bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations
Authors: Aguilar Ruth , Cruz Angeline , Jiménez Alfons , Almuedo Alex , Roca Saumell Carme , Gigante Lopez Marina , Gasch Oriol , Falcó Gemma , Jiménez-Lozano Ana , Martínez-Perez Angela , Sanchez-Collado Consol , Tedesco Andrea , Carlos López Manuel , Jesús Pinazo María , Leonel Thais , Bisoffi Zeno , Färnert Anna , Dobaño Carlota , Requena-Méndez Ana 
Published: July 2023

AbstractBackgroundIn this study we have evaluated the performance of a novel multiplex serological assay with a panel of 8 antigens able to simultaneously detect IgG to HIV, chronic hepatitis B (HBV) and C (HCV), Chagas disease, strongyloidiasis and schistosomiasis as a screening tool for imported diseases in migrants.MethodsSix panels of 40 well-characterized, anonymized serum samples from individuals with the respective confirmed infections (n=240) were used as positive controls to assess the sensitivity of the multiplex assay. One panel of 40 sera from non-infected subjects were used to estimate the seropositivity cutoffs for each infection, and 32 additional non-infected sera were used as negative controls to estimate the sensitivity and specificity for each serology. The multi-infection screening test was validated in a prospective cohort of 48 migrants from endemic areas to assess assay performance.The sensitivity of the Luminex assay was calculated as the proportion of positive test results over all positive samples by the primary reference test. The specificity was calculated using 32 negative samples. Uncertainty was quantified with 95% confidence intervals (CI) using receiver operating characteristic analyses.ResultsThe sensitivity /specificity were 100%/100% for HIV (p41 antigen), 97.5%/100% (AUC:0.99,[95%CI: 0.96-1.00]) for HBV (core antigen), 100%/100% (AUC:1.00,[95%CI 1.00-1.00]) for HCV (core antigen), 92.5%/90.6%,(AUC:0.96,[95%CI 0.91-1.00]) for strongyloidiasis (31-kDa recombinant antigen (NIE)), 97.5%/100%,(AUC:0.97,[95%CI 0.93-1]) for schistosomiasis (combined serpinSchistosoma mansoniandS.haematobiumantigens) and 92.5%/96.9%,(AUC: 0.96,[95%CI 0.92-1.00]) for Chagas disease ([T.cruzikinetoplastid membrane protein-11 (KMP11)]).In the migrant cohort, antibody response to KMP11 correctly identified 14/14(100%) individuals with Chagas disease, whereas HBV-core antigen and NIE-Strongyloides correctly identified 91.7% and 86.4% individuals with chronic hepatitis B and strongyloidiasis respectively.ConclusionsWe have developed a new 8-plex Luminex assay that is robust and accurate, and could facilitate the implementation of screening programmes for imported diseases in migrant populations.
A control engineering perspective on the advantages of efference copies
Authors: Campbell Benjamin P. , Lin Huai-Ti , Krapp Holger G. 
Published: July 2023

AbstractBiological systems have evolved to perform high-speed voluntary movements whilst maintaining robustness and stability. This paper examines a control architecture based on the principles of efference copies found in insect sensorimotor control which we call the fully-separable-degrees-of-freedom (FSDoF) controller. Within a control engineering framework, we benchmark the advantages of this control architecture against two common engineering control schemes: a pure feedback (PFB) controller and a Smith predictor (SP). Our study identifies three advantages of the FSDoF for biology. It is advantageous in controlling systems with sensor delays, and it can effectively handle noise. Thirdly, it allows biological sensors to increase their operating range. We evaluate the robustness of the FSDoF controller and show that it achieves improved performance with equal stability margins and robustness. Finally, we discuss variations of the FSDoF which theoretically provide the same performance.
Signaling specificity and kinetics of the human metabotropic glutamate receptors
Authors: McCullock Tyler W. , Cardani Loren P. , Kammermeier Paul J. 
Published: July 2023

AbstractMetabotropic glutamate receptors (mGluRs) are obligate dimer G protein coupled receptors that can all function as homodimers. Here, each mGluR homodimer was examined for its G protein coupling profile using a BRET based assay that detects the interaction between a split YFP-tagged Gβ1γ2and a Nanoluc tagged free Gβγsensor, MAS-GRK3-ct-NLuc with 14 specific G⍺ proteins heterologously expressed, representing each family. Canonically, the group II and III mGluRs (2&3, and 4, 6, 7&8, respectively) are thought to couple to Gi/oexclusively. In addition, the group I mGluRs (1&5) are known to couple to the Gq/11family, and generally thought to also couple to the PTX-sensitive Gi/ofamily; some reports have suggested Gscoupling is possible as cAMP elevations have been noted. In this study, coupling was observed with all 8 mGluRs through the Gi/oproteins, and only mGluR1&5 through Gq/11, and perhaps surprisingly, not G14. None activated any Gsprotein. Interestingly, coupling was seen with the group I and II, but not the group III mGluRs to G16. Slow but significant coupling to Gzwas also seen with the group II receptors.
The brain hierarchically represents the past and future during multistep anticipation
Authors: Tarder-Stoll Hannah , Baldassano Christopher , Aly Mariam 
Published: July 2023

AbstractMemory for temporal structure enables both planning of future events and retrospection of past events. We investigated how the brain flexibly represents extended temporal sequences into the past and future during anticipation. Participants learned sequences of environments in immersive virtual reality. Pairs of sequences had the same environments in a different order, enabling context-specific learning. During fMRI, participants anticipated upcoming environments multiple steps into the future in a given sequence. Temporal structure was represented in the hippocampus and across higher-order visual regions (1) bidirectionally, with graded representations into the past and future and (2) hierarchically, with further events into the past and future represented in successively more anterior brain regions. In hippocampus, these bidirectional representations were context-specific, and suppression of far-away environments predicted response time costs in anticipation. Together, this work sheds light on how we flexibly represent sequential structure to enable planning over multiple timescales.
Temporal sensitivity for achromatic and chromatic flicker across the visual cortex
Authors: Gentile Carlyn Patterson , Spitschan Manuel , Taskin Huseyin O. , Bock Andrew S. , Aguirre Geoffrey K. 
Published: July 2023

AbstractThe retinal ganglion cells (RGCs) receive different combinations of L, M, and S cone inputs and give rise to one achromatic and two chromatic post-receptoral channels. Beyond the retina, RGC outputs are subject to filtering and normalization along the geniculo-striate pathway, ultimately producing the properties of human vision. The goal of the current study was to determine temporal sensitivity across the three post-receptoral channels in subcortical and cortical regions involved in vision. We measured functional magnetic resonance imaging (MRI) responses at 7 Tesla from three participants (two males, one female) viewing a high-contrast, flickering, spatially-uniform wide field (~140°). Stimulus flicker frequency varied logarithmically between 2 and 64 Hz and targeted the L+M+S, L–M, and S–[L+M] cone combinations. These measurements were used to create temporal sensitivity functions of primary visual cortex (V1) across eccentricity, and spatially averaged responses from lateral geniculate nucleus (LGN), V2/V3, hV4, and V3A/B. Functional MRI responses reflected known properties of the visual system, including higher peak temporal sensitivity to achromatic vs. chromatic stimuli, and low-pass filtering between the LGN and V1. Peak temporal sensitivity increased across levels of the cortical visual hierarchy. Unexpectedly, peak temporal sensitivity varied little across eccentricity within area V1. Measures of adaptation and distributed pattern activity revealed a subtle influence of 64 Hz achromatic flicker in area V1, despite this stimulus evoking only a minimal overall response. Comparison of measured cortical responses to a model of integrated retinal output to our stimuli demonstrates that extensive filtering and amplification is applied to post-retinal signals.Significance StatementWe report the temporal sensitivity of human visual cortex across the three canonical post-receptoral channels from central vision to the far periphery. Functional MRI measurements of responses from the LGN, V1, and higher visual cortical areas demonstrate modification of temporal sensitivity across the visual hierarchy. This includes amplification of chromatic signals between the LGN and V1, and an increase in peak temporal sensitivity in visual areas beyond V1. Within V1, we find a surprising stability of peak temporal sensitivity in the periphery for all three post-receptoral directions. Comparison of our results to a model of retinal output demonstrates the presence of substantial post-retinal filtering, yielding greater uniformity of responses across area V1 than would be predicted from unmodified retinal signals.
The mouse dorsal peduncular cortex encodes fear memory
Authors: Cardoso Rodrigo Campos , Desa Zephyr R. , Fitzgerald Brianna L. , Moore Alana , Duhon Jace , Landar Victoria A. , Clem Roger L. , Cummings Kirstie A. 
Published: July 2023

SummaryThe rodent medial prefrontal cortex (mPFC) is a locus for both the promotion and suppression (e.g. extinction) of fear and is composed of four anatomically distinct subregions, including anterior cingulate 1 (Cg1), prelimbic (PL), infralimbic (IL), and the dorsal peduncular (DP) cortex. A vast majority of studies have focused on Cg1, PL, and IL. The Cg1 and PL have been implicated in the promotion of fear, while the IL has been linked to a role in the suppression, or extinction, of fear. Due to its anatomical location ventral to IL, the DP has been hypothesized to function as a fear-suppressing brain region however, no studies have explicitly tested its role in this function or in the regulation of memory generally. Moreover, some studies have pointed towards a dichotomous role for ventral mPFC in the dual suppression and promotion of fear, but the mechanisms underlying these opposing observations remains unclear. Here, we provide evidence that the DP paradoxically functions as a cued fear-encoding brain region and plays little to no role in fear memory extinction. By using a combination of cFos immunohistochemistry, whole-cell brain slice electrophysiology, fiber photometry, and activity-dependent neural tagging, we demonstrate that DP neurons exhibit learning-related plasticity, acquire cue-associated activity across learning and memory retrieval, and that DP neurons activated by learning are preferentially reactivated upon fear memory retrieval. Further, optogenetic activation and silencing of fear learning-related DP neural ensembles drives the promotion and suppression of freezing, respectively. Overall, these data suggest that the DP plays an unexpected role in fear memory encoding. More broadly, our results reveal new principles of organization across the dorsoventral axis of the mPFC.
Activation of the Aryl Hydrocarbon Receptor in Endothelial Cells Impairs Ischemic Angiogenesis in Chronic Kidney Disease
Authors: Palzkill Victoria R. , Tan Jianna , Yang Qingping , Morcos Juliana , Laitano Orlando , Ryan Terence E. 
Published: July 2023

ABSTRACTRationaleChronic kidney disease (CKD) is a strong risk factor for peripheral artery disease (PAD) that is associated with worsened clinical outcomes. CKD leads to accumulation of tryptophan metabolites that associate with adverse limb events in PAD and are ligands of the aryl hydrocarbon receptor (AHR) which may regulate ischemic angiogenesis.ObjectivesTo test if endothelial cell-specific deletion of the AHR (AHRecKO) alters ischemic angiogenesis and limb function in mice with CKD subjected to femoral artery ligation.FindingsMale AHRecKOmice with CKD displayed better limb perfusion recovery and enhanced ischemic angiogenesis compared to wildtype mice with CKD. However, the improved limb perfusion did not result in better muscle performance. In contrast to male mice, deletion of the AHR in female mice with CKD had no impact on perfusion recovery or angiogenesis. Using primary endothelial cells from male and female mice, treatment with indoxyl sulfate uncovered sex-dependent differences in AHR activating potential and RNA sequencing revealed wide ranging sex-differences in angiogenic signaling pathways.ConclusionEndothelium-specific deletion of the AHR improved ischemic angiogenesis in male, but not female, mice with CKD. There are sex- dependent differences inAhractivating potential within endothelial cells that are independent of sex hormones.
SharePro: an accurate and efficient genetic colocalization method accounting for multiple causal signals
Authors: Zhang Wenmin , Lu Tianyuan , Sladek Robert , Li Yue , Najafabadi Hamed S. , Dupuis Josée 
Published: July 2023

AbstractMotivationColocalization analysis is commonly used to assess whether two or more traits share the same genetic signals identified in genome-wide association studies (GWAS), and is important for prioritizing targets for functional follow-up of GWAS results. Existing colocalization methods can have suboptimal performance when there are multiple causal variants in one genomic locus.ResultsWe propose SharePro to extend the COLOC framework for colocalization analysis. Share-Pro integrates linkage disequilibrium (LD) modelling and colocalization assessment by grouping correlated variants into effect groups. With an efficient variational inference algorithm, posterior colocalization probabilities can be accurately estimated. In simulation studies, SharePro demonstrated increased power with a well-controlled false positive rate at a low computational cost. Through a challenging case of the colocalization analysis of the circulating abundance of R-spondin 3 (RSPO3) GWAS and estimated bone mineral density GWAS, we demonstrated the utility of SharePro in identifying biologically plausible colocalized signals.Availability and ImplementationThe SharePro software for colocalization analysis is openly available athttps://github.com/zhwm/SharePro_colocand the analysis conducted in this study is available athttps://github.com/zhwm/SharePro_coloc_analysis.
Dietary n-3 PUFA enhances DMI in transition cows by regulating taste transduction gene expression in liver associated with rumen microbial alteration
Authors: Sun Xiaoge , Guo Cheng , Wang Qianqian , Zhang Yan , Wang Zhonghan , Cao Zhijun , Wang Wei , Li Shengli 
Published: July 2023

AbstractWe hypothesised that the addition of n-3 polyunsaturated fatty acids (PUFAs) in the diet could affect gene expression in the liver and have beneficial effects on the recovery of cows in the transition phase. A total of 30 multiparous non-lactating Holstein dairy cows (35 days before expected calving) were randomly fed a diet with either 1% dry matter (DM) of hydrogenated fatty acid (C16:00 enriched; CON) or 3.5% DM of extruding flaxseed (n-3 enriched; HN3). Parity, body weight (BW), body condition score (BCS) and milk yield were 2.6 ± 1.2, 757.5 ± 65.8 kg, 3.3 ± 0.2 and 10,286.5 ± 1464.8 kg/d (mean ± SD), respectively, at the beginning of the experiment. The relative abundance ofBacteroidota(P= 0.047) andSpirochaetota(P= 0.091) was higher and that ofPatescibacteria(P= 0.076) was lower in the HN3 group than in the CON group on prepartum day 4. The DMI of cows was positively correlated with the abundance of bacteria in the rumen (Spirochaetota: r = 0.871,P< 0.001;Bacteroidota: r = 0.896,P< 0.001) and the differential expression of genes involved in taste transduction (ACSL1: r = 0.673,P< 0.001; PLIN4: r = 0.632,P< 0.01; CPT1A: r = 0.694,P< 0.001). These results suggest that dietary n-3 PUFA at an appropriate concentration can promote DMI recovery by upregulating the expression of these genes and maintaining the balance of the rumen microbiota.
Microstructure-Based Nuclear Lamina Constitutive Model
Authors: Mostafazadeh Nima , Peng Zhangli 
Published: July 2023

AbstractThe nuclear lamina is widely recognized as the most crucial component in providing mechanical stability to the nucleus. However, it is still a significant challenge to model the mechanics of this multilayered protein network. We developed a constitutive model of the nuclear lamina network based on its microstructure, which accounts for the deformation phases at the dimer level, as well as the orientational arrangement and density of lamin filaments. Instead of relying on homology modeling in the previous studies, we conducted molecular simulations to predict the force-extension response of a highly accurate lamin dimer structure obtained through X-ray diffraction crystallography experimentation. Furthermore, we devised a semi-flexible worm-like chain extension-force model of lamin dimer as a substitute, incorporating phases of initial stretching, uncoiling of the dimer coiled-coil, and transition of secondary structures. Subsequently, we developed a 2D network continuum model for the nuclear lamina by using our extension-force lamin dimer model and derived stress resultants. By comparing with experimentally measured lamina modulus, we found that the lamina network has sharp initial strain-hardening behavior. This also enabled us to carry out finite element simulations of the entire nucleus with an accurate microstructure-based nuclear lamina model. Finally, we conducted simulations of transendothelial transmigration of a nucleus and investigated the impact of varying network density and uncoiling constants on the critical force required for successful transmigration. The model allows us to incorporate the microstructure characteristics of the nuclear lamina into the nucleus model, thereby gaining insights into how laminopathies and mutations affect nuclear mechanics.
HLA-DR4Pred2: an improved method for predicting HLA-DRB1*04:01 binders
Authors: Patiyal Sumeet , Dhall Anjali , Kumar Nishant , Raghava Gajendra P. S. 
Published: July 2023

ABSTRACTHLA-DRB1*04:01 is associated with many disease that include sclerosis, arthritis, diabetes and Covid19. Thus, it is important to scan binders of HLA-DRB1*04:01 in an antigen to develop immunotherapy, vaccine and protection against these diseases. One of the major limitations of existing methods for predicting with HLA-DRB1*04:01 binders is that these methods trained on small datasets. This study present a method HLA-DR4Pred2 developed on a large dataset contain 12676 binders and equal number of non-binders. It is an improved version of HLA-DR4Pred, which was trained on a small dataset contain only 576 binders and equal number of binders. All models in this study were trained, optimized and tested on 80% of data called training datasets using five-fold cross-validation; final models were evaluated on 20% of data called validation/independent dataset. A wide range of machine learning techniques have been employed to develop prediction models and achieved maximum AUC of 0.90 and 0.87 on validation dataset using composition and binary profile features respectively. The performance of our composition based model increased from 0.90 to 0.93 when combined with BLAST search. In addition, we also developed our models on alternate or realistic dataset that contain 12676 binders and 86300 non-binders and achieved maximum AUC 0.99. Our method perform better than existing methods when we compare the performance of our best model with performance of existing methods on validation dataset. Finally, we developed standalone and online version of HLA-DR4Pred2 for predicting, designing and virtual scanning of HLA- DRB1*04:01(https://webs.iiitd.edu.in/raghava/hladr4pred2/;https://github.com/raghavagps/hladr4pred2).Key PointsHLADR4Pred2.0 is an update of HLADR4PredPredict the binding or non-binding peptides for MHC-Class II allele HLA- DRB1*04:01Used alignment free and alignment based hybrid approachMotifs which are highly specific to HLA-DRB1*04:01 bindersBenchmark the performance of the other existing methods with HLADR4Pred2.0Author’s BiographySumeet Patiyal is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, IndiaAnjali Dhall is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.Nishant Kumar is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, IndiaGajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.
Continuous respiratory rate monitoring using photoplethysmography technology in patients with Obstructive Sleep Apnea
Authors: Gehring J.M. , Niel L.C. Saeijs-van , ten Bosch-Paniagua L.P , Frank M.H. 
Published: July 2023

AbstractPurposeRespiratory rate is an important physiological parameter whose abnormality could be, in the presence of other suggestive symptoms, supportive of a diagnose of various serious illnesses. Photoplethysmography (PPG) in wearable sensors potentially plays an important role in early disease detection by making respiratory rate measurements more accessible. We investigated the accuracy of a new non-invasive, continuous, wrist-worn and wireless monitoring PPG device (Corsano CardioWatch 287) in measuring respiratory rate (RR) and heart rate (HR) at rest.MethodsSubjects with and without diagnosed Obstructive Sleep Apnea (OSA) underwent simultaneous, continuous PPG and home sleep apnea testing (HSAT) for one night. We assessed the PPG sensor’s measurement accuracy by calculating root-mean-square accuracy (Arms) and by performing Bland Altman and correlation analysis. Subgroups were defined based on skin type, hair density, age, BMI, gender and OSA severity.ResultsIn 26 participants a total of 31083 RR and 38693 HR measurement pairs were obtained. For RR measurements, Armswas 0.60 breaths per minute (brpm). Correlation was high (r = 0.964 (95%CI 0.963 - 0.965)) and 95% Limits of Agreement (LoA) were −1.28 to 1.71 brpm (mean bias −0.14 brpm). For HR measurements, Armswas 0.95 beats per minute (bpm). Correlation was similarly high (r = 0.996 (95%CI 0.996 - 0.996) and 95% LoA were – 2.09 to 1.17 bpm (mean bias −0.46 bpm). Results were comparable across all subgroups, without significant difference in RR accuracy between subjects with and without diagnosed OSA. In free-living conditions, Armswas 2.43 brpm and 95% LoA were −5.00 to 4.47 brpm (mean bias −0.27 brpm).ConclusionWe showed that the Corsano Cardiowatch 287 using PPG technology can monitor continuous RR and HR with high accuracy in healthy subjects as well as in patients diagnosed with OSA. We conclude that wearable devices like these enable new and more accessible ways to measure health, ultimately improving healthcare delivery. The trial was registered in the ISCRTN registry under referenceISRCTN13965929.