bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual field improvement in neglect after virtual reality intervention: a case study
Authors: Leitner Michael Christian , Hawelka Stefan 
Published: May 2021

AbstractObjectiveStudies on neuropsychological rehabilitation of visual field defects provide an inconsistent picture regarding the effectiveness of so-called “restorative approaches” in visual field recovery (VFR). During a current research project on the clinical evaluation of VFR - in combination with head mounted virtual reality displays (HMD) - a patient (“Patient 7”) suffering from visual neglect was investigated. Although the concept of VFR is originally not intended for patients suffering from higher cortical regions (as in neglect), we hypothesized that due to the strong attention-demanding training situation in HMDs, neglect patients might benefit from these intervention procedures based on restorative approaches.Methods and AnalysisPatient 7 was examined perimetrically using a “Humphrey Field Analyzer”, “Goldmann Perimetry” and our newly developed and validated eye-tracking supported perimetric methodology “Eye tracking based visual field analysis” (EFA). Based on these high resolution results from the EFA, the exact location of the transition area between intact and defect visual field of Patient 7 was assessed. Next, bright light stimuli were placed along this area in our newly developed HMD “Salzburg Visual Field Trainer” (SVFT). The aim was to stimulate neuroplasticity - according to the concept of restitutive approaches - in the corresponding cortical areas of the patient. Patient 7 trained with the SVFT for a time period of 254 days. In 6 appointments the objective and subjective rehabilitation progress was assessed.ResultsPerimetric assessment with the EFA shows an expansion of Patient 7’s visual field of 48.8% (left eye) and 36.8% (right eye) after 254 days of training with the SVFT. Individual areas in the patient’s visual field show a visual improvement of approximately 5.5° to 10.5° of visual angle. Subjective self-report of Patient 7 additionally shows improvements in self-evaluation of up to 317% in visual field functionality compared to self-evaluation on the first assessment date.ConclusionsThe results from Patient 7 indicate that patients suffering from visual neglect potentially benefit from a neuropsychological intervention with HMD based on the restorative concept of visual field recovery. However, further studies with large case numbers and a focus both on daily-life improvements and on a clear distinction between patients with lesions in earlier and higher cortical areas are needed to make empirically valid and generalizing statements about our findings.
Impact of Asian and black donor and recipient ethnicity on the outcomes after deceased donor kidney transplantation in the United Kingdom
Authors: Hakeem Abdul R , Asthana Sonal , Johnson Rachel J , Brown Chloe , Ahmad Niaz 
Published: May 2021

AbstractBackgroundPatients of Asian and black ethnicity face disadvantage on the renal transplant waiting list in the United Kingdom, because of lack of HLA and blood group matched donors from an overwhelmingly white deceased donor pool. This study evaluates outcomes of renal allografts arising from Asian and black donors.MethodsThe UK Transplant Registry was analysed for adult deceased donor kidney only transplants performed during January 2001-December 2015.ResultsAsian and black ethnicity patients constituted 12.4% and 6.7% of all deceased donor recipients but only 1.6% and 1.2% of all deceased donors, respectively. Across all recipients, and unsurprisingly given the predominantly white recipient pool, HLA matching was superior for grafts from white donors than from Asian and black donors (p<0.0001). Unadjusted survival analysis demonstrated significantly inferior long-term allograft outcomes associated with Asian and black donors, compared to white donors (7-year graft survival 71.9%, 74.0% and 80.5%; log-rank p=0.0007, respectively). On Cox regression analysis, Asian donor (HR 1.37 for Asian donors vs. white donors as baseline) and black recipient (HR 1.21 for black recipients vs. white recipient as baseline) ethnicities were associated with poorer outcomes than white counterparts, and on ethnicity matching, compared with the white donor–white recipient baseline group and adjusting for other donor and recipient factors, 5-year graft outcomes were significantly poorer for black donor-black [HR 1.92 (1.11-3.32), p=0.02], Asian donor-white recipient [HR 1.56 (1.09-2.24), p=0.016] and white donor-black recipient [HR 1.22 (1.05-1.42), p=0.011] combinations in decreasing order of worse unadjusted 5-year graft survival.ConclusionsIncreased deceased donation among ethnic minority communities would benefit the entire recipient pool by increasing the numbers of available organs and may specifically benefit the Asian and black recipients by increasing the numbers of blood group and HLA-compatible grafts for allocation but may not improve allograft outcomes.
Multi-omics signatures of the human early life exposome
Authors: Maitre Léa , Bustamante Mariona , Hernández-Ferrer Carles , Thiel Denise , Lau Chung-Ho , Siskos Alexandros , Vives-Usano Marta , Ruiz-Arenas Carlos , Robinson Oliver , Mason Dan , Wright John , Cadiou Solène , Slama Rémy , Heude Barbara , Gallego-Paüls Marta , Casas Maribel , Sunyer Jordi , Papadopoulou Eleni Z. , Gutzkow Kristine B. , Andrusaityte Sandra , Grazuleviciene Regina , Vafeiadi Marina , Chatzi Leda , Sakhi Amrit K. , Thomsen Cathrine , Tamayo Ibon , Nieuwenhuijsen Mark , Urquiza Jose , Borràs Eva , Sabidó Eduard , Quintela Inés , Carracedo Ángel , Estivill Xavier , Coen Muireann , González Juan R. , Keun Hector C. , Vrijheid Martine 
Published: May 2021

SummaryEnvironmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1,301 mother-child pairs, we associated individual exposomes consisting of >100 chemical, physical and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, metabolome and proteins) in childhood. We identified 1,170 associations, 249 in pregnancy and 921 in childhood, which revealed potential biological responses and sources of exposure. The methylome best captures the persistent influence of pregnancy exposures, including maternal smoking; while childhood exposures were associated with features from all omics layers, revealing novel signatures for indoor air quality, essential trace elements, endocrine disruptors and weather conditions. This study provides a unique resource (https://helixomics.isglobal.org/) to guide future investigation on the biological effects of the early life exposome.
Study of PLEKHA1 gene polymorphism and their association with age related macular degeneration in Indian patients
Authors: Gupta Divya , Chawla Shobhit , Phadke Shubha R. 
Published: May 2021

ABSTRACTBackgroundAge-related macular degeneration (AMD) is an important cause of visual impairment in elderly people. AMD is a multifactorial disease in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been found to be associated with AMD.AimThis study was aimed to investigate the association of polymorphisms in PLEKHA1 rs4146894 (G>A) gene with age related macular degeneration (AMD) in Indian patients.MethodGenotyping for the PLEKHA1 rs4146894 (G>A) polymorphism performed in 121 AMD patients and 100 controls by polymerase chain reaction (PCR) and sequencing method.ResultsThis is the first study from India on PLEKHA1 rs4146894 (G>A) polymorphism. In this study, we did not get any change in DNA sequence by sequencing method. So, we can say that the risk allele of PLEKHA1 rs4146894 (G>A) polymorphism is not find in Indian population. On the other hand in Indian population the risk of A allele is not present, and this gene is not playing any significant contribution with AMD in Indian population.ConclusionVery limited literatures are available for PLEKHA1 polymorphism in AMD patients, though, it is quite possible that the variation in the data shows population based differences. So, the present study raises the possibility that PLEKHA1 rs4146894 (G>A) polymorphism may not have a significant association with AMD in Indian patients.
EPHX1mutations cause a lipoatrophic diabetes syndrome due to impaired epoxide hydrolysis and increased cellular senescence
Authors: Gautheron Jérémie , Morisseau Christophe , Chung Wendy K. , Zammouri Jamila , Auclair Martine , Baujat Geneviève , Capel Emilie , Moulin Célia , Wang Yuxin , Yang Jun , Hammock Bruce D , Cerame Barbara , Phan Franck , Fève Bruno , Vigouroux Corinne , Andreelli Fabrizio , Jéru Isabelle 
Published: May 2021

AbstractEpoxide hydrolases (EHs) regulate cellular homeostasis through hydrolysis of epoxides to less reactive diols. The first discovered EH was EPHX1, also known as mEH. EH functions remains partly unknown and no pathogenic variants have been reported in humans. We identified twode novovariants located in EPHX1 catalytic site in patients with a lipoatrophic diabetes characterized by loss of adipose tissue, insulin resistance, and multiple organ dysfunction. Functional analyses revealed that these variants led to the protein aggregation within the endoplasmic reticulum and to a loss of its hydrolysis activity. CRISPR-Cas9-mediatedEphx1knockout (KO) abolished adipocyte differentiation and decreased insulin response. This KO also promoted oxidative stress and cellular senescence, an observation confirmed in patient-derived fibroblasts. A major beneficial effect of metreleptin therapy was observed. This translational study highlights the importance of epoxide regulation for adipocyte function, and provides new insights into the physiological roles of EHs in humans.
Behavioral, Demographic, and Clinical determinants of HIV Status in Zambian Women
Authors: Gebreyohannes Debebe , Shen Ji , Sams Kelley 
Published: May 2021

AbstractThe rate of human immunodeficiency virus (HIV) infection shows a diminishing trend globally while increasing in intensity of mortality, morbidity, and burden of HIV in Sub-Saharan Africa. The intertwined behavioral, demographic, and clinical determinants fueled the incidence of infections in Zambian women. This study aimed to determine the association between demographic, behavioral, and clinical determinants with HIV serostatus in Zambian women. With the conceptual framework of the World Health Organization’s Commission for Social Determinants of Health (CSDH) and the quantitative method of MANOVA, this study examined Zambian Demographic Health Survey data for Zambian women of two ages groups (adolescent and adult). The findings showed statistically significant results in the association between HIV serostatus and self-perceived HIV risk for both groups and in the association between education and HIV serostatus among women in both groups. However, there was no statistically significant association between behavioral, demographic, and clinical determinants of HIV serostatus. These findings imply the need to conduct prospective studies on such determinants to curb HIV and improve women’s community health in Africa.Author SummaryZambia is a country in the Sub-Saharan region of Africa, which is disproportionately facing the risk of HIV increase in infection rate and the number of people impacted. HIV exposure shows an extraordinary rise for women aged 18–49 years old. The behavioral, demographic, and clinical determinants of HIV serostatus form an intricate web that snares adolescent and adult women, deteriorating their quality of life and their mental and emotional well-being.
Independent dynamics of slow, intermediate, and fast intracranial EEG spectral activities during human memory formation
Authors: Marks Victoria S. , Saboo Krishnakant V. , Topçu Çağdaş , Thayib Theodore P. , Nejedly Petr , Kremen Vaclav , Worrell Gregory A. , Kucewicz Michal T. 
Published: May 2021

AbstractA wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various low and high frequencies are spatiotemporally coordinated across the human brain during memory processing is inconclusive. They can either be coordinated together across a wide range of the frequency spectrum or induced in specific bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated slow theta, intermediate alpha and beta, and fast gamma frequency power in discrete cortical sites. A majority of the electrode sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and fast activities propagated in distinct spatiotemporal patterns across the visual, temporal and prefrontal cortical areas as the words were presented for encoding. Our results suggest anatomically and temporally distributed spectral activities in the formation of human memory.
Generic solving of one-compartment toxicokinetic models
Authors: Charles Sandrine , Ratier Aude , Lopes Christelle 
Published: May 2021

AbstractThis paper gives the full analytical solution of the generic set of ordinary differential equations that define one-compartment toxicokinetic models. These models describe uptake and elimination processes taking place within living organisms when exposed to chemical substances. The models solved in this paper consider living organisms as a unique compartment, into which a parent compound enters via several possible exposure routes and from which it is eliminated as well as its potential metabolites. Benefiting from generic solutions of one-compartment toxicokinetic models is particularly useful when fitting them to experimental data, facilitating the writing of the inference algorithms leading to parameter estimates. Additionally, these models are of crucial interest in environmental risk assessment for the calculation of bioaccumulation metrics as required by regulators in support of decision making when they evaluate dossiers for marketing authorisation of active substances.Abstract FigureGraphical abstract
Role of hypocretin in the medial preoptic area in the regulation of sleep, maternal behavior and body temperature of lactating rats
Authors: Rivas Mayda , Serantes Diego , Peña Florencia , González Joaquín , Ferreira Annabel , Torterolo Pablo , Benedetto Luciana 
Published: May 2021

AbstractThe hypocretins (HCRT), also known as orexin, includes two neuroexcitatory peptides, HCRT-1 and HCRT-2 (orexin A y B, respectively), synthesized by neurons located in the postero-lateral hypothalamus, whose projections and receptors are widely distributed throughout the brain, including the medial preoptic area (mPOA). HCRT have been associated with a wide range of physiological functions including sleep-wake cycle, maternal behavior and body temperature, all regulated by the mPOA. Previously we showed that HCRT in the mPOA facilitates certain active maternal behaviors, while the blockade of HCRT-R1 increased the time spent in nursing. As mother rats mainly sleep while they nurse, we hypothesize that HCRT in the mPOA of lactating rats reduce sleep and nursing, while the intra-mPOA administration of the dual orexin receptor antagonist (DORA) would generate the opposite effect. Therefore, the aim of this study was to determine the role of HCRT within the mPOA, in the regulation and integration of the sleep-wake cycle, maternal behavior and body temperature of lactating rats. To evaluate this idea, we assessed the sleep-wake states, maternal behavior and body temperature of lactating rats following microinjections of HCRT-1 (100 and 200 μM) and DORA (5mM) into the mPOA. As expected, our data shows that HCRT-1 in mPOA promoted wakefulness and a slightly increase in body temperature, whereas DORA increased both NREM and REM sleep along with nursing and milk ejection. Taken together, our results strongly suggest that the reduction of the endogenous HCRT within the mPOA of lactating rats is important to promote sleep, nursing and milk ejection.
NERD-seq: A novel approach of Nanopore direct RNA sequencing that expands representation of non-coding RNAs
Authors: Saville Luke , Cheng Yubo , Gollen Babita , Mitchell Liam , Stuart-Edwards Matthew , Haight Travis , Mohajerani Majid , Zovoilis Athanasios 
Published: May 2021

ABSTRACTThe new next-generation sequencing platforms by Oxford Nanopore Technologies for direct RNA sequencing (direct RNA-seq) allow for an in-depth and comprehensive study of the epitranscriptome by enabling direct base calling of RNA modifications. Non-coding RNAs constitute the most frequently documented targets for RNA modifications. However, the current standard direct RNA-seq approach is unable to detect many of these RNAs. Here we present NERD-seq, a sequencing approach which enables the detection of multiple classes of non-coding RNAs excluded by the current standard approach. Using total RNA from a tissue with high known transcriptional and non-coding RNA activity in mouse, the brain hippocampus, we show that, in addition to detecting polyadenylated coding and non-coding transcripts as the standard approach does, NERD-seq is able to significantly expand the representation for other classes of RNAs such as snoRNAs, snRNAs, scRNAs, srpRNAs, tRNAs, rRFs and non-coding RNAs originating from LINE L1 elements. Thus, NERD-seq presents a new comprehensive direct RNA-seq approach for the study of epitranscriptomes in brain tissues and beyond.
Ozone sensitivity of diverse maize genotypes is associated with differences in gene regulation, not gene content
Authors: Nanni Adalena V. , Morse Alison M. , Newman Jeremy R. B. , Choquette Nicole E. , Wedow Jessica M. , Liu Zihao , Leakey Andrew D. B. , Conesa Ana , Ainsworth Elizabeth A. , McIntyre Lauren M 
Published: May 2021

AbstractThe maize pangenome has demonstrate large amounts of presence/absence variation and it has been hypothesized that presence/absence variation contributes to stress response. To uncover whether the observed genetic variation in physiological response to elevated ozone (a secondary air pollutant that causes significant crop yield losses) concentration is due to variation in genic content, and/or variation in gene expression, we examine the impact of sustained elevated ozone concentration on the leaf tissue from 5 diverse maize inbred genotypes (B73, Mo17, Hp301, C123, NC338). Analysis of long reads from the transcriptomes of the 10 conditions found expressed genes in the leaf are part of the shared genome, with 94.5% of expressed genes from syntenic loci. Quantitative analysis of short reads from 120 plants (twelve from each condition) found limited transcriptional response to sustained ozone stress in the ozone resistant B73 genotype (151 genes), while more than 3,300 genes were significantly differentially expressed in the more sensitive NC338 genotype. The genes underpinning the divergence of B73 from the other 4 genotypes implicates ethylene signaling consistent with some findings in Arabidopsis. For the 82 of the 83 genes differentially expressed among all 5 genotypes and the 788 of 789 genes differentially expressed in 4 genotypes (excluding B73) in sensitivity to ozone is associated with oxidative stress tolerance being associated with a weaker response to a reactive oxygen species (ROS) signal and suggests that genetic variation in downstream processes is key to ozone tolerance.
Meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related knee osteoarthritis
Authors: Iijima Hirotaka , Gilmer Gabrielle , Wang Kai , Sivakumar Sruthi , Evans Christopher , Matsui Yusuke , Ambrosio Fabrisia 
Published: May 2021

AbstractIncreased mechanistic insight into the pathogenesis of knee osteoarthritis (KOA) is needed to develop efficacious disease-modifying treatments. Though age-related pathogenic mechanisms are most relevant to the great majority of KOA seen clinically, the bulk of our mechanistic understanding of KOA has been derived using surgically induced post-traumatic OA (PTOA) models. Here, we took an integrated approach of meta-analysis and multi-omics to elucidate pathogenic mechanisms of age-related KOA in murine model. Protein-level data together with transcriptomic profiling revealed inflammation, autophagy, and cellular senescence as primary hallmarks of age-related KOA. Importantly, the molecular profiles of aged cartilage were unique from those in PTOA, with only 1% overlap between the two. At the nexus of aging hallmarks, Advanced Glycation End-Product (AGE)/Receptor for AGE emerged as intrinsically linked to age-related KOA. This pathway was further validated by mass spectrometry. Collectively, these findings implicate dysregulation of AGE-RAGE signaling as a key driver of age-related KOA.
Isotopically Nonstationary13C Metabolic Flux Analysis in Resting and Activated Human Platelets
Authors: Sake Cara L. , Metcalf Alexander J. , Di Paola Jorge , Neeves Keith B. , Boyle Nanette R. 
Published: May 2021

AbstractPlatelet metabolism is linked to platelet hyper- and hypoactivity in numerous human diseases. Developing a detailed understanding of the link between metabolic shifts and platelet activation state is integral to improving human health. Here, we show the first application of isotopically nonstationary13C metabolic flux analysis to quantitatively measure carbon fluxes in both resting and thrombin activated platelets. Resting platelets primarily metabolize glucose to lactate via glycolysis, while acetate is oxidized to fuel the tricarboxylic acid cycle. Upon activation with thrombin, a potent platelet agonist, platelets increase their uptake of glucose 3-fold. This results in an absolute increase in flux throughout central metabolism, but when compared to resting platelets they redistribute carbon dramatically. Activated platelets decrease relative flux to the oxidative pentose phosphate pathway and TCA cycle from glucose and increase relative flux to lactate. These results provide the first report of reaction-level carbon fluxes in platelets and allow us to distinguish metabolic fluxes with much higher resolution than previous studies.
Bergamottin a CYP3A inhibitor found in grapefruit juice inhibits prostate cancer cell growth by downregulating androgen receptor signaling causing cell cycle block and apoptosis
Authors: Vetrichelvan Opalina , Gorjala Priyatham , Goodman Oscar , Mitra Ranjana 
Published: May 2021

AbstractProstate cancer is the second leading cause of cancer related death in American men. Several therapies have been developed to treat advanced prostate cancer, but these therapies often have severe side effects. To improve the outcome with fewer side effects we focused on the furanocoumarin bergamottin, a natural product found in grapefruit juice and a potent CYP3A inhibitor. Our recent studies have shown that CYP3A5 inhibition can block androgen receptor (AR) signaling, critical for prostate cancer growth. We observed that bergamottin reduces prostate cancer (PC) cell growth by decreasing both total and nuclear AR (AR activation) reducing downstream AR signaling. Bergamottin’s role in reducing AR activation was confirmed by confocal microscopy studies and reduction in PSA levels. Further studies revealed that bergamottin promotes cell cycle block and accumulates G0/G1 cells. The cell cycle block was accompanied with reduction in cyclin D, cyclin B, CDK4, P-cdc2 (Y15) and P-wee1 (S642). We also observed that bergamottin triggers apoptosis in prostate cancer cell lines as evident by TUNEL staining and PARP cleavage. Our data suggest that bergamottin may be used as an adjunctive nutritional supplement to suppress prostate cancer growth and is of relevance to AA patients carrying wild type CYP3A5 often presenting aggressive disease.