. 
Published: June 2018

AbstractState-of-the-art approaches in Schizophrenia research investigate neuroanatomical biomarkers using structural Magnetic Resonance Imaging. However, current models are 1) voxel-wise, 2) difficult to interpret in biologically meaningful ways, and 3) difficult to replicate across studies. Here, we propose a machine learning framework that enables the identification of sparse, region-wise grey matter neuroanatomical biomarkers and their underlying biological substrates by integrating well-established statistical and machine learning approaches. We address the computational issues associated with application of machine learning on structural MRI data in Schizophrenia, as discussed in recent reviews, while promoting transparent science using widely available data and software. In this work, a cohort of patients with Schizophrenia and healthy controls was used. It was found that the cortical thickness in left pars orbitalis seems to be the most reliable measure for distinguishing patients with Schizophrenia from healthy controls.HighlightsWe present a sparse machine learning framework to identify biologically meaningful neuroanatomical biomarkers for SchizophreniaOur framework addresses methodological pitfalls associated with application of machine learning on structural MRI data in Schizophrenia raised by several recent reviewsOur pipeline is easy to replicate using widely available software packagesThe presented framework is geared towards identification of specific changes in brain regions that relate directly to the pathology rather than classification per se
Tissue embedding in a silica hydrogel for functional investigations
Authors: Miazzi Fabio , Kaltofen Sabine , Bello Jan E. , Hansson Bill S. , Wicher Dieter 
Published: June 2018

AbstractEmbedding procedures can be challenging for delicate specimens. We present a method based on a sodium metasilicate (waterglass) gel to embed tissue samples for acute physiological studies. We show that the application of such a colloidal gel has minimal effects on the properties of buffered solutions and cell activity, allowing functional investigations on sensitive cells such as ciliated insect olfactory neurons.
Genetic heterogeneity in Anopheles darlingi related to biting behavior in western Amazon
Authors: Campos Melina , Alonso Diego Peres , Conn Jan E. , Vinetz Joseph M. , Emerson Kevin J. , Ribolla Paulo Eduardo Martins 
Published: June 2018

ABSTRACTIn the Amazon Basin, Anopheles (Nyssorhynchus) darlingi is the most aggressive and effective malaria vector. In endemic areas, behavioral aspects of anopheline species such as host preference, biting time and resting location after a blood meal have a key impact on malaria transmission dynamics and transmission control strategies. An. darlingi present a variety in behavior throughout its broad distribution including blood feeding related. To investigate the genetic basis of its biting behaviors, host-seeking An. darlingi were collected in two settlements (Granada and Remansinho) in Acre, Brazil. Mosquitoes were classified by captured location (indoors or outdoors) and time (dusk or dawn). Genome-wide SNPs were used to assess the degree of genetic diversity and structure in these groups. There was evidence of genetic component of biting behavior regarding both location and time in this species. This study supports that An. darlingi blood-feeding behavior has a genetic component. Additional ecological and genomic studies may help to understand the genetic basis of mosquito behavior and address appropriate surveillance and vector control.Author SummaryMalaria is a disease caused by parasite of the genus Plasmodium and is transmitted by mosquitoes of the genus Anopheles. In the Amazon Basin, the main malaria vector is Anopheles darlingi, which is present in high densities in this region. Egg development requires that females of this mosquito seek hosts for blood meals. Anopheles females blood feeding may occur indoor or outdoor the houses and typically from the sunset to dawn. Anopheles darlingi in particular present great variability regarding its behaviour, presenting variety of peak biting times and patterns. This work shows that there is a genetic component that partially explains these two behaviors: location of the blood meal (inside or outside the houses) and time of feeding. Single nucleotide polymorphisms (SNPs) scattered throughout the genome of Anopheles darlingi showed genetic diversity and structure in these groups. A comprehensive understanding of the genetic basis for mosquito behaviour may support innovative vector surveillance and control strategies.
Changes in temperature alter susceptibility to a virus following a host shift
Authors: Roberts Katherine E. , Hadfield Jarrod D. , Sharma Manmohan D. , Longdon Ben 
Published: June 2018

AbstractHost shifts - where a pathogen jumps between different host species - are an important source of emerging infectious disease. With ongoing climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species’ susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, whilst the mean viral load did not, such that as temperature increased the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species’ susceptibility across temperatures and proxies for thermal optima; critical thermal maximum and minimum or basal metabolic rate. These results suggest that whilst the rank order of species susceptibilities can remain the same with changes in temperature, the likelihood of host shifts into a given species may increase or decrease.Author SummaryEmerging infectious diseases are often the result of a host shift, where a pathogen jumps from one host species into another. Understanding the factors underlying host shifts is a major goal for infectious disease researchers. This effort has been further complicated by the fact that host-parasite interactions are now taking place in a period of unprecedented global climatic warming. Here, we ask how host shifts are affected by temperature by carrying out experimental infections using an RNA virus across a wide range of related species, at three different temperatures. We find that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. This has important consequences for our understanding of host shift events in a changing climate, and suggests that temperature changes may affect the likelihood of a host shift into certain species.