bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diurnal changes and topographical distribution of ocular surface epithelial dendritic cells in humans, and repeatability of density and morphology assessment
Authors: Tajbakhsh Zahra , Jalbert Isabelle , Stapleton Fiona , Briggs Nancy , Golebiowski Blanka 
Published: November 2022

AbstractPurposeDendritic cells (DC) play a crucial role in ocular surface defence. DC can be visualisedin vivoby confocal microscopy but have not yet been fully characterised in humans. This study investigated the diurnal variation, topographical distribution, and repeatability of DC density and morphology measurement.MethodsIn vivoconfocal microscopy was conducted on 20 healthy participants (mean age 32.7±6.4 years, 50% F) at baseline and repeated after 30 minutes, 2, 6, and 24 hours. Images were captured at the corneal centre, inferior whorl, corneal periphery, limbus, and bulbar conjunctiva. DC density was counted manually, and morphology of DC was assessed for the largest cell body size, presence of dendrites, presence of long dendrites, and presence of thick dendrites. Mixed model analysis, non-parametric analyses, Bland & Altman plots, the Coefficient of Repeatability (CoR), and kappa were used.ResultsThere were no significant changes in DC density (p≥0.74) or morphology (p>0.07) at any location over the 24-hour period. Highest DC density was observed at the corneal limbus followed by the peripheral cornea (p<0.001), with lowest density at the corneal centre, inferior whorl, and bulbar conjunctiva. Most DC at the corneal periphery, limbus, and bulbar conjunctiva had larger cell bodies compared to the corneal centre (p≤0.01), and presence of long dendrites was observed mostly at non-central locations. DC with thick dendrites were mostly observed at the limbus. Day-to-day CoR for DC density ranged from ±28.1 cells/mm2at the corneal centre to ±56.4 cells/mm2at the limbus. Day-to-day agreement of DC morphology determined by kappa ranged from 0.5 to 0.95 for cell body size, 0.60 to 0.95 for presence of dendrites, and 0.55 to 0.80 for presence of long dendrites, at various locations.ConclusionsNo diurnal changes are apparent in corneal or conjunctival DC. Substantial topographical differences exist in DC density and morphology.In vivoconfocal microscopy provides good repeatability of DC density and acceptable agreement of DC morphology.Key pointsThere was no diurnal variation in dendritic cell density, morphology, or topographical distribution at the ocular surface in healthy individuals.A gradient from high density of dendritic cells at the limbus to low density at the corneal centre was observed inin vivoconfocal microscope images of healthy corneas. Density was lowest in the bulbar conjunctiva.The morphology of dendritic cells at the corneal periphery, limbus and bulbar conjunctiva suggests a greater antigen capture capacity compared to dendritic cells at the corneal centre.
Top-Down Genomic Surveillance Approach to Investigate the Genomic Epidemiology and Antibiotic Resistance Patterns ofEnterococcus faeciumDetected in Cancer Patients in Arkansas
Authors: Udaondo Zulema , Abram Kaleb , Kothari Atul , Jun Se-Ran 
Published: November 2022

AbstractControl of hospital-associatedEnterococcus faeciuminfection is a strenuous task due to the difficulty of identifying transmission routes and the persistence of this nosocomial pathogen despite the implementation of infection control measures that have been successful with other important nosocomial pathogens. This study provides a comprehensive analysis of over one hundredE. faeciumisolates collected from 66 cancer patients at the University of Arkansas for Medical Sciences (UAMS) between June, 2018 and May, 2019. In the top-down approach used in this study we employed, in addition to the 106E. faeciumUAMS isolates, a filtered set of 2167E. faeciumstrains from the GenBank database to assess the current population structure ofE. faeciumspecies and, consequently, to identify the lineages associated with our clinical isolates. We then evaluated the antibiotic resistance and virulence profiles of hospital-associated strains from the species pool, focusing on antibiotics of last resort, in order to establish an updated classification of high-risk and multidrug-resistant nosocomial clones. Further investigation of the clinical isolates collected from UAMS patients using whole genome sequencing analytical methodologies (cgMLST, coreSNP and phylogenomics), with the addition of patient epidemiological data, revealed a polyclonal outbreak of three sequences types occurring simultaneously in different patient wards. The integration of genomic and epidemiological data collected from the patients increased our understanding of the relationships and transmission dynamics of theE. faeciumisolates. Our study provides new insights into genomic surveillance ofE. faeciumto assist in monitoring and further limiting the spread of multidrug-resistantE. faecium.
Monkeypox in the New York metropolitan area, Summer 2022
Authors: Gnanaprakasam Rachel , Keller Marina , Glassman Rebecca , El Khoury Marc Y , Chen Donald , Feola Nicholas , Feldman Jared , Chaturvedi Vishnu 
Published: November 2022

AbstractEarly in the 2022 Monkeypox global outbreak, caseloads in the New York metropolitan area climbed rapidly before other US urban areas. We summarize our monkeypox clinical experience detecting, treating, and vaccinating during a quickly evolving emerging infection.StatementsEthical statementInstitutional Review Board exemption was granted for this study.Funding statementNo funding was obtainedConflict of interestNoneAuthors’ contributionsEach author actively participated in data collection, analysis and editing of the manuscript.CollaboratorsNone
DIFFERENT PERSPECTIVES OF SPANISH PATIENTS AND PROFESSIONALS ON HOW A DIALYSIS UNIT SHOULD BE DESIGNED
Authors: Arenas Jiménez Maria Dolores , Manso Paula , Dapena Fabiola , Hernán David , Portillo Jesús , Balseiro Ana , Sánchez Mónica , López Raul , Pereira Concepción , Gallego Daniel , Julián Juan Carlos , Arellano Manuel , Tombas Antonio , Martin- Crespo Iluminada , Sanz Cristina ,   renal foundation’s Iñigo Álvarez de Toledo work team
Published: November 2022

ABSTRACTPeople with kidney disease on hemodialysis spend 4 hours of their lives three times a week in hemodialysis units. Although the new concept of 21st century medicine gives special prominence to the opinion of patients and family members, the reality is that this is rarely considered when establishing the requirements that a dialysis center should meet.ObjectiveTo know and compare the opinion and preferences of patients, family members and professionals regarding the design of a dialysis unit and the potential activities they believe should be carried out during the session in order to provide architects with real information for the construction of a dialysis center.MethodsAnonymous and voluntary survey in electronic format addressed to patients, relatives and professionals belonging to the 18 hemodialysis centers of the renal foundation and to ALCER and its different delegations, in relation to leisure activities to be carried out in the dialysis center and preferred design of the treatment room. The results obtained between the patient-family group and the professionals were compared.ResultsWe received 331 responses, of which 215 were from patients and family members (65%) and 116 (35%) from professionals. The most represented category among professionals was nursing (53%), followed by assistants (24%) and physicians (12.9%). A higher proportion of patients (66%) preferred rooms in groups of 10-12 patients as opposed to professionals who preferred open-plan rooms (p<0.001). The options that showed the most differences between patients and professionals were chatting with colleagues and intimacy (options most voted by patients/families), versus performing group activities and visibility (professionals).ConclusionsThe professionals’ view of patients’ needs does not always coincide with the patients’ perception. The inclusion of the perspective of people with kidney disease continues to be a pending issue in which we must improve both patient organizations and professionals, and the opinion of professionals and patients must be included in the design of a dialysis unit and the activities to be developed in it.
Two human brain systems micro-structurally associated with obesity
Authors: Kitzbichler Manfred G , Martins Daniel , Bethlehem Richard AI , Dear Richard , Romero-Garcia Rafael , Warrier Varun , Seidlitz Jakob , Dipasquale Ottavia , Turkheimer Federico , Cercignani Mara , Bullmore Edward T , Harrison Neil A 
Published: November 2022

AbstractThe relationship between obesity and brain structure is incompletely understood. Using diffusion-weighted MRI from ∼30,000 UK Biobank participants we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal-temporal-striatal system associated with ISOVF and a medial temporal-occipital-striatal system associated with ICVF. The ISOVF∼WHR system colocated with expression of genes enriched for innate immune functions, decreased glial density, and high mu opioid (MOR) and other neurotransmitter receptor density. Conversely, the ICVF∼WHR system co-located with expression of genes enriched for G-protein coupled receptors and decreased density of MOR and other receptors. To test whether these distinct brain phenotypes might differ in terms of their underlying shared genetics or relationship to maps of the inflammatory marker C-reactive Protein (CRP), we estimated the genetic correlations between WHR and ISOVF (rg= 0.026,P= 0.36) and ICVF (rg= 0.112,P <9 × 10−4) as well as comparing correlations between WHR maps and equivalent CRP maps for ISOVF and ICVF (p<0.05). These correlational results are consistent with a two-way mechanistic model whereby genetically determined differences in neurite density in the medial temporal system may contribute to obesity, whereas water content in the prefrontal system could reflect a consequence of obesity mediated by innate immune system activation.
SLIDE: Significant Latent Factor Interaction Discovery and Exploration across biological domains
Authors: Rahimikollu Javad , Xiao Hanxi , Rosengart Anna E. , Tabib Tracy , Zdinak Paul , He Kun , Bing Xin , Bunea Florentina , Wegkamp Marten , Poholek Amanda C. , Joglekar Alok V , Lafyatis Robert A , Das Jishnu 
Published: November 2022

AbstractModern multi-omic technologies can generate deep multi-scale profiles. However, differences in data modalities, multicollinearity of the data, and large numbers of irrelevant features make the analyses and integration of high-dimensional omic datasets challenging. Here, we present Significant Latent factor Interaction Discovery and Exploration (SLIDE), a first-in-class interpretable machine learning technique for identifying significant interacting latent factors underlying outcomes of interest from high-dimensional omic datasets. SLIDE makes no assumptions regarding data-generating mechanisms, comes with theoretical guarantees regarding identifiability of the latent factors/corresponding inference, outperforms/performs at least as well as state-of-the-art approaches in terms of prediction, and provides inference beyond prediction. Using SLIDE on scRNA-seq data from systemic sclerosis (SSc) patients, we first uncovered significant interacting latent factors underlying SSc pathogenesis. In addition to accurately predicting SSc severity and outperforming existing benchmarks, SLIDE uncovered significant factors that included well-elucidated altered transcriptomic states in myeloid cells and fibroblasts, an intriguing keratinocyte-centric signature validated by protein staining, and a novel mechanism involving altered HLA signaling in myeloid cells, that has support in genetic data. SLIDE also worked well on spatial transcriptomic data and was able to accurately identify significant interacting latent factors underlying immune cell partitioning by 3D location within lymph nodes. Finally, SLIDE leveraged paired scRNA-seq and TCR-seq data to elucidate latent factors underlying extents of clonal expansion of CD4 T cells in a nonobese diabetic model of T1D. The latent factors uncovered by SLIDE included well-known activation markers, inhibitory receptors and intracellular regulators of receptor signaling, but also honed in on several novel naïve and memory states that standard analyses missed. Overall, SLIDE is a versatile engine for biological discovery from modern multi-omic datasets.
Predicting disordered regions driving phase separation of proteins under variable salt concentration
Authors: Meca Esteban , Fritsch Anatol W. , Iglesias-Artola Juan M. , Reber Simone , Wagner Barbara 
Published: November 2022

ABSTRACTWe investigate intrinsically disordered regions (IDRs) of phase separating proteins regarding their impact on liquid-liquid phase separation (LLPS) of the full protein. Our theoretical approach uses a mean-field theory that accounts for sequence-dependent electrostatic interactions via a random-phase approximation (RPA) and in addition allows for variable salt concentration for the condensed and dilute protein phases. The numerical solution of the complete phase diagrams together with the tie lines that we derive for this model system leaves two parameters to be determined by fitting experimental data on concentrations of all species involved in the system. For our comparisons, we focus on two proteins, PGL-3 and FUS, known to undergo LLPS. For PGL-3 we predict that its long IDR near the C-terminus promotes LLPS, which we validate through direct comparison within vitroexperimental results under the same physiological conditions. For the structurally more complex protein FUS the role of the low complexity (LC) domain in LLPS has been intensively studied. Apart from the LC domain we here investigate theoretically two IDRs, one near the N-terminus and another near the C-terminus. Our theoretical analysis of these domains predict that the IDR at the N-terminus (aa 1-285) is the main driver of LLPS of FUS by comparison toin vitroexperiments of the full length protein under the same physiological temperature and salt conditions.SIGNIFICANCEIntrinsically disordered proteins are drivers of cellular liquid-liquid phase separation. However, it remains a challenge to directly predict the phase behaviour of a protein based on its primary sequence, and under physiological conditions. We present a random-phase approximation that allows for variable salt concentration and thus accounts for salt partitioning. We use this to link the sequence of the disordered regions with the behaviour of the complete protein through direct comparisons toin vitrophase-separation assays. In particular, for FUS we determine the exact region responsible for LLPS, weighting in a long-standing debate.
A lysosomal lipid transport pathway that enables cell survival under choline limitation
Authors: Scharenberg Samantha G. , Dong Wentao , Nyame Kwamina , Levin-Konigsberg Roni , Krishnan Aswini R. , Rawat Eshaan S. , Spees Kaitlyn , Bassik Michael C. , Abu-Remaileh Monther 
Published: November 2022

AbstractLysosomes degrade macromolecules and recycle their nutrient content to support cell function and survival over a broad range of metabolic conditions. Yet, the machineries involved in lysosomal recycling of many essential nutrients remain to be discovered, with a notable example being choline, an essential metabolite liberated in large quantities within the lysosome via the degradation of choline-containing lipids. To identify critical lysosomal choline transport pathways, we engineered metabolic dependency on lysosome-derived choline in pancreatic cancer cells. We then exploited this dependency to perform an endolysosome-focused CRISPR-Cas9 negative selection screen for genes mediating lysosomal choline recycling. Our screen identified the orphan lysosomal transmembrane protein SPNS1, whose loss leads to neurodegeneration-like disease in animal models, as critical for cell survival under free choline limitation. We find thatSPNS1loss leads to massive accumulation of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) within the lysosome. Mechanistically, we revealed that SPNS1 is required for the efflux of LPC species from the lysosome to enable their reesterification into choline-containing phospholipids in the cytosol. Using cell-based lipid uptake assays, we determine that SPNS1 functions as a proton gradient-dependent transporter of LPC. Collectively, our work defines a novel lysosomal phospholipid salvage pathway that is required for cell survival under conditions of choline limitation, and more broadly, provides a robust platform to deorphan lysosomal gene functions.
Lactate-derived HDAC6 Lactylation as a new target for neuronal protection in cerebral ischemic reperfusion injury
Authors: Cao Jun , Hong Zexuan , Zeng Fanning , Qin Zaisheng , Lin Miao , Wang Hao , Zuo Daming , Tao Tao 
Published: November 2022

AbstractLactylation is a newly found lactate-derived post-translational modification, which is firstly reported on histone protein lysine residues to regulate gene expression. Here, we provided evidence that higher serum lactate level was possibly associated with better prognosis in ischemic stroke patients. Meanwhile, inhibition of endogenous lactate increased the infarct volume and decreased protein pan-lactylation in the affected brain tissue in cerebral ischemia mice. We further demonstrated that downregulating lactylation level of Hdac6 (Histone Deacetylase 6) in neurons exacerbated ischemic neuronal injury. The underlying mechanisms involved Hdac6 lactylation disturbing calcium homeostasis through binding BiP (Binding immunoglobulin protein), an endoplasmic reticulum-related protein. Collectively, our findings identified a new effect of lactate for neuroprotection through Hdac6 lactylation during cerebral ischemic reperfusion injury which introduced a potential therapeutic approach against ischemic stroke.
Reactivating Positive Personality Traits During Sleep Promotes Positive Self-Referential Processing
Authors: Yao Ziqing , Xia Tao , Wei Jinwen , Zhang Zhiguo , Lin Xuanyi , Zhang Dandan , Qin Pengmin , Ma Yina , Hu Xiaoqing 
Published: November 2022

AbstractPositive self-view is evident by a bias in favor of positive self-referential processing, as individuals tend to endorse positive characteristics over negative ones when making self-judgments. While research suggests that a positivity bias can contribute to psychological well-being, it remains unclear how to enhance positive self-referential processing. Here, we reported an integrated training procedure that aimed at enhancing individuals’ positive self-referential processing. Specifically, participants engaged in a cue-approach training task (CAT) during wakefulness where they gave speeded motor responses to positive personality traits. In a subsequent nap, we unobtrusively re-played half of the trained positive traits during participants’ slow-wave sleep to reactivate memories associated with these positive traits (targeted memory reactivation, TMR). Upon awakening, we found that CAT+TMR enhanced participants’ positive self-referential processing, as evidenced by faster endorsement of positive traits. Further analysis revealed that this enhancement was associated with specific brainwave patterns during sleep: delta (1–4 Hz) traveling waves moving from posterior to anterior brain regions. These findings demonstrate the potential benefits of integrated wakeful cue-approach training and sleep-based memory reactivation in strengthening positive self-referential processing.
Inferring delays in partially observed gene regulatory networks
Authors: Hong Hyukpyo , Cortez Mark Jayson , Cheng Yu-Yu , Kim Hang Joon , Choi Boseung , Josić Krešimir , Kim Jae Kyoung 
Published: November 2022

AbstractMotivationCell function is regulated by gene regulatory networks (GRNs) defined by protein-mediated interaction between constituent genes. Despite advances in experimental techniques, we can still measure only a fraction of the processes that govern GRN dynamics. To infer the properties of GRNs using partial observation, unobserved sequential processes can be replaced with distributed time delays, yielding non-Markovian models. Inference methods based on the resulting model suffer from the curse of dimensionality.ResultsWe develop a simulation-based Bayesian MCMC method for the efficient and accurate inference of GRN parameters when only some of their products are observed. We illustrate our approach using a two-step activation model: An activation signal leads to the accumulation of an unobserved regulatory protein, which triggers the expression of observed fluorescent proteins. With prior information about observed fluorescent protein synthesis, our method successfully infers the dynamics of the unobserved regulatory protein. We can estimate the delay and kinetic parameters characterizing target regulation including transcription, translation, and target searching of an unobserved protein from experimental measurements of the products of its target gene. Our method is scalable and can be used to analyze non-Markovian models with hidden components.AvailabilityAccompanying code in R is available athttps://github.com/Mathbiomed/SimMCMC.Contactjaekkim@kaist.ac.krorkresimir.josic@gmail.comorcbskust@korea.ac.krSupplementary informationSupplementary data are available atBioinformaticsonline.
Parametric information about eye movements is sent to the ears
Authors: Lovich Stephanie N , King Cynthia D , Murphy David LK , Landrum Rachel , Shera Christopher A , Groh Jennifer M 
Published: November 2022

AbstractEye movements alter the relationship between the visual and auditory spatial scenes. Signals related to eye movements affect neural pathways from the ear through auditory cortex and beyond, but how these signals contribute to computing the locations of sounds with respect to the visual scene is poorly understood. Here, we evaluated the information contained in eye movement-related eardrum oscillations (EMREOs), pressure changes recorded in the ear canal that occur in conjunction with simultaneous eye movements. We show that EMREOs contain parametric information about horizontal and vertical eye displacement as well as initial/final eye position with respect to the head. The parametric information in the horizontal and vertical directions can be modelled as combining linearly, allowing accurate prediction of the EMREOs associated with oblique (diagonal) eye movements. Target location can also be inferred from the EMREO signals recorded during eye movements to those targets. We hypothesize that the (currently unknown) mechanism underlying EMREOs could impose a two-dimensional eye-movement related transfer function on any incoming sound, permitting subsequent processing stages to compute the positions of sounds in relation to the visual scene.Significance StatementWhen the eyes move, the alignment between the visual and auditory scenes changes. We are not perceptually aware of these shifts -- which indicates that the brain must incorporate accurate information about eye movements into auditory and visual processing. Here we show that the small sounds generated within the ear by the brain contain accurate information about contemporaneous eye movements in the spatial domain: the direction and amplitude of the eye movements could be inferred from these small sounds. The underlying mechanism(s) likely involve(s) the ear’s various motor structures, and could facilitate the translation of incoming auditory signals into a frame of reference anchored to the direction of the eyes and hence the visual scene.