bluuebunny/crossref_metadata_2025 huggingface dataset:
The atmospheric pressure capillary plasma jet is well-suited to supply H2O2for plasma-driven biocatalysis
Authors: Dirks Tim , Stoesser Davina , Schüttler Steffen , Hollmann Frank , Golda Judith , Bandow Julia E.
Published: January 2025

Plasma-generated H2O2can be used to fuel biocatalytic reactions that require H2O2as co-substrate such as the conversion of ethylbenzene to (R)-1-phenylethanol ((R)-1-PhOl) catalyzed by unspecific peroxygenase fromAgrocybe aegerita(rAaeUPO). Immobilization was recently shown to protect biocatalysts from inactivation by highly reactive plasma-produced species, however, H2O2supply by the employed plasma sources (µAPPJ and DBD) was limiting for rAaeUPO performance. In this study we evaluated a recently introduced capillary plasma jet for suitability to supply H2O2in situ. H2O2production was modulated by varying the water concentration in the feed gas, providing a greater operating window for applications in plasma-driven biocatalysis. In a static system after 80 min of biocatalysis, a turnover number of 44,199 mol(R)-1-PhOlmol-1rAaeUPOwas achieved without significant enzyme inactivation. By exchanging the reaction solution every 5 min, a total product yield of 122 µmol (R)-1-PhOl was achieved in 700 min run time, resulting in a total turnover number of 174,209 mol(R)-1-PhOlmol-1rAaeUPO. We conclude that the capillary plasma jet, due to its flexibility regarding feed gas, admixtures, and power input, is well-suited forin situH2O2generation for plasma-driven biocatalysis tailoring to enzymes with high H2O2turnover.
The Interplay Between Cell-cell Signaling and Negative Feedback Reduces Population Noise While Enhancing Single-cell Variability
Authors: Ren Xinying
Published: January 2025

Negative feedback is a well-known mechanism for attenuating noise and enhancing robustness in biological systems. When coupled with cell-cell signaling, it provides a strategy for achieving population-level control in multicellular systems. While cell-cell signaling alone tends to reduce cell-to-cell variability by averaging fluctuations across cells, its interplay with negative feedback can produce contrasting effects on noise regulation at single-cell and population levels. Therefore, to design population-level controllers that achieve robust behaviors with attenuated noise, a systematically understanding of how different noise sources impact cell gene expressions at these levels become a critical challenge. Here, we investigate noise regulation in a quorum sensing-based negative feedback system, focusing on two extrinsic noise sources: process noise from target gene dynamics and measurement noise from quorum sensing dynamics. Our results reveal that signal-based negative feedback significantly reduces process noise at the population level, especially for dynamic noise. However, at the single-cell level, it enhances variability, with increased noise levels under faster signal diffusion and higher population density. In contrast, measurement noise is consistently attenuated at both single-cell and population levels through the coupled cell-cell signaling and negative feedback, under conditions of faster diffusion and higher density.
Multi-Omics Analysis for Identifying Cell-Type-Specific Druggable Targets in Alzheimer’s Disease
Authors: Liu Shiwei , Cho Min Young , Huang Yen-Ning , Park Tamina , Chaudhuri Soumilee , Rosewood Thea Jacobson , Bice Paula J , Chung Dongjun , Bennett David A. , Ertekin-Taner Nilüfer , Saykin Andrew J , Nho Kwangsik
Published: January 2025

Background

Analyzing disease-linked genetic variants via expression quantitative trait loci (eQTLs) is important for identifying potential disease-causing genes. Previous research prioritized genes by integrating Genome-Wide Association Study (GWAS) results with tissue- level eQTLs. Recent studies have explored brain cell type-specific eQTLs, but they lack a systematic analysis across various Alzheimer’s disease (AD) GWAS datasets, nor did they compare effects between tissue and cell type levels or across different cell type-specific eQTL datasets. In this study, we integrated brain cell type-specific eQTL datasets with AD GWAS datasets to identify potential causal genes at the cell type level.

Methods

To prioritize disease-causing genes, we used Summary Data-Based Mendelian Randomization (SMR) and Bayesian Colocalization (COLOC) to integrate AD GWAS summary statistics with cell-type-specific eQTLs. Combining data from five AD GWAS, three single-cell eQTL datasets, and one bulk tissue eQTL meta-analysis, we identified and confirmed both novel and known candidate causal genes. We investigated gene regulation through enhancer activity using H3K27ac and ATAC-seq data, performed protein-protein interaction and pathway enrichment analyses, and conducted a drug/compound enrichment analysis with the Drug Signatures Database (DSigDB) to support drug repurposing for AD.

Results

We identified 27 candidate causal genes for AD using cell type-specific eQTL datasets, with the highest numbers in microglia, followed by excitatory neurons, astrocytes, inhibitory neurons, oligodendrocytes, and oligodendrocyte precursor cells (OPCs).PABPC1emerged as a novel astrocyte-specific gene. Our analysis revealed protein-protein interaction (PPI) networks for these causal genes in microglia and astrocytes. We found the “regulation of aspartic-type peptidase activity” pathway being the most enriched among all the causal genes. AD-risk variants associated with candidate causal genePABPC1is located near or within enhancers only active in astrocytes. We classified the genes into three drug tiers and identified druggable interactions, with imatinib mesylate emerging as a key candidate. A drug-target gene network was created to explore potential drug targets for AD.

Conclusions

We systematically prioritized AD candidate causal genes based on cell type- specific molecular evidence. The integrative approach enhances our understanding of molecular mechanisms of AD-related genetic variants and facilitates the interpretation of AD GWAS results.
A prospective cohort study to assess if alcohol intake measured by routine pregnancy self-report predicts developmental concerns uncovered by routine health visitor screening of children at 30 months of age
Authors: Tappin David , Mackay Daniel , Reynolds Lucy , Fitzgerald Niamh
Published: January 2025

Background

Stigmatized behaviours are often underreported, especially in pregnancy, making them challenging to address. The Alcohol and Child Development Study (ACDS) seeks to inform prevention of foetal alcohol harm, linking self-report as well as a maternal blood alcohol biomarker with child developmental outcomes.

Methods

Maternity records from all pregnant women in the study city who presented for maternity care during the 12-month period June 2017 – June 2018 were transferred to the safe data facility creating the baseline cohort. Health Visitor routinely recorded child developmental screening data collected when the offspring were 30 months of age were transferred and linked to the cohort. Anonymous analysis was performed to assess associations between self-reported alcohol intake collected at maternity presentation with child development concerns and looked after by the local authority status of offspring at 30 months of age. Chi2 tests of association were used.

Results

14919 maternity records were transferred and 10876 could be linked to developmental screening data collected at 30 months of age. As expected self-reported current alcohol use after conception measured at presentation to maternity care was associated with offspring being looked after by the local authority (chi2=7.85, p=0.005) at age 30 months. 6.6% of children in care were attributable to self-report of current alcohol use during pregnancy. Developmental outcomes were generally inversely associated with self-report of current alcohol use notably concern regarding Social Development (chi2=4.08, p=0.043) and Speech, Language or Communication Development (chi2=4.37, p=0.037).

Conclusions

Explanation for this unexpected inverse relationship may relate to known miss-representation of alcohol intake from maternal self-report (the risk) or inaccurate assessment of offspring development at 30 months (the outcome). However self-report of current intake at maternity presentation prompts an alcohol intervention which if effective might explain the anomalous findings.
Mendelian randomization studies: a metric for quality evaluation
Authors: Rosas-Chavez Fiorella , Merriman Tony R.
Published: January 2025

Background

Mendelian randomization (MR) is a genetic epidemiological method used to infer causal relationships between exposures and outcomes. Its application in hyperuricemia and gout has grown exponentially owing to the ready availability of summary statistics from genome-wide association studies and the ease of applying the two-sample MR technique. However indications of poor study quality suggest the need for systematic evaluation.

Objective

This study evaluated the quality of two-sample MR studies on hyperuricemia and gout and developed a scoring system to help reviewers and readers assess their quality and validity.

Methods

A systematic review was conducted on 86 two-sample MR studies published between 2016 and 2024. Studies were assessed using a scoring system encompassing study design, statistical methods, result interpretation, and adherence to STROBE-MR guidelines. Trends in quality over time were analyzed using regression models.

Results

Study quality scores ranged from 0 to 19, with a mean of 9.1 and median of 11, demonstrating wide variability. High-quality studies adhered to MR assumptions, used independent datasets, and conducted replication analyses, while lower-quality studies often failed to correct the p-value when needed, test for confounders, address dataset overlap or report study power. Despite the increased publication of MR studies, overall quality not improved over time.

Conclusion

There is variability in two-sample MR study quality. Our proposed scoring system offers a practical framework for evaluating MR studies, aiding researchers and clinicians in identifying robust findings while promoting higher methodological standards.
Development and evaluation of a behavioral intervention to reduce household plastic waste burning in rural Guatemala: Study protocol for Ecolectivos, a cluster-randomized community trial
Authors: Thompson Lisa M. , Raheel Hina , Lovvorn Amy E. , Hengstermann-Artiga Mayari , Lopez Maria Renee , Ramirez Alex , Barr Dana Boyd , Higgins Melinda , McCracken John P. , Saikawa Eri , Handley Margaret
Published: January 2025

Objective

Household waste burning, especially of plastics, is a major, but unaddressed environmental and health hazard in countries that lack infrastructure to properly manage waste. This study will implement village-level community working groups that aim to reduce household plastic waste burning and improve health-related quality of life in women of reproductive age in rural Guatemala.

Methods

Using a type 1 hybrid-effectiveness-implementation study design, we will randomize 16 rural villages in Jalapa, Guatemala and randomly select 400 women of reproductive age (25 in each village) who report burning plastic trash as a primary form of waste disposal to participate. In eight intervention villages, we will conduct 12-week community working groups to implement alternatives to burning plastic that are achievable over the subsequent 9 months. We will use the Behavior Change Wheel and RE-AIM, two implementation science frameworks, and a mixed-methods approach, to refine, implement, and evaluate community-initiated interventions that address plastic waste. At baseline, 4 and 12 months, we will measure personal exposures to fine particulate matter and black carbon, and urinary biomarkers of exposure (e.g., bisphenols, phthalates, polycyclic aromatic hydrocarbons, and volatile organic compounds). We will use filter-based 1,3,5-Triphenylbenzene, a known tracer of plastic incineration, to quantify emissions estimates of air pollutants due to plastic burning. Based on plastic waste reductions in intervention villages, we will assess regional impacts of pollutant emissions reduction, using a 3D chemical transport model. This study was registered atClinicalTrials.gov(NCT05130632) on November 23, 2021.

Significance

Our findings will be incorporated into community-driven public health actions to develop programs in other local contexts. This project has direct benefit not only to those residing in Guatemala, but potentially in other areas where open waste burning contributes to air pollutants both regionally and globally.

Contributions to the literature

The Ecolectivos project will engage communities to co-create sustainable alternatives to burning household plastic waste.

Research will be refined during the formative phase, working groups will address behavior change during the main trial, and results will be disseminated using village-level fairs to introduce alternatives to burning plastic in control villages.

This work will expand the evidence on barriers and enablers to implementing alternatives to burning plastic using the capability, opportunity, and motivation domains for key behaviors (guided by the Behavior Change Wheel framework) and focusing on reach and potential for scale-up (guided by RE-AIM framework).
Transcranial Magnetic Stimulation Measures of Corticospinal Excitability in Black and Hispanic/Latino People with Painful Peripheral Neuropathy
Authors: Wong Marlon L. , McTeague Lisa , Gonzalez Gabriel , Gonzalez Juan , Bolanos Jessica , Hosein Peter J. , Cabral Danylo F. , Fried Peter J.
Published: January 2025

This study aims to provide preliminary descriptive data on transcranial magnetic stimulation (TMS) measures obtained in Black and Hispanic/Latino individuals with chronic painful peripheral neuropathy (PN), including those with chemotherapy-induced peripheral neuropathy (CIPN) and diabetic neuropathy (DN). CIPN and DN share similar neuropathic symptoms and underlying physiological mechanisms, in particular altered central nervous system processing. TMS is a non-invasive technique that can assess corticospinal excitability and the function of GABAergic and glutamatergic pathways, potentially serving as a diagnostic tool for PN. This secondary analysis utilized data from a pilot randomized sham-controlled trial of transcutaneous auricular vagus nerve stimulation (taVNS) in people with PN. TMS measures, including resting motor threshold (RMT), unconditioned MEP amplitude (spTMS), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were assessed at baseline over 2 separate visits. Test-retest reliability was evaluated, and changes in TMS measures following transcutaneous auricular vagus nerve stimulation were analyzed. Baseline TMS measures showed no significant differences between CIPN and DN groups. The study found good test-retest reliability for TMS measures, with ICC values between 0.73 and 0.87 for all TMS measures. Post taVNS, neuropathic pain symptoms improved, with a slight decrease in ICF. Overall, TMS measures demonstrated good reliability in this sample of Black and Hispanic/Latino individuals with PN, and these findings provide valuable preliminary data for future studies aimed at establishing the psychometric properties and diagnostic utility of TMS measures in PN.
A priority not guided by policy? A scooping review of policy and strategic framework on Maternal Waiting Homes
Authors: Mwansa Melvin Kunda , Chimpinde Kafiswe , Naidoo Mergan
Published: January 2025

Introduction

Maternal Waiting Homes (MWHs) are lodgings located near health facilities where women await their delivery date and be transferred to a health facility shortly before delivery or earlier should complications arise. They are a critical strategy to improve maternal health outcomes, as they been identified as a tool for reducing maternal and perinatal mortality, especially in low-resourced countries. However, they are limited countries with deliberate policies to promote their implementation. This study aimed to review the policy and strategic framework of modern maternal waiting homes in Africa and Zambia.

Methods

We searched published, unpublished, and grey literature from the following sources: Google Scholar, CINAHL, PubMed, Scopus, Medline, and ResearchGate. Initial search between the 25thand 27thMarch 2024 and the final search was re-run on December 18, 2024. We used relevant synonyms and keywords (such as policy on MWHs, strategies on MWHs, National Development Plans, strategic plans, Health policies, and initiatives on MWHs in developing countries or middle- and low-income countries in the English language. The study further reviewed policies, strategies, development plans, and health strategic plans that facilitated the promotion of maternal health in Zambia.

Results

Database search yielded a total of ninety-four (94) items. Eighteen (18) additional items were located through hand-searching reference at the Zambia National Archives Centre. Ten (10) articles described MWH policies, strategies, and implementation guidelines from the seven (7) countries. From the Zambia National Archives Centre, nine (9) documents comprised policies, national development plans and strategic plans obtained through the national archives centre. Only one country (Timor-Leste) had a deliberate policy on maternal waiting homes. Zambia does not have a policy or strategy in place that promotes maternal waiting homes.

Conclusion

Like in many other African countries, In Zambia, no strategic policy has been implemented to promote maternal waiting homes. While MWHs are acknowledged in various strategic health plans and some policies, they are not consistently prioritised or adequately funded. countries, including Zambia must have MWHs policy that should employ deliberate strategies to reduce maternal and newborn morbidities and mortalities.
Spherical Code of Retinal Orientation-Selectivity Enables Decoding in Ensembled and Retinotopic Operation
Authors: Laniado Dimitrios D. , Maron Yariv , Gemmer John A. , Sabbah Shai
Published: January 2025

Selectivity to orientations of edges is seen at the earliest stages of visual processing, in retinal orientation-selective ganglion cells (OSGCs), thought to prefer vertical or horizontal orientation. However, as stationary edges are projected on the hemispherical retina as lines of longitude or latitude, how edge orientation is encoded, and decoded by the brain, is unknown. Here, by mapping the OS of thousands of OSGCs at known retinal locations in mice, we identified three OSGC types whose preferences match two longitudinal fields, and a fourth type matching two latitudinal fields, the members of each field-pair being non-orthogonal. A geometric decoder revealed that two OS sensors yield optimal orientation decoding when approaching the deviation from orthogonality we observed for OSGC field-pairs. Retinotopically-organized decoding generated type-specific variation in decoding efficiency across the visual field. OS tuning was greater in the dorsal retina, possibly reflecting an evolutionary adaptation to an environmental gradient of edges.
Identification of an ambisense kolmiovirus from birds
Authors: Kishimoto Mai , Imai Sakiho , Igarashi Manabu , Horie Masayuki
Published: January 2025

Viruses in the familyKolmioviridae(KoVs) are unique among RNA viruses in that they have small, highly self-complementary, circular, negative-sense genomes and are satellite viruses requiring the envelope protein of co-infected helper viruses to form infectious virions. For approximately 40 years, only hepatitis D virus (HDV) had been identified, but recent studies have uncovered novel KoVs in diverse animal species. Serinus canaria-associated deltavirus (scKoV) was recently identified form a single RNA-seq data from canary skin. However, only the partial genome sequence corresponding to the transcript encoding DAg has been identified, leaving questions regarding its full genetic composition and origins. In this study, we examined publicly available RNA-seq data and identified multiple complete genome sequences of scKoV. Our results demonstrated that genetically diverse scKoVs infect multiple bird species with recent inter-order transmission. Additionally, scKoV was detected in various tissues including parenchymal organs, suggesting that scKoV is a genuine avian KoV. Notably, analysis of the genome structure and transcriptional pattern clearly revealed that scKoV transcribes a genomic-sense mRNA encoding a novel gene, in addition to the previously known antigenomic-sense DAg transcript. Furthermore, this newly identified gene appears to express two protein isoforms via alternative splicing. These findings mark the first KoV with an ambisense genome that utilizes alternative splicing, which may represent a strategy to increase gene-coding capacity despite the constraints imposed by its small and self-complementarity genome. Moreover, co-infection with avian bornaviruses was detected in most scKoV-positive RNA-seq datasets, suggesting that avian bornaviruses are candidate helper viruses for scKoV. In conclusion, our study on scKoV provides novel insights into the evolution and diversity of KoVs.
Dmrt2Orchestrates Neuronal Development in the Embryonic Cingulate Cortex: Unveiling Sex-Biased Vulnerabilities
Authors: Bermejo-Santos Ana , Torrillas-de la Cal Rodrigo , Rubio-García Miguel , Serrano-Saiz Esther
Published: January 2025

Sexual differences are prevalent in the brain. DMRT family of transcription factors (TF) has been postulated as an important determinant of sex differences. Up to now, the role of DMRTs in the brain has been focused on the DMA subfamily. Here, we show an unprecedented role forDmrt2in regulating the proliferation and neuronal development of cortical neurons in mice.Dmrt2expression is observed in deep-layer neurons of the cingulate cortex (CgCx) throughout development. Downregulation ofDmrt2mRNA in the CgCx primordium results in premature cell cycle exit of embryonic progenitors and subsequent reduction in cortical plate cellular density at later developmental stages.Dmrt2is expressed at higher levels in male embryos during early development, potentially explaining their increased vulnerability toDmrt2depletion. As development progresses,Dmrt2expression is maintained in deeper-layer neurons, where this TF controls distinct terminal processes, including migration, axonal targeting, and neuronal-specific gene expression.

Our findings suggest a potential mechanistic link between the function of aDmrtfamily member and sex-specific susceptibility to neurological disorders. This study expands our understanding ofDmrtgene function in the brain and provides insights into the molecular basis of sexual differences in neurodevelopmental processes.
Human cytomegalovirus gH/gL/gO binding to PDGFRα provides a regulatory signal activating the fusion protein gB that can be blocked by neutralizing antibodies
Authors: Schultz Eric P. , Ponsness Lars , Lanchy Jean-Marc , Zehner Matthias , Klein Florian , Ryckman Brent J.
Published: January 2025

Herpesviruses require membrane fusion for entry and spread, a process facilitated by the fusion glycoprotein B (gB) and the regulatory factor gH/gL. The human cytomegalovirus (HCMV) gH/gL can be modified by the accessory protein gO, or the set of proteins UL128, UL130 and UL131. While the binding of the gH/gL/gO and gH/gL/UL128-131 complexes to cellular receptors including PDFGRα and NRP2 has been well-characterized structurally, the specific role of receptor engagements by the gH/gL/gO and gH/gL/UL128-131 in regulation of fusion has remained unclear. We describe a cell-cell fusion assay that can quantitatively measure fusion on a timescale of minutes and demonstrate that binding of gH/gL/gO to PDGFRα dramatically enhances gB-mediated cell-cell fusion. In contrast, gH/gL/pUL128-131-regulated fusion is significantly slower and gH/gL alone cannot promote gB fusion activity within this timescale. The genetic diversity of gO influenced the observed cell-cell fusion rates, correlating with previously reported effects on HCMV infectivity. Mutations in gL that had no effect on formation of gH/gL/gO or binding to PDGFRα dramatically reduced the cell-cell fusion rate, suggesting that gL plays a critical role in linking the gH/gL/gO-PDGFRα receptor-binding to activation of gB. Several neutralizing human monoclonal antibodies were found to potently block gH/gL/gO-PDGFRα regulated cell-cell fusion, suggesting this mechanism as a therapeutic target.

SIGNIFICANCE

Development of vaccines and therapeutics targeting the fusion apparatus of HCMV has been limited by the lack anin vitrocell-cell fusion assay that faithfully models the receptor-dependent fusion characteristic of HCMV entry. The cell-cell fusion assay described here demonstrated that the binding of gH/gL/gO to its receptor, PDGFRα serves to regulate the activity of the fusion protein gB. Moreover, this regulatory mechanism is specifically vulnerable to inhibition by neutralizing antibodies. The cell-cell fusion assay described here provides a new tool to characterize neutralizing mAbs as therapeutic agents.
Niemann-Pick C-like endo-lysosomal dysfunction in DHDDS patient cells, a congenital disorder of glycosylation, can be treated with miglustat
Authors: Best Hannah L. , Cook Sophie R. , Waller-Evans Helen , Lloyd-Evans Emyr
Published: January 2025

DHDDS (dehydrodolichol diphosphate synthetase) and NgBR (Nogo-B Receptor) collectively form an enzymatic complex important for the synthesis of dolichol – a key component of protein N-glycosylation. Mutations inDHDDSand the gene encoding NgBR (NUS1)are associated with neurodevelopmental disorders that clinically present with epilepsy, motor impairments, and developmental delay. Previous work has demonstrated both DHDDS and NgBR can also interact with NPC2 (Niemann-Pick C (NPC) type 2) – a protein which functions to traffic cholesterol out of the lysosome and, when mutated, can cause a lysosomal storage disorder (NPC disease) characterised by an accumulation of cholesterol and glycosphingolipids. Abnormal cholesterol accumulation has also been reported in cells from individuals and animal models with mutations in NUS1, and suspected lipid storage has been shown in biopsies from individuals with mutations in DHDDS. Our findings provide further evidence for overlap between NPC2 and DHDDS disorders, showing that DHDDS patient fibroblasts have increased lysosomal volume, store cholesterol and ganglioside GM1, and have altered lysosomal Ca2+homeostasis. Treatment of DHDDS cells - with the approved NPC small molecule therapy miglustat - improves these disease-associated phenotypes, identifying a possible therapeutic option for DHDDS patients. These data suggest that treatment options currently approved for NPC disease may be translatable to DHDDS/NUS1 patients.
Human REXO4 is Required for Cell Cycle Progression
Authors: Clutario Kevin M. , Abdusamad Mai , Ramirez Ivan , Rich Kayla J. , Gholkar Ankur A. , Zaragoza Julian , Torres Jorge Z.
Published: January 2025

Human REXO4 is a poorly characterized exonuclease that is overexpressed in human cancers. To better understand the function of REXO4 and its relationship to cellular proliferation, we have undertaken multidisciplinary approaches to characterize its cell cycle phase-dependent subcellular localization and the cis determinants required for this localization, its importance to cell cycle progression and cell viability, its protein-protein association network, and its activity. We show that the localization of REXO4 to the nucleolus in interphase depends on an N-terminal nucleolar localization sequence and that its localization to the perichromosomal layer of mitotic chromosomes is dependent on Ki67. Depletion of REXO4 led to a G1/S cell cycle arrest, and reduced cell viability. REXO4 associated with ribosome components and other proteins involved in rRNA metabolism. We propose a model where REXO4 is important for proper rRNA processing, which is required for ribosome biogenesis, cell cycle progression, and proliferation.

SIGNIFICANCE STATEMENT

REXO4 is a putative RNA exonuclease with limited characterization. The authors used in silico, cell, and molecular biology approaches to characterize its localization, associations, regulation, and function.

They found that during interphase, REXO4 localizes to the nucleolus through an N-terminal nucleolar localization sequence. Whereas during mitosis, REXO4 localized to the perichromosomal layer in a Ki67-dependent manner. REXO4 was required for proper cell cycle progression, and viability.

These results indicated that REXO4 is important for regulating cell proliferation.
Evolutionary sparse learning with paired species contrast reveals the shared genetic basis of convergent traits
Authors: Allard John B. , Sharma Sudip , Patel Ravi , Sanderford Maxwell , Tamura Koichiro , Vucetic Slobodan , Gerhard Glenn S. , Kumar Sudhir
Published: January 2025

Cases abound in which nearly identical traits have appeared in distant species facing similar environments. These unmistakable examples of adaptive evolution offer opportunities to gain insight into their genetic origins and mechanisms through comparative analyses. Here, we present a novel comparative genomics approach to build genetic models that underlie the independent origins of convergent traits using evolutionary sparse learning. We test the hypothesis that common genes and sites are involved in the convergent evolution of two key traits: C4 photosynthesis in grasses and echolocation in mammals. Genetic models were highly predictive of independent cases of convergent evolution of C4 photosynthesis. These results support the involvement of sequence substitutions in many common genetic loci in the evolution of convergent traits studied. Genes contributing to genetic models for echolocation were highly enriched for functional categories related to hearing, sound perception, and deafness (P< 10−6); a pattern that has eluded previous efforts applying standard molecular evolutionary approaches. We conclude that phylogeny-informed machine learning naturally excludes apparent molecular convergences due to shared species history, enhances the signal-to-noise ratio for detecting molecular convergence, and empowers the discovery of common genetic bases of trait convergences.
19S proteasome loss causes monopolar spindles through ubiquitin-independent KIF11 degradation
Authors: Marescal Océane , Cheeseman Iain M.
Published: January 2025

To direct regulated protein degradation, the 26S proteasome recognizes ubiquitinated substrates through its 19S particle and then degrades them in the 20S enzymatic core. Despite this close interdependency between proteasome subunits, we demonstrate that knockouts from different proteasome subcomplexes result in distinct highly cellular phenotypes. In particular, depletion of 19S PSMD lid proteins, but not that of other proteasome subunits, prevents bipolar spindle assembly during mitosis, resulting in a mitotic arrest. We find that the monopolar spindle phenotype is caused by ubiquitin- independent proteasomal degradation of the motor protein KIF11 upon loss of 19S proteins. Thus, negative regulation of 20S-mediated proteasome degradation is essential for mitotic progression and 19S and 20S proteasome components can function independently outside of the canonical 26S structure. This work reveals a role for the proteasome in spindle formation and identifies the effects of ubiquitin- independent degradation on cell cycle control.
WHITE-Net : White matter HyperIntensities Tissue Extraction using deep learning Network
Authors: Cathala Camille , Kherif Ferath , Thiran Jean-Philippe , Bussy Aurélie , Draganski Bogdan
Published: January 2025

Given the high prevalence of aging-associated cerebral small vessel disease in the general population, accurate detection of the related white matter hyperintensities (WMH) in large-scale magnetic resonance imaging (MRI) studies is of critical importance. The performance of currently available semi-automated and automated methods for WMH classification is hampered by their inherent dependence on MRI contrast parameters and long computational processing time. We sought to improve the accuracy and computational cost of automated WMH detection by creating a whole-brain deep learning-based framework: WHITE-Net. We use a 3D ResUNet architecture trained on manually segmented WMHs from fluid-attenuated inversion recovery MRI (n=141) and test its accuracy in a large-scale dataset (n=192). We demonstrate a good generalizability across WMH lesion loads, different MRI scanner vendors, field strengths, imaging protocols, and MR contrasts. The comparison to existing WMH segmentation tools shows a similar to superior accuracy performance at significantly lower computational cost. WHITE-Net tool performance makes it well-suited for application to large-scale MRI datasets, enabling the study of the aging brain while offering the advantage of detecting early or subtle WMH changes often missed by other methods.
Quantifying potential immortal time bias in observational studies in acute severe infection
Authors: Yates Tom A. , Parks Tom , Dodd Peter J.
Published: January 2025

KEY POINTS

Immortal time bias exaggerates estimates of treatment efficacy in naïve analyses of observational data. We developed a tool to estimate the extent of this bias. The benefits of giving intravenous immunoglobulin in streptococcal toxic shock syndrome have likely been overstated

Background

Immortal time bias is a spurious or exaggerated protective association that commonly arises in naive analyses of observational data. It occurs when people receive the intervention because they survive, rather than survive because they received the intervention. Studies in conditions with substantial early mortality, such as acute severe infections, are particularly vulnerable. The bias can be avoided by fitting the intervention as a time-varying exposure.

Methods

We developed IMMORTOOL, an R package accessible via a user-friendly web interface. This tool will estimate the potential for immortal time bias using empiric or assumed data on the distributions of time to intervention and time to event. Assumptions are that no other biases are present and that the intervention does not impact the outcome. The tool was benchmarked using studies presenting both naive analyses and analyses with the intervention fit as a time-varying exposure. We applied IMMORTOOL to a set of influential observational studies that used naive analyses when estimating the impact of polyclonal intravenous immunoglobulin (IVIG) on survival in streptococcal toxic shock syndrome (STSS).

Results

IMMORTOOL demonstrated that published estimates suggesting a survival advantage from giving IVIG in STSS are explained, at least in part, by immortal time bias.

Conclusions

IMMORTOOL can quantify the potential for immortal time bias in observational analyses. This may help readers interrogate published studies. We do not advocate IMMORTOOL being used to justify naive analyses where the intervention could be fit as a time-varying exposure. To what extent giving IVIG in STSS improves survival remains uncertain.
Dark Matter Search Results from
1.54  Tonne·Year
Exposure of PandaX-4T
Authors: Bo Zihao , Chen Wei , Chen Xun , Chen Yunhua , Cheng Zhaokan , Cui Xiangyi , Fan Yingjie , Fang Deqing , Gao Zhixing , Geng Lisheng , Giboni Karl , Guo Xunan , Guo Xuyuan , Guo Zichao , Han Chencheng , Han Ke , He Changda , He Jinrong , Huang Di , Huang Houqi , Huang Junting , Hou Ruquan , Hou Yu , Ji Xiangdong , Ji Xiangpan , Ju Yonglin , Li Chenxiang , Li Jiafu , Li Mingchuan , Li Shuaijie , Li Tao , Li Zhiyuan , Lin Qing , Liu Jianglai , Lu Congcong , Lu Xiaoying , Luo Lingyin , Luo Yunyang , Ma Wenbo , Ma Yugang , Mao Yajun , Meng Yue , Ning Xuyang , Pang Binyu , Qi Ningchun , Qian Zhicheng , Ren Xiangxiang , Shan Dong , Shang Xiaofeng , Shao Xiyuan , Shen Guofang , Shen Manbin , Sun Wenliang , Tao Yi , Wang Anqing , Wang Guanbo , Wang Hao , Wang Jiamin , Wang Lei , Wang Meng , Wang Qiuhong , Wang Shaobo , Wang Siguang , Wang Wei , Wang Xiuli , Wang Xu , Wang Zhou , Wei Yuehuan , Wu Weihao , Wu Yuan , Xiao Mengjiao , Xiao Xiang , Xiong Kaizhi , Xu Yifan , Yao Shunyu , Yan Binbin , Yan Xiyu , Yang Yong , Ye Peihua , Yu Chunxu , Yuan Ying , Yuan Zhe , Yun Youhui , Zeng Xinning , Zhang Minzhen , Zhang Peng , Zhang Shibo , Zhang Shu , Zhang Tao , Zhang Wei , Zhang Yang , Zhang Yingxin , Zhang Yuanyuan , Zhao Li , Zhou Jifang , Zhou Jiaxu , Zhou Jiayi , Zhou Ning , Zhou Xiaopeng , Zhou Yubo , Zhou Zhizhen ,   PandaX Collaboration
Published: January 2025

In this Letter, we report the dark matter search results from the commissioning run (Run0) and the first science run (Run1) of the PandaX-4T experiment. The two datasets were processed with a unified procedure, with the Run1 data treated blindly. The data processing is improved compared to previous work, unifying the low-level signal reconstruction in a wide energy range up to 120 keV. With a total exposure of 1.54  tonne·year, no significant excess of nuclear recoil events is found. The lowest 90% confidence level exclusion on the spin-independent cross section is 1.6×10−47  cm2 at a dark matter mass of 40  GeV/c2. Our results represent the most stringent constraint for a dark matter mass above 100  GeV/c2.

Published by the American Physical Society
2025
Scalable circuit depth reduction in feedback-based quantum optimization with a quadratic approximation
Authors: Arai Don , Okada Ken N. , Nakano Yuichiro , Mitarai Kosuke , Fujii Keisuke
Published: January 2025

Combinatorial optimization problems are one of the areas where near-term noisy quantum computers may have practical advantage against classical computers. Recently, a feedback-based quantum optimization algorithm has been proposed by Magann , . The method explicitly determines quantum circuit parameters by feeding back measurement results thus avoids classical parameter optimization that is known to cause significant trouble in quantum approximate optimization algorithm, the well-studied near-term algorithm. Meanwhile, a significant drawback of the feedback-based quantum optimization is that it requires deep circuits, rendering the method unsuitable to noisy quantum devices. In this study we propose a feedback law for parameter determination by introducing the second-order approximation with respect to time interval, a hyperparameter in the feedback-based quantum optimization. This allows one to take larger time interval, leading to acceleration of convergence to solutions. In numerical simulations on the maximum cut problem we demonstrate that our proposal significantly reduces circuit depth, with its linear scaling with the problem size smaller by more than an order of magnitude. We expect that the feedback law proposed in this work may pave the way for feedback-based quantum optimization with near-term noisy quantum computers.

Published by the American Physical Society
2025
Effect of ultra-high aspect ratio wings and distributed propulsion on the viability of fully electric regional aircraft
Authors: Gilbrook Aaron , Ma Yiyuan , Elham Ali
Published: January 2025

Purpose

Revolutionary advances in aircraft technology and performance are needed for fuel-efficient and sustainable next-generation air transportation. This study aims to explore the influence of integrating distributed propulsion with ultra-high aspect ratio (AR) wings (UHARW) on the realization of fully electric regional aviation.

Design/methodology/approach

The strut-braced wing (SBW) configuration is advantageous for UHARW due to its additional support. A conceptual design and analysis framework for UHARW aircraft with SBW and distributed propulsion configurations is developed by enhancing and integrating several methods and tools. Based on the mission profile and top-level requirements, a fully electric regional SBW aircraft with distributed propulsion is designed and analyzed.

Findings

Integrating distributed propulsion with a high AR SBW configuration in a fully electric regional aircraft results in notable energy efficiencies. The design achieves a 2.85% increase in the lift-to-drag ratio and a 2.62% reduction in drag during cruise. Sensitivity analysis indicates optimal performance with an AR up to 22, beyond which structural weight penalties diminish benefits. The aircraft’s energy efficiency improves by 9.9% during climb and 6% during cruise, highlighting the importance of propulsion integration.

Practical implications

This research provides a viable framework for designing fully electric regional aircraft by integrating distributed propulsion with high AR SBW configurations. The findings provide practical guidance for enhancing energy efficiency and reducing structural weight, supporting the development of more sustainable and efficient aircraft designs.

Social implications

The findings support the development of sustainable aviation technologies, potentially reducing the environmental footprint of regional air travel and contributing to global efforts toward greener transportation solutions.

Originality/value

This study presents a comprehensive methodology for designing and analyzing UHARW aircraft with SBW and distributed propulsion, contributing to the feasibility assessment of fully electric regional aviation.
Ownership with a green twist: the role of top managers in driving environmental innovation
Authors: Yue Shanshan , Bajuri Norkhairul Hafiz B. , Khatib Saleh F.A. , Alshareef Mohammed Naif
Published: January 2025

Purpose

This study aims to explore the relationship between managerial ownership and environmental innovation, particularly focusing on the impact of minority shareholder protection within the context of China’s A-share listed companies.

Design/methodology/approach

The study employs a fixed effect model over a decade-long sample, analysing secondary data from nonfinancial Chinese A-share firms. The two-stage least squares (2SLS) method is adopted to address endogeneity concerns.

Findings

The results demonstrate a significant positive influence of managerial ownership on environmental innovation, suggesting that top managers who have a say in the boardroom are inclined towards sustainable development. The presence of minority shareholders' protection positively moderates this relationship, underlining their roles in fostering environmentally friendly development. The subsample analysis showed that these relationships vary between state-owned enterprises (SOEs) and non-SOEs. It also differs between heavily and lightly polluting industries, which indicates that it is not enough to just have internal self-management, and more external pressure is necessary in heavily polluting industries.

Research limitations/implications

Our study underscores the importance for managers to recognize the potential of aligning their ownership interests with environmental objectives. Companies can enhance their commitment to sustainability by fostering an internal environment that supports minority shareholder rights.

Originality/value

This study specifically focuses on the role of top managers and minority shareholders, providing new empirical evidence on how their influence can drive sustainable development initiatives. It is also among the few studies that differentiate between firm characteristics and pollution intensity, which provides valuable insights into how the impact of managerial ownership and minority shareholder protection varies across different contexts.
Learning on the go! Increased job crafting in healthcare sector
Authors: Tripathy Saswati , Padhi Mousumi , Pattnaik Subhra
Published: January 2025

Purpose

The purpose is to explore the job crafting behavior that arises as a consequence of rapid learning.

Design/methodology/approach

Focused group discussion (FGDs) and in-depth interviews were conducted with healthcare professionals in three hospitals in India. Data was collected between July 2021 and February 2022 during second wave of pandemic.

Findings

It was found that healthcare professionals exhibited task, relational and cognitive crafting of the job as an outcome of instant contextual learning and crafted their tasks, relations and cognitive abilities to take proactive measures, related to patient and attendant care.

Research limitations/implications

Due to prevalence of COVID-19 protocols wider sampling was not feasible. A comparative study with a control group not having underwent rapid learning would have brought out final nuance.

Practical implications

This study highlights the role mentoring, job shadowing, workshop, simulation as means of enhancing rapid learning.

Social implications

In crisis situations how extra manpower can be successfully deployed by way of capability enhancement mechanism and this will lead to effective handling of emergency situations in future.

Originality/value

This paper rests on an under-researched area at the junction of crisis management, organizational learning, and job crafting. It’s different from the phenomenon of usual long term learning and gradual job crafting.
Interweaving academic insights: advancing university knowledge management through a strategic data fabric framework
Authors: Nguyen Thi Kim Lan , Nguyen Hoang Son , Nguyen Hoa N.
Published: January 2025

Purpose

Effective knowledge management in large academic institutions is crucial for fostering innovation and improving educational practices. However, these institutions often face challenges, such as data fragmentation, siloed information systems and the complexity of integrating different data sources from various departments with complex hierarchical structures. To address these problems, the authors proposed a data fabric strategic framework that improves and enhances knowledge management by leveraging ontologies and knowledge graphs. This study aims to investigate the potential of knowledge graphs, ontological knowledge modelling and knowledge representation to improve knowledge management in large academic institutions. It also describes how technology can enhance knowledge accessibility and exchanges and improve decision-making processes based on insights from complex educational systems.

Design/methodology/approach

This study uses coordination theory as a foundational framework to analyse intricate data systems in preparation for constructing, the Wizard of Oz method to facilitate the systematic organisation and management of information and the execution of an ontology-based data fabric framework and knowledge graphs. The authors propose a data fabric strategic framework aimed at improving knowledge management by leveraging ontologies and knowledge graphs.

Findings

The final evaluation demonstrates that this approach effectively breaks down data silos, promotes research collaboration and improves decision-making processes in large academic settings, offering solution-oriented data fabric technologies applicable to universities and university federations globally.

Practical implications

The proposed system provides a more efficient way of managing and connecting fragmented academic resources, improving accessibility for both learners and educators. By interconnecting and streaming knowledge management process, the system can reduce not only operational costs but also expenses on doing scientific research.

Originality/value

Academic institutions prioritise time efficiency when acquiring vital data for improved scientific results. This emphasis extends beyond data governance to focus on how collective intelligence might improve organisational performance. The academic community has enhanced data utilisation through the implementation of data fabric technologies to improve data accessibility and data line tracking.