bluuebunny/crossref_metadata_2025 huggingface dataset:
Crosstalk of the MAP3K1 and EGFR pathways mediates gene-environment interactions that disrupt developmental tissue closure
Authors: Wang Jingjing , Xiao Bo , Kimura Eiki , Mongan Maureen , Hsu Wei-Wen , Medvedovic Mario , Puga Alvaro , Xia Ying
Published: March 2024

Aberrant signal transduction pathways can adversely derail developmental processes. One such process is embryonic eyelid closure that requires MAP3K1.Map3k1knockout mice have defective eyelid closure and an autosomal recessive eye-open at birth phenotype.In uteroexposure to dioxin, a persistent environmental toxicant, causes the same eye defect inMap3k1+/-hemizygous but not wild type pups. Here we explore the mechanisms ofMap3k1(gene) and dioxin (environment) interactions (GxE) in the tissue closure defect. We show that, acting through the AHR, dioxin activates EGFR signaling, which in turn depresses MAP3K1-dependent JNK activity. This effect of dioxin is exacerbated byMap3k1heterozygosity. Therefore, dioxin exposedMap3k1+/-embryonic eyelids have a marked reduction of JNK activity, accelerated differentiation and impeded polarization in the epithelial cells. Knocking outAhrorEgfrin eyelid epithelium attenuates the open-eye defects in dioxin-treatedMap3k1+/-pups, whereas knockout ofJnk1andS1pr, encoding the S1P receptors upstream of the MAP3K1-JNK pathway, potentiates dioxin toxicity. Our novel findings suggest that dioxin and genes of the AHR, EGFR and S1P-MAP3K1-JNK pathways constitute a multifactorial mechanism underlying tissue closure abnormalities.

Summary statement

The crosstalk between a global environmental pollutant and the pre-existing genetic conditions is mediated through interactive signaling pathways, resulting in anatomical tissue closure abnormalities in development.
BAK knockdown delays bleaching and alleviates oxidative DNA damage in a reef-building coral
Authors: Majerová Eva , Steinle Camryn , Drury Crawford
Published: March 2024

Climate change is rapidly pushing coral reefs towards extinction. Efforts to restore and protect these ecosystems using resilient corals are increasing, but our understanding of cellular mechanisms of thermal resilience and trade-offs remains limited. Here, we demonstrate downregulation of pa-BAK slows bleaching and stabilizes the symbiosis during acute heat stress inPocillopora acuta. Counterintuitively, oxidative DNA damage – a hallmark of the thermal stress response in corals – was prevented in corals with such “forced” symbiosis stability, possibly through alterations in mitochondrial ROS release. Using expression data of genes representing various stress-response pathways, we propose a model that coral heat stress response is mediated via the AMPK/Foxo3/Nrf2 signaling network. Developing our understanding of heat-stress defense mechanisms promoting stability in the coral-algal symbiosis is fundamental for effective modern coral reef restoration practices based on improving system resilience.
Interventions for the management of post COVID-19 condition (long COVID): Protocol for a living systematic review & network meta-analysis
Authors: Zeraatkar Dena , Ling Michael , Kirsh Sarah , Jassal Tanvir , Pitre Tyler , Chakraborty Samantha , Turner Tari , Turkstra Lyn , McIntyre Roger S. , Izcovich Ariel , Mbuagbaw Lawrence , Agoritsas Thomas , Flottorp Signe A. , Garner Paul , Couban Rachel , Busse Jason W.
Published: March 2024

Background

Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia, and impaired cognitive function, termed post COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.

Objective

To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.

Methods

Eligible trials will randomize adults with long COVID, to pharmacologic or non-pharmacologic interventions, placebo, sham, or usual care. We will identify eligible studies by searches of MEDLINE, EMBASE, CINAHL, PsycInfo, AMED, and CENTRAL, from inception, without language restrictions.

Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest, and assess risk of bias. Our outcomes of interest will include fatigue, pain, post-exertional malaise, changes in education or employment status, cognitive function, mental health, dyspnea, quality of life, patient-reported physical function, recovery, and serious adverse events.

For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The GRADE approach will guide our assessment of the certainty of evidence.

We will update our living review biannually, upon the publication of a seminal trial, or when new evidence emerges that may change clinical practice.

Conclusion

This living systematic review and network meta-analysis will provide comprehensive, trustworthy, and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline producing organizations to inform their recommendations.
Genetic variation inHIF1Ais associated with smoldering inflammation and disease progression in Multiple Sclerosis
Authors: Giordano Antonino , Stridh Pernilla , Preziosa Paolo , Pisa Marco , Sorosina Melissa , Mascia Elisabetta , Santoro Silvia , Misra Kaalindi , Clarelli Ferdinando , Ferrè Laura , Needhamsen Maria , Manouchehrinia Ali , Cannizzaro Miryam , Moridi Thomas , Shchetynsky Klementy , Ouellette Russell , Harroud Adil , Sandberg Elisabeth , Kuttikkatte Subita Balaram , Piehl Fredrik , Alfredsson Lars , Hillert Jan , Olsson Tomas , Fugger Lars , Attfield Kate , Granberg Tobias , Jagodic Maja , DeLuca Gabriele Carmine , Rocca Mara , Filippi Massimo , Kockum Ingrid , Esposito Federica
Published: March 2024

Background

Understanding the mechanisms underlying disease progression in Multiple Sclerosis (MS) is fundamental to pave the way to treatment advances. Smoldering demyelinating inflammation characterized by iron deposition is observed at the edges of chronic active lesions and represents a relevant substrate of disease progression in MS. However, the influence of genetic factors on these mechanisms is not known. Leveraging the importance of iron deposition in smoldering inflammation, we assessed whether variants in genes belonging to iron-related pathways affect disease progression in MS.

Methods

We investigated the association between Single Nucleotide Polymorphisms (SNPs) mapping to 334 genes in iron-related pathways and the risk of disease progression, studying 2,817 MS patients from Italy (n=755) and Sweden (n=2,062), and comparing relapsing-remitting (RR-MS) with secondary progressive (SP-MS) disease course. To better understand the link of the identified variant with smoldering inflammation, we applied a multilayered approach using independent cohorts from Italy, Sweden and the United Kingdom and encompassing gene expression, PRL analysis, neurofilament levels, post-mortem spinal cord pathology and pharmacogenomics.

Results

We found an association between a locus in the Hypoxia-Inducible Factor 1-alpha (HIF1A) gene and the odds of SP-MS transition in the Italian cohort (rs11621525; SP-MS OR 0.57, 95% CI 0.44-0.72; P=3.30×10-6), which was replicated in the Swedish dataset (rs1951795; OR 0.79, 95% CI 0.67-0.95; P=0.0079). Additional analyses showed that patients carrying the protective allele exhibited reducedHIF1Aexpression in the immune cells, lower PRL volume, lower plasma/cerebrospinal fluid neurofilament levels, and lower inflammation and acute axonal injury in the post-mortem spinal cord. Moreover, the variant influenced the response to dimethyl fumarate, an approved MS drug with effect on mechanisms shared withHIF1Apathway.

Conclusion

A novel locus in theHIF1Agene, a crucial hub for iron-binding capacity, inflammation, and hypoxia response, is associated with the risk of disease progression in MS. Converging lines of evidence support the role of this locus in smoldering inflammation, prompting future studies to explore the potential ofHIF1Aas a therapeutic target in progressive MS.
Cytokine release syndrome after treatment with immune checkpoint inhibitors: an observational cohort study of 2672 patients from Karolinska University Hospital in Sweden
Authors: Hamida Osama , Karlsson Frans , Lundqvist Andreas , Gerling Marco , Liu Lisa L.
Published: March 2024

Immune checkpoint inhibitors (ICIs) are linked to diverse immune-related adverse events (irAEs). Rare irAEs surface first in clinical practice. Here, we systematically studied the rare irAE, cytokine-release syndrome (CRS), in a cohort of 2672 patients treated with ICIs at Karolinska University Hospital in Stockholm, Sweden. We find that the risk of ICI-induced CRS – defined as fever, negative microbiological findings and absence of other probable causes within 30 days after ICI treatment – is approximately 1%, higher than previously reported. ICI-induced CRS was often mild and ICI rechallenge was generally safe. Two out of 28 patients experienced high-grade CRS, and one was fatal. While C-reactive protein and procalcitonin were not discriminative of fatal CRS, our data suggest that the quick Sequential Organ Failure Assessment (qSOFA) score might identify high-risk patients. These data provide a framework for CRS risk assessment and motivate multicenter studies to improve early CRS diagnosis.

Highlights

Cytokine release syndrome following immune checkpoint inhibition is rare and often mild.

Risk assessment using quick Sequential Organ Failure Assessment, but not serum CRP, can potentially detect severe cytokine release syndrome and improve treatment decisions.

Rechallenge with immune checkpoint inhibitors after mild cytokine release syndrome is generally well tolerated.
Perceived and endocrine acute and chronic stress indicators in fibromyalgia syndrome
Authors: Beiner Eva , Hermes Michelle , Reichert Julian , Kleinke Kristian , Vock Stephanie , Löffler Annette , Ader Leonie , Sirazitdinov Andrei , Keil Sebastian , Schmidt Tim , Schick Anita , Löffler Martin , Hopp Micheal , Ruckes Christian , Hesser Jürgen , Reininghaus Ulrich , Flor Herta , Eich Wolfgang , Friederich Hans-Christoph , Tesarz Jonas ,   PerPAIN consortium
Published: March 2024

Introduction

Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue and tenderness and closely associated with high levels of stress. FMS is therefore often considered a stress-related disease.

Methods

A comparative study was conducted with 99 individuals diagnosed with FMS and a control group of 50 pain-free individuals. Stress indicators were classified into three categories: perceived stress assessed using the Perceived Stress Scale, and daily average salivary cortisol and hair cortisol concentrations as indicators of acute and chronic stress levels related to the hypothalamic-pituitary-adrenal axis. Analysis of variance and covariance were used to identify group differences and the influence of covariates age, sex, and body mass index. Correlational analyses further elucidated the relationship between stress indicators and clinical symptoms.

Results

Participants with FMS reported significantly higher perceived stress levels than controls (p< .001, ηp2= .3), which were positively correlated with symptom burden (r= .64,p< .001). In contrast, there were no significant differences in the endocrinological stress indicators salivary and hair cortisol between the groups (p> .05), nor were these indicators associated with clinical symptoms.

Conclusion

The study highlights the central role of perceived stress in FMS, whereas endocrinological indicators did not differentiate FMS from controls. This finding calls for a nuanced approach to clinical assessment and therapeutic interventions tailored to patients with FMS, emphasizing the management of perceived stressors.
Colorectal cancer screening based on predicted risk: a pilot randomized controlled trial
Authors: Plys Ekaterina , Bulliard Jean-Luc , Chaouch Aziz , Durand Marie-Anne , van Duuren Luuk A. , Braendle Karen , Auer Reto , Froehlich Florian , Vogelaar Iris Lansdorp , Corley Douglas A. , Selby Kevin
Published: March 2024

Background & Aims

Colorectal cancer (CRC) screening relies primarily on colonoscopy and fecal immunochemical testing (FIT). Aligning utilization of these options with individual CRC risk (i.e. personalized screening) may maximize benefit with lower risks, individual burdens, and societal costs. We studied the effect of communicating personalized CRC risk and corresponding screening recommendations on appropriate screening uptake in an organized screening setting.

Methods

Pilot randomized controlled trial among residents aged 50-69 years old not yet invited for screening in Vaud, Switzerland. The intervention was a mailed brochure communicating individual 15-year CRC risk and corresponding screening recommendation. The control group received a brochure comparing FIT and colonoscopy. The primary outcome was self-reported risk-appropriate screening (FIT if <3% risk, FIT or colonoscopy if ≥3% and <6%, colonoscopy if ≥6%), assessed by a mailed questionnaire at 6 months. A secondary outcome was overall screening uptake.

Results

Of 5396 invitations, 1059 people responded (19%), of whom 258 were randomized to intervention and 257 to control materials (average 15-year risk 1.4% (SD 0.5), age 52.2 years (SD 2.2), 51% women). Risk-appropriate screening completion was 37% in the intervention group and 23% in the control group (absolute difference 14%, 95%CI 6%-22%, p<0.001). Overall screening uptake was 50% in the intervention and 49% in the control group (absolute difference 1%, 95CI −7%−10%, p=0.758).

Conclusions

In a population not known to be at elevated CRC risk, brochures providing personalized CRC risk and screening recommendations improved risk-appropriate screening without impacting overall screening uptake. This approach could be helpful for aligning screening methods, risks, and benefits with cancer risk.Trial registration:Clinicaltrials.govNCT05357508.

What You Need to Know

Background

Colorectal cancer can be effectively prevented by screening using colonoscopy or fecal immunochemical test (FIT). Optimizing use of colonoscopy resources is crucial to reduce screening burden for patients and society.

Findings

After reading our intervention brochure, participants were 14% more likely to choose the screening test appropriate to their risk level. This result did not impact overall screening participation.

Implications for patient care

Risk-based screening recommendations for FIT or colonoscopy could be a means of better allocating colonoscopy resources in countries relying heavily on colonoscopy for screening, thus decreasing the burden of CRC screening for low-risk participants.
Scoping review of factors associated with stem cell mobilisation and collection in allogeneic stem cell donors
Authors: Peck Rachel C , Knapp-Wilson Amber , Burley Kate , Dorée Carolyn , Griffin James , Mumford Andrew D , Stanworth Simon , Sharplin Kirsty
Published: March 2024

Background

There is a large inter-individual variation in CD34+ cell yield after G-CSF mobilisation and collection from peripheral blood in healthy allogenic haematopoietic stem cell donors. Donor characteristics including gender and age, baseline and pre-collection blood results, mobilisation factors and collection factors have been associated with CD34+ cell concentration in the blood after G-CSF mobilisation and/or CD34+ cell yield after collection. Since the literature reporting these associations is heterogeneous, we here clarify the determinants of CD34+ cell concentration and yield through a scoping literature review.

Materials and Methods

MEDLINE, Embase, PubMed and Stem Cell Evidence were searched for studies published between 2000 and 2023. The inclusion criteria were studies of allogeneic donors undergoing G-CSF mobilisation and peripheral blood stem cell collection (PBSC). Eligible studies assessed an outcome of mobilisation or collection efficacy, indicated by the blood CD34+ cell concentration after 4 or 5 days of G-CSF treatment and/or CD34+cell yield in the first PBSC collection after mobilisation. Included studies assessed associations between these outcomes and donor factors (such as age, gender, weight, ethnicity), mobilisation factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) and laboratory factors (such as blood cell counts at baseline and after mobilisation).

Results

The 51 eligible studies evaluated between 23 and 20,884 donors. 43 studies were retrospective, 32 assessed blood CD34+ cell concentration after mobilisation and 37 assessed CD34+ cell yield. In studies that recorded both outcomes, blood CD34+ cell concentration always predicted CD34+ cell yield. The most frequently assessed factor was donor age for which most studies reported that younger donors had a higher blood CD34+ cell concentration and CD34+ cell yield. Non-European ancestry was associated with both higher blood CD34+ cell concentration and yield although this finding was inconsistent.

Conclusions

There remains poor consensus about the best predictors of blood CD34+ cell concentration and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor may require re-evaluation.
Domain-specific LLM Development and Evaluation – A Case-study for Prostate Cancer
Authors: Tariq Amara , Luo Man , Urooj Aisha , Das Avisha , Jeong Jiwoong , Trivedi Shubham , Patel Bhavik , Banerjee Imon
Published: March 2024

In this work, we present our strategy for developing domain-specific large language models which cover the vocabulary of the target domain and train on reliable sources of clinical information. Prostate cancer was chosen as a use-case for this study. We collected more than 1.8 million clinical notes and radiology and pathology reports for 15341 patients treated for prostate cancer in Mayo Clinic across three sites and outpatient clinics. In addition to domain-specific training data, we built domain-specific tokenizers and devised knowledge-guided training strategies for LLM development. During the self-supervised training, LLM was forced to predict domain-specific information by marking clinical terms using UMLS parser. We evaluated the model for downstream tasks of clinical information prediction and question answering using quantitative and user evaluation study to measure the accuracy, reliability and information completeness. We compared the domain-specific model against similarly sized general purpose model GPT-2 and a three-times larger domain specialized model. i.e., BioGPT. Our model outperformed GPT-2 on both tasks by a wide margin. Our model was also able to outperform BioGPT on clinical information prediction tasks and showed some advantages over BioGPT in question-answering tasks.
Generation of densely labeled oligonucleotides for the detection of small genomic elements
Authors: Steinek Clemens , Ortiz Miguel Guirao , Stumberger Gabriela , Tölke Annika J. , Hörl David , Carell Thomas , Harz Hartmann , Leonhardt Heinrich
Published: March 2024

The genome contains numerous regulatory elements that may undergo complex interactions and contribute to the establishment, maintenance, and change of cellular identity. Three-dimensional genome organization can be explored with fluorescence in situ hybridization (FISH) at the single-cell level, but the detection of small genomic loci remains challenging. Here, we provide a rapid and simple protocol for the generation of bright FISH probes suited for the detection of small genomic elements. We systematically optimized probe design and synthesis, screened polymerases for their ability to incorporate dye-labeled nucleotides and streamlined purification conditions to yield nanoscopy-compatible oligonucleotides with dyes in variable arrays (NOVA-probes). With these probes, we detect genomic loci ranging from genome-wide repetitive regions down to non-repetitive loci below the kilobase scale. In conclusion, we introduce a simple workflow to generate densely labeled oligonucleotide pools that facilitate detection and nanoscopic measurements of small genomic elements in single cells.
Measuring integrin force loading rates using a two-step DNA tension sensor
Authors: Combs J. Dale , Foote Alexander K. , Ogasawara Hiroaki , Velusamy Arventh , Rashid Sk Aysha , Mancuso Joseph Nicholas , Salaita Khalid
Published: March 2024

Cells apply forces to extracellular matrix (ECM) ligands through transmembrane integrin receptors: an interaction which is intimately involved in cell motility, wound healing, cancer invasion and metastasis. These small (pN) forces exerted by cells have been studied by molecular tension fluorescence microscopy (MTFM), which utilizes a force-induced conformational change of a probe to detect mechanical events. MTFM has revealed the force magnitude for integrins receptors in a variety of cell models including primary cells. However, force dynamics and specifically the force loading rate (LR) have important implications in receptor signaling and adhesion formation and remain poorly characterized. Here, we develop a LR probe which is comprised of an engineered DNA structures that undergoes two mechanical transitions at distinct force thresholds: a low force threshold at 4.7 pN corresponding to hairpin unfolding and a high force threshold at 56 pN triggered through duplex shearing. These transitions yield distinct fluorescence signatures observed through single-molecule fluorescence microscopy in live-cells. Automated analysis of tens of thousands of events from 8 cells showed that the bond lifetime of integrins that engage their ligands and transmit a force >4.7 pN decays exponentially with a τ of 45.6 sec. A small subset of these events (<10%) mature in magnitude to >56pN with a median loading rate of 1.3 pNs-1with these mechanical ramp events localizing at the periphery of the cell-substrate junction. Importantly, the LR probe design is modular and can be adapted to measure force ramp rates for a broad range of mechanoreceptors and cell models, thus aiding in the study of mechanotransduction.

TOC
Functional exploration of in vivo and in vitro lignocellulose-fed rumen bacterial microbiomes reveals novel enzymes involved in polysaccharide breakdown
Authors: Ufarte Lisa , Laville Elisabeth , Lazuka Adele , Lajus Sophie , Bouhajja Emna , Cecchini Davide , Rizzo Angeline , Amblard Emilie , Drula Elodie , Lombard Vincent , Terrapon Nicolas , Henrissat Bernard , Cleret Megane , Morgavi Diego P. , Dumon Claire , Robe Patrick , Klopp Christophe , Bozonnet Sophie , Hernandez-Raquet Guillermina , Potocki-Veronese Gabrielle
Published: March 2024

Background: Plant cell walls are the main carbon sources for ruminal bacteria, which have evolved to produce sophisticated multi-functional enzyme cocktails in response to the structural diversity of lignocelulloses. Since a large proportion of ruminal bacteria are not yet cultured, we developed a high-throughput activity-based metagenomic approach to gain insight into this enzymatic diversity. Results: A multi-step screening methodology was implemented to identify metagenomic clones acting on polysaccharides and polyaromatic compounds. This approach was used to explore the functional potential of two different microbial consortia derived from in vivo and in vitro enrichments of the bovine rumen microbiome on wheat straw. One hundred and sixty-eight fosmid clones were isolated from libraries. Five to seven times more β-mannanase and β-glucanase clones, and seven times less xylanase clones were obtained from the in vitro enrichment compared to the in vivo one. The sequencing of 51 fosmids, covering in total 1.4 Gb of metagenomic DNA, enabled the identification of various novel glycoside-hydrolases, esterases and oxidoreductases mostly encoded by unknown bacterial genera. Functional analysis showed that most of the identified xylanases belonged to Firmicutes members that were not enriched in the fermenter, while most cellulases and mannanases originate from Bacteroidetes. Conclusion: These enzymes, that, for most of them, had not been previously identified by in depth-metagenome sequencing, present a high potential for biotechnological applications, as they could be used alone or in cocktails to break down plant cell walls. The relationships established between enzyme function and taxonomy highlight the complementary roles played by ruminal Firmicutes and Bacteroidetes in plant cell wall degradation.
asteRIa enables robust interaction modeling between chromatin modifications and epigenetic readers
Authors: Stadler Mara , Lukauskas Saulius , Bartke Till , Müller Christian L.
Published: March 2024

Chromatin, the nucleoprotein complex consisting of DNA and histone proteins, plays a crucial role in regulating gene expression by controlling access to DNA. Chromatin modifications are key players in this regulation, as they help to orchestrate DNA transcription, replication, and repair. These modifications recruit epigenetic “reader” proteins, which mediate downstream events. Most modifications occur in distinctive combinations within a nucleosome, suggesting that epigenetic information can be encoded in combinatorial chromatin modifications. A detailed understanding of how multiple modifications cooperate in recruiting such proteins has, however, remained largely elusive. Here, we integrate nucleosome affinity purification data with high-throughput quantitative proteomics and hierarchical interaction modeling to estimate combinatorial effects of chromatin modifications on protein recruitment. This is facilitated by the computational workflowasteRIawhich combines hierarchical interaction modeling, stability-based model selection, and replicate-consistency checks fora stableestimation ofRobustInteractions among chromatin modifications.asteRIaidentifies several epigenetic reader candidates responding to specificinteractionsbetween chromatin modifications. For the polycomb protein CBX8, we independently validate our results using genome-wide ChIP-Seq and bisulphite datasets. We provide the first quantitative framework for identifying cooperative effects of chromatin modifications on protein binding.
A prenatal window for enhancing spatial resolution of cortical barrel maps
Authors: Aníbal-Martínez Mar , Puche-Aroca Lorenzo , Pumo Gabriele , Madrigal M. Pilar , Rodríguez-Malmierca Luis M. , Martini Francisco J. , Rijli Filippo M. , López-Bendito Guillermina
Published: March 2024

Precise mapping of peripheral inputs onto cortical areas is required for appropriate sensory processing. In the mouse primary somatosensory cortex, mystacial whiskers are represented in large barrels, while upper lip whiskers are in smaller, less defined barrels. Barrel size and definition of these two functionally distinct barrel maps are believed to be determined by the type of whisker input and peripheral receptor density. However, spontaneous activity and transcriptional programs at prenatal developmental stages can influence somatosensory map development independently of sensory experience. Thus, the mechanisms defining distinct barrel field territories, including their size and definition, remain poorly understood. Here, we show that prenatal ablation of mystacial whiskers remap somatosensory cortical territories resulting in enhancement of the functional and anatomical definition of upper lip whisker barrels. These changes do not result from alterations in receptor type but rather stem from thalamic upper lip input-receiving neurons adopting a mystacial-like transcriptional profile. Our results unveil a regulated prenatal mechanism within the thalamus that maps available somatosensory input to ensure sufficient cortical barrel size and functional spatial resolution for sensory processing, irrespective of peripheral receptor type and density.
Evolution of temperature preference behaviour among drosophilids
Authors: Kafle Tane , Grub Manuel , Sakagiannis Panagiotis , Nawrot Martin Paul , Arguello Roman
Published: March 2024

Small-bodied ectotherms are acutely vulnerable to temperature changes, but diverse thermotactic behaviours have contributed to their ability to inhabit broad climatic niches. Understanding how - and how quickly - these behaviours evolve are outstanding biological questions that are also relevant to conservation. Among insects,Drosophila melanogasteris a preeminent ectothermic model for temperate sensing and thermotaxis. However, little is known about how its temperature-related behaviours have evolved in comparison to its closely related species. We have thermo-profiled over 2400 larvae from eight closely related species ofDrosophilafrom different thermal habitats. Consistent with local adaptation, we found substantial variation in temperature preference and fine-scale navigational behaviours amongst these species. Agent-based modelling of the larval thermotaxis circuit suggests that it is the balance between cool and warm avoidance circuits, rather than changes in temperature sensitivity, that drive differences in temperature preference. Our findings highlight the recurrent evolution of temperature-related behaviours in an experimentally tractable cross-species system.
Impact of extracellular current flow on action potential propagation in myelinated axons
Authors: Abdollahi Nooshin , Prescott Steven A
Published: March 2024

Myelinated axons conduct action potentials, or spikes, in a saltatory manner. Inward current caused by a spike occurring at one node of Ranvier spreads axially to the next node, which regenerates the spike when depolarized enough for voltage-gated sodium channels to activate, and so on. The rate at which this process progresses dictates the velocity at which the spike is conducted, and depends on several factors including axial resistivity and axon diameter that directly affect axial current. Here we show through computational simulations in modified double-cable axon models that conduction velocity also depends on extracellular factors whose effects can be explained by their indirect influence on axial current. Specifically, we show that a conventional double-cable model, with its outside layer connected to ground, transmits less axial current than a model whose outside layer is less absorptive. A more resistive barrier exists when an axon is packed tightly between other myelinated fibers, for example. We show that realistically resistive boundary conditions can significantly increase the velocity and energy efficiency of spike propagation, while also protecting against propagation failure. Certain factors like myelin thickness may be less important than typically thought if extracellular conditions are more resistive than normally considered. We also show how realistically resistive boundary conditions affect ephaptic interactions. Overall, these results highlight the unappreciated importance of extracellular conditions for axon function.

SIGNIFICANCE STATEMENT

Axons transmit spikes over long distances. Transmission is sped up and made more efficient by myelination, which allows spikes to jump between nodes of Ranvier without activating the intervening (internodal) membrane. Conduction velocity depends on the current transmitted axially from one node to the next. Axial current is known to depend on a variety of features intrinsic to myelinated fibers (e.g. axon diameter, myelin thickness) but we show here, through detailed biophysical simulations, how extracellular conditions (e.g. axon packing density) are also important. The effects ultimately boil down to the variety of paths current can follow, and the amount of current taking alternative paths rather than flowing directly from one node to the next.
Antecedents to service quality in the National Parks of Ecuador: leadership, talent management, work climate and training
Authors: Rivas Carolina , Tarí Juan José , Pereira-Moliner Jorge
Published: March 2024

Purpose

This paper analyzes how quality management in Ecuador’s national parks is explained through the quality practices contained in Deming’s quality principles from the point of view of employees.

Design/methodology/approach

Quantitative research was conducted with the participation of 254 employees from all national parks in Ecuador who rated the quality management practices (leadership, talent management, work climate and training) in their respective parks.

Findings

The results show that leadership, talent management, work climate and training significantly explain the service quality in the national parks. This study contributes to the adaptation of Deming’s quality principles to national parks via individual and joint analysis of the relationship between leadership, talent management, work climate and training with service quality in order to highlight which practices are the most important to service quality.

Originality/value

The paper provides a comprehensive overview of the key factors that influence service quality in the National Parks of Ecuador. Its multidisciplinary approach and exhaustive research make this work an invaluable tool for understanding and improving the preservation of natural resources and the tourism experience in these protected areas.
Over half a decade into the adoption of IFRS 9: a systematic literature review
Authors: Awuye Isaac S. , Taylor Daniel
Published: March 2024

Purpose

In 2018, the International Financial Reporting Standard 9-Financial Instruments became mandatory, effectively changing the underlying accounting principles of financial instruments. This paper systematically reviews the academic literature on the implementation effects of IFRS 9, providing a coherent picture of the state of the empirical literature on IFRS 9.

Design/methodology/approach

The study thrives on a systematic review approach by analyzing existing academic studies along the following three broad categories: adoption and implementation, impact on financial reporting, and risk management and provisioning. The study concludes by providing research prospects to fill the identified gaps.

Findings

We document data-related issues, forecasting uncertainties and the interaction of IFRS 9 with other regulatory standards as implementation challenges encountered. Also, we observe cross-country heterogeneity in reporting quality. Furthermore, contrary to pre-implementation expectations, we find improvement in risk management. This suggests that despite the complexities of the new regulatory standard on financial instruments, it appears to be more successful in achieving the intended objective of enhancing better market discipline and transparency rather than being a regulatory overreach.

Originality/value

As the literature on IFRS 9 is burgeoning, we provide state-of-the-art guidance and direction for researchers with a keen interest in the economic significance and implications of IFRS 9 adoption. The study identifies gaps in the literature that require further research, specifically, IFRS 9 adoption and firm’s hedging activities, IFRS 9 implications on non-financial firms. Lastly, existing studies are mostly focused on Europe and underscore the need for more research in under-researched jurisdictions, particularly in Asia and Africa. Also, to standard setters, policymakers and practitioners, we provide some insight to aid the formulation and application of standards.
Diversity as value driver in Euro Stoxx 50 companies
Authors: Gomez-Martinez Raul , Medrano-Garcia María Luisa
Published: March 2024

Purpose

Corporate diversity encompasses the different talents, knowledge, cultures, experiences and values of its employees. This diversity is reflected in multiple characteristics, such as race, age, gender, social class, religion, sexual orientation, ethnicity, culture and disability. The objective of this study is to identify if diversity is a value driver.

Design/methodology/approach

We take the diversity score from the Diversity Leaders Index 2023 published by Financial Times (FT) and Statista; this will be our independent variable in linear regression models whose objective variables are relevant fundamental indicators of the Euro Stoxx 50 companies. It is, therefore, a cross-sectional sample with financial data taken as of the current date. We have 37 Euro Stoxx 50 components included in the diversity ranking.

Findings

The results indicate that diversity is not a value driver for trading volume, for its revenue, or for systematic risk measured by the beta parameter. However, it is observed, in a confidence interval of 90%, that the most diverse companies are larger (according to their market capitalization). In addition, the most diverse companies are more profitable [return on assets (ROA)] and valued by the market [price to earnings ratio (PER)] in a confidence interval of 95%.

Originality/value

These results indicate that companies should promote corporate diversity as a management strategy, as it is observed that more diverse companies are more profitable and valued by the market. This study provides a quantitative vision in the context of homogeneous companies such as the Euro Stoxx 50 Index on the aspects in which diversity is a value driver.
Managerial decision-making: exploration strategies in dynamic environments
Authors: Wan Claire K. , Chih Mingchang
Published: March 2024

Purpose

We argue that a fundamental issue regarding how to search and how to switch between different cognitive modes lies in the decision rules that influence the dynamics of learning and exploration. We examine the search logics underlying these decision rules and propose conceptual prompts that can be applied mentally or computationally to aid managers’ decision-making.

Design/methodology/approach

By applying Multi-Armed Bandit (MAB) modeling to simulate agents’ interaction with dynamic environments, we compared the patterns and performance of selected MAB algorithms under different configurations of environmental conditions.

Findings

We develop three conceptual prompts. First, the simple heuristic-based exploration strategy works well in conditions of low environmental variability and few alternatives. Second, an exploration strategy that combines simple and de-biasing heuristics is suitable for most dynamic and complex decision environments. Third, the uncertainty-based exploration strategy is more applicable in the condition of high environmental unpredictability as it can more effectively recognize deviated patterns.

Research limitations/implications

This study contributes to emerging research on using algorithms to develop novel concepts and combining heuristics and algorithmic intelligence in strategic decision-making.

Practical implications

This study offers insights that there are different possibilities for exploration strategies for managers to apply conceptually and that the adaptability of cognitive-distant search may be underestimated in turbulent environments.

Originality/value

Drawing on insights from machine learning and cognitive psychology research, we demonstrate the fitness of different exploration strategies in different dynamic environmental configurations by comparing the different search logics that underlie the three MAB algorithms.
An update on clinical trials for cutaneous lupus erythematosus
Authors: Xie Lillian , Lopes Almeida Gomes Lais , Stone Caroline J. , Faden Daniella Forman , Werth Victoria P.
Published: March 2024

Cutaneous lupus erythematosus (CLE) comprises dermatologic manifestations that may occur independently or with systemic lupus erythematosus (SLE). Despite advancements in refining CLE classification, establishing precise subtype criteria remains challenging due to overlapping presentations and difficulty in distinguishing morphology. Current treatments encompass preventive measures, topical therapies, and systemic approaches. Hydroxychloroquine and glucocorticoids are the sole US Food and Drug Administration (FDA)‐approved medications for CLE, with numerous off‐label treatments available. However, these treatments are often not covered by insurance, imposing a significant financial burden on patients. The exclusion of most CLE patients, particularly those without concurrent SLE, from trials designed for SLE has resulted in a lack of targeted treatments for CLE. To develop effective CLE treatments, validated outcome measures for tracking patient responsiveness are essential. The Cutaneous Lupus Erythematosus Disease Area and Severity Index is widely utilized for its reliability, validity, and ability to differentiate between skin activity and damage. In contrast, the FDA mandates the use of the Investigator's Global Assessment, a five‐point Likert scale related to lesion characteristics, for skin‐related therapeutic trials. It requires the disease to resolve or almost completely resolve to demonstrate improvement, which can be difficult when there is residual erythema or incomplete clearance that is meaningfully improved from a patient perspective. Various classes of skin lupus medications target diverse pathways, allowing tailored treatment based on the patient's lupus inflammatory profile, resulting in improved outcomes. Promising targeted therapeutic drugs include anifrolumab (anti‐type 1 interferon), deucravacitinib (allosteric tyrosine kinase 2 inhibitor), litifilimab (plasmacytoid dendritic cell‐directed therapy), iberdomide (cereblon‐targeting ligand), and belimumab (B‐cell directed therapy). Despite the significant impact of CLE on quality of life, therapeutic options remain inadequate. While promising treatments for cutaneous lupus are emerging, it is crucial to underscore the urgency for skin‐focused treatment outcomes and the implementation of validated measures to assess therapeutic effectiveness in clinical trials.
The effect of dead standing (marcescent) biomass on litter decomposition in herbaceous flora is governed by plant functional group
Authors: Angst Šárka , Mudrák Ondřej , Frouz Jan , Jílková Veronika , Schnablová Renáta , Straková Petra , Veselá Hana , Angst Gerrit
Published: March 2024

In autumn, temperate herbs begin to senesce and gradually shed their litter. However, surprisingly large amounts of dead biomass remain standing, that is, marcescent. The consequences of marcescence for the decomposition of biomass once it finally reaches the soil are largely unknown.

Here, we aimed to determine whether marcescence affects subsequent litter decomposition in the organic layer to such an extent that its mass loss and chemistry are distinguishable from those of directly shed biomass. We further aimed to disentangle the role of plant functional traits and groups (forbs vs. grasses) concerning the marcescence effect on decomposition.

To this end, we sampled the living, marcescent and shed senescent biomass of 39 herbaceous plant species grown in a common garden experiment, determined plant functional traits and incubated the marcescent and shed plant tissues in the field in an allochthonous organic layer for 6 months. We determined the mass loss, C and N contents, chemical composition and microbial community structure of the decomposed tissues.

Our results show that marcescent tissues decomposed more slowly than directly shed tissues (mass loss 37.3% vs. 63.2% for forbs, 43.5% vs. 45.5% for grasses), likely due to more favourable conditions for decomposition in the organic layer. These were reflected in a significantly higher microbial colonization of shed (~333 and 708 μg biomass C g−1 for forbs and grasses, respectively) than marcescent tissue (~189 and 543 μg biomass C g−1 for forbs and grasses, respectively) even after 6 months in the organic layer. Moreover, higher relative contributions of aliphatics and polyphenolics in shed tissues indicated a more advanced stage of decomposition. Notably, marcescent tissues of forbs, with a more complex growth architecture (being composed of stems [marcescent] and leaves [shed]), decomposed substantially more slowly than directly shed tissues. In contrast, differences in decomposition between marcescent and shed tissues of grasses, with a more uniform growth architecture, were substantially less pronounced.

These findings highlight that marcescence in the temperate herbaceous flora can strongly affect litter decomposition and thus C and nutrient cycling through temperate ecosystems, but that the extent to which marcescence affects decomposition depends on plant functional group.
Postpartum long‐acting reversible contraceptive adoption after a statewide initiative
Authors: Gifford Katie , McColl Rebecca , McDuffie Mary Joan , Boudreaux Michel
Published: March 2024

Objectives

To examine the effects of a comprehensive, multiyear (2015–2020) statewide contraceptive access intervention in Delaware on the contraceptive initiation of postpartum Medicaid patients. The program aimed to increase access to all contraceptives, including long‐acting reversible contraceptives (LARC). The program included interventions specifically targeting postpartum patients (Medicaid payment reform and hospital‐based immediate postpartum (IPP) LARC training) and interventions in outpatient settings (provider training and operational supports).

Data Sources and Study Setting

We used Medicaid claims data between 2012 and 2019, from Delaware and Maryland (a comparison state), to identify births and postpartum contraceptive methods up to 60 days postpartum among patients aged 15–44 years who were covered in a full‐benefit eligibility category.

Study Design

Using difference‐in‐differences, we assessed changes in LARC, tubal ligation, and short‐acting methods (oral contraceptive, injectable, patch/ring). LARC rates were assessed at 60 days after delivery and on an immediate postpartum basis. Other methods were only assessed at 60 days. Analyses were conducted separately for an early‐adopting high‐capacity hospital (that delivers approximately half of all Medicaid financed births) and for all other later‐adopting hospitals in the state.

Data Collection/Extraction Methods

Data were extracted from administrative claims.

Principal Findings

The program increased postpartum LARC insertions by 60 days after delivery by 11.7 percentage points (95% CI: 10.7, 12.8) in the early‐adopting hospital and 6.9 percentage points (95% CI: 4.8, 5.9) in later‐adopting hospitals. Increases in IPP versus outpatient LARC drove the change, but we did not find evidence that IPP crowded‐out outpatient LARC services. We observed decreases in short‐acting methods, suggesting substitution between methods, but the share of patients with any method increased at the early‐adopting hospital (5.2 percentage points; 95% CI: 3.5, 6.9) and was not statistically significantly different at the later‐adopting hospitals.

Conclusions

Direct reimbursement for IPP LARC, in combination with provider training, had a meaningful impact on the share of Medicaid‐enrolled postpartum women with LARC claims.