bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Hypodensity Detection Tool improves clinician identification of hypodensity on non-contrast CT in stroke patients
Authors: Dos Santos A , Visser M , Lin L , Bivard A , Churilov L , Parsons M 
Published: November 2023

AbstractBackgroundIn acute stroke, identifying early changes (parenchymal hypodensity) on non-contrast CT (NCCT) can be challenging. We aimed to identify whether the accuracy of clinicians in detecting acute hypodensity in ischaemic stroke patients on a non-contrast CT is improved with the use of an automated HDT algorithm using MRI-DWI as the gold standard.MethodsThe study employed a case-crossover within-clinician design, where clinicians were tasked with identifying hypodensity lesions on NCCT scans for five a priori selected patient cases, before and after viewing the HDT. The DICE Similarity Coefficient (DICE score) was the primary measure of accuracy. Statistical analysis compared DICE scores with and without HDT using mixed-effects linear regression, with individual NCCT scans and clinicians as nested random effects.ResultsThe HDT had a mean DICE score of 0.62 for detecting hypodensity across all NCCT scans and clinicians overall mean DICE score of 0.33 (SD 0.31) before HDT implementation and 0.40 (SD 0.27) after implementation. HDT use was associated with an increase of 0.07 (95% CI: 0.02-0.11, p=0.003) in DICE score accounting for individual scan and clinician effects. For scans with small lesions, clinicians achieved a mean increase in DICE score of 0.08 (95% CI: 0.02, 0.13, p=0.004) following HDT use. In a subgroup of 15 trainees, DICE score improved with HDT implementation (mean difference in DICE 0.09 [95% CI: 0.03, 0.14, p=0.004]).ConclusionsThe Hypodensity Detection Tool (HDT) has potential to enhance accuracy of detecting hypodensity in acute stroke diagnosis, especially for smaller lesions, and notably for less experienced clinicians.
High-throughput single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenicStaphylococcus aureuscommunities
Authors: Hira Jonathan , Singh Bhupender , Halder Tirthankar , Mahmutovic Anel , Ajayi Clement , Sekh Arif Ahmed , Hegstad Kristin , Johannessen Mona , Lentz Christian S. 
Published: November 2023

AbstractIsogenic bacterial cell populations are phenotypically heterogenous and may include subpopulations of antibiotic tolerant or heteroresistant cells. The reversible nature of these phenotypes and lack of biomarkers to differentiate functionally different, but morphologically identical cells is a challenge for research and clinical detection. To overcome this, we present ‘CellularPhenotypicProfiling and backTracing (CPPT)’, a flexible fluorescence-activated cell sorting platform, that uses optical probes to visualize and quantify cellular traits and connects the resulting phenotypic profile with a cell’s experimentally determined fate in single cell-derived growth and antibiotic susceptibility analysis. By applying CPPT onStaphylococcus aureuspopulations we recorded phenotypic signatures for dormant cells, exposed microanatomy-independent bimodal growth patterns in colony-derived cells, and revealed different culturability of single cells on solid compared to liquid media. We demonstrate that vancomycin-bodipyFL marks cellular subpopulations with increased likelihood to survive antibiotic exposure, showcasing the value of CPPT for discovery of clinically relevant biomarkers.
Characterizing constitutive promoters across the Proteobacteria
Authors: Schuster Layla , Mejia Catalina , Rodriguez Lidimarie Trujillo , Kairalla Emily , Reisch Christopher R. , Chevrette Marc G. , Dias Raquel 
Published: November 2023

AbstractAlthough research on promoters has spanned decades, the precise prediction of promoter activity from DNA sequence remains a challenge even in model organisms. Recent literature has identified important differences in the core sequence of σ70promoters across classes of Proteobacteria as well as a lack of transferability when promoters are moved from host to host. Currently, there is a need for synthetic constitutive promoters spanning a range of expression levels in species outside ofEscherichia coli.Additionally, characterization data defining behavior of the same promoter across multiple species would be extremely valuable to the field. Here, we analyzed promoter activity in three classes of Proteobacteria, which enabled us to better understand the sequence elements correlated with a strong promoter in different hosts. In doing so, we identified and characterized constitutive promoters spanning a range of expression in these species for community use and described the portability of a subset of these promoters as they were moved between hosts. These promoter libraries have broad applications as predictable genetic tools to control gene expression in diverse species (1–3). This work adds to the toolkit for gene expression in non-model bacteria and is a step towards the larger goal of accurate promoter prediction in a given host from ade novosequence.
Targeting editing of tomatoSPEECHLESScis-regulatory regions generates plants with altered stomatal density in response to changing climate conditions
Authors: Nir Ido , Budrys Alanta , Smoot N. Katherine , Erberich Joel , Bergmann Dominique C. 
Published: November 2023

AbstractFlexible developmental programs enable plants to customize their organ size and cellular composition. In leaves of eudicots, the stomatal lineage produces two essential cell types, stomata and pavement cells, but the total numbers and ratio of these cell types can vary. Central to this flexibility is the stomatal lineage initiating transcription factor, SPEECHLESS (SPCH). Here we show, by multiplex CRISPR/Cas9 editing ofSlSPCH cis-regulatory sequences in tomato, that we can identify variants with altered stomatal development responses to light and temperature cues. Analysis of tomato leaf development across different conditions, aided by newly-created tools for live-cell imaging and translational reporters of SlSPCH and its paralogues SlMUTE and SlFAMA, revealed the series of cellular events that lead to the environmental change-driven responses in leaf form. Plants bearing the novel SlSPCH variants generated in this study are powerful resources for fundamental and applied studies of tomato resilience in response to climate change.Significance statementPlants can change their shape, size and cellular composition in response to environmental cues. Here, by precise gene editing of a core stomatal development regulator gene in tomato, we generate new alleles with enhanced or dampened responses to light and temperature cues. Combined with live imaging of development, we show the genetic and cellular pathways that contribute to customization of the leaf epidermis, and how this could lead to better climate-adapted varieties.
Temporal Insights into Molecular and Cellular Responses during rAAV Production in HEK293T Cells
Authors: Patra Alok Tanala , Tan Evan , Kok Yee Jiun , Ng Say Kong , Bi Xuezhi 
Published: November 2023

AbstractThe gene therapy field is actively pursuing cost-effective, large-scale production of recombinant adeno-associated virus (rAAV) vectors for therapeutic applications, which demand high dosages. Enhanced yield is essential but presents technical and cost challenges. Strategies like suspension cell culture, transfection optimization, and cultivation conditions have shown moderate success but fall short for large-scale applications. In this study, we explore the host cell proteome of HEK293T cell lines used for AAV2 production under different transfection conditions (standard, sub-optimal, optimal) using SWATH-MS. To understand molecular and cellular mechanisms, we created a tailored spectral library for HEK293T-AAV interactions. Our gene ontology and pathway analysis revealed significant protein expression variations, particularly in processes related to cellular homeostasis, metabolic regulation, vesicular transport, ribosomal biogenesis, and cellular proliferation under optimal transfection conditions. These conditions increased rAAV titre by 50% compared to standard protocols. Furthermore, we identified alterations in host cell proteins crucial for AAV mRNA stability and gene translation, particularly regarding AAV capsid transcripts in optimal transfection conditions. This study provides insights into cellular mechanisms during rAAV production in HEK293T cells and offers potential advancements in scalability and cost-efficiency for gene therapy vector production.SignificanceGenerating AAV is challenging and the amount produced is limited, despite the success of gene therapy. Thus, it is necessary to enhance the productivity of host cells through various engineering techniques. The replication and transduction of viruses cause numerous modifications to the host cell’s proteome. Viruses exploit the processes of the host cell, influencing the availability, post-translational adjustments, associations, or placement of its proteins during the replication/growth cycle. Comprehending the fluctuations in biological processes during AAV replication is essential to grasping how virus-host relations shape the result of infection and viral protein expression.
Paradoxical dominant negative activity of an immunodeficiency-associated activatingPIK3R1variant
Authors: Tomlinson Patsy R. , Knox Rachel , Perisic Olga , Su Helen C. , Brierley Gemma V. , Williams Roger L. , Semple Robert K. 
Published: November 2023

AbstractPIK3R1encodes three regulatory subunits of class IA phosphoinositide 3-kinase (PI3K), each associating with any of three catalytic subunits, namely p110α, p110β or p110δ. ConstitutionalPIK3R1mutations cause diseases with a genotype-phenotype relationship not yet fully explained: heterozygous loss-of-function mutations cause SHORT syndrome, featuring insulin resistance and short stature attributed to reduced p110α function, while heterozygous activating mutations cause immunodeficiency, attributed to p110δ activation and known as APDS2. Surprisingly, APDS2 patients do not show features of p110α hyperactivation, but do commonly have SHORT syndrome-like features, suggesting p110α hypofunction. We sought to investigate this. In dermal fibroblasts from an APDS2 patient, we found no increased PI3K signalling, with p110δ expression markedly reduced. In preadipocytes, the APDS2 variant was potently dominant negative, associating with Irs1 and Irs2 but failing to heterodimerise with p110α. This attenuation of p110α signalling by a p110δ-activating PIK3R1 variant potentially explains co-incidence of gain-of-function and loss-of-functionPIK3R1phenotypes.
A mitochondrial carrier transports glycolytic intermediates to link cytosolic and mitochondrial glycolysis in the human gut parasiteBlastocystis
Authors: Pyrihová Eva , King Martin S. , King Alannah C. , Toleco M. Rey , van der Giezen Mark , Kunji Edmund R.S. 
Published: November 2023

AbstractStramenopiles form a clade of diverse eukaryotic organisms, including multicellular algae, the fish and plant pathogenic oomycetes, such as the potato blightPhytophthora,and the human intestinal protozoanBlastocystis. In most eukaryotes, glycolysis is a strictly cytosolic metabolic pathway that converts glucose to pyruvate, resulting in the production of NADH and ATP. In contrast, stramenopiles have a branched glycolysis in which the enzymes of the pay-off phase are located in both the cytosol and the mitochondrial matrix. Here, we identify a mitochondrial carrier inBlastocystisthat can transport glycolytic intermediates, such as dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, across the mitochondrial inner membrane, linking the cytosolic and mitochondrial branches of glycolysis. Comparative analyses with the phylogenetically-related human mitochondrial oxoglutarate carrier (SLC25A11) and dicarboxylate carrier (SLC25A10) show that the glycolytic intermediate carrier has lost its ability to transport the canonical substrates malate and oxoglutarate.Blastocystislacks several key components of oxidative phosphorylation required for the generation of mitochondrial ATP, such as complexes III and IV, ATP synthase and ADP/ATP carriers. The presence of the glycolytic pay-off phase in the mitochondrial matrix generates ATP, which powers energy-requiring processes, such as macromolecular synthesis, as well as NADH, used by mitochondrial complex I to generate a proton motive force to drive the import of proteins and molecules. Given its unique substrate specificity and central role in carbon and energy metabolism, the carrier for glycolytic intermediates identified here represents a specific drug and pesticide target against stramenopile pathogens, which are of great economic importance.
Dissecting unique and common variance across body and brain health indicators using age prediction
Authors: Beck Dani , de Lange Ann-Marie G. , Gurholt Tiril P. , Voldsbekk Irene , Maximov Ivan I. , Subramaniapillai Sivaniya , Schindler Louise , Hindley Guy , Leonardsen Esten H. , Rahman Zillur , van der Meer Dennis , Korbmacher Max , Linge Jennifer , Leinhard Olof D. , Kalleberg Karl T. , Engvig Andreas , Sønderby Ida , Andreassen Ole A. , Westlye Lars T. 
Published: November 2023

AbstractAgeing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses inter-individual heterogeneity in the multisystem ageing process. Using machine-learning regression models on the UK Biobank dataset (N = 32,593, age range 44.6-82.3, mean age 64.1 years), we first estimated tissue-specific brain age for white and gray matter based on diffusion and T1-weighted magnetic resonance imaging (MRI) data, respectively. Next, bodily health traits including cardiometabolic, anthropometric, and body composition measures of adipose and muscle tissue from bioimpedance and body MRI were combined to predict ‘body age’. The results showed that the body age model demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. The correlation between body age and brain age predictions was 0.62 for the T1 and 0.64 for the diffusion-based model, indicating a degree of unique variance in brain and bodily ageing processes. Bayesian multilevel modelling carried out to quantify the associations between health traits and predicted age discrepancies showed that higher systolic blood pressure and higher muscle-fat infiltration were related to older-appearing body age compared to brain age. Conversely, higher hand-grip strength and muscle volume were related to a younger-appearing body age. Our findings corroborate the common notion of a close connection between somatic and brain health. However, they also suggest that health traits may differentially influence age predictions beyond what is captured by the brain imaging data, potentially contributing to heterogeneous ageing rates across biological systems and individuals.
The role of maternal secretor status and human milk oligosaccharides on early childhood development: A systematic review and meta-analysis
Authors: Mulinge Martin M. , Abisi Hellen K. , Kabahweza Hellen M. , Okutoyi Lydia , Wamalwa Dalton C. , Nduati Ruth W. 
Published: November 2023

ABSTRACTBreast milk is the gold standard of infant nutrition, delivering nutrients and bioactive molecules as needed to support optimal infant growth and neurodevelopment. Increasing evidence links the human milk oligosaccharides (HMOs) to these early childhood development milestones. In this PRISMA-compliant systematic review and meta-analysis, we summarised evidence on HMOs and infant brain development, physical growth, and cognitive development. In addition, we compared HMO concentrations between secretor and non-secretor mothers. Searches in PubMed, Scopus, and Web of Science yielded 245 articles, 27 of which were included in the systematic review and 12 in the meta-analysis. The meta-analysis revealed a substantial between-study heterogeneity, I2= 97.3%. The pooled effect was 0.21 (95% CI, −0.41 - 0.83), p = 0.484, indicating that secretors had higher HMO concentrations, though this difference was not statistically significant. At one month of age, 2’FL, 3FL, and 3’SL play an important role in brain maturation and thus play a critical role in cognitive development. Secretors secrete higher concentrations of 2’FL and 3’SL, explaining the benefits to infants of secretor mothers. Growth velocity was correlated to fucosylated and sialylated HMO concentrations, with lower concentrations linked to stunting. In conclusion, evidence from the systematically reviewed articles indicates that HMOs are important for a child’s early development, but the extent to which they have an impact is dependent on maternal secretor status.
Does an effective audit committee influence firm performance? –The moderation role of knowledge intensity
Authors: Singhania Abhisheck Kumar , Panda Nagari Mohan 
Published: November 2023

Purpose
This study aims to examine the relationship between audit committee (AC) effectiveness and firm performance (FP) with the moderation of knowledge intensity while observing the varying effect of each AC characteristic’s influence on its effectiveness.

Design/methodology/approach
This study examines 133 companies covering five years from 2016 to 2020 using the partial least squares-structural equation model and weighing AC effectiveness-related characteristics through multiple regression between AC characteristics and the AC effectiveness construct.

Findings
The results indicate that the knowledge intensity of the firms negatively influences the relationship between their AC effectiveness and FP, implying that the ACs are not sophisticated enough to monitor the knowledge component of the firm’s assets. Among AC characteristics, six attributes have a significant positive impact, two have a negative impact and three have no significant influence on AC effectiveness while influencing FP.

Research limitations/implications
Apart from guiding the regulators, managers and other stakeholders to choose an appropriate mix of AC characteristics for enhancing FP, the study contributes to the existing literature by providing evidence that ACs are ineffective in monitoring the knowledge assets of the company compared to physical assets.

Originality/value
This study is pioneering in investigating the moderation role of knowledge intensity on the relationship between AC effectiveness and FP. While providing a comprehensive and holistic view of AC effectiveness by considering 11 AC characteristics’ individual as well as aggregate effects on FP, it removes the obsolescence of earlier research in the Indian context owing to the latest regulatory reforms.
A numerical and experimental study of a buoy interacting with waves
Authors: Núñez Aedo Jonathan , Cruchaga Marcela A. , Storti Mario A. 
Published: November 2023

Purpose
This paper aims to report the study of a fluid buoy system that includes wave effects, with particular emphasis on validating the numerical results with experimental data.

Design/methodology/approach
A fluid–solid coupled algorithm is proposed to describe the motion of a rigid buoy under the effects of waves. The Navier–Stokes equations are solved with the open-source finite volume package Code Saturne, in which a free-surface capture technique and equations of motion for the solid are implemented. An ad hoc experiment on a laboratory scale is built. A buoy is placed into a tank partially filled with water; the tank is mounted into a shake table and subjected to controlled motion that promotes waves. The experiment allows for recording the evolution of the free surface at the control points using the ultrasonic sensors and the movement of the buoy by tracking the markers by postprocessing the recorded videos. The numerical results are validated by comparison with the experimental data.

Findings
The implemented free-surface technique, developed within the framework of the finite-volume method, is validated. The best-obtained agreement is for small amplitudes compatible with the waves evolving under deep-water conditions. Second, the algorithm proposed to describe rigid-body motion, including wave analysis, is validated. The numerical body motion and wave pattern satisfactorily matched the experimental data. The complete 3D proposed model can realistically describe buoy motions under the effects of stationary waves.

Originality/value
The novel aspects of this study encompass the implementation of a fluid–structure interaction strategy to describe rigid-body motion, including wave effects in a finite-volume context, and the reported free-surface and buoy position measurements from experiments. To the best of the authors’ knowledge, the numerical strategy, the validation of the computed results and the experimental data are all original contributions of this work.
Clearance compatibility and design principle of the single-structured hybrid gas-magnetic bearing
Authors: Liu Qing , Wang Li , Feng Ming 
Published: November 2023

Purpose
This paper aims to study the clearance compatibility of active magnetic bearing (AMB) and gas bearing (GB) to achieve a single-structured hybrid gas-magnetic bearing (HGMB), which uses a single bearing structure to realize both the functions of gas bearing and magnetic bearing.

Design/methodology/approach
Because the radial clearance size of the AMB is typically ten times larger than that of the GB, radial clearance compatibility of GB and AMB needs to maximize the radial clearance of GB by adjusting structural parameters. Parametric analysis of structural parameters of GB is explored. Furthermore, a general structural design principle based on static analysis, rotordynamic performance and system stability is established for the single-structured HGMB.

Findings
Load capacity is vastly reduced due to the enlarged radial clearance of the GB. A minimum clearance needs to be ensured by increasing the bearing diameter or width to compensate for the reduced load capacity, yet indirectly raising the bearing load. Increased bearing load is conducive to stability, yet it raises the risk of rotor abrasion. In addition, excessively large bearing diameter leads to system instability, and inappropriate bearing width affects critical speeds. A general structural design principle is established and the designed HGMB–rotor processes optimal performances.

Originality/value
A single-structured HGMB is proposed to address the urgent demand for high-speed, cryogenic turboexpanders with frequent starts/stops. This design applies a single-bearing structure to realize the characteristics of both GB and AMB, greatly simplifying the implementation, reducing air friction loss and raising critical speeds. This paper provides a fresh perspective on the development of cryogenic turboexpanders for hydrogen liquefaction. It theoretically validates the feasibility and provides a design guide for a single-structured HGMB system.