bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Omega-3 Fatty Acid Supplementation for Treatment of Dry Eye Disease: A Meta-Analysis of Randomized Clinical Trials
Authors: Giannaccare Giuseppe , Pellegrini Marco , Sebastiani Stefano , Bernabei Federico , Roda Matilde , Taroni Leonardo , Versura Piera , Campos Emilio C. 
Published: February 2019

Purpose:
To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease.

Methods:
We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I2 tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity.

Results:
Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554–1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043–0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564–1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564–1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India.

Conclusions:
This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.
Reward Dysfunction in the Manic Spectrum: Unable to Win? The Use of Biographical Information to Refine Neurobiological Modeling
Authors: KAHN DAVID A. 
Published: February 2019

Objective:The manic spectrum is thought to be characterized by a hypersensitive biobehavioral reward system, the behavioral activation system. Evidence for this framework comes from questionnaire-based, self-report data collected in cross-sectional and prospective studies of mania, mania in remission, and proneness to hypomania, and from functional neuroimaging investigations of brain reward circuit activity during incentivized choice protocols. Although heightened reward anticipation is consistently documented, the status of later goal attainment activity, hedonic responses, and satiety reactions is less clear. This report examines the status of such reward receipt processes as they operate in the manic spectrum.Methods:A case report of a typical subject with bipolar II disorder with a hyperthymic temperament is presented using longitudinal, biographical data.Results:Diminished reward receipt, pleasure, and satiety were demonstrated indicating impaired hedonic processing in hyperthymic temperament. This impairment indicates a dissociation between early, intensified reward pursuit processes and later, blunted, reward attainment activity.Conclusions:The experience and neural correlates of hedonic processing may be impaired in the manic spectrum. Possible mechanisms for this impairment and its dissociation from the earlier stage of reward processing characterized by hyperactive reward pursuit are considered. Clinical reports and longitudinal, life-based follow-up can provide important data to supplement more experimentally based neurobiological models of reward dysfunction in bipolar disorders.
Psychosis Risk Syndrome: What Now?
Authors: SENTISSI OTHMAN , ANDREOU MARIA A. , MOEGLIN CLOTILDE , CURTIS LOGOS , SANTOS BROSCH MICAELA 
Published: February 2019

Background:
Schizophrenia is a chronic psychiatric disorder that generally begins in late adolescence or early adulthood. This early onset is often linked with a devastating lifelong impact on both the social network and work capacities of the affected subjects. Beginning in the mid-1990s, several sets of diagnostic criteria aiming to identify “high-risk” patients were developed and applied in clinical studies. Short-term rates of onset of psychosis in this subgroup of subjects ranged from 20% to 40%. However, 20 years later, the proposal to introduce “psychosis risk syndrome” as a coded diagnostic category in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders remained controversial and was finally rejected. Instead, “attenuated psychosis syndrome” was included in section III of the newly published manual as a condition for further studies.

Objective:
The goal of this article is to review the extant literature concerning the advantages and risks of early assessment of psychotic symptoms (“prodrome” and “psychosis-risk syndrome”) and concerning available therapeutic options, both psychosocial and pharmacological.

Conclusions:
“Attenuated psychosis syndrome” is a clinically useful concept. It identifies help-seeking individuals with mental health problems who need an intervention and who, if no treatment strategy is proposed, present a higher likelihood of developing a psychosis spectrum disorder in the years following their first contact with a mental health facility. In parallel with the clinical utility of this concept, additional research focused on this group of patients is warranted to further understand the emerging phase of psychotic disorders and to develop effective and efficient evidence-based prevention strategies.
Experience-related alterations in white matter structure and gene expression in adult rats
Authors: Vallès Astrid , Sampaio-Baptista Cassandra , Khrapitchev Alexandre A. , Akkermans Guus , Winkler Anderson , Foxley Sean , Sibson Nicola R. , Roberts Mark , Miller Karla , Diamond Mathew E. , Martens Gerard J.M. , Weerd Peter De , Johansen-Berg Heidi 
Published: February 2019

ABSTRACTWhite matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI). However, it remains unclear which mechanisms drive or underlie WM plasticity in adulthood. Here, we combined DTI and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. Somatosensory experience resulted in differences in WM and grey matter structure. C-FOS mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the structural WM measures, suggesting that WM plasticity is activity-dependent. Analysis of myelin-related genes revealed higher myelin basic protein expression in WM, while genome-wide RNA sequencing analysis identified 134 differentially-expressed genes regulating proteins involved in functions related to cell proliferation and differentiation, neuronal activity modulation and regulation of myelination. In conclusion, the macroscale measures of WM differences identified in response to somatosensory experience are supported by molecular evidence, which strongly suggest myelination as, at least, one of the underlying mechanisms.
Transfer learning of deep neural network representations for fMRI decoding
Authors: Svanera Michele , Savardi Mattia , Benini Sergio , Signoroni Alberto , Raz Gal , Hendler Talma , Muckli Lars , Goebel Rainer , Valente Giancarlo 
Published: February 2019

AbstractBackgroundDeep neural networks have revolutionised machine learning, with unparalleled performance in object classification. However, in brain imaging (e.g. fMRI), the direct application of Convolutional Neural Networks (CNN) to decoding subject states or perception from imaging data seems impractical given the scarcity of available data.New methodIn this work we propose a robust method to transfer information from deep learning (DL) features to brain fMRI data with the goal of decoding. By adopting Reduced Rank Regression with Ridge Regularisation we establish a multivariate link between imaging data and the fully connected layer (fc7) of a CNN. We exploit the reconstructed fc7 features by performing an object image classification task on two datasets: one of the largest fMRI databases, taken from different scanners from more than two hundred subjects watching different movie clips, and another with fMRI data taken while watching static images,ResultsThe fc7 features could be significantly reconstructed from the imaging data, and led to significant decoding performance.Comparison with existing methodsThe decoding based on reconstructed fc7 outperformed the decoding based on imaging data alone.ConclusionIn this work we show how to improve fMRI-based decoding benefiting from the mapping between functional data and CNN features. The potential advantage of the proposed method is twofold: the extraction of stimuli representations by means of an automatic procedure (unsupervised) and the embedding of high-dimensional neuroimaging data onto a space designed for visual object discrimination, leading to a more manageable space from dimensionality point of view.
HABIT – a webserver for interactive T cell neoepitope discovery
Authors: Martins Joana , Magalhães Carlos , Vieira Vítor , Rocha Miguel , Osório Nuno S. 
Published: February 2019

SummaryNeoepitopes generated by amino acid variants specifically found in pathogens or cancer cells are gaining momentum in immunotherapy development. HABIT (HLA Binding InTelligence) is a web platform designed to generate and analyse machine learning-based T cell epitope predictions for improved neoepitope discovery.Availability and ImplementationHABIT is available at http://habit.evobiomed.com. Peptide-HLA binding predictions by NetMHCpan 4.0 and NetMHCIIpan 3.1 were implemented in a web application for interactive data exploration using shiny package powered by RStudio.Contactnosorio@med.uminho.ptSupplementary informationSupplementary data and video tutorials are available online.
New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania
Authors:   Malaria Genomic Epidemiology Network
Published: February 2019

AbstractWe conducted a genome-wide association study of host resistance to severePlasmodium falciparummalaria in over 17,000 individuals from 11 malaria-endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association inATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.
Bacterial Glycogen as a Durable Energy Reserve Contributing to Persistence: An Updated Bibliography and Mathematical Model
Authors: Wang Liang , Liu Qinghua , Tan Xinle , Yang Ting , Tang Daoquan , Wang Wei , Wise Michael J. 
Published: February 2019

AbstractGlycogen is conventionally viewed as a transient energy reserve that can be rapidly synthesized for glucose accumulation or mobilized for ATP production and blood glucose homeostasis in higher organisms. However, this understanding is not completely applicable to prokaryotes due to glycogen structural heterogeneity. A number of studies have noted that glycogen with short average chain lengthgcin bacteria has the potential to degrade slowly, which might prolong bacterial survival in the environment and thus enhance potential for transmission to new hosts. This phenomenon has been examined over the past few years and called the durable energy storage mechanism hypothesis (DESM). In this updated bibliography, we summarize recent progress and provide a mathematical model of glycogen as a durable energy reserve.
Learning of Spatial Properties of a Large-scale Virtual City with an Interactive Map
Authors: König Sabine U. , Kakerbeck Viviane , Nolte Debora , Duesberg Laura , Kuske Nicolas , König Peter 
Published: February 2019

AbstractOn the basis of embodied/-enacted theories of the mind, investigations of spatial cognition related to real world environments have become current research interests. How this perspective relates to acquiring spatial knowledge not by active exploration, but through map learning, however, remains unresolved. Therefore, we designed a large virtual city comprised of over 200 houses, suitable for active exploration or spatial learning based on a map. Here, we report our results after single and repeated 30-minute training sessions using an interactive city map. We tested subjects’ knowledge of the orientation of houses towards cardinal north and of two houses relative to each other and the locations of two houses towards each other in a pointing task. Our results revealed that a single training session was sufficient to repeatedly view the majority of houses covering a large area of the city. However, repeated training sessions were necessary to improve the performance level and reveal significant differences between tasks. In contrast to a previous study in a real world city, performance in the two orientation tasks was better than in the pointing task. The lack of distance and the lack of angular difference effects onto task performance suggest the use of a global reference frame. Performance was positively correlated with a self-report on spatial abilities (FRS) in the absolute orientation and pointing task but not the relative orientation task. Overall, our results suggest that training with an interactive city map enhances abstract knowledge, not directly available from an embodied perspective.
SLC19A1 is an importer of the immunotransmitter cGAMP
Authors: Cordova Anthony F. , Ritchie Christopher , Hess Gaelen T. , Bassik Michael C. , Li Lingyin 
Published: February 2019

Abstract2’3’-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral Stimulator of Interferon Genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2′3′-bisphosphosphothioate-cyclic-di-AMP (2′3′-CDAS). These discoveries will provide insight into cGAMP’s role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.
Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner
Authors: Duarte-Guterman Paula , Hamson Dwayne K. , Wainwright Steven R. , Chow Carmen , Chaiton Jessica , Lieblich Stephanie , Watson Neil V. , Galea Liisa A.M. 
Published: February 2019

AbstractAndrogens (testosterone and dihydrotestosterone) increase adult hippocampal neurogenesis by increasing new neuron survival in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in females and whether the effect is age-dependent. We investigated the effects of dihydrotestosterone, a potent androgen, on neurogenesis in adult and middle-aged males and females. Rats were gonadectomized and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU). The following day rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and new neuron survival (BrdU and BrdU/NeuN) in the hippocampus of male and female rats using immunohistochemistry. As expected, DHT increased new neuron survival in young males but surprisingly not in middle-aged male rats. In females, DHT did not significantly affect adult neurogenesis in young or middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.
A Novel Neoantigen Discovery Approach based on Chromatin High Order Conformation: Mapping the Neoantigen to 3D Genome
Authors: Shang Xueying , Zhang Mingxuan , Meng Luming , Su Xianbin , Li Qingjiao , Lin Mengna , Zou Xin , Luo Qing , Zhai Yangyang , He Kunyan , Wang Lan , Da Lintai , Cai Tom Weidong , Han Ze-guang , Shi Yi 
Published: February 2019

AbstractThe high-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate immune response of the T cells. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Here we retrospect the DNA origins of the immune-positive and non-negative neoantigens in the context of 3D genome and discovered that 1) DNA loci of the immuno-positive neoantigens tend to cluster genome-wise. 2) DNA loci of the immuno-positive neoantigens tend to belong to active chromosomal compartment (compartment A) in some chromosomes. 3). DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We believe that the 3D genome information will help more precise neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.
Toll-like receptor 2 stimulation augments esophageal epithelial barrier integrity
Authors: Ruffner Melanie A. , Song Li , Maurer Kelly , Shi Lihua , Carroll Margaret C. , Wang Joshua X. , Muir Amanda B. , Spergel Jonathan M. , Sullivan Kathleen E. 
Published: February 2019

AbstractBackgroundA key concept of the hygiene hypothesis is that the microbiome modulates both epithelial barrier integrity as well as host immune responses. Defective expression of tight junction complex proteins alters this homeostatic process, and plays a role in atopic disorders including eosinophilic esophagitis. We tested the hypothesis that Toll-like receptor 2 (TLR2) stimulation improves esophageal barrier function in a cell-intrinsic manner by upregulation of TJ-protein expression using an in vitro model of human epithelium.MethodsPattern recognition receptor expression was assessed in esophageal epithelial cells from patients with EoE and non-EoE control patients. Functional consequences of TLR2 stimulation were investigated using human esophageal EPC2-hTERT cells in the three-dimensional air-liquid interface culture (ALI) model to evaluate transepithelial electrical resistance (TEER) and FITC-Dextran permeability. Characterization of TLR2-stimulated ALI cultures was performed by histology, immunohistochemistry, western blotting and chromatin immunoprecipitation.ResultsTLR2 stimulation increased TEER (1.28 to 1.31-fold) and decreased paracellular permeability to FITC-Dextran. Notably, TLR2 stimulation-induced increases in TEER were abolished by treatment with anti-TLR2 blocking antibody. Tight junction complex proteins claudin 1 and zonula occludens 1 were increased following TLR2 stimulation, and chromatin immunoprecipitation analysis demonstrated significant increase in histone 4 acetyl binding at the CLDN1 enhancer and promoter following zymosan treatment, implying the occurrence of durable chromatin changes in the esophageal epithelium.ConclusionsOur findings reveal that the TLR2 pathway may play a regulatory role as a mechanism that maintains epithelial barrier homeostasis in the esophagus.
Dual role of protease activated receptor 4 in acute kidney injury: contributing to renal injury and inflammation, while maintaining the renal filtration barrier upon acute renal ischemia reperfusion injury
Authors: Jansen Marcel. P. B. , Claessen Nike , Larsen Per W.B. , Butter Loes M. , Florquin Sandrine , Roelofs Joris J.T.H. 
Published: February 2019

AbstractIschemia reperfusion (I/R) injury triggers the activation of coagulation and inflammation processes involved in the pathophysiology of acute kidney injury (AKI). Coagulation proteases upregulated upon renal I/R injury activate protease activated receptors (PARs), which form an important molecular link between inflammation and coagulation. PAR4 is the major thrombin receptor on mouse platelets, and the only PAR that is expressed on both human and murine platelets. In addition, PAR4 is expressed on other cells including podocytes. We here sought to determine the contribution of PAR4 in the host response to renal I/R injury. Hence, we subjected PAR4 knockout and wild-type mice to renal I/R injury. PAR4 knockout mice exhibited an increased tolerance to renal tubular necrosis and showed a decreased neutrophil influx in response to renal I/R, independent from platelet PAR4. On the other hand, PAR4 deficiency resulted in albumin cast formation in peritubular capillaries and showed a tendency towards albuminuria. Transmission Electron Microscopy revealed an increase in podocyte foot process effacement. Our findings suggest that PAR4 contributes to renal injury likely through facilitating neutrophil migration, independent from platelet PAR4. In addition, PAR4 fulfils an important function in the maintenance of podocyte integrity following renal I/R insult. Subsequently, loss of PAR4 results in albuminuria.
Cataract among elderly in Sri Lanka
Authors: Nilanga Nishad A.A. , Hewage S.A. , Arulmoly K. , Amaratunge M.S. , de Silva J , Kasturiratne KTAA , Abeysundara PK , Wickramasinghe AR 
Published: February 2019

AbstractOut of 39 billion people who are blind around the world, 20 billion (51.3%) is due to cataract, which is preventable. This study intended to assess the prevalence and factors associated with cataract among elderly in a divisional secretariat area in Sri Lanka. This community based cross sectional study assessed randomly selected470 adults over 60 years of age. Diagnosis of cataract was made by a slit lamp examination by medical officers, and classified according to Oxford Lens Opacity Classification system (LOCS III). Majority was between 60-69 age groups and 71% was females. The prevalence of cataract was estimated to be 80.6% including operated eye and 73.6% excluding the operated eye, with a female preponderance in lower age categories. Commonest type of cataract was the nuclear type (n=422; 44.9%), with a majority in grade 2 (218; 23.2%). The prevalence of cataract surgery in the diseased population was as low as 7%. Cataract leading to blindness is very prevalent among adults over 60 years of age in the studied area. Females tend to develop the disease at an early age than males. These findings warrant screening programme for elderly at community level, targeting females at a younger age than males. Future studies are recommended to assess the coverage and barriers for cataract surgeries at national level, which would be immensely useful in planning and improving health services.