bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Design of Brainstem Interfaces: Characterisation of Physiological Artefacts and Implications for Closed-loop Algorithms
Authors: Deli Alceste , Toth Robert , Zamora Mayela , Divanbeighi Zand Amir P. , Green Alexander L. , Denison Timothy 
Published: February 2023

AbstractSurgical neuromodulation through implantable devices allows for stimulation delivery to subcortical regions, crucial for symptom control in many debilitating neurological conditions. Novel closed-loop algorithms deliver therapy tailor-made to endogenous physiological activity, however rely on precise sensing of signals such as subcortical oscillations. The frequency of such intrinsic activity can vary depending on subcortical target nucleus, while factors such as regional anatomy may also contribute to variability in sensing signals. While artefact parameters have been explored in more ‘standard’ and commonly used targets (such as the basal ganglia, which are implanted in movement disorders), characterisation in novel candidate nuclei is still under investigation. One such important area is the brainstem, which contains nuclei crucial for arousal and autonomic regulation. The brainstem provides additional implantation targets for treatment indications in disorders of consciousness and sleep, yet poses distinct anatomical challenges compared to central subcortical targets. Here we investigate the region-specific artefacts encountered during activity and rest while streaming data from brainstem implants with a cranially-mounted device in two patients. Such artefacts result from this complex anatomical environment and its interactions with physiological parameters such as head movement and cardiac functions. The implications of the micromotion-induced artefacts, and potential mitigation, are then considered for future closed-loop stimulation methods.
LimoRhyde2: genomic analysis of biological rhythms based on effect sizes
Authors: Obodo Dora , Outland Elliot H. , Hughey Jacob J. 
Published: February 2023

AbstractGenome-scale data have revealed daily rhythms in various species and tissues. However, current methods to assess rhythmicity largely restrict their focus to quantifying statistical significance, which may not reflect biological relevance. To address this limitation, we developed a method called LimoRhyde2 (the successor to our method LimoRhyde), which focuses instead on rhythm-related effect sizes and their uncertainty. For each genomic feature, LimoRhyde2 fits a curve using a series of linear models based on periodic splines, moderates the fits using an Empirical Bayes approach called multivariate adaptive shrinkage (Mash), then uses the moderated fits to calculate rhythm statistics such as peak-to-trough amplitude. The periodic splines capture non-sinusoidal rhythmicity, while Mash uses patterns in the data to account for different fits having different levels of noise. To demonstrate LimoRhyde2’s utility, we applied it to multiple circadian transcriptome datasets. Overall, LimoRhyde2 prioritized genes having high-amplitude rhythms in expression, whereas a prior method (BooteJTK) prioritized “statistically significant” genes whose amplitudes could be relatively small. Thus, quantifying effect sizes using approaches such as LimoRhyde2 has the potential to transform interpretation of genomic data related to biological rhythms.
PCP4 immunoreactivity suggests the presence of hippocampal region CA2 in solitary, social and eusocial mole-rat species
Authors: Stöber Tristan M. , Oosthuizen Maria K. 
Published: February 2023

AbstractBecause African mole-rats express diverse social behaviors, they are prime candidates to study the effect of sociability on the evolution of brain circuits. This study compared the expression of Purkinje Cell Protein 4 (PCP4) in hippocampal slices of solitary Cape mole-rats, social Highveld mole-rats, and eusocial Damaraland and naked mole-rats. PCP4 is an established marker for pyramidal cells of hippocampal region CA2, a key structure for social memory and aggression. We observed prominent PCP4 immunoreactivity in the central part of thecornu Ammonisfor all mole-rat species. While further verification is required, these findings suggest the extend of CA2 does not drastically differ despite varying social behaviors. Future studies may use this work as a starting point to explore the relationship between environmental requirements and the functional role of CA2.
Auditory memory of complex sounds in sparsely distributed, highly correlated neurons in the auditory cortex
Authors: Kang HiJee , Kanold Patrick O. 
Published: February 2023

AbstractListening in complex sound environments requires rapid segregation of different sound sources e.g., speakers from each other, speakers from other sounds, or different instruments in an orchestra, and also adjust auditory processing on the prevailing sound conditions. Thus, fast encoding of inputs and identifying and adapting to reoccurring sounds are necessary for efficient and agile sound perception. This adaptation process represents an early phase of developing implicit learning of sound statistics and thus represents a form of auditory memory. The auditory cortex (ACtx) is known to play a key role in this encoding process but the underlying circuits and if hierarchical processing exists are not known. To identify ACtx regions and cells involved in this process, we simultaneously imaged population of neurons in different ACtx subfields using in vivo 2-photon imaging in awake mice. We used an experimental stimulus paradigm adapted from human studies that triggers rapid and robust implicit learning to passively present complex sounds and imaged A1 Layer 4 (L4), A1 L2/3, and A2 L2/3. In this paradigm, a frozen spectro-temporally complex ‘Target’ sound would be randomly re-occurring within a stream of random other complex sounds. We find distinct groups of cells that are specifically responsive to complex acoustic sequences across all subregions indicating that even the initial thalamocortical input layers (A1 L4) respond to complex sounds. Cells in all imaged regions showed decreased response amplitude for reoccurring Target sounds indicating that a memory signature is present even in the thalamocortical input layers. On the population level we find increased synchronized activity across cells to the Target sound and that this synchronized activity was more consistent across cells regardless of the duration of frozen token within Target sounds in A2, compared to A1. These findings suggest that ACtx and its input layers play a role in auditory memory for complex sounds and suggest a hierarchical structure of processes for auditory memory.
Bioinformatics of cyanophycin metabolism genes and characterization of promiscuous isoaspartyl dipeptidases that catalyze the final step of cyanophycin degradation
Authors: Sharon Itai , Schmeing T. Martin 
Published: February 2023

AbstractCyanophycin is a bacterial biopolymer used for storage of fixed nitrogen. It is composed of a backbone of L-aspartate residues with L-arginines attached to each of their side chains. Cyanophycin is produced by cyanophycin synthetase 1 (CphA1) using Arg, Asp and ATP, and is degraded in two steps. First, cyanophycinase breaks down the backbone peptide bonds, releasing β-Asp-Arg dipeptides. Then, these dipeptides are broken down into free Asp and Arg by enzymes with isoaspartyl dipeptidase activity. Two bacterial enzymes are known to possess promiscuous isoaspartyl dipeptidase activity: isoaspartyl dipeptidase (IadA) and isoaspartyl aminopeptidase (IaaA). We performed a bioinformatic analysis to investigate whether genes for cyanophycin metabolism enzymes cluster together or are spread around the microbial genomes. Many genomes showed incomplete contingents of known cyanophycin metabolizing genes. Cyanophycin synthetase and cyanophycinase are usually clustered together when recognizable genes for each are found within a genome. Cyanophycinase and isoaspartyl dipeptidase genes typically cluster within genomes lackingcphA1. About one-third of genomes with genes for CphA1, cyanophycinase and IaaA show these genes clustered together, while the proportion is around one-sixth for CphA1, cyanophycinase and IadA. We used X-ray crystallography and biochemical studies to characterize an IadA and an IaaA from two such clusters. The enzymes retained their promiscuous nature, showing that being associated with cyanophycin-related genes did not make them specific for β-Asp-Arg dipeptides derived from cyanophycin degradation.
Plant diversity in the diet of Costa Rican primates in contrasting habitats: a meta-analysis
Authors: Chaves Óscar M. , Morales-Cerdas Vanessa , Calderón-Quirós Jazmín , Azofeifa-Rojas Inés , Riba-Hernández Pablo , Solano-Rojas Daniela , Chaves-Cordero Catalina , Chacón-Madrigal Eduardo , Melin Amanda D. 
Published: February 2023

AbstractIn human-modified tropical landscapes, the survival of arboreal vertebrates, particularly primates, depends on their plant dietary diversity. Here, we assessed diversity of plants included in the diet of Costa Rican non-human primates, CR-NHP (i.e.Alouatta palliata palliata,Ateles geoffroyi,Cebus imitator, andSaimiri oerstedii) inhabiting different habitat types across the country. Specifically, we assessed by analyzing 37 published and unpublished datasets: (i) richness and dietary α-plant diversity, (ii) the β-diversity of dietary plant species and the relative importance of plant species turnover and nestedness contributing to these patterns, and (iii) the main ecological drivers of the observed patterns in dietary plant . Diet data were available for 34Alouatta, 16Cebus, 8Ateles, and 5Saimirigroups. Overall dietary plant species richness was higher inAlouatta(476 spp.), followed byAteles(329 spp.),Cebus(236 spp.), andSaimiri(183 spp.). However, rarefaction curves showed that α-diversity of plant species was higher inAtelesthan in the other three primate species. The γ-diversity of plants was 868 species (95% C.I.=829-907 species). The three most frequently reported food species for all CR-NHP wereSpondias mombin,Bursera simaruba, andSamanea saman. In general, plant species turnover, rather than nestedness, explained the dissimilarity in plant diet diversity (βsim> 0.60) of CR_NHP. Finally, primate species, habitat type (life zone and disturbance level) and, to a lesser degree, sampling effort were the best predictors of the dietary plant assemblages. Our findings suggest that CR-NHP diets were diverse, even in severely-disturbed habitats.
Structure Primed Embedding on the Transcription Factor Manifold Enables Transparent Model Architectures for Gene Regulatory Network and Latent Activity Inference
Authors: Tjärnberg Andreas , Beheler-Amass Maggie , Jackson Christopher A , Christiaen Lionel A , Gresham David , Bonneau Richard 
Published: February 2023

AbstractThe modeling of gene regulatory networks (GRNs) is limited due to a lack of direct measurements of regulatory features in genome-wide screens. Most GRN inference methods are therefore forced to model relationships between regulatory genes and their targets with expression as a proxy for the upstream independent features, complicating validation and predictions produced by modeling frameworks. Separating covariance and regulatory influence requires aggregation of independent and complementary sets of evidence, such as transcription factor (TF) binding and target gene expression. However, the complete regulatory state of the system,e.g. TF activity (TFA) is unknown due to a lack of experimental feasibility, making regulatory relations difficult to infer. Some methods attempt to account for this by modeling TFA as a latent feature, but these models often use linear frameworks that are unable to account for non-linearities such as saturation, TF-TF interactions, and other higher order features. Deep learning frameworks may offer a solution, as they are capable of modeling complex interactions and capturing higher-order latent features. However, these methods often discard central concepts in biological systems modeling, such as sparsity and latent feature interpretability, in favor of increased model complexity. We propose a novel deep learning autoencoder-based framework,StrUcture Primed Inference of Regulation using latent Factor ACTivity(SupirFactor), that scales to single cell genomic data and maintains interpretability to perform GRN inference and estimate TFA as a latent feature. We demonstrate that SupirFactor outperforms current leading GRN inference methods, predicts biologically relevant TFA and elucidates functional regulatory pathways through aggregation of TFs.
A hybrid method for discovering interferon-gamma inducing peptides in human and mouse
Authors: Dhall Anjali , Patiyal Sumeet , Raghava Gajendra P. S. 
Published: February 2023

AbstractA host-specific technique has been developed for annotating interferon-gamma (IFN-γ) inducing peptides, it is an updated version of IFNepitope. In this study, dataset used for developing prediction method contain experimentally validated 25492 and 7983 IFN-γ inducing peptides in human and mouse host, respectively. In initial phase, machine learning techniques have been exploited to develop classification model using wide range of peptide features. In most of the case, models based on extra tree perform better than other machine learning techniques. In case of peptide features, compositional feature particularly dipeptide composition performs better than one-hot encoding or binary profile. Our best machine learning based models achieved AUROC 0.89 and 0.83 for human and mouse host, respectively. In order to improve machine learning based models or alignment free models, we explore potential of similarity-based technique BLAST. Finally, a hybrid model has been developed that combine best machine learning based model with BLAST and achieved AUROC 0.90 and 0.85 for human and mouse host, respectively. All models have been evaluated on an independent/validation dataset not used for training or testing these models. Newly developed method performs better than existing method on independent dataset. The major objective of this study is to predict, design and scan IFN-γ inducing peptides, thus server/software have been developed (https://webs.iiitd.edu.in/raghava/ifnepitope2/).HighlightsAn updated method for predicting interferon-gamma (IFN-γ) inducing peptides.A wide range of features have been generated using Pfeature tool.Models were trained and tested on experimentally validated datasets.Hybrid models developed by combining machine-learning and BLAST.IFNepitope2 server is available to design subunit or peptide-based vaccines.
Mapping evidence on cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa- A Scoping Review Protocol
Authors: Dlamini Khululiwe , Moetlhoa Boitumelo , Turner Astrid , Maluleke Kuhlula , Mashamba-Thompson Tivani 
Published: February 2023

AbstractIntroductionInfections of the central nervous system are a considerable basis of mortality in people living with Human immunodeficiency virus (HIV), with progression to cryptococcal meningitis documented at around 15% of HIV-associated mortality globally, with nearly three-quarters occurring in the sub-Saharan Africa. Discoveries from previous studies preluded that mortality amid cryptococcal antigen (CrAg) positive persisted to be elevated than in CrAg negative persons. One feasible interpretation of this could be due to undiagnosed cryptococcus. Laboratory investigations towards prompt identification of cryptococcal disease prior to cryptococcal meningitis has progressed to point-of-care testing with high sensitivity and specificity as seen with the CrAg lateral flow assay screening to expedite treatment. The aim of the study is to map and translate evidence on CrAg infection among HIV-infected persons in sub-Saharan Africa (SSA).MethodologyThe proposed scoping review will be conducted using guidelines proposed by Arksey and O’Malley methodological framework and Levac et al advanced method. It will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews. A comprehensive literature search of studies published from the first relevant publication to 2022 will be conducted on multiple electronic databases. Additional sources (grey literature) will also be searched. The search strategy will be generated and implemented by the principal investigator with assistance from a subject specialist, and an information specialist. Two reviewers will screen eligible studies. The screening will be guided by an inclusion and exclusion criteria. The mixed method appraisal tool (MMAT) version 2018 will be used to appraise the quality of the empirical studies.DiscussionThe proposed scoping review will map and translate evidence on CrAg infection among HIV-infected persons in sub-Saharan Africa. Synthesising and sharing recent evidence in this area has potential to help guide future research and interventions aimed at improving the management of CrAg infection among HIV-infected persons in sub-Saharan Africa and other high HIV-burdened settings.
Accuracy and reliability of self-administered visual acuity tests: Systematic review of pragmatic trials
Authors: Thirunavukarasu Arun James , Hassan Refaat , Limonard Aaron , Savant Shalom Vitreous 
Published: February 2023

AbstractBackgroundRemote self-administered visual acuity (VA) tests have the potential to allow patients and non-specialists to assess vision without eye health professional input. Validation in pragmatic trials is necessary to demonstrate the accuracy and reliability of tests in relevant settings to justify deployment.MethodsA systematic review was undertaken in accordance with a preregistered protocol (CRD42022385045). The Cochrane Library, Embase, MEDLINE, and Scopus were searched. Screening was conducted according to the following criteria: (1) English languge; (2) primary research article; (3) visual acuity test conducted remotely; (4) no clinical administration of remote test; (5) accuracy or reliability of remote test analysed. There were no restrictions on trial participants. Quality assessment was conducted with QUADAS-2.ResultsOf 1227 identified reports, 10 studies were ultimately included. One study was at high risk of bias and two studies exhibited concerning features of bias; all studies were applicable. Three trials—of DigiVis, iSight Professional, and Peek Acuity—from two studies suggested that accuracy of the remote tests was comparable to clinical assessment. All other trials exhibited inferior accuracy, including conflicting results from a pooled study of iSight Professional and Peek Acuity. Two studies evaluated test-retest agreement—one trial provided evidence that DigiVis is as reliable as clinical assessment. The three most accurate tests required access to digital devices. Reporting was inconsistent and often incomplete, particularly with regards to describing methods and conducting statistical analysis.ConclusionsRemote self-administered VA tests appear promising, but further pragmatic trials are indicated to justify deployment at scale to facilitate patient or non-specialist led assessment which could augment teleophthalmology, non-specialist eye assessment, pre-consultation triage, and autonomous long-term monitoring of vision.
Prognostic impact of dynamic evolution in renal function among patients undergoing elective percutaneous coronary intervention
Authors: Xiang Yifei , Lin Xueqin , Cai Xiaoling , Zhang Liwei , Luo Manqing , Zeng Jilang , Guo Yansong , Lin Kai-Yang 
Published: February 2023

AbstractBackgroundPrevious studies have shown that chronic kidney disease(CKD) affected the long-term prognosis of patients underwent the elective percutaneous coronary intervention(EPCI). However, the prognostic impact in patients with the development of the contrast-associated acute kidney injury(CA-AKI) and recovery or progression of CA-AKI were controversial. For the moment, little attention has been paid to the relationship between the dynamic evolution of renal function and its prognosis.MethodsWe used three stages to characterize the dynamic evolution of renal function, namely the occurrence of CKD at baseline, the occurrence of CA-AKI in the postoperative period and the occurrence of post kindey injury(PKI) at 3 - 6 months postoperatively. Cardiac death and all-cause mortality were used as the endpoint of the study. PKI(+) was defined as CA-AKI not recovered or an increase in absolute serum creatinine (SCr) ≤0.3 mg/dl or a SCr relative increase in creatinine ≤ 50% after 3 - 6 months. PKI(-) was defined as CA-AKI recovered or SCr elevation not meeting the PKI(+) requirement.ResultsWe prospectively enrolled 2951 patients who underwent EPCI from 2012 to 2018. They were divided into three groups according to baseline CKD and CA-AKI: STAGE I[Unimpaired renal function group, CKD(-)/CA-AKI(-) (n=1247)], STAGE II[Partially impaired renal function group, IIa: CKD(-)/CA-AKI(+) (n=91) and IIb: CKD(+)/CA-AKI(-) (n=1472)] and STAGE III[severely impaired renal function group, CKD(+)/CA-AKI(+) (n=141)]. Subsequently, based on the occurrence of PKI, they were divided into six groups: STAGE I/PKI(-) (n=1212), STAGE I/PKI(+) (n=35), STAGE II/PKI(-) (n=1508), STAGE II/PKI(+) (n=55), STAGE III/PKI(-) (n=108), STAGE III/PKI(+) (n=33). In a mean follow-up period of 3.33± 1.39 years, we found that from STAGE I, STAGE II to STAGE III at baseline groups, the incidence of the primary outcome significantly increased. Meanwhile, from the baseline groups to the follow-up groups, the dynamic changes in renal function were observed. At the follow-uo groups, the occurrence of PKI did not affect the prognosis of patients in the STAGE I group(hazard ratio [HR] = 0.94, 95%CI: 0.15–8.11, p = 0.949) and the STAGE III group(hazard ratio [HR] = 1.19, 95%CI: 0.50–2.83 p = 0.689). However, for the STAGE II group (hazard ratio [HR] = 2.65, 95%CI: 1.42–4.94, p = 0.002), the development of PKI would lead to a poor prognosis for patients.ConclusionIn patients undergoing EPCI, the occurrence of CKD and CA-AKI affected the long-term prognosis of patients. The prognostic impact of the occurrence of PKI depended on the renal function of patients. In patients with unimpaired renal function or severely impaired renal function, the prognostic impact of PKI was negligible. However, in patients with partially impaired renal function, avoidance of PKI could beneficial for their long-term prognosis.