bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial and Ethnic Disparities in the Utilization and Outcomes with WATCHMAN FLX: A SURPASS analysis of the NCDR LAAO Registry
Authors: Alli Oluseun O , Garg Jalaj , Boursiquot Brian C. , Kapadia Samir R , Yeh Robert W , Price Matthew J , Piccini Jonathan P , Nair Devi G , Hsu Jonathan C , Gibson Douglas N , Alloco TDominic , Christen Thomas , Sutton Brad , Freeman James V
Published: May 2024

Background

Left atrial appendage occlusion (LAAO) is increasingly used as an alternative to oral anticoagulation for stroke prevention in select patients with atrial fibrillation. Data on outcomes in racial and ethnic minority individuals are limited. This analysis assessed differences in the utilization and outcomes of LAAO by race and ethnicity in a large national registry.

Methods

This analysis acquired data on WATCHMAN FLX patients from the National Cardiovascular Data Registry (NCDR) LAAO Registry through September 2022. All patients with an attempted WATCHMAN FLX implantation and known race and ethnicity were included. Baseline characteristics and 1 year event rates were compared.

Results

A total of 97,185 patients were analyzed; 87,339 were White (90%), 3,750 Black (Black/African American 3.9%), and 2,866 Hispanic ([Hispanic/Latinx] 2.9%). Black and Hispanic patients were younger with a higher incidence of prior stroke and significant bleeding compared to White patients. Black and Hispanic patients were treated with LAAO in smaller numbers relative to their proportion of the US population. Rates of procedural success were similar between groups. Though direct oral anticoagulants were prescribed in most patients across the groups, dual and single antiplatelet therapy were prescribed more often in Black patients. Black patients had significantly higher rates of 1-year death and bleeding compared to White and Hispanic patients.

Conclusions

Patients from racial and ethnic minority groups comprise a disproportionately small fraction of all patients who undergo LAAO. Black and Hispanic patients were younger but had significantly higher comorbidities compared to White patients. Procedural success was similar amongst the groups but Black patients experienced higher rates of death and bleeding at 1 year.

Graphic Abstract

What is known

There is underutilization of LAAO among racial and ethnic minority patients with AF and there are racial and ethnic differences in periprocedural outcomes.

What this study adds

In this study from a large US national registry of patients undergoing LAAO, Black patients were younger but had higher baseline comorbidities and experienced higher rates of bleeding at 45 days and 1-year and higher 1-year mortality. Further work is needed to enroll diverse patients into research trials and to provide equitable AF-related access to advanced care and intra- procedural and post-procedural care in US real-world practice.
KAS-ATAC reveals the genome-wide single-stranded accessible chromatin landscape of the human genome
Authors: Kim Samuel H. , Marinov Georgi K. , Greenleaf William J.
Published: May 2024

Gene regulation in most eukaryotes involves two fundamental physical processes – alterations in the packaging of the genome by nucleosomes, with activecis-regulatory elements (CREs) generally characterized by an open-chromatin configuration, and the activation of transcription. Mapping these physical properties and biochemical activities genome-wide – through profiling chromatin accessibility and active transcription – are key tools used to understand the logic and mechanisms of transcription and its regulation. However, the relationship between these two states has until now not been accessible to simultaneous measurement. To address this, we developed KAS-ATAC, a combination of the KAS-seq (Kethoxal-Assisted SsDNA sequencing and ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) methods for mapping single-stranded DNA (and thus active transcription) and chromatin accessibility, respectively, enabling the genome-wide identification of DNA fragments that are simultaneously accessible and contain ssDNA. We use KAS-ATAC to evaluate levels of active transcription over different classes of regulatory elements in the human genome, to estimate the absolute levels of transcribed accessible DNA over CREs, to map the nucleosomal configurations associated with RNA polymerase activities, and to assess transcription factor association with transcribed DNA through transcription factor binding site (TFBS) footprinting. We observe lower levels of transcription over distal enhancers compared to promoters, surprisingly high abundance of ssDNA immediately around/within CTCF occupancy footprints, and distinct nucleosomal configurations around transcription initiation sites associated with active transcription. Remarkably, most TFs associate equally with transcribed and non-transcribed DNA but a few factors specifically do not exhibit footprints over ssDNA-containing fragments. We anticipate KAS-ATAC to continue to derive useful insights into chromatin organization and transcriptional regulation in other contexts in the future.
State- and circuit-dependent opponent-processing of fear
Authors: Yau Joanna Oi-Yue , Li Amy , Abdallah Lauren , Lisowksi Leszek , McNally Gavan P.
Published: May 2024

The presence of valence coding neurons in the basolateral amygdala (BLA) that form distinct projections to other brain regions implies functional opposition between aversion and reward during learning. However, evidence for opponent interactions in fear learning is sparse and may only be apparent under certain conditions. Here we test this possibility by studying the roles of the BLA➔central amygdala (CeA) and BLA➔nucleus accumbens (Acb) pathways in fear learning in male rats. First, we assessed the organisation of these pathways in the rat brain. BLA➔CeA and BLA➔Acb pathways were largely segregated in the BLA but shared overlapping molecular profiles. Then we assessed activity of the BLA➔CeA and BLA➔Acb pathways during two different forms of fear learning - fear learning in a neutral context and fear learning in a reward context. BLA ➔ CeA neurons were robustly recruited by footshock regardless of where fear learning occurred whereas recruitment of BLA➔Acb neurons was state-dependent because footshock only recruited this pathway in a reward context. Finally, we assessed the causal roles of activity in these pathways in fear learning. Photoinhibition of the BLA➔CeA pathway during the footshock US impaired fear learning, regardless of where fear learning occurred. In contrast, photoinhibition of the BLA➔Acb pathway augmented fear learning, but only in the reward context. Taken together, our findings show circuit- and state-dependent opponent processing of fear. Footshock-driven activity in the BLA➔Acb pathway can functionally oppose the BLA➔CeA pathway to limit how much fear is learned.

Significance Statement

Here we identify a fear opponent process in the brain. We show that an aversive event can recruit distinct populations of neurons in the rat basolateral amygdala. One population projects to the central amygdala to promote fear learning. A second population projects to the nucleus accumbens to oppose fear learning. These nucleus accumbens projecting neurons limit how much fear is learned and are candidates for therapeutic targeting to minimize the amount of fear learned after a traumatic experience.
Engineered Oxalate decarboxylase boosts activity and stability for biological applications
Authors: Dindo Mirco , Conter Carolina , Uechi Gen-ichiro , Pampalone Gioena , Ruta Luana , Pey Angel L. , Rossi Luigia , Laurino Paola , Magnani Mauro , Cellini Barbara
Published: May 2024

Oxalate decarboxylase (OxDC) fromBacillus subtilisis a Mn-dependent hexameric enzyme which converts oxalate to carbon dioxide and formate. Recently, OxDC has attracted the interest of the scientific community, due to its biotechnological and medical applications for the treatment of hyperoxalurias, a group of pathologic conditions associated with excessive oxalate urinary excretion due to either increased endogenous production or increased exogenous absorption. The fact that OxDC displays optimum pH in the acidic range, represents a big limitation for most biotechnological applications involving processes occurring at neutral pH, where the activity and stability of the enzyme are remarkably reduced. Here, through bioinformatics-guided protein engineering, followed by combinatorial mutagenesis and analyses of activity and thermodynamic stability, we identified a double mutant of OxDC endowed with enhanced catalytic efficiency and stability under physiological conditions. The obtained engineered form of OxDC offers a potential tool for improved intestinal oxalate degradation in hyperoxaluria patients.
Pore formation in complex biological membranes: torn between evolutionary needs
Authors: Starke Leonhard J. , Allolio Christoph , Hub Jochen S.
Published: May 2024

The primary function of biological membranes is to enable compartmentalization among cells and organelles. Loss of integrity by the formation of membrane pores would trigger uncontrolled depolarization or influx of toxic compounds, posing a fatal thread to living cells. How the lipid complexity of biological membranes enables mechanical stability against pore formation while simultaneously allowing ongoing membrane remodeling is largely enigmatic. We performed molecular dynamics simulations of eight complex lipid membranes including the plasma membrane and membranes of the organelles ER, Golgi, lysosome, and mitochondrion. To quantify the mechanical stability of these membranes, we computed the free energies for nucleating a transmembrane pore as well as the line tension along the rim of open pores. Our simulations reveal that complex biological membranes are overall remarkably stable, however with the plasma membrane standing out as exceptionally stable, which aligns with its crucial role as a protective layer. We observe that sterol content is the main regulator for biomembrane stability, and that lateral sorting among lipid mixtures influences the energetics of membrane pores. A comparison of 25 model membranes with varying sterol content, tail length, tail saturation, and head group type shows that the pore nucleation free energy is mostly associated with the lipid tilt modulus, whereas the line tension along the pore rim is determined by the lipid intrinsic curvature. Together, our study provides an atomistic and energetic view on the role of lipid complexity on biomembrane stability.

Significance statement

Biomembranes have evolved to fulfill seemingly conflicting requirements. Membranes form a protective layer against bacterial or viral infection and against external mechanical and toxic stress, thus requiring mechanical stability. However, membranes are furthermore involved in ongoing remodeling for homeostasis, signaling, trafficking, and morphogenesis, necessitating a high degree of plasticity. How the chemical diversity of membranes, comprising hundreds of lipid species, contributes to enable both stability and plasticity is not well understood. We used molecular simulations and free energy calculations of pore formation in complex biomembranes to reveal how mechanical and geometric properties of lipids as well as lateral lipid sorting control the integrity of complex membranes.
Evidence of optimal control theory over active inference in corticospinal excitability modulations
Authors: Brandt I.M. , Grünbaum T. , Christensen M.S.
Published: May 2024

Two theories, optimal control theory and active inference, dominate the motor control field. We use transcranial magnetic stimulation (TMS) in force and angle tasks to examine whether corticospinal excitability represents a motor command, as proposed by the optimal control theory, or a proprioceptive prediction, as proposed by active inference. Our results strongly support optimal control theory. We encourage comparisons of the theories against each other based on empirically testable predictions.
Peripheral B Lymphocyte Serves as A Reservoir for The Persistently Covert Infection of MandarinfishSiniperca chuatsiRanavirus
Authors: Zhang Wenfeng , Gong Hui , Sun Qianqian , Fu Yuting , Wu Xiaosi , Deng Hengwei , Weng Shaoping , He Jianguo , Dong Chuanfu
Published: May 2024

GenusRanavirusin familyIridoviridaeis composed of large members with various genomic sizes and viral gene contents, infecting a variety of ectothermic vertebrates including reptile, amphibians and bony fish worldwide. Mandarinfish ranavirus (MRV) is a very distinctive member among genusRanavirus. Persistently convert infection of MRV were previously observed in natural outbreak of MRV, but the underlying mechanism remains unclear. We here evidenced that mandarinfish peripheral B lymphocytes are implemented as viral reservoirs to maintain persistent and covert infection. When mandarinfish were infected with sublethal dosage of MRV under nonpermissive temperature (19 ºC) and permissive temperature (26 ºC), respectively, all fish in 19 ºC group survived and entered persistent phase of infection characterized with very low viral load in white blood cell, whereas partial fish died of MRV infection in 26 ºC group, and the survivals then initiated persistent status. Gradually raising temperature, vaccination and dexamethasone treatment can reactivate the quiescent MRV to replicate and result in partial mortality. The viral reservoir investigates showed that IgM+-labelled B lymphocytes but not CD3Δ+-labelled T lymphocytes and MRC-1+-labelled macrophages are target cells for the persistent infection of MRV. Moreover, the quiescent MRV could not be reactivated by heat-killedEscherichia coli, indicating a very different reactivation mechanism from that of other known rannaviral member. Collectively, we are the first to confirm the presence of B cell-dependent persistent and covert infection of ranavirus, and provide a new clue for better understanding the complex infection mechanism of vertebrate iridovirus, especially regarding ranavirus.

IMPORTANCE

Viruses known as HIV, HBV and EBV etc. evade host immune clearance by establishing long-term even lifelong persistent or latent infection. In vertebrate iridovirus, FV3, the type species of genusRanaviruswas evidenced to establish persistent infection by usingXenopusperitoneal macrophages as reservoirs. MRV is a very distinctive ranavirus from FV3 with very different genomic content and host species. We here uncovered MRV establishes persistent and covert infection by using peripheral B lymphocytes as virus reservoirs. During persistent infection, very low copies of quiescent MRV were harbored in peripheral B lymphocytes. Water temperature stress, vaccination stimulation, and dexamethasone treatment can reactivate quiescent MRV to replicate in abundance via a non-TLR5-mediated manner, and results in recurrence of MRV disease. Our finding suggests the diversity and complexity of the pathogenic mechanisms among ranaviruses, and also has important scientific significance for in-depth understanding of the infection and immunity interaction of vertebrate iridoviruses.
Validation and identification of new QTLs for plant and fruit developmental and composition traits in eggplant under low N conditions
Authors: Villanueva Gloria , Vilanova Santiago , Plazas Mariola , Gramazio Pietro , Prohens Jaime
Published: May 2024

Enhancing plant adaptation to low input conditions is a fundamental goal for implementing sustainable agriculture. In the present study, two eggplant (Solanum melongena) accessions (MEL1 and MEL5), two introgression lines (ILs) derived from eggplant wild relativesS. dasyphyllum(IL-M1-D1) andS. insanum(IL-M5-I9), and a heterozygous version of this last IL (ILHet-M5-I9), along with hybrids among them were evaluated under low N (LN) conditions. IL-M1-D1 carries an introgressed fragment of 4.9 Mb in homozygosis fromS. dasyphyllumon chromosome 2, while IL-M5-I9 and ILHet-M5-I9 carry an introgression of 21.5 Mb on chromosome 9 in homozygosis and heterozygosis, respectively, fromS. insanum. Multiple quantitative trait loci (QTLs) for several traits of interest were associated with both introgressions under LN conditions in a previous study with segregating advanced backcrosses. Here we evaluated the performance of these materials for 22 agronomic and developmental traits under low N fertilization (LN) conditions. Hybrids with the ILs enabled the study of genetic background effects on QTLs expression. The materials evaluated showed a significant phenotypic variation, particularly within hybrids segregating for the introgression fromS. insanumin chromosome 9. Statistical analysis revealed no significant differences among hybrids carrying or not the introgression on chromosome 2 ofS. dasyphyllum, and only slight differences were observed between the IL-M1-D1 and its recurrent parentS. melongenaMEL1, suggesting a limited impact of this introgression on chromosome 2 on the phenotype variation. However, the differences observed between IL-M5-I9 and its recurrent parentS. melongenaMEL5, together with the association between genotypic and phenotypic variation in hybrids segregating for this introgression, allowed the identification of 13 QTLs on chromosome 9. These results successfully validated the previously identified QTLs for flavonol content in leaves, nitrogen balanced index, fruit mean weight, and nitrogen content in leaves and, also revealed nine new QTLs associated with the introgressed genomic region in chromosome 9. This study emphasizes the influence of environmental conditions, genotypes, and genetic backgrounds on the phenotypic expression of eggplant QTLs introgressed from wild relatives and highlights the importance of QTL validation. These findings contribute valuable insights for developing new eggplant cultivars for a more sustainable agriculture, particularly with adaptation to LN conditions.
Prognostic importance of splicing-triggered aberrations of protein complex interfaces in cancer
Authors: Newaz Khalique , Schaefers Christoph , Weisel Katja , Baumbach Jan , Frishman Dmitrij
Published: May 2024

Aberrant alternative splicing (AS) is a prominent hallmark of cancer. AS can perturb protein-protein interactions (PPIs) by adding or removing interface regions encoded by individual exons. Identifying prognostic exon-exon interactions (EEIs) from PPI interfaces can help discover AS-affected cancer-driving PPIs that can serve as potential drug targets. Here, we assessed the prognostic significance of EEIs across 15 cancer types by integrating RNA-seq data with three-dimensional (3D) structures of protein complexes. By analyzing the resulting EEI network we identified patient-specific perturbed EEIs (i.e., EEIs present in healthy samples but absent from the paired cancer samples or vice versa) that were significantly associated with survival. We provide the first evidence that EEIs can be used as prognostic biomarkers for cancer patient survival. Our findings provide mechanistic insights into AS-affected PPI interfaces. Given the ongoing expansion of available RNA-seq data and the number of 3D structurally-resolved (or confidently predicted) protein complexes, our computational framework will help accelerate the discovery of clinically important cancer-promoting AS events.
Design of a new model yeast consortium for ecological studies of enological fermentation
Authors: Pourcelot Eléonore , Vigna Audrey , Marlin Thérèse , Galeote Virginie , Nidelet Thibault
Published: May 2024

Wine fermentation involves complex microbial communities of non-Saccharomycesyeast species besides the well-knownSaccharomyces cerevisiae. While extensive research has enhanced our understanding ofS. cerevisiae, the development of multi-species fermentation starters has led to increased interest in yeast interactions and the role of microbial diversity in winemaking. Consequently, molecular methods have emerged to identify the different species at different stages of the winemaking process. Model microbial communities or consortia, which provide simplified systems resembling natural microbial diversity, offer opportunities to investigate population dynamics and understand the role of community diversity in ecosystem performance.

Here, this work aims to design a yeast consortium reflecting the diversity of wine yeasts and to develop a method for accurately tracking their population dynamics during fermentation. We developed and characterized a six-species consortium, withS. cerevisiae,Hanseniaspora uvarum,Starmerella bacillaris,Metschnikowia pulcherrima,Lachancea thermotoleransandTorulaspora delbrueckii. By tagging each yeast species with distinct fluorescent markers, the study enables real-time monitoring of individual species within the consortium using flow cytometry. We have carried out a complete analysis of this consortium, studying the evolution of populations over time and examining factors such as metabolite production and fermentation kinetics.

In addition, the yeast consortium was used to test the diversity-function relationship as a proof of concept. We sought to determine the impact of the initial evenness on communities’ performances subjected to osmotic stress. To this end, ten randomly designed consortia with varying initial species proportions were followed in enological fermentation with 200 and 280 g/L of initial sugars. The initial proportion of certain species affected the population dynamics and metabolite production however no demonstrable effect of the initial evenness on the response to osmotic stress was shown.

These results demonstrated the usefulness of the presented consortium, which is now available to the scientific community and can contribute to future work trying to decipher multispecies dynamics and the role of yeast diversity in wine fermentation.
Jchain-DTRMice Allow for Diphtheria Toxin-Mediated Depletion of Antibody-Secreting Cells and Evaluation of Their Differentiation Kinetics
Authors: Pioli KimAnh T. , Ritchie Matthew , Haq Hira , Pioli Peter D.
Published: May 2024

Antibody-secreting cells (ASCs) are generated following B cell activation and constitutively secrete antibodies. As such, ASCs are key mediators of humoral immunity whether it be in the context of pathogen exposure, vaccination or even homeostatic clearance of cellular debris. Therefore, understanding basic tenants of ASC biology such as their differentiation kinetics following B cell stimulation is of importance. Towards that aim, we developed a mouse model which expresses simianHBEGF(a.k.a., diphtheria toxin receptor (DTR)) under the control of the endogenousJchainlocus (or J-DTR). ASCs from these mice expressed high levels of cell surface DTR and were acutely depleted following diphtheria toxin treatment. Furthermore, proof-of-principle experiments demonstrated the ability to use these mice to track ASC reconstitution following depletion in 3 distinct organs. Overall, J-DTR mice provide a new and highly effective genetic tool allowing for the study of ASC biology in a wide range of potential applications.
Campylobacterinfection of young children in Colombia and its impact on the gastrointestinal environment
Authors: Burcham Zachary M. , Tweedie Jessie L. , Farfán-García AE , Nolan Vikki G. , Donohoe Dallas , Gómez-Duarte Oscar G. , Johnson Jeremiah G.
Published: May 2024

Campylobacterinfections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low-and-middle income countries. It remains unclear howCampylobacterimpacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia that were either infected or uninfected withCampylobacterduring a case-controlled study on acute diarrheal disease. Here, we report that the microbiome ofCampylobacter-infected children only changed in their abundance ofCampylobacterspp. despite the inclusion of children with or without diarrhea. In addition to increasedCampylobacter,computational models were used to identify fecal metabolites that were associated withCampylobacterinfection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggest that colonocyte metabolism are impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted byCampylobacterinfection, but were elevated in uninfected children with diarrhea.

Importance

Gastrointestinal infection with pathogenicCampylobacterspecies has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low-and-middle income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association ofCampylobacterspecies with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected withCampylobacterspecies, and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.
Impact of the elderly lung mucosa onMycobacterium tuberculosismetabolic adaptation during infection of alveolar epithelial cells
Authors: Olmo-Fontánez Angélica M. , Allué-Guardia Anna , Garcia-Vilanova Andreu , Glenn Jeremy , Wang Shu-Hua , Merritt Robert E. , Schlesinger Larry S. , Turner Joanne , Wang Yufeng , Torrelles Jordi B.
Published: May 2024

Background

Tuberculosis (TB) is one of the top leading causes of death due to a single infectious agent. Upon infection,Mycobacterium tuberculosis(M.tb) is deposited in the alveoli and encounters the lung mucosa or alveolar lining fluid (ALF). We previously determined that increasedM.tbreplication in human macrophages and alveolar epithelial cells (ATs) is mediated by age-associated changes in human ALF. Here we determine the transcriptional profile ofM.tbwhen exposed to healthy ALF from adult (A-ALF) or elderly (E-ALF) individuals before and during infection of ATs.

Results

Prior to infection, exposure to E-ALF upregulatesM.tbgenes associated with the ESX-4 secretion system, immunomodulatory proteins from the ESX-5 system, and genes encoding phospholipases, phosphatases, and proteases. During infection, E-ALF exposure upregulates keyM.tbgenes from the ESX-5 secretion system, genes associated with PDIMs biosynthesis and transport, and genes linked to bacterial oxidative stress defense mechanisms.

Conclusions

These findings demonstrate how altered ALF in old age can impact the metabolic status ofM.tb, enabling greater adaptation to the host and potentially explainingMtb’s increased survival within host cells. Importantly, we present the first transcriptomic analysis on the impact of the elderly lung mucosa onM.tbpathogenesis during intracellular replication in ATs.
Protection againstClostridioides difficiledisease by a naturally avirulentC. difficilestrain
Authors: Dong Qiwen , Harper Stephen , McSpadden Emma , Son Sophie S. , Allen Marie-Maude , Lin Huaiying , Smith Rita C. , Metcalfe Carolyn , Burgo Victoria , Woodson Che , Sundararajan Anitha , Rose Amber , McMillin Mary , Moran David , Little Jessica , Mullowney Michael , Sidebottom Ashley M. , Shen Aimee , Fortier Louis-Charles , Pamer Eric G.
Published: May 2024

Clostridioides difficile (C. difficile)strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75, that is avirulent in mice despite densely colonizing the colon. Here, we show that co-infecting mice with the avirulent ST1-75 and virulent R20291 strains protects mice from colitis due to rapid clearance of the virulent strain and persistence of the avirulent strain. Although avirulence of ST1-75 is due to a mutation in thecdtRgene, which encodes a response regulator that modulates the production of all threeC. difficiletoxins, the ability of ST1-75 to protect against acute colitis is not directly attributable to thecdtRmutation. Metabolomic analyses indicate that the ST1-75 strain depletes amino acids more rapidly than the R20291 strain and supplementation with amino acids ablates ST1-75’s competitive advantage, suggesting that the ST1-75 strain limits the growth of virulent R20291 bacteria by amino acid depletion. Since the germination kinetics and sensitivity to the co-germinant glycine are similar for the ST1-75 and R20291 strains, our results identify the rapidity ofin vivonutrient depletion as a mechanism providing strain-specific, virulence-independent competitive advantages to different BI/NAP1/027 strains. They also suggest that the ST1-75 strain may, as a biotherapeutic agent, enhance resistance to CDI in high-risk patients.

Importance

Clostridioides difficileinfections (CDI) are prevalent in healthcare settings and are associated with high recurrence rates. Therapies to prevent CDI, including recent FDA-approved live biotherapeutic products, are costly and have not been used to prevent primary infections. While a nontoxigenicC. difficilestrain (NTCD-M3) protects against virulent CDI in animals and reduced CDI recurrence in a phase 2 clinical trial, protection against CDI recurrence in humans was variable and required high doses of the nontoxigenic strain. Here we show that an avirulentC. difficileisolate, ST1-75, efficiently outcompetes virulentC. difficilestrains in mice when co-infected at a 1:1 ratio. Our data suggest that inter-strain competition results from ST1-75’s more rapid depletion of amino acids than the virulent R20291 strain. Our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI.
Chronic abolition of evoked vesicle release from layer 5 projection neurons disrupts the laminar distribution of parvalbumin interneurons in the adult cortex
Authors: Szabó Florina P , Sigutova Veronika , Schneider Anna M , Hoerder-Suabedissen Anna , Molnár Zoltán
Published: May 2024

Establishing precisely built neuronal networks during cortical development requires appropriate proportions of glutamatergic and GABAergic neurons. Developmental disturbances in pyramidal neuron activity can impede the development of GABAergic neurons with long-lasting effects on inhibitory networks. However, the role of deep-layer pyramidal neurons in instructing the development and distribution of GABAergic neurons remains unknown. To unravel the role of deep-layer pyramidal neuron activity in orchestrating the spatial and laminar organisation of parvalbumin neurons, we selectively manipulated the activity of projection neurons in layer 5 of the cortex. By ablating SNAP25 from subsets of glutamatergic L5 projection neurons across the cortical mantle, we abolished Ca2+-dependent vesicle release from Rbp4-Cre+ pyramidal neurons. We explored thelocal(location of the cell bodies) and theglobal(subcortical projection sites) effects of chronically silencing cortical L5 neurons on parvalbumin interneurons. We found that the chronic cessation of vesicle release from L5 projection neurons left the density, distribution, and developmental trajectory of cortical and subcortical PV neurons intact during the second and third postnatal week; however, it resulted in the reorganisation of the laminar distribution of cortical PV neurons in layer 4 of S1 in the adult cortex. The abolition of evoked vesicle release from L5 also affected the perineuronal nets in the adult motor cortex and revealed a significant decrease in the density of VVA+ and PV-VVA+ cells in L5 of M1 at 3 months of age. The alterations in the laminar arrangement of VVA+ neurons may imply that Ca2+-dependent synaptic transmission from L5 may control PNN density in adult networks. We also discovered that the absence of L5 activity only had a transient effect on the morphology of striatal PV neurons. The correlation between PV and VVA neurons was contingent on brain regions and cortical layers, therefore the link between the perineuronal net and PV neurons is significantly more intricate than previously believed. The present study will aid our understanding of the bidirectional relationship between deep-layer pyramidal cells and GABAergic neurons while uncovering the long-term effects of chronically disrupting pyramidal neurons on inhibitory networks.
Exploring the Efficacy and Potential of Large Language Models for Depression: A Systematic Review
Authors: Omar Mahmud , Levkovich Inbar
Published: May 2024

Background and Objective

Depression is a substantial public health issue, with global ramifications. While initial literature reviews explored the intersection between artificial intelligence (AI) and mental health, they have not yet critically assessed the specific contributions of Large Language Models (LLMs) in this domain. The objective of this systematic review was to examine the usefulness of LLMs in diagnosing and managing depression, as well as to investigate their incorporation into clinical practice.

Methods

This review was based on a thorough search of the PubMed, Embase, Web of Science, and Scopus databases for the period January 2018 through March 2024. The search used PROSPERO and adhered to PRISMA guidelines. Original research articles, preprints, and conference papers were included, while non-English and non-research publications were excluded. Data extraction was standardized, and the risk of bias was evaluated using the ROBINS-I, QUADAS-2, and PROBAST tools.

Results

Our review included 34 studies that focused on the application of LLMs in detecting and classifying depression through clinical data and social media texts. LLMs such as RoBERTa and BERT demonstrated high effectiveness, particularly in early detection and symptom classification. Nevertheless, the integration of LLMs into clinical practice is in its nascent stage, with ongoing concerns about data privacy and ethical implications.

Conclusion

LLMs exhibit significant potential for transforming strategies for diagnosing and treating depression. Nonetheless, full integration of LLMs into clinical practice requires rigorous testing, ethical considerations, and enhanced privacy measures to ensure their safe and effective use.

A visual abstract
Genomic epidemiology of early SARS-CoV-2 transmission dynamics in Bangladesh
Authors: Carnegie L. , McCrone J.T. , du Plessis L. , Hasan M. , Ali M.Z. , Begum R. , Hassan M.Z. , Islam S. , Rahman M.H. , Uddin A.S.M. , Sarker M.S. , Das T. , Hossain M. , Khan M. , Razu M.H. , Akram A. , Arina S. , Hoque E. , Molla M.M.A. , Nafisaa T. , Angra P. , Rambaut A. , Pullan S.T. , Osman K.L , Hoque M.A. , Biswas P. , Flora M.S. , Raghwani J. , Fournié G. , Samad M.A. , Hill S.C.
Published: May 2024

Background

Genomic epidemiology has helped reconstruct the global and regional movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is still a lack of understanding of SARS-CoV-2 spread in some of the world’s least developed countries (LDCs).

Methods

To begin to address this disparity, we studied the transmission dynamics of the virus in Bangladesh during the country’s first COVID-19 wave by analysing case reports and whole-genome sequences from all eight divisions of the country.

Results

We detected >50 virus introductions to the country during the period, including during a period of national lockdown. Additionally, through discrete phylogeographic analyses, we identified that geographical distance and population -density and/or -size influenced virus spatial dispersal in Bangladesh.

Conclusions

Overall, this study expands our knowledge of SARS-CoV-2 genomic epidemiology in Bangladesh, shedding light on crucial transmission characteristics within the country, while also acknowledging resemblances and differences to patterns observed in other nations.
A cooperatively breeding mouse shows flexible use of its vocal repertoire according to social context
Authors: Perrier Léo , de Witasse-Thézy Aude , Pradeau Aurélie , Schradin Carsten , Greenfield Michael D. , Mathevon Nicolas , Levréro Florence
Published: May 2024

Mice exchange information using chemical, visual and acoustic signals. Long ignored, mouse ultrasonic communication is now considered to be an important aspect of their social life, transferring information such as individual identity or stress levels. However, whether and how mice modulate their acoustic communications is largely unknown. Here we show that a wild mouse species with a complex social system controls its vocal production both qualitatively and quantitatively, depending on social context. We found that the African striped mouseRhabdomys pumilio, a cooperatively breeding species, has a vocal repertoire consisting of seven call types, which it uses differently depending on whether the individuals encounter another mouse that is familiar, unfamiliar, of the same or different sex. Familiar individuals, whether of the same or different sex, vocalize more than two unfamiliar same-sex individuals. The greatest diversity of vocalisations is recorded when a female and a male first encounter, suggesting that certain calls are reserved for courtship. Our results highlight that familiar mice alternate their vocalisations (turn-taking) while unfamiliar individuals tend to overlap one another. These observations suggest that African striped mice control the production and temporal dynamics of their vocalisations, addressing targeted information to specific receivers via the acoustic channel.
First genome assembly of the order Strepsiptera using PacBio HiFi reads reveals a miniature genome
Authors: Castaño María Isabel , Ye Xinhai , Uy Floria MK
Published: May 2024

Twisted-wing insects (Strepsiptera) are an enigmatic order of parasites with unusual life histories and striking sexual dimorphism. Males emerge from hosts as free-living winged adults, while females from most species remain as endoparasites that retain larval traits. Due to scarce genomic data and phylogenetic controversies, Strepsiptera was only recently placed as the closest living relative to beetles (Coleoptera). Here, we report the first PacBio HiFi genome assembly of the strepsipteranXenos peckii(Xenidae). Thisde novoassembly size is 72.1 Mb, with a BUSCO score of 87.4%, N50 of 7.3 Mb, 23.4% GC content and 38.41% repeat content. We identified 8 contigs that contain > 75% of the assembly and reflect the haploid chromosome number reported from karyotypic data, and 3 contigs that exhibit sex chromosome coverage patterns. Additionally, the mitochondrial genome is 16,111 bp long and has 34 genes. This long-read assembly for Strepsiptera reveals a miniature genome and provides a unique tool to understand complex genome evolution associated with a parasitic lifestyle and extreme sexual dimorphism.
Stability of plane Couette flow with constant wall transpiration
Authors: Sun W. , Yalcin A. , Oberlack M.
Published: May 2024

Plane Couette flow with constant wall transpiration, i.e., constant blowing from below and constant suction from above, is a solution of the Navier-Stokes equations in terms of exponentials. It is characterized by two Reynolds numbers Re and ReV, where Re parametrizes the moving wall and ReV describes the influence of the transpiration. For this flow the modified Orr-Sommerfeld equation admits one of the very few exact solutions in terms of hypergeometric functions. Based on this, we solve the stability problem, though for the main part focus on temporal stability. For small wall-transpiration rates up to ReV≃6.71, the flow remains unconditionally stable, analogous to the classical Couette flow for arbitrary Reynolds numbers Re. By further increasing ReV an instability sets in and a minimum critical Reynolds number of Re=668350.491 is reached at ReV=9.799. Hence, around this point, the destabilizing effect of blowing outweighs the stabilizing effect of suction. By further increasing the transpiration rate beyond this point, the corresponding critical Reynolds number Re increases again and continues to grow. This limiting case is accompanied by the development of a strong boundary-layer-like velocity profile near the upper wall and the flow transitions to the asymptotic suction boundary layer (ASBL). Thus, the present analysis comprises the whole range from classical Couette flows extended by transpiration to the ASBL, which is known to have a strongly stabilizing effect.

Published by the American Physical Society
2024
Blending logics with performance management systems in an NGO setting
Authors: Thambar Paul J. , Ferreira Aldónio , Thoradeniya Prabanga
Published: May 2024

Purpose

This study aims to examine the role of performance management systems (PMSs) in enabling logic blending to manage institutional complexity and tensions arising from coexisting institutional logics.

Design/methodology/approach

This research uses a case study of an Australian non-government organisation (NGO) operating in an institutional field dominated by the state government, in which policy reform jolted the balance between institutional logics. Data was collected through semi-structured interviews, archival documents and observations.

Findings

We find the policy reform required the NGO to transform from a wholly care focus to accommodate a more balanced approach with a focus on care coupled with efficiency, outcome delivery and performance measurement. The NGO responded by revising its purpose, strategy and operational model and by seeking to address the imperatives of two dominant and often competing care and managerial logics. We find this was achieved through logic blending, in which PMSs played a pivotal role, with the formalisation and collaboration processes mobilising different elements of PMSs, mobilising some elements differently or not mobilising some elements at all.

Originality/value

This study highlights the central role of PMSs in managing tensions between and the complexity arising from coexisting institutional logics through logic blending, a form of enduring compromise. This study extends the accounting logics and performance management literature by developing the understanding of what constitutes logic blending and how it is distinct from other forms of compromise.
Effect of team identification on employee constructive deviance: the role of moral justification and environmental instability
Authors: Liu Tingting , Shao Danping , Li Yulei , Liu Chang-E , He Wei
Published: May 2024

Purpose

Despite an emerging interest in constructive deviance, the exploration of its antecedents is still limited, particularly from an ethical perspective. This study aims to uses moral disengagement theory to investigate how team identification, moral justification and team environmental instability interact to affect employee constructive deviance.

Design/methodology/approach

With survey data collected in two waves from 315 employees of 49 work teams in five service companies in China, this study develops four hypotheses and tests them through hierarchical linear model.

Findings

The survey results support the complete mediating effect of moral justification on the positive impact of team identification on constructive deviance. They also confirm the moderating effect of environmental instability on the relationship between team identification, moral justification and constructive deviance.

Originality/value

This study explores the sources of constructive deviance at team level from the ethical decision-making perspective and reveals the mechanism and contingency factors in the relationship between identity and constructive deviance. In practice, the study findings imply that managers should encourage their employees to cultivate their identification with their team and align their moral justification with the team’s norms especially when the team faces turbulent environment.
Defying the odds? Multiple disadvantage as a source of entrepreneurial action
Authors: Hussain Sundas , Vershinina Natalia , Carey Charlotte
Published: May 2024

Purpose

The link between entrepreneurial intention and positive attitudes towards entrepreneurship for established and nascent entrepreneurs has been well documented in the extant literature, with the theory of planned behaviour (TPB) viewing entrepreneurial intention as a pre-requisite for entrepreneurial pursuit. Whilst scholars generally agree on these insights, little empirical evidence exists on how marginalised social groups can convert their intentions into action. This study aims to understand to what extent the elements of TPB, the attitudes towards entrepreneurship, self-efficacy and subjective norms, help explain the emergence of entrepreneurial activity amongst marginalised demographic groups.

Design/methodology/approach

This research focuses on unemployed women residing in social housing located in a deprived urban area of the United Kingdom to empirically examine how multiple layers of disadvantage faced by this group shape their motivations and intentions for entrepreneurial pursuit. A multi-source qualitative methodology was adopted, drawing upon inductive storytelling narratives and extensive fieldwork on a sample of unemployed ethnic minority women residing in social housing in a deprived urban area of the United Kingdom. Community organisation representatives and housing association employees within the social housing system were included to assess the interpretive capacity of TPB.

Findings

The findings display that TPB illuminates why and how marginalised groups engage in entrepreneurship. Critically, women’s entrepreneurial intentions emerge as a result of their experiences of multiple layers of disadvantage, their positionality and the specificity of few resources they can activate from their disadvantageous position for entrepreneurial activity.

Originality/value

By illuminating the linkages between marginalised women’s positionality and their associated access to the limited pool of resources using the TPB lens, this study contributes to emerging works on disadvantaged populations and entrepreneurial intention-action debate. This work posits that despite facing significant additional challenges through their positionality and reduced ability to mobilise resources, women in social housing can defy the odds and develop ways to overcome limited capacity and structural disadvantage.