bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome-level genome assembly of the European Green woodpeckerPicus viridis
Authors: Forest Thomas , Achaz Guillaume , Marbouty Martial , Bignaud Amaury , Thierry Agnès , Koszul Romain , Milhes Marine , Lledo Joanna , Pons Jean-Marc , Fuchs Jérôme
Published: December 2023

The European Green Woodpecker,Picus viridis, is a widely distributed species found in the Western Palearctic region. Here we assembled a highly contiguous genome assembly for this species using a combination of short and long reads sequencing and scaffolded with chromatin conformation capture (Hi-C). The final genome assembly was 1.28 Gb and features a scaffold N50 of 37Mb and a scaffold L50 of 39.165 Mb. The assembly incorporates 89.4% of the genes identified in birds in OrthoDB. Gene and repetitive content annotation on the assembly detected 15,805 genes and a ∼30.1% occurrence of repetitive elements, respectively. Analysis of synteny demonstrates the fragmented nature of thePicus viridisgenome when compared to the chicken (Gallus gallus). The assembly and annotations produced in this study will certainly help for further research into the genomics ofP. viridisand the comparative evolution of woodpeckers.
SGLT2 inhibitors attenuate endothelial to mesenchymal transition and cardiac fibroblast activation
Authors: Schmidt Kevin , Schmidt Arne , Groß Sonja , Just Annette , Pfanne Angelika , Fuchs Maximilian , Jordan Maria , Mohr Elisa , Pich Andreas , Fiedler Jan , Thum Thomas
Published: December 2023

Beneficial effects of sodium glucose co-transporter 2 inhibitors (SGLT2is) in cardiovascular diseases have been extensively reported leading to the inclusion of these drugs in the treatment guidelines for heart failure. However, molecular actions especially on non-myocyte cells remain uncertain. We observed dose-dependent inhibitory effects of two SGLT2is, dapagliflozin (DAPA) and empagliflozin (EMPA), on inflammatory signaling in human umbilical vein endothelial cells (HUVECs). Proteomics analyses and subsequent enrichment analyses discovered profound effects of these SGLT2is on proteins involved in mitochondrial respiration and actin cytoskeleton. Validation in functional oxygen consumption measurements as well as tube formation and migration assays revealed strong impacts of DAPA. Considering that most influenced parameters played central roles in endothelial to mesenchymal transition (EndMT), we performedin vitroEndMT assays and identified substantial reduction of mesenchymal and fibrosis marker expression as well as changes in cellular morphology upon treatment with SGLT2is. In line, human cardiac fibroblasts (HCFs) exposed to DAPA showed less proliferation, reduced ATP production, and decelerated migration capacity while less extensive impacts were observed upon EMPA. Mechanistically, sodium proton exchanger 1 (NHE1) as well as sodium-myoinositol cotransporter (SMIT) and sodium-multivitamin cotransporter (SMVT) could be identified as relevant targets of SGLT2is in non-myocyte cardiovascular cells as validated by individual siRNA-knockdown experiments. In summary, we found comprehensive beneficial effects of SGLT2is on human endothelial cells and cardiac fibroblasts. The results of this study therefore support a distinct effect of selected SGLT2i on non-myocyte cardiovascular cells and grant further insights into potential molecular mode of action of these drugs.
Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy
Authors: Bodansky Aaron , Yu David JL , Rallistan Alysa , Kalaycioglu Muge , Boonyaratanakornkit Jim , Green Damian J. , Gauthier Jordan , Turtle Cameron J. , Zorn Kelsey , O’Donovan Brian , Mandel-Brehm Caleigh , Asaki James , Kortbawi Hannah , Kung Andrew F. , Rackaityte Elze , Wang Chung-Yu , Saxena Aditi , de Dios Kimberly , Masi Gianvito , Nowak Richard J. , O’Connor Kevin C. , Li Hao , Diaz Valentina E. , Casaletto Kaitlin B. , Gontrum Eva Q. , Chan Brandon , Kramer Joel H. , Wilson Michael R. , Utz Paul J. , Hill Joshua A. , Jackson Shaun W. , Anderson Mark S. , DeRisi Joseph L.
Published: December 2023

The prevalence and burden of autoimmune and autoantibody mediated disease is increasing worldwide, yet most disease etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leverage advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of proteome-wide autoantibody profiles in both health and disease. We demonstrate that each individual, regardless of disease state, possesses a distinct set of autoreactivities constituting a unique immunological fingerprint, or “autoreactome”, that is remarkably stable over years. In addition to uncovering important new biology, the autoreactome can be used to better evaluate the relative effectiveness of various therapies in altering autoantibody repertoires. We find that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly alter an individual’s autoreactome, while anti-CD19 and CD-20 therapies have minimal effects, strongly suggesting a rationale for BCMA or other plasma cell targeted therapies in autoantibody mediated diseases.
ChatGPT for tinnitus information and support: response accuracy and retest after three months
Authors: Jedrzejczak W. Wiktor , Skarzynski Piotr H. , Raj-Koziak Danuta , Sanfins Milaine Dominici , Hatzopoulos Stavros , Kochanek Krzysztof
Published: December 2023

Background

ChatGPT – a conversational tool based on artificial intelligence – has recently been tested on a range of topics. However most of the testing has involved broad domains of knowledge. Here we test ChatGPT’s knowledge of tinnitus, an important but specialized aspect of audiology and otolaryngology. Testing involved evaluating ChatGPT’s answers to a defined set of 10 questions on tinnitus. Furthermore, given the technology is advancing quickly, we re-evaluated the responses to the same 10 questions 3 months later.

Material and method

ChatGPT (free version 3.5) was asked 10 questions on tinnitus at two points of time – August 2023 and November 2023. The accuracy of the responses was rated by 6 experts using a Likert scale ranging from 1 to 5. The number of words in each response was also counted, and responses were specifically examined for whether references were provided or whether consultation with a specialist was suggested.

Results

Most of ChatGPT’s responses were rated as satisfactory or better. However, we did detect a few instances where the responses were not accurate and might be considered somewhat misleading. The responses from ChatGPT were quite long (averaging over 400 words) and they occasionally tended to stray off-topic. No solid references to sources of information were ever supplied, and when references were specifically asked for the sources were artificial. For most responses consultation with a specialist was suggested. It is worth noting that after 3 months the responses generally improved.

Conclusions

ChatGPT provided surprisingly good responses, given that the questions were quite specific. Although no potentially harmful errors were identified, some mistakes could be seen as somewhat misleading. No solid references were ever supplied. ChatGPT shows great potential if further developed by experts in specific areas, but for now it is not yet ready for serious application.
Genomic analysis identifies risk factors in restless legs syndrome
Authors: Akçimen Fulya , Chia Ruth , Saez-Atienzar Sara , Ruffo Paola , Rasheed Memoona , Ross Jay P. , Liao Calwing , Ray Anindita , Dion Patrick A. , Scholz Sonja W. , Rouleau Guy A. , Traynor Bryan J.
Published: December 2023

Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. Here, we present a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in three population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE). Genome-wide association analysis identified nine independent risk loci, of which eight had been previously reported, and one was a novel risk locus (LMX1B, rs35196838, OR = 1.14, 95% CI = 1.09-1.19,p-value = 2.2 × 10-9). A genome-wide, gene-based common variant analysis identifiedGLO1as an additional risk gene (p-value = 8.45 × 10-7). Furthermore, a transcriptome-wide association study also identifiedGLO1and a previously unreported gene,ELFN1. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (rg= 0.40, se = 0.08,p-value = 5.4 × 10-7), depression (rg= 0.35, se = 0.06,p-value = 2.17 × 10-8), and intelligence (rg= -0.20, se = 0.06,p-value = 4.0 × 10-4). Our study expands the understanding of the genetic architecture of RLS and highlights the contributions of common variants to this prevalent neurological disorder.
Sub-Optimal Oral Health, Multimorbidity and Access to Dental Care
Authors: Limo L , Nicholson K , Stranges S , Gomaa N
Published: December 2023

INTRODUCTION

Emerging research on the links between sub-optimal oral health and multimorbidity (MM), or the co-existence of multiple chronic conditions, has raised queries on whether enhancing access to dental care may mitigate the MM burden, especially in older age. Here, we aim to assess the association between sub-optimal oral health and MM and whether access to dental care can mitigate the risk of MM in individuals with sub-optimal oral health.

METHODS

We conducted a cross-sectional analysis using data from the Canadian Longitudinal Study on Aging (CLSA) (n=44,815, 45-84 years old). Edentulism, self-reported oral health (SROH), and other oral health problems (e.g., toothache, bleeding gums), were each used as indicators of sub-optimal oral health. MM was defined according to the Public Health Agency of Canada as having 2 or more chronic conditions out of cancer, cardiovascular diseases, chronic respiratory diseases, diabetes, and mental illnesses. Variables for access to dental care included the number of dental visits within the last year, dental insurance status, and cost barriers to dental care. We constructed multivariable step-wise logistic regression models and interaction terms with 95% confidence intervals and estimated prevalence ratio (PR) to assess the associations of interest, adjusting fora prioridetermined sociodemographic and behavioural factors.

RESULTS

Each of the sub-optimal oral health indicators were significantly associated with MM (edentulism PR=1.48, 95%CI 1.31, 1.68; poor SROH PR=1.81, 95%CI 1.62, 2.01; other oral health problems PR = 1.91, 95%CI 1.78, 2.06). The magnitude of this association was exacerbated in individuals who lacked dental insurance, could not afford dental care, and those who reported fewer dental visits within the last year.

CONCLUSION

The association between sub-optimal oral health and MM may be exacerbated by the lack of access to dental care. Policies aiming to enhance access to dental care may help mitigate the risk of MM.
Large Language Models Facilitate the Generation of Electronic Health Record Phenotyping Algorithms
Authors: Yan Chao , Ong Henry H. , Grabowska Monika E. , Krantz Matthew S. , Su Wu-Chen , Dickson Alyson L. , Peterson Josh F. , Feng QiPing , Roden Dan M. , Stein C. Michael , Kerchberger V. Eric , Malin Bradley A. , Wei Wei-Qi
Published: December 2023

Objectives

Phenotyping is a core task in observational health research utilizing electronic health records (EHRs). Developing an accurate algorithm demands substantial input from domain experts, involving extensive literature review and evidence synthesis. This burdensome process limits scalability and delays knowledge discovery. We investigate the potential for leveraging large language models (LLMs) to enhance the efficiency of EHR phenotyping by generating high-quality algorithm drafts.

Materials and Methods

We prompted four LLMs—GPT-4 and GPT-3.5 of ChatGPT, Claude 2, and Bard—in October 2023, asking them to generate executable phenotyping algorithms in the form of SQL queries adhering to a common data model (CDM) for three phenotypes (i.e., type 2 diabetes mellitus, dementia, and hypothyroidism). Three phenotyping experts evaluated the returned algorithms across several critical metrics. We further implemented the top-rated algorithms and compared them against clinician-validated phenotyping algorithms from the Electronic Medical Records and Genomics (eMERGE) network.

Results

GPT-4 and GPT-3.5 exhibited significantly higher overall expert evaluation scores in instruction following, algorithmic logic, and SQL executability, when compared to Claude 2 and Bard. Although GPT-4 and GPT-3.5 effectively identified relevant clinical concepts, they exhibited immature capability in organizing phenotyping criteria with the proper logic, leading to phenotyping algorithms that were either excessively restrictive (with low recall) or overly broad (with low positive predictive values).

Conclusion

GPT versions 3.5 and 4 are capable of drafting phenotyping algorithms by identifying relevant clinical criteria aligned with a CDM. However, expertise in informatics and clinical experience is still required to assess and further refine generated algorithms.
Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification among Patients with Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-Income Countries
Authors: Dupnik Kathryn , Rivera Vanessa R. , Dorvil Nancy , Akbarnejad Hanane , Gao Yipeng , Liu Jingyi , Apollon Alexandra , Dumond Emelyne , Riviere Cynthia , Severe Patrice , Lavoile Kerlyne , Duran Mendicuti Maria Alejandra , Pierre Samuel , Rouzier Vanessa , Walsh Kathleen F. , Byrne Anthony L. , Joseph Patrice , Cremieux Pierre-Yves , Pape Jean William , Koenig Serena P.
Published: December 2023

Article Summary

We assessed the association between C-reactive protein (CRP) andMycobacterium tuberculosis(TB) diagnosis in symptomatic patients at HIV diagnosis. We found that CRP concentrations can improve tuberculosis risk stratification, facilitating decision making about whether (specific) tuberculosis testing is indicated before antiretroviral therapy initiation.

Background

The World Health Organization recommends initiating same-day ART while tuberculosis testing is underway for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve tuberculosis risk stratification in this population.

Methods

In this baseline analysis of 498 adults (>18 years) with tuberculosis symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP (≥3 mg/dL) using generalized linear models.

Results

Eighty-seven (17.5%) patients were diagnosed with baseline TB. The median CRP was 33.0 mg/L (IQR: 5.1, 85.5) in those with TB, and 2.6 mg/L (IQR: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4%, and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART, and 0.8% to 5.0% would have untreated TB at ART initiation.

Conclusions

CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3-fold to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.
Specialization of the Human Hippocampal Long Axis Revisited
Authors: Angeli Peter A. , DiNicola Lauren M. , Saadon-Grosman Noam , Eldaief Mark C. , Buckner Randy L.
Published: December 2023

The hippocampus possesses anatomical differences along its long axis. Here the functional specialization of the human hippocampal long axis was explored using network-anchored precision functional MRI (N = 11) paired with behavioral analyses (N=266). Functional connectivity analyses demonstrated that the anterior hippocampus was preferentially correlated with a cerebral network associated with remembering, while the posterior hippocampus was correlated with a distinct network associated with behavioral salience. Seed regions placed within the hippocampus recapitulated the distinct cerebral networks. Functional characterization using task data within the same intensively sampled individuals discovered a functional double dissociation between the anterior and posterior hippocampal regions. The anterior hippocampal region was sensitive to remembering and imagining the future, specifically tracking the process of scene construction, while the posterior hippocampal region displayed transient responses to targets in an oddball detection task and to transitions between task blocks. These findings suggest specialization along the long axis of the hippocampus with differential responses reflecting the functional properties of the partner cerebral networks.
c-fosinduction in the choroid plexus, tanycytes and pars tuberalis is an early indicator of spontaneous arousal from torpor in a deep hibernator
Authors: Markussen Fredrik A.F , Cázarez-Marquez Fernando , Melum Vebjørn J. , Hazlerigg David , Wood Shona
Published: December 2023

Hibernation is an extreme state of seasonal energy conservation, reducing metabolic rate to as little as 1% of the active state. During the hibernation season, many species of hibernating mammals cycle repeatedly between the active (aroused) and hibernating (torpid) states (T-A cycling), using brown adipose tissue (BAT) to drive cyclical rewarming. The regulatory mechanisms controlling this process remain undefined but are presumed to involve thermoregulatory centres in the hypothalamus. Here, we use the golden hamster (Mesocricetus auratus), and high-resolution monitoring of BAT, core body temperature (Tb), and ventilation rate, to sample at precisely defined phases of the T-A cycle. Usingc-fosas a marker of cellular activity we show that although the dorso-medial hypothalamus (DMH) is active during torpor entry, neither it nor the pre-optic area (POA) show any significant changes during the earliest stages of spontaneous arousal. Contrastingly, in 3 non-neuronal sites previously linked to control of metabolic physiology over seasonal and daily timescales, the choroid plexus (CP), pars tuberalis (PT) and third ventricle tanycytes, peakc-fosexpression is seen at arousal initiation. We suggest that through their sensitivity to factors in the blood or cerebrospinal fluid (CSF), these sites may mediate metabolic feedback-based initiation of the spontaneous arousal process.
Distinct roles of H3K27me3 and H3K36me3 in vernalization response, maintenance and resetting in winter wheat
Authors: Liu Xuemei , Lin Xuelei , Deng Min , Shi Bingxin , Chen Jinchao , Li Haoran , Xu Shujuan , Bie Xiaomin , Zhang Xiansheng , Chong Kang , Xiao Jun
Published: December 2023

Winter plants rely on vernalization, a vital process for adapting to cold and ensuring successful reproduction. However, understanding the role of histone modifications in guiding the vernalization process in winter wheat is limited. In this study, we investigate the transcriptome and chromatin dynamics in the shoot apex throughout the life cycle of winter wheat in the field. Two core histone modifications, H3K27me3 and H3K36me3, exhibit opposite pattern on the key vernalization geneVERNALIZATION1(VRN1), correlated with its induction during cold exposure. Additionally, H3K36me3 remains high atVRN1after cold exposure, maintaining its active state. Mutations in FERTILIZATION-INDEPENDENT ENDOSPERM (TaFIE) and SET DOMAIN GROUP 8 (TaSDG8), writer complex components of H3K27me3 and H3K36me3, respectively, affect flowering time. Interestingly,VRN1loses its high expression after cold exposure memory in the absence of H3K36me3. During embryo development,VRN1is silenced with the removal of H3K36me3 in both winter and spring alleles. H3K27me3 is selectively added to the winter allele, influencing the cold exposure requirement for the next generation. Integrating gene expression with H3K27me3 and H3K36me3 patterns identified potential regulators of flowering. This study reveals distinct roles of H3K27me3 and H3K36me3 in controlling vernalization response, maintenance, and resetting in winter wheat.

Significance Statement

Vernalization, initially observed in cereals, lacks a comprehensive understanding of its underlying mechanism, particularly regarding chromatin-mediated transcriptional regulation in winter wheat. By delving into the transcriptome and chromatin dynamics in the shoot apex throughout winter wheat’s life cycle, we pinpointed two crucial histone modifications, H3K27me3 and H3K36me3, each playing distinct roles at different vernalization stages. H3K27me3 is implicated in establishing and resetting the extended cold exposure requirement for winter wheat, gradually diminishing during vernalization. On the other hand, H3K36me3 is crucial for maintainingVRN1’s active state post-cold exposure, contributing to the memory of the vernalization treatment. Additionally, the integration of transcriptome and histone modification profiles unveiled potential novel regulators of flowering in winter wheat.
Zelda is dispensable forDrosophila melanogasterhistone gene regulation
Authors: O’Haren Tommy , Aoki Tsutomu , Rieder Leila E.
Published: December 2023

To ensure that the embryo can package exponentially increasing amounts of DNA, replication-dependent histones are some of the earliest transcribed genes from the zygotic genome. However, how the histone genes are identified is not known. The pioneer factors Zelda and CLAMP collaborate at a subset of genes to regulate zygotic genome activation in Drosophila melanogaster and target early activated genes to induce transcription. CLAMP also regulates the embryonic histone genes and helps establish the histone locus body, a suite of factors that controls histone mRNA biosynthesis. The relationship between Zelda and CLAMP led us to hypothesize that Zelda helps identify histone genes for early embryonic expression. We found that Zelda targets the histone locus early during embryogenesis, prior to histone gene expression. However, depletion ofzeldain the early embryo does not affect histone mRNA levels or histone locus body formation. While surprising, these results concur with other investigations into Zelda’s role in the early embryo, suggesting the earliest factors responsible for specifying the zygotic histone genes remain undiscovered.
Replay shapes abstract cognitive maps for efficient social navigation
Authors: Son Jae-Young , Vives Marc-Lluis , Bhandari Apoorva , FeldmanHall Oriel
Published: December 2023

To make adaptive social decisions, people must anticipate how information flows through their social network. While this requires knowledge of how people are connected, networks are too large to have firsthand experience with every possible route between individuals. How, then, are people able to accurately track information flow through social networks? We find that people immediately cache abstract knowledge about social network structure as they learn who is friends with whom, which enables the identification of efficient routes between remotely-connected individuals. These cognitive maps of social networks, which are built while learning, are then reshaped through overnight rest. During these extended periods of rest, a replay-like mechanism helps to make these maps increasingly abstract, which privileges improvements in social navigation accuracy for the longest communication paths that span distinct communities within the network. Together, these findings provide mechanistic insight into the sophisticated mental representations humans use for social navigation.
Unraveling the Role of P450 Reductase in Herbicide Metabolic Resistance Mechanism
Authors: Rigon Carlos Alberto Gonsiorkiewicz , Iwakami Satoshi , Gaines Todd A. , Dayan Franck E.
Published: December 2023

Plants require cytochrome P450 reductase (CPR) to supply two electrons for cytochrome P450 monooxygenase enzymes (P450) to react with an organic substrate. The transfer of electrons to the P450 active site in the P450 catalytic site relies on a robust and intricate CPR:P450 complex in the endoplasmic reticulum membrane. Transgenic Arabidopsis plants carryingCYP81A12fromEchinochloa phyllopogon, which metabolizes a broad spectrum of herbicides, were crossed with CPR knockoutatr1oratr2mutant lines. Homozygous gene knockout was confirmed using PCR, and gene copy number ofCYP81A12was determined using ddPCR. Arabidopsis lines expressingCYP81A12in combination withatr1oratr2knockout were used for herbicide dose-response and metabolism studies. Knocking outATR1in transgenic ArabidopsisCYP81A12significantly reduced herbicide resistance. Transgenic mutant plants (CYP81A12 atr1-b) had a 3.6-, 5.6-, 6.8- and at least 26-fold reduction in resistance to mesotrione, 2,4-D, penoxsulam and chlorsulfuron, respectively, in the dose-response assay. Knockouts of theATR2also decreased herbicide resistance, but to a lower magnitude thanATR1. These results corroborate ½ MS medium assay, and herbicide resistance reduction was observed for additional tested herbicides, bensulfuron, propoxycarbazone and bentazon. Our findings highlight the importance of CPRs in metabolic herbicide resistance in plants, by identifying that a single CPR knockout can reverse herbicide sensitivity . The different CPRs found in weeds have potential as target genes to manage metabolic herbicide resistance evolution. We further provide an in-depth exploration of the evolutionary implications in weed management arising from the results.

HIGHLIGHTS

Knocking out cytochrome P450 reductase 1 in herbicide tolerant Arabidopsis reduces herbicide resistance, highlighting CPRs as targets for managing herbicide resistance evolution in weeds.
A new method for the reproducible development of aptamers (Neomers)
Authors: Meehan Cathal , Hamilton Erika L. , Mansour Chloé G. , Lecocq Soizic , Drake Cole J. , An Yisi , Rodrigues Emily , Penner Gregory
Published: December 2023

The development of aptamers has been almost exclusively performed based on the SELEX method since their inception. While this method represents a powerful means of harnessing the in vitro evolution of sequences that bind to a given target, there are significant constraints in the design. The most significant constraint has been the reliance on counter selection on off-targets to drive specificity. Counter selection has not been as effective at driving aptamer specificity as the presence of immune tolerance, the capacity of the immune system to remove antibodies that bind to host targets, is for antibody development. This deficiency has constrained the commercial efficacy of aptamers to date. These limitations have been addressed with our design of a novel platform for aptamer identification. This new design is based on what we refer to as a Neomer library with sixteen random nucleotides interspersed with fixed sequences. The fixed sequences are designed to minimize the potential for hybridization, such that secondary structure is driven by the random nucleotides. The use of sixteen random nucleotides reduces the possible library sequences to 4.29 × 109. This enables the application of the same sequences to either the same target or different targets while maintaining a high level of structural diversity. In effect, this introduces the capacity for reproducibility in aptamer selection and in silico approach to replicating immune tolerance We provide here an overview of the new method and a description of the performance of aptamers selected for interleukin 6 developed using this approach.
Live-imaging reveals Coordinated Cell Migration and Cardiac Fate Determination during Mammalian Gastrulation
Authors: Abukar Shayma , Embacher Peter A. , Ciccarelli Alessandro , Varsani-Brown Sunita , North Isabel G.W. , Dean Jamie A. , Briscoe James , Ivanovitch Kenzo
Published: December 2023

Heart development involves the specification of cardiac progenitors at distinct stages and locations. Using live-imaging of mouse embryos between gastrulation and heart tube formation, we tracked individual mesodermal cells and reconstructed their lineage trees for up to five cell divisions. We found independent unipotent progenitors emerging at specific times, contributing exclusively to either left ventricle/atrioventricular canal (LV/AVC) or atrial myocytes. LV/AVC progenitors differentiated early to form the cardiac crescent, while atrial progenitors later generated the heart tube’s inflow tract during morphogenesis. We also identified short-lived bipotent progenitors with broad potential, illustrating early developmental plasticity. Sister cells from bipotent progenitors displayed greater dispersion and more diverse migratory trajectories within the anterior mesoderm than those from unipotent progenitors. Bipotent progenitors contributing to extraembryonic mesoderm (ExEm) exhibited the fastest and most dispersed migrations, whereas those giving rise to endocardial, LV/AVC, and pericardial cells showed a more gradual divergence, with late-stage behavioural shifts: endocardial cells increased in speed, while pericardial cells slowed relative to LV/AVC cells. Together the data reveal the regulation of individual cell directionality and cardiac fate allocation within the seemingly unorganised migratory pattern of mesoderm cells.
Matrix Linear Models for connecting metabolite composition to individual characteristics
Authors: Farage Gregory , Zhao Chenhao , Choi Hyo Young , Garrett Timothy J. , Kechris Katerina , Elam Marshall B. , Sen Śaunak
Published: December 2023

Abstract

High-throughput metabolomics data provide a detailed molecular window into biological processes. We consider the problem of assessing how the association of metabolite levels with individual (sample) characteristics such as sex or treatment may depend on metabolite characteristics such as pathway. Typically this is one in a two-step process: In the first step we assess the association of each metabolite with individual characteristics. In the second step an enrichment analysis is performed by metabolite characteristics among significant associations. We combine the two steps using a bilinear model based on the matrix linear model (MLM) framework we have previously developed for high-throughput genetic screens. Our framework can estimate relationships in metabolites sharing known characteristics, whether categorical (such as type of lipid or pathway) or numerical (such as number of double bonds in triglycerides). We demonstrate how MLM offers flexibility and interpretability by applying our method to three metabolomic studies. We show that our approach can separate the contribution of the overlapping triglycerides characteristics, such as the number of double bonds and the number of carbon atoms. The proposed method have been implemented in the open-source Julia package,MatrixLM. Data analysis scripts with example data analyses are also available.
A single computational objective drives specialization of streams in visual cortex
Authors: Finzi Dawn , Margalit Eshed , Kay Kendrick , Yamins Daniel L. K. , Grill-Spector Kalanit
Published: December 2023

Human visual cortex is organized into Dorsal, Lateral, and Ventral streams. A long-standing hypothesis is that the functional organization into streams emerged to support distinct visual behaviors. Here, we use a neural network-based computational model and a massive fMRI dataset to test why visual streams emerge. We find that models trained for stream-specific visual behaviors poorly capture neural responses and organization. Instead, a self-supervised Topographic Deep Artificial Neural Network, which encourages nearby units to respond similarly, successfully predicts neural responses, spatial segregation, and functional differentiation across streams. These findings challenge the prevailing view that streams evolved to separately support different behaviors, and suggest instead that functional organization arises from a single principle: balancing the learning of generally useful representations from visual inputs with local spatial constraints.
Using a decision tree to predict the number of COVID cases: a tutorial for beginners
Authors: Moctezuma Lucy , Rivera Lorena Benitez , van Nouhuijs Florentine , Orcales Faye , Kim Allen , Campbell Ross , Fuse Megumi , Pennings Pleuni S.
Published: December 2023

This manuscript describes the development of a module that is part of a learning platform named “NIGMS Sandbox for Cloud-based Learning”https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorialNIGMS Sandboxat the beginning of this Supplement. This module delivers learning materials on machine learning and decision tree concepts in an interactive format that uses appropriate cloud resources for data access and analyses.

Machine learning (ML) is an important tool in biomedical research and can lead to improvements in diagnosis, treatment, and prevention of diseases. During the COVID pandemic ML was used for predictions at the patient and community levels. Given its ubiquity, it is important that future doctors, researchers and teachers get acquainted with ML and its contributions to research. Our goal is to make it easier for everyone to learn about machine learning. The learning module we present here is based on a small COVID dataset, videos, annotated code and the use of Google Colab or the Google Cloud Platform (GCP). The benefit of these platforms is that students do not have to set up a programming environment on their computer which saves time and is also an important democratization factor. The module focuses on learning the basics of decision trees by applying them to COVID data. It introduces basic terminology used in supervised machine learning and its relevance to research. Our experience with biology students at San Francisco State University suggests that the material increases interest in ML.
A systematic review of the methods used to ensure rigour, transparency and validity in rapid evaluations, rapid appraisals and rapid assessments
Authors: Clark Sigrún Eyrúnardóttir , San Juan Norha Vera , Moniz Thomas , Appleton Rebecca , Barnett Phoebe , Vindrola-Padros Cecilia
Published: December 2023

Rapid approaches are essential when resources are limited in research settings and in the real-time evaluation of changing services. Limitations exist in their design and implementation which can lead to a reduced level of trust in findings. This study identified the methods used across rapid evaluations, appraisals and assessments to improve rigour, transparency and validity. Four scientific databases and one search engine were searched between 11-16th August 2022. Screening led to the inclusion of 169 articles that provided a much-needed repository of methods that can be used during the design and implementation of rapid studies to improve rigour. We suggest that this repository of methods inform the development of transparent reporting standards for future rapid evaluations, appraisals and assessments.
Higher-order thalamocortical projections selectively control excitability via NMDAR and mGluRI-mediated mechanisms
Authors: Brandalise Federico , Chéreau Ronan , Raig Claudia Morin , Bawa Tanika , Mule Nandkishor , Pagès Stéphane , Markopoulos Foivos , Holtmaat Anthony
Published: December 2023

The apical dendrites of layer (L) 2/3 pyramidal neurons in the mouse somatosensory cortex integrate synaptic input from long-range projections. Among those, inputs from the higher-order thalamic posteromedial nucleus may facilitate sensory-evoked cortical activity, but it remains elusive how this role emerges. Here we show usingex vivodendritic recordings that these projections provide dense synaptic input to broad tufted neurons residing predominantly in L2 and cooperate with other inputs to produce NMDA spikes. They have the unique capacity to block two-pore domain potassium leak channels via group 1 metabotropic glutamate receptor (mGluRI) signaling, which increases excitability. Slender tufted L2/3 neurons and other long-range projections fail to invoke these mechanisms.In vivoimaging of calcium signals confirms the presence of mGluRI-dependent modulation of feedback-mediated spiking in L2. Our results imply that higher-order thalamocortical projections regulate neuronal excitability in a cell type and input-selective manner through fast NMDAR and mGluRI-dependent mechanisms.
Event Detection and Classification from Multimodal Time Series with Application to Neural Data
Authors: Sadras Nitin , Pesaran Bijan , Shanechi Maryam M.
Published: December 2023

The detection of events in time-series data is a common signal-processing problem. When the data can be modeled as a known template signal with an unknown delay in Gaussian noise, detection of the template signal can be done with a traditional matched filter. However, in many applications, the event of interest is represented in multimodal data consisting of both Gaussian and point-process time series. Neuroscience experiments, for example, can simultaneously record multimodal neural signals such as local field potentials (LFPs), which can be modeled as Gaussian, and neuronal spikes, which can be modeled as point processes. Currently, no method exists for event detection from such multimodal data, and as such our objective in this work is to develop a method to meet this need. Here we address this challenge by developing the multimodal event detector (MED) algorithm which simultaneously estimates event times and classes. To do this, we write a multimodal likelihood function for Gaussian and point-process observations and derive the associated maximum likelihood estimator of simultaneous event times and classes. We additionally introduce a cross-modal scaling parameter to account for model mismatch in real datasets. We validate this method in extensive simulations as well as in a neural spike-LFP dataset recorded during an eye-movement task, where the events of interest are eye movements with unknown times and directions. We show that the MED can successfully detect eye movement onset and classify eye movement direction. Further, the MED successfully combines information across data modalities, with multimodal performance exceeding unimodal performance. This method can facilitate applications such as the discovery of latent events in multimodal neural population activity and the development of brain-computer interfaces for naturalistic settings without constrained tasks or prior knowledge of event times.
From data to data asset: conceptual evolution and strategic imperatives in the digital economy era
Authors: Xu Tao , Shi Hanning , Shi Yongjiang , You Jianxin
Published: December 2023

Purpose

The purpose of this paper is to explore the concept of data assets and how companies can assetize their data. Using the literature review methodology, the paper first summarizes the conceptual controversies over data assets in the existing literature. Subsequently, the paper defines the concept of data assets. Finally, keywords from the existing research literature are presented visually and a foundational framework for achieving data assetization is proposed.

Design/methodology/approach

This paper uses a systematic literature review approach to discuss the conceptual evolution and strategic imperatives of data assets. To establish a robust research methodology, this paper takes into account two main aspects. First, it conducts a comprehensive review of the existing literature on digital technology and data assets, which enables the derivation of an evolutionary path of data assets and the development of a clear and concise definition of the concept. Second, the paper uses Citespace, a widely used software for literature review, to examine the research framework of enterprise data assetization.

Findings

The paper offers pivotal insights into the realm of data assets. It highlights the changing perceptions of data assets with digital progression and addresses debates on data asset categorization, value attributes and ownership. The study introduces a definitive concept of data assets as electronically recorded data resources with real or potential value under legal parameters. Moreover, it delineates strategic imperatives for harnessing data assets, presenting a practical framework that charts the stages of “resource readiness, capacity building, and data application”, guiding businesses in optimizing their data throughout its lifecycle.

Originality/value

This paper comprehensively explores the issue of data assets, clarifying controversial concepts and categorizations and bridging gaps in the existing literature. The paper introduces a clear conceptualization of data assets, bridging the gap between academia and practice. In addition, the study proposes a strategic framework for data assetization. This study not only helps to promote a unified understanding among academics and professionals but also helps businesses to understand the process of data assetization.
Why employees engage in proactive career behavior: examining the role of family motivation
Authors: Wang Yating , Hou Qinghui , Xue Zewei , Li Huan
Published: December 2023

Purpose

This study established and examined a moderated mediation model connecting family motivation with proactive career behavior (PCB). Drawing on social cognitive career theory model of career self-management and person-environment fit theory, the authors posit that the influence of family motivation on PCB is mediated by career goal setting (CGS) and moderated by career support climate (CSC).

Design/methodology/approach

Using multilevel modeling techniques, data were collected from 98 leaders and 416 employees at two-time points.

Findings

Results show that family motivation has a positive direct and indirect effect on PCB through CGS. Additionally, CSC strengthens the positive effect of family motivation on PCB through CGS.

Practical implications

For employees, proactive career management and the establishment of clear career goals are vital for fulfilling family responsibilities. Simultaneously, for managers and organizations, creating a supportive work environment is crucial to encourage employees in career management.

Originality/value

While existing research highlights the detrimental effect of fulfilling family caregiving responsibilities on employees' career development, the comprehension of this relationship remains limited. Taking a family motivation perspective, this study explores the mechanisms through which family motivation stimulates employees to engage in PCB, with a specific focus on the moderating influence of CSC. The findings offer fresh insights into the role of family motivation in career development, contributing significantly to the broader literature on the intersection of family and careers.
Modeling and simulation analysis of current transformer based on magnetizing current as the solution variable
Authors: You Hongsen , Gan Mengying , Duan Dapeng , Zhao Cheng , Chi Yuan , Gao Shuai , Yuan Jiansheng
Published: December 2023

Purpose

This paper aims to develop a model that reflects the current transformer (CT) core materials nonlinearity. The model enables simulation and analysis of the CT excitation current that includes the inductive magnetizing current and the resistive excitation current.

Design/methodology/approach

A nonlinear CT model is established with the magnetizing current as the solution variable. This model presents the form of a nonlinear differential equation and can be solved discretely using the Runge–Kutta method.

Findings

By simulating variations in the excitation current for different primary currents, loads and core materials, the results demonstrate that enhancing the permeability of the B–H curve leads to a more significant improvement in the CT ratio error at low primary currents.

Originality/value

The proposed model has three obvious advantages over the previous models with the secondary current as the solution variable: (1) The differential equation is simpler and easier to solve. Previous models contain the time differential terms of the secondary current and excitation flux or the integral term of the flux, making the iterative solution complicated. The proposed model only contains the time differential of the magnetizing current. (2) The accuracy of the excitation current obtained by the proposed model is higher. Previous models calculate the excitation current by subtracting the secondary current from the converted primary current. Because these two currents are much greater than the excitation current, the error of calculating the small excitation current by subtracting two large numbers is greatly enlarged. (3) The proposed model can calculate the distorted waveform of the excitation current and error for any form of time-domain primary current, while previous models can only obtain the effective value.
A systematic review of lean implementation frameworks and roadmaps: lessons learned and the way forward
Authors: Mamoojee-Khatib Hafeeza , Antony Jiju , Teeroovengadum Viraiyan , Garza-Reyes Jose Arturo , Tortorella Guilherme Luz , Foster Monika , Cudney Elizabeth A.
Published: December 2023

Purpose

The purpose of this study is to carry out a comprehensive systematic review of lean implementation frameworks and roadmaps developed over the past decade and report the key findings along with the limitations and the way forward.

Design/methodology/approach

A systematic review methodology proposed by Tranfield (2003), was followed to identify the relevant works on the research topic. Articles were searched using a set of inclusion criteria in various databases including Google Scholar, Web of Science and Science Direct over a period of 30 years.

Findings

The high failure rate of lean system implementation, reaching a range between 70 and 90% in almost all industries, is a matter of concern. This failure rate is still high even though numerous frameworks and roadmap models exist to streamline lean implementation. There is no standard framework or roadmap identified in the literature and many organisations are implementing lean in their unique ways. However, it would be desirable to develop a practical and systematic roadmap on lean-looking into the cultural and leadership dimensions rather than focusing on a set of tools. Moreover, most frameworks and roadmaps lack the sustenance aspects of lean implementation.

Research limitations/implications

This research only identifies the fundamental gaps with the existing frameworks and roadmaps on lean implementation. The next phase of the research is to develop a roadmap and validate it with a number of organisations in different cultural contexts and leadership styles.

Originality/value

The authors argue that this is one of the most comprehensive systematic review on lean frameworks and roadmaps, ever produced in the literature to date.
Is Hong Kong still an entrepôt under the Sino‐U.S. trade war?
Authors: Chong Terence Tai Leung , Lo Vincent Pok Ho
Published: December 2023

This paper studies the Hong Kong economy from a trade intermediary's perspective. Using a structural vector autoregression (SVAR) framework, we discover that trade‐related external shocks mainly affect the economy through re‐exports channel over the offshore trade channel. We observe that re‐exports shock does not transmit to the real economy through the employment channel. A puzzling phenomenon is that trade‐related employment has been in decline since 2008. Moreover, we notice that although the Sino‐U.S. trade war exerted much downward pressure on economic growth between 2018 and 2019, the trade intermediary sector swiftly recovered in 2020, reflecting the versatility of the external trade sector in Hong Kong.