bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of pathologist panels for achieving consensus in NASH histologic scoring in clinical trials: Data from a phase 3 study
Authors: Sanyal Arun J. , Loomba Rohit , Anstee Quentin M. , Ratziu Vlad , Kowdley Kris V. , Rinella Mary E. , Harrison Stephen A. , Resnick Murray B. , Capozza Thomas , Sawhney Sangeeta , Shelat Nirav , Younossi Zobair M.
Published: December 2023

Background:

Liver histopathologic assessment is the accepted surrogate endpoint in NASH trials; however, the scoring of NASH Clinical Research Network (CRN) histologic parameters is limited by intraobserver and interobserver variability. We designed a consensus panel approach to minimize variability when using this scoring system. We assessed agreement between readers, estimated linear weighted kappas between 2 panels, compared them with published pairwise kappa estimates, and addressed how agreement or disagreement might impact the precision and validity of the surrogate efficacy endpoint in NASH trials.

Methods:

Two panels, each comprising 3 liver fellowship-trained pathologists who underwent NASH histology training, independently evaluated scanned whole slide images, scoring fibrosis, inflammation, hepatocyte ballooning, and steatosis from baseline and month 18 biopsies for 100 patients from the precirrhotic NASH study REGENERATE. The consensus score for each parameter was defined as agreement by ≥2 pathologists. If consensus was not reached, all 3 pathologists read the slide jointly to achieve a consensus score.

Results:

Between the 2 panels, the consensus was 97%–99% for steatosis, 91%–93% for fibrosis, 88%–92% for hepatocyte ballooning, and 84%–91% for inflammation. Linear weighted kappa scores between panels were similar to published NASH CRN values.

Conclusions:

A panel of 3 trained pathologists independently scoring 4 NASH CRN histology parameters produced high consensus rates. Interpanel kappa values were comparable to NASH CRN metrics, supporting the accuracy and reproducibility of this method. The high concordance for fibrosis scoring was reassuring, as fibrosis is predictive of liver-specific outcomes and all-cause mortality.
Visual Quality Assessment and Comparison of Monofocal and Multifocal Scleral Lens Designs: A Pilot Study
Authors: Privado-Aroco Ana , Valdes-Soria Gonzalo , Romaguera María , Serramito María , Carracedo Gonzalo
Published: December 2023

Purpose:

To compare visual quality, contrast sensitivity, stereopsis, subjective vision, and comfort between monofocal and multifocal scleral lens (SL) designs.

Methods:

An experimental, cross over and short-term pilot study has been performed. Nineteen presbyopic patients (51.9±3.8 years) with regular corneas participated voluntarily in the study and Onefit MED monofocal and multifocal SL designs were fitted bilaterally. Subjective vision and comfort, contrast sensitivity function, stereopsis, high- and low-contrast visual acuity (VA) at 4 m and 40 cm under photopic and mesopic conditions, and defocus curves were measured. Data analysis was performed with nonparametric tests. P<0.05 was considered as statistically significant.

Results:

Mean addition power of the prescribed lenses was 1.72±0.38 diopters. Multifocal design showed a statistically significant improvement for intermediate and near vision in the defocus curve under photopic and mesopic conditions (P<0.05), however, worsening in stereopsis (P<0.05) and contrast sensitivity for high spatial frequencies (P<0.05). Distance visual acuity (VA) showed significantly lower values under mesopic conditions for high- and low-contrast tests (P<0.05), and on low-contrast test under photopic conditions (P<0.001) with the multifocal design.

Conclusion:

Multifocal SLs showed better visual performance at intermediate and near distances without compromising distance vision under photopic conditions for a high-contrast test when compared with monofocal design.
Prospective Study of the Multisite Spread of a Medication Safety Intervention: Factors Common to Hospitals With Improved Outcomes
Authors: Kaplan Heather C. , Goldstein Stuart L. , Rubinson Claude , Daraiseh Nancy , Zhang Fang , Rodgers Isabelle M. , Dahale Devesh S. , Askenazi David J. , Somers Michael J. G. , Zaritsky Joshua J. , Misurac Jason , Chadha Vimal , Yonekawa Karyn E. , Sutherland Scott M. , Weng Patricia L. , Walsh Kathleen E.
Published: December 2023

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly.
Risk evaluation of splenic hilar lymph node metastasis and survival analysis of patients with advanced gastric cancer
Authors: Niu Guangcai , Zhu Youlong , Xiong Xuanxuan
Published: December 2023

Background

There is no consensus regarding the influence of prophylactic no. 10 lymph node (LN) dissection in patients with advanced gastric cancer (AGC). We aimed to evaluate whether patients with AGC could benefit from no. 10 LN dissection and to explore the clinicopathological indicators of no. 10 LN metastasis.

Methods

We analyzed the data of 218 patients with AGC who underwent standard D2 lymphadenectomy (SD2; n = 108) or modified D2 lymphadenectomy (MD2; n = 110) between January 2017 and January 2021. In addition, we examined factors influencing no. 10 LN metastasis in the SD2 group.

Results

Differentiation, tumor location, and no. 4 positive LNs were significantly correlated with no. 10 LN metastasis (P < 0.05). Borrmann classification, differentiation, depth of invasion, LN metastasis (N), and tumor size were found to correlate with survival in univariate analyses. Age, sex, extent of gastrectomy, tumor location, and extent of lymphadenectomy were not associated with survival (P > 0.05). The median survival times were 72.23 and 68.56 months for the SD2 and MD2 groups, respectively (P = 0.635). Postoperative major morbidity and mortality rates were 37.96% and 3.70% in the SD2 group, and 23.64% and 1.82% in the MD2 group, respectively.

Conclusions

Based on our findings, prophylactic no. 10 lymphadenectomy may be recommended in patients with AGC who exhibit positive no. 4 LN status, poor differentiation, and tumors located on the greater curvature.
Factors Related to the Utilization of Digital Adherence Technologies in Tuberculosis Care: A Qualitative Study Among Adults in DS-TB Treatment, Health Care Providers and Other Key Stakeholders in Tanzania
Authors: Gonçalves Tasca Bianca , Mganga Andrew , Leung Chung Lam , Shilugu Lucas , Pell Christopher , Onjare Baraka , Luvanda Nicholaus , de Groot Liza , van Kalmthout Kristian , Fielding Katherine , Jerene Degu
Published: December 2023

Numerous challenges, such as lengthy treatmenst courses, side effects, and distance to healthcare facilities contribute to suboptimal Tuberculosis (TB) treatment completion. Digital adherence technologies (DATs), such as smart pillboxes and medication labels, could be an alternative to facilitate TB treatment continuation.

In-depth interviews with people undergoing treatment for drug susceptible TB, health care providers (HCPs) and other key stakeholders were conducted to evaluate their experiences with DATs in ten health facilities across four different regions in Tanzania. This study is part of a multi country cluster randomized trials conducted under the ASCENT consortium.

Interviews were conducted with a total of 41 individuals, 19 people with TB and 22 HCPs and key stakeholders. One of the main findings indicates that participants found that the daily reminders provided by the DATs, particularly the alarm from the smart pillboxes, helped in supporting treatment continuation and establishing a routine around medicine intake. DATs use was linked with reducing the financial burden of treatment, improving people with TB-HCPs relationship, and decreasing workload for HCPs. Although DATs were generally perceived as reliable, occasional technical malfunctions, such as battery depletion in smart pillboxes, were reported. The requirement of having access to a cellphone and a power source emerged as specific barriers for medication label users.

This study highlights the initial willingness and sustained enthusiasm for using DATs among respondents. DATs were perceived as useful tools, aiding individuals with treatment continuation through daily reminders and fostering stronger connections with HCPs. Nevertheless, issues such as poor network connectivity and the need for access to a working cellphone posed difficulties in usage. Findings from this study suggest the potential for improvements in the technologies and indicate that a thorough assessment of people’s life conditions and needs prior to treatment initiations is important to determine the suitability of providing a DAT.
Visuo-motor updating in individuals with heightened autistic traits
Authors: Pomè Antonella , Zimmermann Eckart
Published: December 2023

Autism Spectrum Disorder (ASD) presents a range of challenges, including heightened sensory sensitivities. Here, we examine the idea that sensory overload in ASD may be linked to issues with efference copy mechanisms, which predict the sensory outcomes of self-generated actions, such as eye movements. Efference copies play a vital role in maintaining visual and motor stability. Disrupted efference copies hinder precise predictions, leading to increased reliance on actual feedback and potential distortions in perceptions across eye movements. In our first experiment, we tested how well healthy individuals with varying levels of autistic traits updated their mental map after making eye movements. We found that those with more autistic traits had difficulty using information from their eye movements to update the spatial representation of their mental map, resulting in significant errors in object localization. In the second experiment, we looked at how participants perceived an object displacement after making eye movements. Using a trans-saccadic spatial updating task, we found that those with higher autism scores exhibited a greater bias, indicating under-compensation of eye movements and a failure to maintain spatial stability during saccades. Overall, our study underscores efference copy’s vital role in visuo-motor stability, aligning with Bayesian theories of autism, potentially informing interventions for improved action-perception integration in autism.
A near-complete dataset of plant growth form, life history, and woodiness for all Australian plants
Authors: Wenk Elizabeth , Coleman David , Gallagher Rachael , Falster Daniel
Published: December 2023

Tabular records of plant trait data are essential for diverse research purposes. Here we present scorings for a trio of core plant traits, plant growth form, woodiness, and life history, for nearly all accepted taxon concepts included in the Australian Plant Census (APC). This dataset is predominately derived from Australia’s state and national floras, supplemented by the taxonomic literature and diverse web resources. In total, 29,993 species and infraspecific taxa were scored for plant growth form, 30,279 for woodiness, and 30,056 for life history, with taxa scored as displaying a single or multiple trait values, as appropriate. This resource will enable rapid assessment of plant responses to disturbance events and new biogeographic analyses of trait distributions.
Loss of Function of the Cytoplasmic Fe-S Assembly Protein CIAO1 Causes a Neuromuscular Disorder with Compromise of Nucleocytoplasmic Fe-S Enzymes
Authors: Maio Nunziata , Orbach Rotem , Zaharieva Irina , Töpf Ana , Donkervoort Sandra , Munot Pinki , Mueller Juliane , Willis Tracey , Verma Sumit , Peric Stojan , Krishnakumar Deepa , Sudhakar Sniya , Foley Aileen Reghan , Silverstein Sarah , Douglas Ganka , Pais Lynn , DiTroia Stephanie , Grunseich Christopher , Hu Ying , Sewry Caroline , Sarkozy Anna , Straub Volker , Muntoni Francesco , Rouault Tracey , Bönnemann Carsten Gerhart
Published: December 2023

Cytoplasmic and nuclear iron-sulfur enzymes that are essential for genome maintenance and replication depend on the cytoplasmic iron-sulfur assembly (CIA) machinery for cluster acquisition. Here we report that patients with biallelic loss of function inCIAO1, a key CIA component, develop proximal and axial muscle weakness, fluctuating creatine kinase elevation and respiratory insufficiency. In addition, they present with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, macrocytic anemia and gastrointestinal symptoms. Mutational analysis and functional assays revealed reduced stability of the variants compared to wild-type CIAO1. Loss of CIAO1 impaired DNA helicases, polymerases and repair enzymes which rely on the CIA complex to acquire their Fe-S cofactors, with lentiviral restoration reversing all patient-derived cellular abnormalities. Our study identifiesCIAO1as a novel human disease gene and provides insights into the broader implications of the iron-sulfur assembly pathway in human health and disease.
1D confinement mimicking microvessel geometry controls pericyte shape and motility
Authors: Sagnimorte Aude , Adler Marie R. , de Tournemire Gaspard , Sáez Pablo J. , Gonzalez-Rodriguez David , Dessalles Claire A. , Babataheri Avin
Published: December 2023

Pericytes are mural cells of the microvasculature, characterised by their elongated distinct shape. Pericytes span along the axis of the vessels they adhere to, therefore they experience extreme lateral and longitudinal confinement. Pericyte shape is key for their function during vascular regulation and their spatial distribution is established by cell migration during the embryonic stage and maintained through controlled motility in the adult. However, how pericyte morphology is associated with migration and function remains unknown. We use micropatterns to mimic pericyte adhesion to vessels, and to reproduce in vitro the shapes adopted by pericytes in vivo. We show that lateral confinement controls cell shape and produces in vivo-like phenotype. Modelling the pericyte as an incompressible linear elastic material predicts strain and shape of pericytes as a function of lateral confinement. Pericyte kinetics on both laterally confining lanes, and longitudinally constraining motifs is described by dry friction theory. Pericytes are capable of crossing gaps of different sizes. The percentage of crossings is correctly predicted by the likelihood of a fluctuating system to overcome an energy barrier. Our joint experimental and theoretical approach demonstrates the effect of in vivo-like geometrical confinement on pericyte morphology and migration which is accurately described by dry friction theory.
The Art of Brainwaves: A Survey on Event-Related Potential Visualization Practices
Authors: Mikheev Vladimir , Skukies René , Ehinger Benedikt V.
Published: December 2023

Electroencephalography (EEG) and event-related potentials (ERPs) have been analyzed for more than 70 years. Yet, we know little about how practitioners visualize the results of their analyses. Here, we designed an online survey (n=213) targeting M/EEG practitioners from novice to expert level. Our primary goal is to better understand the visualization tools currently in use, the challenges researchers face, and their experiences and opinions on how best to display their brain data. Finally, we explored whether researchers are aware of more general visualization issues. In this paper we provide an overview of the most popular ERP visualization tools. Then, we found that the community does not have a unique nomenclature to refer to some plot types, and we propose a set of recommendations to name the most popular ERP plot types. Finally, we provide an analysis of practitioner feature preferences for software developers and conclude with further recommendations for ERP practitioners.
Addressing Heterogeneity in direct analysis of Extracellular Vesicles and analogues using Membrane-Sensing Peptides as Pan-Affinity Probes
Authors: Gori Alessandro , Frigerio Roberto , Gagni Paola , Burrello Jacopo , Panella Stefano , Raimondi Andrea , Bergamaschi Greta , Lodigiani Giulia , Romano Miriam , Zendrini Andrea , Radeghieri Annalisa , Barile Lucio , Cretich Marina
Published: December 2023

Extracellular vesicles (EVs), crucial mediators of cell-to-cell communication, hold immense potential for diagnostic applications due to their ability to enrich protein biomarkers in body fluids. However, challenges in isolating EVs from complex biological specimens hinder their widespread use. In this frame, integrated isolation-and-analysis workflows are the go-to strategy, most of which see the prevalence of immunoaffinity methods. Yet, the high heterogeneity of EVs poses challenges, as proposed ubiquitous markers are less homogenously prevalent than believed, raising concerns about the reliability of downstream biomarker discovery programs. This issue extends to the burgeoning field of engineered EV-mimetics and bio-nanoparticles, where conventional immune-affinity methods may lack applicability. Addressing these challenges, we introduce the use Membrane Sensing Peptides (MSP) as “universal” affinity ligands for both EVs and EV-analogues. Employing a streamlined process integrating on-bead capture and vesicle phenotyping through Single Molecule Array (SiMoA) technology, we showcase the application of MSP ligands in the integrated analysis of circulating EVs in blood derivatives, eliminating the need for prior EV isolation. Demonstrating the possible clinical translation of MSP technology, we directly detect an EV-associated epitope signature in serum and plasma samples, demonstrating its potential for distinguishing patients with myocardial infarction versus stable angina. At last, notably, MSP exhibits a unique capability to enable the analysis of tetraspanin-lacking Red Blood Cell derived EVs (RBC-EVs). Overall, unlike traditional antibody-based methods, MSP probes work agnostically, overcoming limitations associated with surface protein abundance or scarcity. This highlights the potential of MSP in advancing EV analysis for clinical diagnostics and beyond. Of note, this represents also the first-ever peptide-based application in SiMoA technology.
Age-Related Differences in Human Cortical Microstructure Depend on the Distance to the Nearest Vein
Authors: Knoll Christoph , Doehler Juliane , Northall Alicia , Schreiber Stefanie , Rotta Johanna , Mattern Hendrik , Kuehn Esther
Published: December 2023

Age-related differences in cortical microstructure are used to understand the neuronal mechanisms that underlie human brain ageing. The cerebral vasculature contributes to cortical ageing, but its precise interaction with cortical microstructure is poorly understood. In a cross-sectional study, we combine venous imaging with vessel distance mapping (VDM) to investigate the interaction between venous distances and age-related differences in the microstructural architecture of the primary somatosensory cortex (S1), the primary motor cortex (M1), and additional areas in frontal cortex as non-sensorimotor control regions. We scanned 18 younger adults and 17 older adults using 7T-MRI to measure age-related changes in quantitative T1 (qT1) values, positive QSM (pQSM) values, and negative QSM (nQSM) values at 0.5 mm isotropic resolution. We modelled different cortical depths using an equi-volume approach and assessed the distance of each voxel to its nearest vein using VDM. Our data reveal a dependence of cortical qT1 and pQSM values on venous distance. In addition, there is an interaction between venous distance and age on qT1 values, driven by lower qT1 values in older compared to younger adults in voxels that are closer to a vein. Together, our data show that the local venous architecture explains a significant amount of variance in standard measures of cortical microstructure and should be considered in neurobiological models of human brain organisation and cortical ageing.
Endangered Przewalski’s horse,Equus przewalskii, cloned from historically cryopreserved cells
Authors: Novak Ben J. , Ryder Oliver A. , Houck Marlys L. , Putnam Andrea S. , Walker Kelcey , Russell Lexie , Russell Blake , Walker Shawn , Arenivas Sanaz Sadeghieh , Aston Lauren , Veneklasen Gregg , Ivy Jamie A. , Koepfli Klaus-Peter , Rusnak Anna , Simek Jaroslav , Zhuk Anna , Phelan Ryan
Published: December 2023

Two endangered Przewalski’s horse stallions were cloned from fibroblast cells cultured and cryopreserved in 1980. These stallions are clones of a male that lived from 1975-1998 that pedigree analyses identified as a genetically valuable male for present-day conservation breeding. This is the first time that multiple healthy clones have been produced for an endangered species.
Single cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions
Authors: Karra Laila , Finger Anna-Marie , Shechtman Lauren , Krush Milana , Huang Rita Meng-Yao , Prinz Morgan , Tennvooren Iliana , Bahl Kriti , Hysienaj Lisiena , Gonzalez Paulina G. , Combes Alexis J. , Gonzalez Hugo , Argüello Rafael J , Spitzer Matthew H. , Roose Jeroen P.
Published: December 2023

Normal hematopoiesis requires constant prolific production of different blood cell lineages by multipotent hematopoietic stem cells (HSC). Stem- and progenitor- cells need to balance dormancy with proliferation. How genetic alterations impact frequency, lineage potential, and metabolism of HSC is largely unknown. Here, we compared induced expression of KRASG12Dor RasGRP1 to normal hematopoiesis. At low-resolution, both Ras pathway lesions result in skewing towards myeloid lineages. Single-cell resolution CyTOF proteomics unmasked an expansion of HSC- and progenitor- compartments for RasGRP1, contrasted by a depletion for KRASG12D. SCENITH™ quantitates protein synthesis with single-cell precision and corroborated that immature cells display low metabolic SCENITH™ rates. Both RasGRP1 and KRASG12Delevated mean SCENITH™ signals in immature cells. However, RasGRP1-overexpressing stem cells retain a metabolically quiescent cell-fraction, whereas this fraction diminishes for KRASG12D. Our temporal single cell proteomics and metabolomics datasets provide a resource of mechanistic insights into altered hematopoiesis at single cell resolution.
Nanopore adaptive sampling to identify the NLR-gene family in melon (Cucumis meloL.)
Authors: Belinchon-Moreno Javier , Berard Aurelie , Canaguier Aurelie , Chovelon Véronique , Cruaud Corinne , Engelen Stéfan , Feriche-Linares Rafael , Le-Clainche Isabelle , Marande William , Rittener-Ruff Vincent , Lagnel Jacques , Hinsinger Damien , Boissot Nathalie , Faivre Rampant Patricia
Published: December 2023

Background

Nanopore Adaptive Sampling (NAS) offers a promising approach for assessing genetic diversity in targeted genomic regions. Herein, we design and validate an experiment to enrich a set of resistance genes in several melon cultivars as a proof of concept.

Results

We showed that each of the 15 regions we identified in two newly assembled melon genomes (subspeciesmelo) were successfully and accurately reconstructed as well as in a third cultivar from theagrestissubspecies. We obtained a fourfold enrichment, independently from the samples, but with some variations according to the enriched regions. In theagrestiscultivar, we further confirmed our assembly by PCR. We discussed parameters that can influence enrichment and accuracy of assemblies generated through NAS.

Conclusions

Altogether, we demonstrated NAS as a simple and efficient approach to explore complex genomic regions. This approach finally unlocks the characterization of resistance genes for a large number of individuals, as required for breeding new cultivars responding to the agroecological transition.
Proinflammatory Cytokines Suppress Nonsense-Mediated RNA Decay to Impair Regulated Transcript Isoform Processing in Pancreatic β-Cells
Authors: Ghiasi Seyed. M. , Marchetti Piero , Piemonti Lorenzo , Nielsen Jens H. , Porse Bo T. , Mandrup-Poulsen Thomas , Rutter Guy A.
Published: December 2023

Proinflammatory cytokines are implicated in pancreatic β-cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of Nonsense-Mediated RNA Decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in β-cells. A luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-βH3 or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. Gain- or loss-of function of two key NMD components UPF3B and UPF2 is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques. Cyt attenuate NMD activity in insulin-producing cell lines and primary human β-cells. These effects are found to involve ER stress and are associated with downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing, raises or lowers Cyt-induced cell death, respectively, in EndoC-βH3 cells, and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increase alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in extracellular matrix (ECM) including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitises β-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signalling, potentially serving as a protective response against Cyt-induced NMD component expression. Our findings highlight the central importance of RNA turnover in β-cell responses to inflammatory stress.
Comparative Hox genes expression within the dimorphic annelidStreblospio benedictireveals patterning variation during development
Authors: Aguilar-Camacho Jose Maria , Harry Nathan D. , Zakas Christina
Published: December 2023

Hox genes are transcriptional regulators that elicit cell positional identity along the anterior-posterior region of the body plan across different lineages of Metazoan. Comparison of Hox gene expression across distinct species reveals their evolutionary conservation, however their gains and losses in different lineages can correlate with body plan modifications and morphological novelty. We compare the expression of eleven Hox genes found withinStreblospio benedicti,a marine annelid that produces two types of offspring with distinct developmental and morphological features. For these two distinct larval types, we compare Hox gene expression through ontogeny using HCR (hybridization chain reaction) probes forin-situhybridization and RNA-seq data. We find that Hox gene expression patterning for both types is typically similar at equivalent developmental stages. However, some Hox genes have spatial or temporal differences between the larval types that are associated with morphological and life-history differences. This is the first comparison of developmental divergence in Hox genes expression within a single species and these changes reveal how body plan differences may arise in larval evolution.
A subcortical switchboard for exploratory, exploitatory, and disengaged states
Authors: Ahmadlou Mehran , Shirazi Maryam Yasamin , Zhang Pan , Rogers Isaac L. M. , Dziubek Julia , Hofer Sonja B.
Published: December 2023

To survive in evolving environments with uncertain resources, animals need to dynamically adapt their behavior and exhibit flexibility in choosing appropriate behavioral strategies, for example, to exploit familiar choices, to explore and acquire novel information, or to disengage altogether. Previous studies have mainly investigated how forebrain regions represent choice costs and values as well as optimal decision strategies during explore/exploit trade-offs. However, the neural mechanisms by which the brain implements alternative behavioral strategies such as exploiting, exploring or disengaging from the environment, remains poorly understood. Here we identify a neural hub critical for flexible switching between behavioral strategies, the median raphe nucleus (MRN). Using cell-type specific optogenetic manipulations, calcium fiber photometry and circuit tracing in mice performing diverse instinctive and learnt behavioral tasks, we found that the MRN’s main cell types, GABAergic, glutamatergic (VGluT2-positive), and serotonergic neurons, have complementary functions and drive exploitation, exploration and disengagement, respectively. Suppression of MRN GABAergic neurons, for instance through inhibitory input from lateral hypothalamus which conveys strong positive valence to the MRN, leads to perseverance in current actions and goals, and thus promotes exploitatory behavior. In contrast, activation of MRN VGluT2+ neurons drives exploratory behavior. Activity of serotonergic MRN neurons is necessary for general task engagement. Input from the lateral habenula conveying negative valence suppresses serotonergic MRN neurons, leading to disengagement. These findings establish the MRN as a central behavioral switchboard, uniquely positioned to flexibly control behavioral strategies. These circuits thus may also play an important role in the etiology and possible treatment of major mental pathologies such as depressive or obsessive-compulsive disorders.
Identification of new ciliary signaling pathways in the brain and insights into neurological disorders
Authors: Loukil Abdelhalim , Ebright Emma , Uezu Akiyoshi , Gao Yudong , Soderling Scott H , Goetz Sarah C.
Published: December 2023

Primary cilia are conserved sensory hubs essential for signaling transduction and embryonic development. Ciliary dysfunction causes a variety of developmental syndromes with neurological features and cognitive impairment, whose basis mostly remains unknown. Despite connections to neural function, the primary cilium remains an overlooked organelle in the brain. Most neurons have a primary cilium; however, it is still unclear how this organelle modulates brain architecture and function, given the lack of any systemic dissection of neuronal ciliary signaling. Here, we present the first in vivo glance at the molecular composition of cilia in the mouse brain. We have adaptedin vivoBioID (iBioID), targeting the biotin ligase BioID2 to primary cilia in neurons. We identified tissue-specific signaling networks enriched in neuronal cilia, including Eph/Ephrin and GABA receptor signaling pathways. Our iBioID ciliary network presents a wealth of neural ciliary hits that provides new insights into neurological disorders. Our findings are a promising first step in defining the fundamentals of ciliary signaling and their roles in shaping neural circuits and behavior. This work can be extended to pathological conditions of the brain, aiming to identify the molecular pathways disrupted in the brain cilium. Hence, finding novel therapeutic strategies will help uncover and leverage the therapeutic potential of the neuronal cilium.
Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity
Authors: Wang Lijin , Sesachalam Pratap Veerabrahma , Chua Ruiming , Ghosh Sujoy
Published: December 2023

Objective

Visceral adiposity is associated with increased proinflammatory activity, insulin resistance, diabetes risk and mortality rate. Numerous individual genes have been associated with obesity, but studies investigating gene-regulatory networks in human visceral obesity are lacking.

Methods

We analyzed gene-regulatory networks in human visceral adipose tissue (VAT) from 48 obese and 11 non-obese Chinese subjects using gene co-expression and network construction with RNA-sequencing data. We also conducted RNA interference-based tests on selected genes for adipocyte differentiation effects.

Results

A scale-free gene co-expression network was constructed from 360 differentially expressed genes between obese and non-obese VAT (absolute log fold-change >1, FDR<0.05) with edge probability >0.8. Gene regulatory network analysis identified candidate transcription factors associated with differentially expressed genes. Fifteen subnetworks (communities) displayed altered connectivity patterns between obese and non-obese networks. Genes in pro-inflammatory pathways showed increased network connectivities in obese VAT whereas the oxidative phosphorylation pathway displayed reduced connections (enrichment FDR<0.05). Functional screening via RNA interference identifiedSOX30andOSBPL3as potential network-derived gene candidates influencing adipocyte differentiation.

Conclusions

This interactome-based approach highlights the network architecture, identifies novel candidate genes, and leads to new hypotheses regarding network-assisted gene regulation in obese vs. non-obese VAT.

What is already known about this subject?

Visceral adipose tissue (VAT) is associated with increased levels of proinflammatory activity, insulin resistance, diabetes risk and mortality rate.

Gene expression studies have identified candidate genes associated with proinflammatory function in VAT.

What are the new findings in your manuscript?

Using integrative network-science, we identified co-expression and gene regulatory networks that are differentially regulated in VAT samples from subjects with and without obesity

We used functional testing (adipocyte differentiation) to validate a subset of novel candidate genes with minimal prior reported associations to obesity

How might your results change the direction of research or the focus of clinical practice

Network biology-based investigation provides a new avenue to our understanding of gene function in visceral adiposity

Functional validation screen allows for the identification of novel gene candidates that may be targeted for the treatment of adipose tissue dysfunction in obesity
Revisiting chromatin packaging in mouse sperm
Authors: Yin Qiangzong , Yang Chih-Hsiang , Strelkova Olga S. , Wu Jingyi , Sun Yu , Gopalan Sneha , Yang Liyan , Dekker Job , Fazzio Thomas G. , Li Xin Zhiguo , Gibcus Johan , Rando Oliver J.
Published: December 2023

Mammalian sperm show an unusual and heavily compacted genomic packaging state. In addition to its role in organizing the compact and hydrodynamic sperm head, it has been proposed that sperm chromatin architecture helps to program gene expression in the early embryo. Scores of genome-wide surveys in sperm have reported patterns of chromatin accessibility, nucleosome localization, histone modification, and chromosome folding. Here, we revisit these studies in light of recent reports that sperm obtained from the mouse epididymis are contaminated with low levels of cell-free chromatin. In the absence of proper sperm lysis, we readily recapitulate multiple prominent genome-wide surveys of sperm chromatin, suggesting that these profiles primarily reflect contaminating cell-free chromatin. Removal of cell-free DNA, and appropriate lysis conditions, are together required to reveal a sperm chromatin state distinct from most previous reports. Using ATAC-seq to explore relatively accessible genomic loci, we identify a landscape of open loci associated with early development and transcriptional control. Histone modification and chromosome folding profiles also strongly support the hypothesis that prior studies suffer from contamination, but technical challenges associated with reliably preserving the architecture of the compacted sperm head prevent us from confidently assaying true localization patterns for these epigenetic marks. Together, our studies show that our knowledge of chromosome packaging in mammalian sperm remains largely incomplete, and motivate future efforts to more accurately characterize genome organization in mature sperm.
De novo transcriptome assembly of mouse male germ cells reveals novel genes, stage-specific bidirectional promoter activity, and noncoding RNA expression
Authors: Gill Mark E. , Rohmer Alexia , Erkek-Ozhan Serap , Liang Ching-Yeu , Chun Sunwoo , Ozonov Evgeniy A. , Peters Antoine H.F.M.
Published: December 2023

In mammals, the adult testis is the tissue with the highest diversity in gene expression. Much of that diversity is attributed to germ cells, primarily meiotic spermatocytes and postmeiotic haploid spermatids. Exploiting a newly developed cell purification method, we profiled the transcriptomes of such postmitotic germ cells of mice. We used a de novo transcriptome assembly approach and identified thousands of novel expressed transcripts characterized by features distinct from those of known genes. Novel loci tend to be short in length, monoexonic, and lowly expressed. Most novel genes have arisen recently in evolutionary time and possess low coding potential. Nonetheless, we identify several novel protein-coding genes harboring open reading frames that encode proteins containing matches to conserved protein domains. Analysis of mass-spectrometry data from adult mouse testes confirms protein production from several of these novel genes. We also examine overlap between transcripts and repetitive elements. We find that although distinct families of repeats are expressed with differing temporal dynamics during spermatogenesis, we do not observe a general mode of regulation wherein repeats drive expression of nonrepetitive sequences in a cell type–specific manner. Finally, we observe many fairly long antisense transcripts originating from canonical gene promoters, pointing to pervasive bidirectional promoter activity during spermatogenesis that is distinct and more frequent compared with somatic cells.
Mall relevance, shoppers' well-being and mall loyalty: moderating role of social media celebrity
Authors: Javed Hafiz Muhammad Usama , Yaqub Rana Muhammad Shahid , Ali Saqib , Sulaiman Mohammed Ali Bait Ali
Published: December 2023

Purpose

The purpose of this study is to test the relationship between mall relevance dimensions [(functional relevance (FNR), symbolic relevance (SYR), social relevance (SOR) and environmental relevance (ENR)] and shoppers' well-being (SWB), which in turn influences mall loyalty (ML). In addition, this study aims to investigate the moderating effect of social media celebrities (SMCs) on the association between SWB and ML.

Design/methodology/approach

A mall intercept survey was used to collect responses from mall shoppers. The authors received 426 valid responses from mall shoppers in Pakistan's three metropolitan cities (i.e. Karachi, Lahore and Islamabad). To test the hypotheses, partial least squares structural equation modelling (PLS-SEM) was used.

Findings

Findings reveal that FNR, SYR, ENR and SOR significantly and positively influence SWB. Similarly, SWB significantly affects ML. Moreover, SMCs moderate the positive relationship between SWB and ML.

Originality/value

This study is one of the pioneer studies examining mall relevance dimensions on SWB. In addition, this study contributes to the retailing literature by testing the moderation effect of SMCs on the relationship between SWB and ML. Likewise, this study provides insights for mall administration to focus on mall relevance in terms of FNR, SYR, ENR and SOR to enhance the current and prospects' SWB. Next, SMCs play a key role in enhancing SWB and ML.
Making it safe: linking healthcare workers' social media use to task performance during public health crises
Authors: Wang Youying , Zhang Shuqin , Gong Lei , Huang Qian
Published: December 2023

Purpose

This study aims to investigate the effect of social media use on healthcare workers’ psychological safety and task performance and the moderating role of perceived respect from patients during public health crises.

Design/methodology/approach

To test the proposed moderated mediation model, a survey was conducted in 12 Chinese medical institutions. A total of 637 valid questionnaires were collected for data analysis.

Findings

The results revealed that psychological safety mediated the relationships between task-related social media (TSM) use and social-related social media (SSM) use and task performance. In addition, perceived respect from patients moderated the relationship between TSM use and psychological safety, as well as the indirect relationship between TSM use and task performance through psychological safety.

Originality/value

This study sheds new light on understanding how different types of social media use influence task performance in the context of public health crises. Furthermore, this study considers the interactions of healthcare workers with colleagues and patients and examines the potential synergistic effects of these interactions on healthcare workers’ psychological state and task performance.
An economic geography approach to the implementation of circular economy – comparing three examples of industry-specific networks in West Sweden
Authors: Ström Patrik , Hermelin Brita
Published: December 2023

Purpose

The circular economy (CE) has been endorsed as representing a model that is able to achieve environmental protection through decreased use of raw materials, together with changing economic values and social inclusion thanks to its demand for a wide variety of skill profiles. This has motivated many policy initiatives to support the implementation of the CE. The purpose of this study is to follow such policy initiatives in three geographically anchored industry-specific networks.

Design/methodology/approach

The study contributes to the research debate on the CE through a spatial approach with a focus on how the implementation of the CE is conditioned by spatial and regional contexts. The authors investigate three different networks in Sweden for CE with different locations and industrial profiles.

Findings

The findings reveal the difficulty that exist in relation to the implementation of the CE. The network and support functions in combination with private industry are vital. The risk of sustaining an uneven regional economic development is evident.

Originality/value

Although research on the development of the CE has proliferated, geographical approaches to this development are comparably rare to date. The authors seek to contextualise the strategy development and policy implementation of a CE policy.
Employee workplace wellbeing amid disruptions
Authors: Mattar Dorine Maurice , Haddad Joy , Nammour Celine
Published: December 2023

Purpose

This study aims to assess the effect of job insecurity, customer incivility and work–life imbalance on Lebanese bank employee workplace well-being (EWW), while investigating the moderating role that positive and negative affect might have.

Design/methodology/approach

Quantitative data was collected from 202 respondents and analyzed using structural equation modeling system through IBM SPSS and AMOS.

Findings

Results revealed that each of the independent variables has a negative, statistically significant effect on Lebanese bank EWW. The positive affect and the negative one are shown to have a moderating effect that lessens and boosts, respectively, these negative effects.

Theoretical implications

The study adds to the literature on EWW while highlighting the high-power distance and collectivist society that the research took place in.

Research limitations/implications

Limitations include the sample size that was hoped to be larger, in addition to the self-reporting issue and what it entails in the data collection process.

Practical implications

The study has many practical implications, including the validation of a questionnaire in a developing Arab country, hence providing a reliable tool for researchers. HR specialists should lean toward applicants with positive affect, ensuring that their workplace is occupied by members with enhanced resilience. Furthermore, employers should support their employees’ professional growth, thus, boosting their employability during turmoil and consequently making them less vulnerable in times of economic recession.

Originality/value

The study’s unique context, depicted in the harsh economic and financial crisis, makes the findings on EWW of a high value.
Early‐season mass‐flowering crop cover dilutes wild bee abundance and species richness in temperate regions: A quantitative synthesis
Authors: Riggi L. G. A. , Raderschall C. A. , Fijen T. P. M. , Scheper J. , Smith H. G. , Kleijn D. , Holzschuh A. , Aguilera G. , Badenhausser I. , Bänsch S. , Beyer N. , Blitzer E. J. , Bommarco R. , Danforth B. , González‐Varo J. P. , Grab H. , Le Provost G. , Poveda K. , Potts S. G. , Rundlöf M. , Steffan‐Dewenter I. , Tscharntke T. , Vilà M. , Westphal C. , Berggren Å. , Lundin O.
Published: December 2023

Pollinators benefit from increasing floral resources in agricultural landscapes, which could be an underexplored co‐benefit of mass‐flowering crop cultivation. However, the impacts of mass‐flowering crops on pollinator communities are complex and appear to be context‐dependent, mediated by factors such as crop flowering time and the availability of other flower resources in the landscape. A synthesis of research is needed to develop management recommendations for effective pollinator conservation in agroecosystems.

By combining 22 datasets from 13 publications conducted in nine temperate countries (20 European, 2 North American), we investigated if mass‐flowering crop flowering time (early or late season), bloom state (during or after crop flowering) and extent of non‐crop habitat cover in the landscape moderated the effect of mass‐flowering crop cover on wild pollinator abundance and species richness in mass‐flowering crop and non‐crop habitats.

During bloom, wild bee abundance and richness are negatively related to mass‐flowering crop cover. Dilution effects were predominant in crop habitats and early in the season, except for bumblebees, which declined with mass‐flowering crop cover irrespective of habitat or season. Late in the season and in non‐crop habitats, several of these negative relationships were either absent or reversed. Late‐season mass‐flowering crop cover is positively related to honeybee abundance in crop habitats and to other bee abundance in non‐crop habitats. These results indicate that crop‐adapted species, like honeybees, move to forage and concentrate on late‐season mass‐flowering crops at a time when flower availability in the landscape is limited, potentially alleviating competition for flower resources in non‐crop habitats. We found no evidence of pollinators moving from mass‐flowering crop to non‐crop habitats after crop bloom.

Synthesis and applications: Our results confirm that increasing early‐season mass‐flowering crop cover dilutes wild pollinators in crop habitats during bloom. We find that dilution effects were absent late in the season. While mass‐flowering crop cultivation alone is unlikely to be sufficient for maintaining pollinators, as part of carefully designed diverse crop rotations or mixtures combined with the preservation of permanent non‐crop habitats, it might provide valuable supplementary food resources for pollinators in temperate agroecosystems, particularly later in the season when alternative flower resources are scarce.