bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Insights into the Diagnosis of Smell and Taste Disorders in the United States
Authors: Naimi Bita R. , Hunter Stephanie R. , Boateng Katie , Rawson Nancy E. , Garvey Emily , Dalton Pamela H. , Trachtman Jenifer , Murphy Claire , Joseph Paule V. , Schrandt Suz , Silberman Pamela , Duffy Alexander , Nyquist Gurston G. 
Published: September 2023

ABSTRACTOBJECTIVESDiagnosis of smell/taste dysfunction is necessary for appropriate medical care. This study examines factors affecting testing and diagnosis of smell/taste disorders.METHODSThe onlineUSA Smell and Taste Patient Surveywas made available to US patients with smell/taste disorders between April 6-20, 2022. 4,728 respondents were included.RESULTS1,791 (38%) patients reported a documented diagnosis. Patients most often saw family practitioners (34%), otolaryngologists (20%), and Taste/Smell clinics (6%) for smell/taste dysfunction. 64% of patients who went to Taste/Smell clinics received smell testing, followed by 39% of patients who saw otolaryngologists, and 31% of patients who saw family practitioners. Factors associated with increased odds of diagnosis included age (25-39 years (OR 2.97, 95% CI [2.25, 3.95]), 40-60 (OR 3.3, 95% CI [2.56, 4.52]), and >60 (OR 4.25, 95% CI [3.21, 5.67]) vs. 18-24 years), male gender (OR 1.26, 95% CI [1.07, 1.48]), insurance status (private (OR 1.61, 95% CI [1.15, 2.30]) or public (OR 2.03, 95% CI [1.42, 2.95]) vs. uninsured), perception of their family practitioner to be knowledgeable (OR 2.12, 95% CI [1.16, 3.90]), otolaryngologic evaluation (OR 6.17, 95% CI [5.16, 7.38]), and psychophysical smell testing (OR 1.77, 95% CI [1.42, 2.22]).CONCLUSIONPsychophysical testing, otolaryngologic evaluation, patient assessment of family practitioner knowledge level, insurance, age, and gender are significant factors in obtaining smell/taste dysfunction diagnosis. This study identifies barriers to diagnosis including lack of insurance or access to specialist evaluation and highlights the importance of educating family practitioners in diagnosis and management of patients with smell/taste disorders.
Development and validation of a deep-learning model to predict 10-year ASCVD risk from retinal images using the UK Biobank and EyePACS 10K datasets
Authors: Vaghefi Ehsan , Squirrell David , Yang Song , An Songyang , Xie Li , Durbin Mary K. , Hou Huiyuan , Marshall John , Shreibati Jacqueline , McConnell Michael V , Budoff Matthew 
Published: September 2023

AbstractBackgroundAtherosclerotic Cardiovascular Disease (ASCVD) is a leading cause of death globally, and early detection of high-risk individuals is essential for initiating timely interventions. The authors aimed to develop and validate a deep learning (DL) model to predict an individual’s elevated 10-year ASCVD risk score based on retinal images and limited demographic data.MethodsThe study used 89,894 retinal fundus images from 44,176 UK Biobank participants (96% non-Hispanic White, 5% diabetic) to train and test the DL model. The DL model was developed using retinal images plus age, race/ethnicity, and sex at birth to predict an individual’s 10-year ASCVD risk score using the Pooled Cohort Equation (PCE) as the ground truth. This model was then tested on the US EyePACS 10K dataset (5.8% Non-Hispanic white 99.9% diabetic), composed of 18,900 images from 8,969 diabetic individuals. Elevated ASCVD risk was defined as a PCE score of ≥7.5%.ResultsIn the UK Biobank internal validation dataset, the DL model achieved area under the receiver operating characteristic curve (AUROC) of 0.89, sensitivity 84%, and specificity 90%, for detecting individuals with elevated ASCVD risk scores. In the EyePACS 10K and with the addition of a regression-derived diabetes modifier, it achieved sensitivity 94%, specificity 72%, mean error −0.2%, and mean absolute error 3.1%.ConclusionThis study demonstrates that DL models using retinal images can provide an additional approach to estimating ASCVD risk, and the value of applying DL models to different external datasets and opportunities about ASCVD risk assessment in patients living with diabetes.
The brain time estimation system is dynamically assembled by non-temporal perceptual states
Authors: Han Wenhao , Feng Tingting , Han Yifei , Sun Yawen , Jiang Yi , Zhang Tao 
Published: September 2023

AbstractTo investigate how neural integration of visual signals distorts human time perception, we developed a novel apparent motion paradigm. We found that the higher the frequency of visual events defined by spatial location, the longer the perception duration. At the same visual event frequency, perceptual duration was shorter when motion perception was evoked. We propose that the non-temporal perceptual states dynamically determine which core brain region (read-out system) and which group of activated neurons (timing units) assemble into a time estimation system. Timing units have activation delays in integrating input signals, which results in shorter perceptual time since perceptual duration depends only on the outputs of timing units. The read-out system consumes operating time to accumulate each timing unit, this results in a longer perception time the more timing units are accumulated in the same physical duration. Subsequently, experiments further validated two predictions of our perceptual assembly model.
Differential and lasting gene expression changes in circulating CD8 T cells in chronic HCV infection with cirrhosis and related insights on the role of Hedgehog signaling
Authors: Li Jiafeng , Vranjkovic Agatha , Read Daniel , Delaney Sean P , Stanford William L , Cooper Curtis L , Crawley Angela M 
Published: September 2023

AbstractThe impact of chronic hepatic infection on antigen non-specific immune cells in circulation is not well understood and may influence long term health. We reported lasting global hyperfunction of circulating CD8 T cells in HCV-infected individuals with cirrhosis. Whether gene expression patterns in bulk CD8 T cells are associated with the severity of liver fibrosis in HCV infection is not known. RNA sequencing of blood CD8 T cells from treatment-naïve, HCV-infected individuals with minimal (Metavir F0-1 ≤ 7.0 kPa) or advanced fibrosis or cirrhosis (F4 ≥ 12.5 kPa), before and after direct-acting antiviral therapy, was performed. Principal component analyses determined robust differences in over 350 genes expressed by CD8 T cells from HCV-infected individuals with minimal or advanced fibrosis and data suggests this remains relatively stable after viral clearance. Gene ontology analyses identified disaggregated gene expression related to cellular metabolism, including upregulated phospholipase, phosphatidyl-choline/inositol activity and second-messenger-mediated signaling, while genes in pathways associated with nuclear processes, RNA transport and cytoskeletal dynamics were reduced. Gene Set Enrichment Analysis identified decreased expression of genes regulated by the cMyc and E2f transcription factors in cirrhotics, compared to the minimal fibrosis group, as well as reduced expression of genes linked to oxidative phosphorylation, mTOR signaling, and more. Upregulated gene sets in cirrhotics included IFN-α, -γ, TGF-β response genes, apoptosis and apical surface pathways, among others. The hedgehog (Hh) signaling pathway was the top featured gene set upregulated in cirrhotics. Inhibition of Hh signaling with cyclopamine ablated CD8 T cell IFN-γ production, suggesting its involvement in hyperfunction. This is the first analysis of bulk CD8 T cell gene expression profiles in HCV infection in the context of liver fibrosis severity, and suggests cirrhosis significantly reprograms the CD8 T cell pool. The novel finding of increased Hh signaling in cirrhosis may contribute to generalized CD8 T cell hyperfunction observed in chronic HCV infection. Understanding the lasting nature of immune cell dysfunction may help mitigate remaining clinical challenges after HCV clearance and more generally, improve long term outcomes for individuals with severe liver disease.
Genetic diversity of the Atacama Desert shrubHuidobria chilensisin the context of geography and climate
Authors: Bechir Ferchichi K. , Böhnert T. , Ritter B. , Harpke D. , Stoll A. , Morales P. , Fiedler S. , Mu F. , Bechteler J. , Münker C. , Koch M.A. , Wiehe T. , Quandt D. 
Published: September 2023

AbstractSurvival in hyperarid deserts is a major challenge for plant life, requiring the development of evolutionary strategies. The Atacama Desert presents harsh conditions such as limited rainfall, crusted soils, high soil salinity, high altitude, and intense solar radiation. These conditions, together with paleoclimatic variability since the past millions of years, have influenced the genetic structure and connectivity of plant populations, resulting in a diverse flora with high endemism. However, the diversification of most lineages appears to be relatively recent, in contrast to proposed age of the Atacama Desert and the onset, evolution and expansion of hyperarid conditions since the Late Oligocene and Early Miocene. A prominent exception is the Atacama paleoendemicHuidobria chilensis(Loasaceae), which is thought to be adapted to such conditions since the Eocene. Still, the environmental limits and thresholds for life in the Atacama remain poorly understood. To investigate the genetic structure in relation to the history of the Atacama Desert, we studied 186 individuals from 11 populations using genotyping-by-sequencing (GBS). Genome-wide single nucleotide polymorphisms (SNPs) were analyzed for population structure and genetic diversity. We identified three genetic clusters corresponding to geographic regions: the coastal region south of Tocopilla, the Coastal Cordillera around Chañaral, and the Copiapó watershed in the south. These clusters as well as genetic diversity were analyzed alongside rainfall, altitude, and landscape data. Although the genetic data generally supports isolation by distance as a major factor for genetic variation between populations, the study also reveals the influence of the topography on the distribution ofH. chilensisand highlights the role of hydrologically connected watersheds and rivers in plant migration and colonization. This shapes the species’ evolutionary trajectory and genetic diversity. Understanding these patterns provides insights into the adaptation and survival strategies of plants in extreme desert environments such as the Atacama.
Developmental effect of RASopathy mutations on neuronal network activity on a chip
Authors: Weiss Eva-Maria , Guhathakurta Debarpan , Petrušková Aneta , Hundrup Verena , Zenker Martin , Fejtová Anna 
Published: September 2023

AbstractRASopathies are a group of genetic disorders caused by mutations in genes encoding components and regulators of the RAS/MAPK signaling pathway, resulting in overactivation of signaling. RASopathy patients exhibit distinctive facial features, cardiopathies, growth and skeletal abnormalities, and varying degrees of developmental delay, neurocognitive impairment, intellectual disabilities, and attention deficits. At present, it is unclear how RASopathy mutations cause neurocognitive impairment and what their neuron-specific cellular and network phenotypes are. Such knowledge would be crucial for the development of specific therapies, which are still lacking for the treatment of the neurocognitive and behavioral symptoms in RASopathies. Here, we investigated the effect of RASopathy mutations on the establishment and functional maturation of neuronal networks. We isolated cortical neurons from RASopathy mouse models and cultured them for several weeks in multiwell plates with implanted multielectrode arrays. The arrays were used for longitudinal recordings of spontaneous activity in developing networks as well as for recordings of evoked responses in mature neurons. To facilitate the analysis of large and complex data sets resulting from long-term multielectrode recordings, we developed MATLAB-based tools for data processing, analysis and statistical evaluation. Longitudinal analysis of spontaneous network activity revealed a convergent developmental phenotype in neurons carrying the gain-of-function RASopathy mutationsPtpn11D61YandKrasV14l. The phenotype was more pronounced at early time points and faded out over time, suggesting compensatory effects during network maturation. Nevertheless, persistent differences in excitatory/inhibitory balance and network excitability were observed in mature networks. This study improves the understanding of the complex relationship between genetic mutations and clinical manifestations in RASopathies by adding insights into functional network processes as an additional piece of the puzzle.
Coordinated Human-Exoskeleton Locomotion Emerges from Regulating Virtual Energy
Authors: Nasiri Rezvan , Dinovitzer Hannah , Arami Arash 
Published: September 2023

AbstractLower-limb exoskeletons showed great potential for the gait rehabilitation of individuals with motor impairments; however, maintaining human-exoskeleton coordination is still a challenge. Human-exoskeleton coordination problem, referred to as any mismatch or asynchrony between the user’s intended trajectories and exoskeleton desired trajectories, results in sub-optimal gait performance, particularly for the individuals with residual motor ability. Here, we investigate the virtual energy regulator (VER)’s ability to generate coordinated locomotion in lower limb exoskeleton in a study on nine individuals. A comprehensive analysis of metrics obtained at three different speeds demonstrates the emergence of natural and coordinated locomotion as a result of a shared control between human and exoskeleton maintained with the VER. We also introduce a metric to measure the user’s contribution to gait and demonstrated that the resultant locomotion limit cycle is a linear combination of human-intended limit cycle and the VER’s limit cycle. This results may have implications about how central nervous system controls our locomotion.
Dopamine and schizophrenia from bench to bedside: Discovery of a striatal co-expression risk gene set that predicts in vivo measures of striatal function
Authors: Sportelli Leonardo , Eisenberg Daniel P. , Passiatore Roberta , D’Ambrosio Enrico , Antonucci Linda A. , Chen Qiang , Czarapata Jasmine , Goldman Aaron L. , Gregory Michael , Griffiths Kira , Hyde Thomas M. , Kleinman Joel E. , Pardiñas Antonio F. , Parihar Madhur , Popolizio Teresa , Rampino Antonio , Shin Joo Heon , Veronese Mattia , Ulrich William S. , Zink Caroline F. , Bertolino Alessandro , Howes Oliver D. , Berman Karen F. , Weinberger Daniel R. , Pergola Giulio 
Published: September 2023

AbstractSchizophrenia (SCZ) is characterized by a polygenic risk architecture implicating diverse molecular pathways important for synaptic function. However, how polygenic risk funnels through these pathways to translate into syndromic illness is unanswered. To evaluate biologically meaningful pathways of risk, we used tensor decomposition to characterize gene co-expression in post-mortem brain (of neurotypicals: N=154; patients with SCZ: N=84; and GTEX samples N=120) from caudate nucleus (CN), hippocampus (HP), and dorsolateral prefrontal cortex (DLPFC). We identified a CN-predominant gene set showing dopaminergic selectivity that was enriched for genes associated with clinical state and for genes associated with SCZ risk. Parsing polygenic risk score for SCZ based on this specific gene set (parsed-PRS), we found that greater pathway-specific SCZ risk predicted greaterin vivostriatal dopamine synthesis capacity measured by [18F]-FDOPA PET in three independent cohorts of neurotypicals and patients (total N=235) and greater fMRI striatal activation during reward anticipation in two additional independent neurotypical cohorts (total N=141). These results reveal a ‘bench to bedside’ translation of dopamine-linked genetic risk variation in drivingin vivostriatal neurochemical and hemodynamic phenotypes that have long been implicated in the pathophysiology of SCZ.
A muscle hypertrophy-derived myokine reprograms the stromal vascular fractions differentiation towards thermogenic adipocytes in subcutaneous adipose tissue
Authors: Yao Xiangping , Mai Xudong , Tian Ye , Liu Yifan , Jin Guanghui , Li Ze , Chen Shujie , Dai Xiaoshuang , Jin Xuejie , Huang Liujing , Han Mulan , Fan Zijing , Xiao Lanling , Pan Guihua , Pan Xiaohan , Lin Ziying , Li Xiangmin , Sun Jia , Ou Jingxing , Chen Hong , Xie Liwei 
Published: September 2023

AbstractSkeletal muscle plays a significant role in both local and systemic energy metabolism; however, the cross-talk between skeletal muscle and adipose tissue remains largely unexplored. In this study, we identify the HIF2α-Bambi-Thbs4 axis as a critical driver of muscle hypertrophy and metabolic improvement. Deletion ofBambiinduces muscle hypertrophy and oxidative switching, thereby enhancing local and systemic metabolism under conditions of rodent chow and high-fat diets (HFD). Other than the metabolic regulation of skeletal muscle hypertrophy, we hypothesize that a portion of this improvement may be attributed to the metabolic reprogramming of the stromal vascular fraction (SVFs) of iWAT, promoting the development of beige adipocytes. Leveraging multi-omics approaches, we establish Thbs4 as a newly identified, muscle hypertrophy-derived myokine that serves as an essential regulator of this metabolic reprogramming. Thbs4 is upregulated in skeletal muscle during hypertrophy and aerobic exercise, localizes to the iWAT membrane, and facilitates the transformation of white adipocytes into beige adipocytes under conditions such as cold exposure, muscle hypertrophy, or aerobic exercise. Moreover, overexpression of Thbs4 elevates its plasma levels and leads to the transformation of white to beige adipocytes, therefore offering long-term protection against HFD-induced metabolic disorders. Conversely,Thbs4knockout (Thbs4-KO) disrupts the metabolic reprogramming of SVFs and exacerbates metabolic syndromes induced by an HFD, mirroring the observed decline in Thbs4 levels in aged mice. Therefore, our findings underscore Thbs4’s potential as both a long-term metabolic protective factor and a therapeutic target for the treatment of metabolic disorders.Graphical AbstractHighlightsBambi, a direct target gene of HIF2α in skeletal muscle, when deleted, triggers muscle hypertrophy and the transformation of white into beige adipocytes, improving systemic energy metabolism.The metabolic reprogramming of stromal vascular fractions (SVFs) contributes to the observed improvements in energy metabolism and adipocyte hyperplasia.Thbs4, a novel myokine produced in skeletal muscle during hypertrophy and aerobic exercise, plays a key role in the transformation of white into beige adipocytes.Overexpression of Thbs4 provides enduring protection against high-fat diet (HFD)-induced metabolic disorders, demonstrating its potential as a therapeutic target.Thbs4deletion abrogates the beneficial metabolic reprogramming of SVFs and exacerbates HFD-induced metabolic syndromes, further underlining its crucial role in metabolic regulation.
Viable mutants of essential genes inPhyscomitrium patensas tools for studying primary metabolic processes
Authors: Haslam Tegan M. , Herrfurth Cornelia , Feussner Ivo 
Published: September 2023

AbstractSphingolipids are essential components of plant cells, which have been notoriously difficult to study in part due to pleiotropic or lethal knock-out mutant phenotypes. By relying on alternative end-joining of double stranded breaks, we successfully used CRISPR/Cas9 mutagenesis to generate a population of diverse, viable mutant alleles of genes required for sphingolipid assembly in totipotent protoplasts of the mossPhyscomitrium patens. We targeted theINOSITOL PHOSPHORYLCERAMIDE SYNTHASE(IPCS) gene family, which catalyzes the committed step in the synthesis of glycosyl inositol phosphorylceramides (GIPCs), the most abundant class of sphingolipids found in plants. We isolated knock-out single mutants and knock-down higher-order mutants showing a spectrum of deficiencies in GIPC content. Remarkably, we also identified two mutant alleles accumulating inositol phosphorylceramides, the direct products of IPCS activity, and provide our best explanation for this unexpected phenotype. Our approach is broadly applicable for studying essential genes and gene families, and for obtaining unusual lesions within a gene of interest.
Systems-wide analysis of the ROK-family regulatory generokL6and its role in the control of glucosamine toxicity inStreptomyces coelicolor
Authors: Li Chao , Urem Mia , Du Chao , Zhang Le , van Wezel Gilles P. 
Published: September 2023

ABSTRACTStreptomycetes are saprophytic bacteria that grow on complex polysaccharides, such as cellulose, starch, chitin and chitosan. For the monomeric building blocks glucose, maltose andN-acetylglucosamine (GlcNAc), the metabolic pathways are well documented, but that of glucosamine (GlcN) is largely unknown.Streptomyces nagBmutants, which lack glucosamine-6-phosphate deaminase activity, fail to grow in the presence of high concentrations of GlcN. Here we report that mutations in the gene for the ROK-family transcriptional regulator RokL6 relieve the toxicity of GlcN innagBmutants, as a result of elevated expression of the Major Facilitator Superfamily (MFS) exporter SCO1448. Systems- wide analysis using RNA sequencing, ChIP-Seq, EMSAs, 5’RACE, bioinformatics and genetics revealed that RokL6 is an autoregulator that represses transcription of sco1448 by binding to overlapping promoters in therokL6-sco1448 intergenic region. RokL6-independent expression of sco1448 fully relieved toxicity of GlcN tonagBmutants. Taken together, our data show a novel system of RokL6 as a regulator that controls the expression of the MFS transporter SCO1448, which in turn protects cells against GlcN toxicity, most likely by exporting toxic metabolites out of the cell.IMPORTANCECentral metabolism plays a key role in the control of growth and antibiotic production in streptomycetes. Specifically, aminosugars act as signaling molecules that affect development and antibiotic production, via metabolic interference with the global repressor DasR. While aminosugar metabolism directly connects to other major metabolic routes such as glycolysis and cell wall synthesis, several important aspects of their metabolism are yet unresolved. Accumulation ofN-acetylglucosamine 6-phosphate (GlcNAc-6P) or glucosamine 6-phosphate (GlcN-6P) is lethal to many bacteria, a yet unresolved phenomenon referred to as “aminosugar sensitivity”. We made use of this concept by selecting for suppressors in genes related to GlcN toxicity innagBmutants, which showed that the gene pair ofrok-family regulatory generokL6and MFS transporter gene sco1448 forms a cryptic rescue mechanism. Inactivation ofrokL6resulted in the expression of sco1448, which then prevents toxicity of amino sugar-derived metabolites inStreptomyces. The systems biology of RokL6 and its transcriptional control of sco1448 sheds new light on aminosugar metabolism in streptomycetes and on the response of bacteria to aminosugar toxicity.