bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood biomarker profiles in young-onset neurocognitive disorders: a cohort study
Authors: Bhalala Oneil G. , Beamish Jessica , Eratne Dhamidhu , Summerell Patrick , Porter Tenielle , Laws Simon M. , Kang Matthew JY , Huq Aamira J. , Chiu Wei-Hsuan , Cadwallader Claire , Walterfang Mark , Farrand Sarah , Evans Andrew H. , Kelso Wendy , Churilov Leonid , Watson Rosie , Yassi Nawaf , Velakoulis Dennis , Loi Samantha M. 
Published: July 2024

AbstractINTRODUCTIONYoung-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the BeYOND (Biomarkers in Younger-Onset Neurocognitive Disorders) cohort, a study of individuals less than 65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses.METHODSSixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorised as either early-onset Alzheimer’s disease (EOAD, n=18), non-AD neurodegeneration (nAD-ND, n=23) or primary psychiatric disorders (PPD, n=24). Levels of neurofilament light chain, glial fibrillary acidic protein and phosphorylated-tau 181, apolipoprotein E genotype and late-onset AD polygenic risk scores were determined. Information-theoretic model selection identified discriminatory factors.RESULTSNeurofilament light chain, glial fibrillary acidic protein and phosphorylated-tau 181 levels were elevated in EOAD compared to other diagnostic categories. A multi-omic model selection identified that a combination of cognitive and blood biomarkers, but not the polygenic risk score, discriminated between EOAD and PPD (AUC≥0.975, 95% CI: 0.825-1.000). Phosphorylated-tau 181 alone significantly discriminated between EOAD and nAD-ND causes (AUC=0.950, 95% CI: 0.877-1.00).DISCUSSIONDiscriminating between EOAD, nAD-ND and PPD causes of young-onset neurocognitive symptoms is possible by combining cognitive profiles with blood biomarkers. These results support utilising blood biomarkers for the work-up of young-onset neurocognitive symptoms and highlight the need for the development of a young-onset AD-specific polygenic risk score.
Streamlined screening platforms lead to the discovery of pachysiphine synthase fromTabernanthe iboga
Authors: Kamileen Mohamed O. , Nakamura Yoko , Luck Katrin , Heinicke Sarah , Hong Benke , Colinas Maite , Lichman Benjamin R. , O’Connor Sarah E. 
Published: July 2024

SummaryPlant-specialized metabolism is largely driven by the oxidative tailoring of key chemical scaffolds catalyzed by cytochrome P450 (CYP450s) enzymes. The monoterpene indole alkaloids tabersonine and pseudo-tabersonine, found in the medicinal plantTabernanthe iboga, are extensively modified by oxidative reactions. Here we developed a streamlined screening strategy to screen the activity ofT. ibogaCYP450s inNicotiana benthamiana.Using multigene constructs encoding the biosynthesis of tabersonine and pseudo-tabersonine scaffolds, we set out to uncover the CYP450s responsible for oxidative transformations of these scaffolds. Our approach identified twoT. ibogacytochrome P450 enzymes: pachysiphine synthase (PS) and 16-hydroxy-tabersonine synthase (T16H). These enzymes catalyze an epoxidation and site-specific hydroxylation of tabersonine to produce pachysiphine and 16-OH-tabersonine, respectively. We further demonstrated that these genes produced the expected products when expressed inCatharanthus roseusflowers. This work provides new insights into the biosynthetic pathways of MIAs and underscores the utility ofN. benthamianaandC. roseusas platforms for the functional characterization of plant enzymes.
Endothelial Zmiz1 modulates physiological and pathophysiological angiogenesis during retinal development
Authors: Patel Nehal R , K C Rajan , Chiang Mark Y , Meadows Stryder M 
Published: July 2024

AbstractAngiogenesis is a highly coordinated process involving the control of various endothelial cell behaviors. Mechanisms for transcription factor involvement in the regulation of endothelial cell dynamics and angiogenesis have become better understood, however much remains unknown, especially the role of non-DNA binding transcriptional cofactors. Here, we show that Zmiz1, a transcription cofactor, is enriched in the endothelium and critical for embryonic vascular development, postnatal retinal angiogenesis, and pathological angiogenesis in oxygen induced retinopathy (OIR). In mice, endothelial cell-specific deletion ofZmiz1during embryogenesis led to lethality due to abnormal angiogenesis and vascular defects. Inducible endothelial cell-specific ablation ofZmiz1postnatally resulted in impaired retinal vascular outgrowth, decreased vascular density, and increased vessel regression. In addition, angiogenic sprouting in the superficial and deep layers of the retina was markedly reduced. Correspondingly, vascular sprouting in fibrin bead assays was significantly reduced in the absence of Zmiz1, while furtherin vitroandin vivoevidence also suggested deficits in EC migration. In agreement with the defective sprouting angiogenesis phenotype, gene expression analysis of isolated retinal endothelial cells revealed downregulation of tip-cell enriched genes upon inactivation ofZmiz1. Lastly, our study suggested that endothelial Zmiz1 is critical for intraretinal revascularization following hypoxia exposure in the OIR model. Taken together, these findings begin to define the previously unspecified role of endothelial Zmiz1 in physiological and pathological angiogenesis.
Leveraging Basecaller’s Move Table to Generate a Lightweight k-mer Model
Authors: Samarakoon Hiruna , Wan Yuk Kei , Parameswaran Sri , Göke Jonathan , Gamaarachchi Hasindu , Deveson Ira W. 
Published: July 2024

AbstractNanopore sequencing by Oxford Nanopore Technologies (ONT) enables direct analysis of DNA and RNA by capturing raw electrical signals. Different nanopore chemistries have varied k-mer lengths, current levels, and standard deviations, which are stored in k-mer models. Particularly in cases where official models are lacking or unsuitable for specific sequencing conditions, tailored k-mer models are crucial to ensure precise signal-to-sequence alignment and interpretation. The process of transforming raw signals into nucleotide sequences, known as basecalling, is a fundamental step in nanopore sequencing. In this study, we leverage the basecaller’s move table to create a lightweight denovo k-mer model for RNA004 chemistry. We showcase the effectiveness of our custom k-mer model through high alignment rates (97.48%) compared to larger default models. Additionally, our 5-mer model exhibits similar performance as the default 9-mer models in m6A methylation detection.
Genetic susceptibility to neurodevelopmental conditions associates with neonatal DNA methylation patterns in the general population: an individual participant data meta-analysis
Authors: Schuurmans I. K. , Smajlagic D. , Baltramonaityte V. , Malmberg A. L. K. , Neumann A. , Creasey N. , Felix J. F. , Tiemeier H , Pingault J. B. , Czamara D. , Raïkkönen K. , Page C. M. , Lyle R. , Havdahl A. , Lahti J. , Walton E. , Bekkhus M. , Cecil C. A. M. 
Published: July 2024

AbstractBackgroundAutism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) are highly heritable and linked to disruptions in foetal (neuro)development. While epigenetic processes are considered an important underlying pathway between genetic susceptibility and neurodevelopmental conditions, it is unclear (i) whether genetic susceptibility to these conditions is associated with epigenetic patterns, specifically DNA methylation (DNAm), already at birth; (ii) to what extent DNAm patterns are unique or shared across conditions, and (iii) whether these neonatal DNAm patterns can be leveraged to enhance genetic prediction of (neuro)developmental outcomes.MethodsWe conducted epigenome-wide meta-analyses of genetic susceptibility to ASD, ADHD, and schizophrenia, quantified using polygenic scores (PGSs) on cord blood DNAm, using four population-based cohorts (npooled=5,802), all North European. Heterogeneity statistics were used to estimate overlap in DNAm patterns between PGSs. Subsequently, DNAm-based measures of PGSs were built in a target sample, and used as predictors to test incremental variance explained over PGS in 130 (neuro)developmental outcomes spanning birth to 14 years.OutcomesIn probe-level analyses, SCZ-PGS associated with neonatal DNAm at 246 loci (p<9×10−8), predominantly in the major histocompatibility complex. Functional characterization of these DNAm loci confirmed strong genetic effects, significant blood-brain concordance and enrichment for immune-related pathways. 8 loci were identified for ASD-PGS (mapping toFDFT1andMFHAS1), and none for ADHD-PGS. Regional analyses indicated a large number of differentially methylated regions for all PGSs (SCZ-PGS: 157, ASD-PGS: 130, ADHD-PGS: 166). DNAm signals showed little overlap between PGSs. We found suggestive evidence that incorporating DNAm-based measures of genetic susceptibility at birth increases explained variance for several child cognitive and motor outcomes over and above PGS.InterpretationGenetic susceptibility for neurodevelopmental conditions, particularly schizophrenia, is detectable in cord blood DNAm at birth in a population-based sample, with largely distinct DNAm patterns between PGSs. These findings support an early-origins perspective on schizophrenia.FundingHorizonEurope; European Research CouncilAbstract Figure
Ocular Surface Microbiome: Influences of Physiological, Environmental, and Lifestyle Factors
Authors: Rizzuto Vincenzo , Settino Marzia , Stroffolini Giacomo , Covello Giuseppe , Vanags Juris , Naccarato Marta , Montanari Roberto , Rocha de Lossada Carlos , Mazzotta Cosimo , Adornetto Carlo , Rechichi Miguel , Ricca Francesco , Greco Gianluigi , Laganovska Guna , Borroni Davide 
Published: July 2024

AbstractPurposePurpose: The ocular surface (OS) microbiome is influenced by various factors and impacts ocular health. Understanding its composition and dynamics is crucial for developing targeted interventions for ocular diseases. This study aims to identify host variables, including physiological, environmental, and lifestyle (PEL) factors, that influence the ocular microbiome composition and establish valid associations between the ocular microbiome and health outcomes.MethodsThe 16S rRNA gene sequencing was performed on OS samples collected using eSwab. DNA was extracted, libraries prepared, and PCR products purified and analyzed. PEL confounding factors were identified, and a cross-validation strategy using various bioinformatics methods including Machine learning was used to identify features that classify microbial profiles.ResultsNationality, sport practice, and eyeglasses usage are significant PEL confounding factors influencing the eye microbiome. Alpha-diversity analysis showed higher microbial richness in Spanish subjects compared to Italian subjects and higher biodiversity in sports practitioners. Beta-diversity analysis indicated significant differences in microbial community composition based on nationality, age, sport, and eyeglasses usage. Differential abundance analysis identified several microbial genera associated with these PEL factors. ML approach confirmed the significance of nationality in classifying microbial profiles.ConclusionThis study underscores the importance of considering PEL factors when studying the ocular microbiome. Our findings highlight the complex interplay between environmental, lifestyle, and demographic factors in shaping the OS microbiome. Future research should further explore these interactions to develop personalized approaches for managing ocular health.Key PointsIdentify confounding factors influencing the ocular microbiome composition;Characterize the ocular surface microbiome;Analyse 16S rRNA gene sequencing data from ocular surface samples;Perform Diversity Analysis (i.e.; Alpha-diversity and Beta-diversity) and Difference Abundance Analysis;
Down regulation ofEngaseinCaenorhabditis elegansmay improve its stresses adaptivity
Authors: Lu Xinrong , Tong Yongliang , Wu Mengting , Lyu Shaoxian , Fan Jiale , Zheng Junyu , Zou Lin , Shen Danfeng , Rao Lin , Hou Linlin , Chen Cuiying , Cheng Xunjia , Sun Guiqin , Shao Zhiyong , Chen Li 
Published: July 2024

AbstractEndo-beta-N-acetylglucosaminidase (ENGASE) is one of the key enzymes involved in the regulation of structure and function of glycoproteins. It is conserved from prokaryotic to eukaryotic cells. Although their activitiesin vitroand applications have been well studied, the biological function of ENGASE remains to be illustrated. In this study, we analyzed the molecular and physiological function ofEngasefromCaenorhabditis eleganshomologeng-1(CeEngase). We found thatCeEngaseknockout or knockdown increased the environmental stresses adaptability, such as heat stress and osmotic stress. Preliminary glycomics analysis showed that the basement membrane proteins of extracellular matrix may be the main targets of CeENGASE. In addition, CeENGASE may selectively prefer to N2H7 glycans on glycoproteins. In conclusion, our data illustrated that the defection and/or down regulation ofCeEngasemay provide a beneficially adaptation for stresses.
Interhemispheric Connectivity of the Human Temporal Lobes
Authors: Binder Jeffrey R. , Giraldo-Chica Mónica , Mathis Jedediah , Tong Jia-Qing , Schoenrock Sidney , Arpinar Volkan , Heffernan Joseph , Muftuler L. Tugan 
Published: July 2024

AbstractMuch is known regarding the major white matter pathways connecting the right and left temporal lobes, which project through the posterior corpus callosum, the anterior commissure, and the dorsal hippocampal commissure. However, details about the spatial location of these tracts are unclear, including their exact course and proximity to cortical and subcortical structures, the spatial relations between corpus callosum and anterior commissure projections, and the caudal extent of transcallosal connections within the splenium. We present an atlas of these tracts derived from high angular resolution diffusion tractography maps, providing improved visualization of the spatial relationships of these tracts. The data show several new details, including branching of the transcallosal pathway into medial and lateral divisions, projections of the transcallosal pathway into the external capsule and claustrum, complex patterns of overlap and interdigitation of the transcallosal and anterior commissure tracts, distinct dorsal and ventral regions of the splenium with high tract densities, and absence of temporal lobe projections in the caudal third of the splenium. Intersection of individual tract probability maps with individual cortical surfaces were used to identify likely regions with relatively higher cortical termination densities. These data should be useful for planning surgical approaches involving the temporal lobe and for developing functional-anatomical models of processes that depend on interhemispheric temporal lobe integration, including speech perception, semantic memory, and social cognition.HighlightsInterhemispheric connections of the human temporal lobes were visualized using high angular resolution diffusion tensor imaging tractography.Results are displayed on serial orthogonal sections to reveal detailed spatial relationships.Corpus callosum projections through the splenium form distinct dorsal and ventral bundles and are absent from the caudal splenium.The transcallosal pathway consists of distinct medial and lateral divisions.The results reveal projections to the external capsule and claustrum not previously described.Transcallosal and anterior commissural pathways show complex patterns of overlap and interdigitation.Surface mapping revealed areas with relatively high density of projections to the cortical surface.
Universal chemical formula dependence of
ab initio
low-energy effective Hamiltonian in single-layer carrier-doped cuprate superconductors: Study using a hierarchical dependence extraction algorithm
Authors: Morée Jean-Baptiste , Arita Ryotaro 
Published: July 2024

We explore the possibility to control the superconducting transition temperature at optimal hole doping Tcopt in cuprates by tuning the chemical formula (CF). Tcopt can be theoretically predicted from the parameters of the low-energy effective Hamiltonian with one antibonding (AB) Cu3dx2−y2/O2pσ orbital per Cu atom in the CuO2 plane, notably the nearest-neighbor hopping amplitude |t1| and the ratio u=U/|t1|, where U is the onsite effective Coulomb repulsion. However, the CF dependence of |t1| and u is a highly nontrivial question. In this paper, we propose the universal dependence of |t1| and u on the CF and structural features in hole doped cuprates with a single CuO2 layer sandwiched between block layers. To do so, we perform extensive calculations of |t1| and u and analyze the results by employing a machine-learning method called hierarchical dependence extraction (HDE). The main results are (a) |t1| has a main-order dependence on the radii RX and RA of the apical anion X and cation A in the block layer. (|t1| increases when RX or RA decreases.) (b) u has a main-order dependence on the ionic charge ZX of X and the hole doping δ of the AB orbital. (u decreases when |ZX| increases or δ increases.) We elucidate and discuss the microscopic mechanism of items (a) and (b). We demonstrate the predictive power of the HDE by showing the consistency between items (a) and (b) and results from previous works. The present results provide a basis for optimizing superconducting properties in cuprates and possibly akin materials. Also, the HDE method offers a general platform to identify dependencies between physical quantities.

Published by the American Physical Society
2024
Extreme heterogeneity in the microrheology of lamellar surfactant gels analyzed with neural networks
Authors: Watts Moore Owen , Lewis Conor , Ross Thomas , Waigh Thomas Andrew , Korabel Nickolay , Mendoza Cesar 
Published: July 2024

The heterogeneity of the viscoelasticity of a lamellar gel network based on cetyl-trimethylammonium chloride and cetostearyl alcohol was studied using particle-tracking microrheology. A recurrent neural network (RNN) architecture was used for estimating the Hurst exponent, H, on small sections of tracks of probe spheres moving with fractional Brownian motion. Thus, dynamic segmentation of tracks via neural networks was used in microrheology and it is significantly more accurate than using mean square displacements (MSDs). An ensemble of 414 particles produces a MSD that is subdiffusive in time, t, with a power law of the form t0.74±0.02, indicating power law viscoelasticity. RNN analysis of the probability distributions of H, combined with detailed analysis of the time-averaged MSDs of individual tracks, revealed diverse diffusion processes belied by the simple scaling of the ensemble MSD, such as caging phenomena, which give rise to the complex viscoelasticity of lamellar gels.

Published by the American Physical Society
2024
Social network analysis for identifying the significant drivers of off-site construction adoption in Egypt
Authors: Shaker Rana Ahmed , Elbeltagi Emad , Motawa Ibrahim , Elmasoudi Islam , Elnabwy Mohamed T. 
Published: July 2024

PurposeRapid urbanization and the shortcomings of traditional construction methods motivate construction professionals to explore faster and more sustainable approaches such as off-site construction (OSC). Thus, the purpose of this paper is to identify the drivers influencing OSC adoption and to explore the key drivers of its widespread adoption in Egypt.Design/methodology/approachA comprehensive global literature review was performed initially to develop an up-to-date list of OSC adoption drivers, which was confirmed in the Egyptian context through a pilot study. Then, social network analysis (SNA) was utilized to determine the most influential drivers as well as shortlist them to construct the final questionnaire survey. A total of 57 stakeholders in the Egyptian construction industry responded. Lastly, the relative importance index (RII) was calculated to rank the drivers, revealing the key drivers.FindingsThe results revealed that higher productivity, improving project quality control, shortening construction time, improving product quality and improving supervision and inspection are the top five drivers. On the contrary, government policies and regulations is the least significant driver.Originality/valueThis research contributes to the body of knowledge by introducing a comprehensive, up-to-date list of drivers, which helps the stakeholders gain a better understanding of the driving enablers of adopting OSC generally and helps Egyptian stakeholders make more informed decisions about its implementation specifically.
Improved air gap permeance modelling for single-slice magnetic equivalent circuits of skewed induction motors
Authors: Desenfans Philip , Gong Zifeng , Vanoost Dries , Gryllias Konstantinos , Boydens Jeroen , De Gersem Herbert , Pissoort Davy 
Published: July 2024

Purpose
When rotor and stator teeth are close, the connecting air gap flux tube's cross-sectional area exceeds the tooth overlap area. This flux fringing effect is disregarded in the air gap permeance calculation of single-slice magnetic equivalent circuits (MECs) of electric motors with skewed rotors. This paper aims to extend an air gap permeance calculation method incorporating flux fringing for unskewed rotors to skewed and radially eccentric rotors.

Design/methodology/approach
Assuming axial independence, the unskewed air gap permeance is rotated according to the skew and integrated along the axial dimension, resulting in a first method. The integral is approximated analytically, resulting in a second method. Results are compared to a commonly used reference method and validated using a non-linear finite element method (FEM) simulation.

Findings
The proposed methods provide better alignment with the FEM validation compared to the reference method for skewed rotors and common rotor eccentricity, i.e. below 50% of the air gap length. The analytical method is shown to be competitive with the reference method regarding computational time cost.

Originality/value
Two novel air gap permeance methods are proposed for single-slice MECs with skewed rotors. Their characteristics are discussed and validated.