bluuebunny/crossref_metadata_2025 huggingface dataset:
Robustness of ancestral sequence reconstruction to among-site evolutionary heterogeneity and epistasis
Authors: Muñiz-Trejo Ricardo , Park Yeonwoo , Thornton Joseph W
Published: December 2024

Ancestral sequence reconstruction (ASR) is typically performed using homogeneous evolutionary models, which assume that the same substitution propensities affect all sites and lineages. These assumptions are routinely violated: heterogeneous structural and functional constraints favor different amino acid states at different sites, and these constraints often change among lineages as epistatic substitutions accrue at other sites. To evaluate how realistic violations of the homogeneity assumption affect ASR, we developed site-specific substitution models and parameterized them using data from deep mutational scanning experiments on three protein families; we then used these models to perform ASR on the empirical alignments and on alignments simulated under heterogeneous conditions derived from the experiments. Extensive among-site and -lineage heterogeneity is present in these datasets, but the sequences reconstructed from empirical alignments are almost identical, irrespective of whether heterogeneous or homogeneous models are used for ASR. The rare differences occur primarily when phylogenetic signal is weak — at fast-evolving sites and nodes connected by long branches. When ASR is performed on simulated data, errors in the reconstructed sequences become more likely as branch lengths increase, but incorporating heterogeneity into the model does not improve accuracy. These data establish that ASR is robust to unincorporated realistic forms of evolutionary heterogeneity, because the primary determinant of ASR is phylogenetic signal, not the substitution model. The best way to improve accuracy is therefore not to develop more elaborate models but to apply ASR to densely sampled alignments that maximize phylogenetic signal at the nodes of interest.
Killer Toxin K28 resistance in yeast relies on COG complex mediated trafficking of the defence factor Ktd1
Authors: Laidlaw Kamilla ME. , Nadir Hatwan H. , Milburn Amy , Xelhuantzi Martha S.C. , Stanislovas Justas , Droop Alastair P. , MacDonald Sandy , Andreev Ilya , Leech Andrew , Ungar Daniel , Sadhu Meru , MacDonald Chris
Published: December 2024

A/B toxins are a diverse family of protein toxins that enter host cells via endocytosis and induce cell death. In yeast, the A/B toxin K28 is internalised to endosomes of susceptible yeast, before following the retrograde trafficking pathway and ultimately triggering cell cycle arrest. The endolysosomal defence factor Ktd1 protects against K28, but its regulation remains unclear. Cog7, a subunit of the Golgi-associated tethering COG complex, has been implicated in K28 defence, though the mechanism is unknown. We developed a high throughput K28 sensitivity assay and bespoke analysis package to show that all lobe B COG subunits (Cog5 - 8) are required for K28 resistance. Although the COG complex modulates glycosylation of the surface molecules required to bind extracellular K28, our experiments reveal that the hypersensitivity ofcogmutants is primarily explained by defects in Ktd1 trafficking. Ktd1 mis-localisation incogmutants is reminiscent to disruptions in Snc1, a surface cargo that recycles multiple times via the Golgi. This work suggests not only that the COG complex is required for the precise trafficking Ktd1 required to mediate toxin defence, but that Ktd1 may survey endolysosomal compartments for internalised K28. This work underpins the importance of Ktd1 in defence against the A/B toxin K28, and implies various membrane trafficking regulators might influence toxin effects in other eukaryotic systems.
Towards a comprehensive framework for digital inclusion: a comparison of international measurements
Authors: Jia Shiwei , Du Jia Tina , Yan Hui
Published: December 2024

Purpose

Measuring the extent of digital inclusion is a complex task. This study aims to monitor existing digital inclusion indices at the national level, compare their consistencies and differences and based on this, develop a more comprehensive measurement framework.

Design/methodology/approach

The study selected the existing digital inclusion indices that met the screening criteria through a literature survey. Eight digital inclusion indices were included in the final selection and their measurement methodologies were collected. Thereafter, the study adopted a content analysis method to examine and compare the methodologies of the selected digital inclusion indices, with the coding framework grounded on the literature review.

Findings

Results suggest that five dimensions of digital inclusion – Access, Skills, Usage, Acceptance and Impact – were measured. Access is the first priority dimension that all digital inclusion indices pay attention to. Skills and Usage are under-measured by methodological limitations in practical measurement tools. Acceptance and Impact are the least covered dimensions both in academic research and practical measurement. Based on this, we propose three suggestions for developing a more comprehensive global framework: designing from the national lens, using more objective and original data sources and improving the framework and indicators with theory.

Originality/value

The study provides scholars and policymakers in the field of digital inclusion with a reference point to create a more comprehensive measurement framework for digital inclusion.
Online controversial events: leveraging consumer engagement with users’ positive buzz
Authors: Li Xiaoling , Fan Tingting , Yu Hongyu , Yang Pianpian
Published: December 2024

Purpose

Social media have escalated the frequency and intensity of brands’ online controversial events (OCEs), which differs conceptually from negative events. Despite this, there remains a scarcity of research exploring the nature of OCEs. This paper aims to investigate the impact of positive buzz on consumer engagement during OCEs.

Design/methodology/approach

Using 47,468 posts from two popular Chinese social media (i.e. Weibo and Zhihu), we employ a zero-inflated negative binomial regression and content analysis to test our hypotheses.

Findings

The results indicate that positive buzz informativeness and sentiment positively affect consumer engagement in online brand communities, moderated by community type and time-related factors. Expert communities (vs social communities) weaken main effects, while date distance strengthens them.

Originality/value

This study is the first to propose the nature of brand’s OCEs and explores how positive buzz affects consumer engagement, highlighting the moderating roles of community type and date distance. This paper contributes to literature on user-generated content (UGC), OCEs and dual process theory, offering valuable insights for brands, consumers and community owners.
Modelling temperature distribution in three-side protected steel beams using evolutionary regression and gradient boosting to predict conductive heat flux
Authors: Li Yang , Guo Kangrui
Published: December 2024

Purpose

The aim of the paper is to propose a simple and effective calculation method for a three-side protected steel beam temperature field.

Design/methodology/approach

The calculation model is based on temperature increment equation of EN1993-1-2 and the Fourier's law to calculate the conductive heat flux. The ABAQUS heat transfer simulation is used to establish temperatures and heat flux database at the joints. The ratio of simulation and calculated heat flux is predicted by evolutionary regression and gradient boosting method.

Findings

Combined evolutionary regression analysis (CERA) including both linear and polynomial regression reduce the residual of mean square error (MSE) by 7.1% compared to linear regression analysis (linear evolutionary regression analysis (LERA)). The evolutionary regression analysis (ERA) effectively reduces the temperature discrepancy with increase of evolution numbers. Gradient boosting predicts the k value and temperatures with the least residual of MSE. The average residual of MSE is 53.23 °C for the upper flange, 16.18 °C for the web and 19.44 °C for the lower flange.

Originality/value

This paper proposed an effective and fast temperature distribution model for the three-side protected steel beam combining machine learning methods to converge the conductive heat flux between specimens. A novel ERA able to fit output data with multiple inputs with explainable equations is proposed and validated by effectively converging the conductive heat flux to simulation results.
Easy‐Curing and pH‐Regulated CRISPR‐Cas9 Plasmids for Gene Editing and Plasmid Curing in Lactococcus cremoris
Authors: Garay‐Novillo Javier Nicolás , Ruiz‐Masó José Ángel , del Solar Gloria , Barra José Luis
Published: December 2024

In this work, we developed a plasmid‐based CRISPR‐Cas9 strategy for editing Lactococcus cremoris, which allows easy generation of plasmid‐free strains with the desired modification. We constructed versatile shuttle vectors based on the theta‐type pAMβ1 promiscuous replicon and p15A ori, expressing both the Cas9 nuclease gene (under pH‐regulated promoters derived from P170) and a single‐guide RNA for specific targeting (under a strong constitutive promoter). The vectors designed for plasmid targeting were very effective for low‐ and high‐copy‐number plasmid curing in L. cremoris, and their targeting efficiency was shown to be tunable by regulating cas9 expression. For chromosome editing, we implemented a host‐independent method that enhances double‐homologous recombination events using plasmids expressing the genes encoding λRed‐phage Redβ recombinase and Escherichia coli single‐stranded DNA binding protein (EcSSB). By coupling either the endogenous recombination machinery or the Redβ‐EcSSB‐assisted recombination system with our novel chromosome‐targeting CRISPR‐Cas9 plasmids, we efficiently generated and selected thousands of gene‐edited cells. Examination of the impact of the constructed CRISPR‐Cas9 vectors on host fitness revealed no Cas9‐associated toxicity, and, remarkably, these vectors exhibited a very high loss rate when growing the bacterial host cells in the absence of selective pressure.
Risk Stratification and Adjuvant Chemotherapy for High‐Risk Stage IA Lung Adenocarcinoma: The Unmet Needs
Authors: Shen Chen , Liu Haoran , Li Bofei , Wang Jiaming , Wang Yiyang , Bao Feichao , Gu Zhitao , Fang Wentao
Published: December 2024

Introduction

To identify high‐risk patients for recurrence in resected stage IA lung adenocarcinoma and evaluate the impact of adjuvant chemotherapy (ACT) on their prognosis, as well as explore potential novel adjuvant therapies.

Methods

Consecutive stage IA patients with ≥ 5% solid or micropapillary subtypes were analyzed. A nomogram was developed using Cox proportional hazards regression to predict recurrence‐free survival (RFS). In the high‐risk group after stratification, RFS was compared between patients receiving ACT and those under observation, as well as between patients with and without driver gene alterations.

Results

This real‐world study included 1328 patients, with a 5‐year RFS of 79.0%. T stage and predominant subtype were independent risk factors for RFS. Patients with T1c or solid/micropapillary‐predominant tumors were stratified into a high‐risk group (n = 483) using the nomogram. A significant difference in 5‐year RFS was observed between the high‐ and low‐risk groups (73.6% vs. 84.3%, p < 0.001). Among high‐risk patients, sixty‐seven (13.8%) received ACT; however, there was no improvement in 5‐year RFS compared to observation alone (69.1% vs. 75.0%, p = 0.655). Testing rates for EGFR mutation and ALK fusion among high‐risk patients were only 52.4% and 43.9%, respectively, while mutation rates reached up to 55.7% and 9.4%, respectively. These molecular alterations exhibited numerically worse 5‐year RFS compared to wild‐type (EGFR mutation, 70.6% vs. 87.8%, p = 0.108; ALK fusion, 66.3% vs. 73.6%, p = 0.404), though not significant.

Conclusions

ACT failed to meet the needs of stage IA patients with histological high‐risk features. Further exploration of effective adjuvant target therapies is warranted for this patient subgroup.
Association of intravitreal and topical anti‐inflammatory therapies on short‐term anatomical and functional outcomes following epiretinal membrane surgery
Authors: Sutinen Pinja , Hecht Idan , Karesvuo Minna , Jeon Sohee , Karesvuo Petteri , Tuuminen Raimo
Published: December 2024

Purpose

Here we examine the association of anti‐inflammatory therapy with anatomical and functional outcomes of epiretinal membrane surgery.

Methods

The study included consecutive patients having gone through epiretinal membrane surgery at Helsinki University Hospital, Finland, between 2017 and 2021. The association of perioperative intravitreal and postoperative topical anti‐inflammatory therapies with surgical outcomes was assessed.

Results

In total, 214 eyes of 214 patients with a mean age of 71.2 ± 8.2 years were studied. At 1‐month, perioperative intravitreal use of triamcinolone acetonide (n = 27) was associated with a significant proportional and absolute improvement in foveal thickness (−15.9 ± 18.4% vs. −4.2 ± 25.6%, p = 0.003 and −86.2 ± 109.6 μm vs. −33.7 ± 94.3 μm, p = 0.004), and central subfield macular thickness (−14.7 ± 16.5% vs. −6.3 ± 16.9%, p = 0.009 and −80.6 ± 102.8 μm vs. −36.1 ± 75.9 μm, p = 0.004) when compared to those without triamcinolone acetonide. Furthermore, best‐corrected visual acuity (BCVA) gain showed a non‐significant yet corresponding trend favouring intraoperative intravitreal use of triamcinolone acetonide (0.21 ± 0.27 vs. 0.09 ± 0.28 LogMAR units, p = 0.062). Postoperative use of topical non‐steroidal anti‐inflammatory drugs (NSAIDs) (n = 36) as adjunct therapy showed no significant advantage in anatomical outcomes or BCVA gain when compared to those without NSAIDs (all p > 0.05). Triamcinolone acetonide remained significant for proportional and absolute improvement in foveal thickness (p = 0.019 and p = 0.006) and in central subfield macular thickness (p = 0.013 and p = 0.006) when controlled for confounding factors patient age and gender and topical NSAID use.

Conclusions

Intraoperative intravitreal use of triamcinolone acetonide improved short‐term anatomical outcomes in patients who underwent epiretinal membrane surgery.
Lycorine Suppresses Non‐Small‐Cell Lung Cancer Progression Through Activating STING Pathway and Stimulating an Antitumor Immune Response
Authors: Jiang Ze‐Bo , Xu Cong , Xu Pan , Huang Dong‐Hui , Kang Li‐Ping
Published: December 2024

Non‐small‐cell lung cancer (NSCLC) stands as a primary contributor to cancer‐related deaths worldwide. It has been demonstrated that Lycorine (LYD), a naturally occurring active sesquiterpene present in Chinese medicinal plants, exhibits anti‐cancer properties across various cancer cell lines. However, the underlying mechanisms of LYD‐induced anti‐tumor in NSCLC are not fully known. This study demonstrated that LYD significantly reduced the proliferation of NSCLC and induced apoptosis by increasing intracellular ROS levels. The inhibition of ROS using N‐acetylcysteine (NAC) eliminated the apoptosis effects of LYD, resulting in increased cell viability. Additionally, LYD treatment significantly activated the STING pathway in NSCLC and induced the expression of CXCL10, CXCL9 and CCL5 in NSCLC cells. Mechanistically, LYD was found to significantly reduce the protein levels of P70S6K and S6K, which are key proteins involved in cell growth and survival. Notably, in vivo experiments demonstrated that LYD significantly inhibited the growth of H358 xenograft and LLC1 tumor, exhibiting anti‐tumor activity by elevating CD8+ T cells in the NSCLC mouse model. Our findings suggest that LYD possesses potent anti‐cancer properties in NSCLC by inducing apoptosis through ROS generation and modulating the STING pathway and key chemokines. Furthermore, LYD also exerts its antitumor effects by inhibiting crucial proteins involved in cell growth. Overall, LYD shows promise as a potential therapeutic agent for NSCLC treatment.
Family Experience of Detention for Migratory Reasons: Findings From a Qualitative Systematic Review
Authors: Gervais Christine , Souza Sophie Lampron‐de , Pariseau‐Legault Pierre , Chammas Grace , Côté Isabel , Cliche Karolane
Published: December 2024

In response to growing international migration, several states have adopted controversial measures, including detaining migrants, which have detrimental impacts on migrants' physical, mental and social health. Although family is often at the heart of migratory decisions, few studies have used a family lens to examine this phenomenon. This paper reports on the findings of a qualitative systematic review that aims to describe the experience of migrant families dealing with detention. Articles were searched in relevant databases, and the quality of studies was assessed independently by two reviewers using the JBI Critical Appraisal Checklists. Twenty‐two out of 897 articles met the inclusion criteria and were subsequently included. Three themes emerged from the thematic synthesis that capture the experience of migrant families affected by detention: (1) alterations of the family structure, (2) disruptions in instrumental and emotional functioning and (3) weakening of the family identity. Results robustly evidenced the detrimental effects of detention on families and the urge to stop this practice. Limitations included the difficulty of distinguishing between the experience of detention and deportation in some studies, as well as limited information about the long‐term effect of detention on family health and integration in the host society.
Comparative effectiveness of Roux‐en‐Y gastric bypass and sleeve gastrectomy in achieving diabetes remission in patients with diabetes‐related vascular diseases: A multicentred study
Authors: Ghusn Wissam , Ma Pearl , Ikemiya Kayla , Salame Marita , Hage Karl , Mosleh Kamal Abi , Storm Andrew C. , Kendrick Michael , Abu Dayyeh Barham K. , Higa Kelvin , Ghanem Omar M.
Published: December 2024

Metabolic and bariatric surgeries (MBS), including Roux‐en‐Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG), have proven effective in promoting long‐term diabetes remission among patients with type‐2 diabetes (T2D). In this multicentre retrospective cohort study, we investigated the effectiveness of RYGB and SG in achieving diabetes remission, specifically among patients with T2D and vascular complications, while accounting for similar baseline diabetes severity. Although various scores predict diabetes remission after bariatric surgery, they do not consider diabetes‐related vascular complications, which can influence outcomes even in patients with similar baseline T2D severity. We collected preoperative data on microvascular (retinopathy, nephropathy, neuropathy) and macrovascular comorbidities (coronary artery disease, cerebrovascular accidents, peripheral artery disease) to compare the efficacy of RYGB and SG. Among 961 patients analysed, those with vascular complications showed higher remission rates with RYGB (OR: 1.97) compared to SG, despite similar baseline diabetes severity. Notably, RYGB patients with microvascular complications had a significant advantage in achieving T2D remission (OR: 2.95). However, no significant differences in remission were observed in patients with macrovascular complications. These findings suggest that RYGB may be more effective than SG in specific patient populations, particularly those with microvascular complications, emphasizing the need for personalized treatment strategies.
Contact heat evoked potentials reveal distinct patterns of spinal cord impairment in degenerative cervical myelopathy beyond MRI lesions
Authors: Scheuren Paulina Simonne , Hupp Markus , Pfender Nikolai , Seif Maryam , Zipser Carl Moritz , Wanivenhaus Florian , Spirig José Miguel , Betz Michael , Freund Patrick , Schubert Martin , Farshad Mazda , Curt Armin , Hubli Michèle , Rosner Jan
Published: December 2024

Background

Magnetic resonance imaging may suggest spinal cord compression and structural lesions in degenerative cervical myelopathy (DCM) but cannot reveal functional impairments in spinal pathways. We aimed to assess the value of contact heat evoked potentials (CHEPs) in addition to MRI and hypothesized that abnormal CHEPs may be evident in DCM independent of MR‐lesions and are related to dynamic mechanical cord stress.

Methods

Individuals with DCM underwent neurologic examination including segmental sensory (pinprick, light touch) and motor testing. The presence or absence of hyperintense signal on T2‐weighted MRI (T2‐positive/negative) was assessed. Phase‐contrast MRI was used to assess spinal cord motion as an indicator of dynamic mechanical stress. Dermatomal somatosensory evoked potentials and CHEPs were recorded after stimulation of dermatomes C6, C8, and T4 (CHEPs only) to assess spinal cord integrity.

Results

Of 138 individuals included in this study (age 56 ± 13 years), 35% (N = 48) presented with T2‐positive and 65% (N = 90) presented with T2‐negative DCM. Abnormal CHEPs were present in T2‐positive DCM (C6:41%; C8:32%; T4:24%) and T2‐negative DCM (C6:35%; C8:54%; T4:26%). Multisegmental CHEP abnormalities at C6 and C8 were related to increased spinal cord motion (p = 0.030; ϵ2 = 0.072), and reduced upper extremity pinprick (p = 0.046; ϵ2 = 0.063) and motor scores (p = 0.005; ϵ2 = 0.108).

Conclusions

CHEPs revealed distinct patterns of spinal cord impairment independent of structural T2‐positive lesions, which were associated with measures of cord motion. CHEPs thus provide valuable complementary diagnostic insights into spinal cord integrity beyond MRI. This is especially important in incipient myelopathy to inform early diagnosis and timely interventions before the development of definite cord lesions.
Prognostic factors and impact of management strategies for status epilepticus: The STEPPER study in the Emilia‐Romagna region, Italy
Authors: Di Vito Lidia , Matteo Eleonora , Meletti Stefano , Zenesini Corrado , Bernabè Giorgia , Bomprezzi Chiara , Casadio Maria Chiara , Castioni Carlo Alberto , Cesnik Edward , Coniglio Carlo , Currò‐Dossi Marco , De Massis Patrizia , Fallica Elisa , Florindo Irene , Giovannini Giada , Guarino Maria , Marchesi Elena , Marudi Andrea , Merli Elena , Monti Giulia , Orlandi Niccolò , Pasini Elena , Passarelli Daniela , Rinaldi Rita , Rizzi Romana , Romoli Michele , Santangelo Mario , Tontini Valentina , Turchi Giulia , Volpini Mirco , Zini Andrea , Zinno Lucia , Michelucci Roberto , Vignatelli Luca , Tinuper Paolo , Bisulli Francesca ,   the STEPPER study group
Published: December 2024

Objective

The STEPPER (Status Epilepticus in Emilia‐Romagna) study aimed to investigate the clinical characteristics, prognostic factors, and treatment approaches of status epilepticus (SE) in adults of the Emilia‐Romagna region (ERR), Northern Italy.

Methods

STEPPER, an observational, prospective, multicentric cohort study, was conducted across neurology units, emergency departments, and intensive care units of the ERR over 24 months (October 2019–October 2021), encompassing incident cases of SE. Patients were followed up for 30 days.

Results

A total of 578 cases were recruited (56% female, mean age = 70 years, 32% with previous diagnosis of epilepsy, 43% with in‐hospital onset, 35% stuporous/comatose, 46% with nonconvulsive SE). Etiology was known in 87% (acute 43%, remote 24%, progressive 17%, definite epileptic syndrome 3%). The mean pre‐SE Rankin Scale score was 2, the Status Epilepticus Severity Score was ≥4 in 33%, the Epidemiology‐Based Mortality Score in Status Epilepticus score was ≥64 in 61%, and 34% were refractory. The sequence of treatments followed current clinical practice guidelines in 63%. Benzodiazepines (BDZs) were underused as first‐line therapy (71%), especially in in‐hospital onset cases; 15% were treated with continuous intravenous anesthetic drugs. Mortality was 24%; 63% of survivors had functional worsening. At the two‐step multivariable analysis, incorrect versus correct treatment sequence with correct BDZ dose was the strongest predictor of failure to resolve SE in the in‐hospital group (odds ratio [OR] = 4.42, 95% confidence interval [CI] = 1.86–10.5), with a similar trend in the out‐of‐hospital group (OR = 2.22, 95% CI = .98–5.02). In turn, failure to resolve was the strongest predictor of 30‐day mortality (OR = 11.3, 95% CI = 4.16–30.9, out‐of‐hospital SE; OR = 6.42, 95% CI = 2.79–14.8, in‐hospital SE) and functional worsening (OR = 5.83, 95% CI = 2.05–16.6, out‐of‐hospital SE; OR = 9.30, 95% CI 2.22–32.3, in‐hospital SE).

Significance

The STEPPER study offers insights into real‐world SE management, highlighting its significant morbidity and functional decline implications. Although nonmodifiable clinical factors contribute to SE severity, modifiable factors such as optimized first‐line therapies and adherence to guidelines can potentially influence prognosis.
Rare dysfunctional SCN2A variants are associated with malformation of cortical development
Authors: Clatot Jérôme , Thompson Christopher H. , Sotardi Susan , Jiang Jinan , Trivisano Marina , Balestrini Simona , Ward D. Isum , Ginn Natalie , Guaragni Brunetta , Malerba Laura , Vakrinou Angeliki , Sherer Mia , Helbig Ingo , Somarowthu Ala , Sisodiya Sanjay M. , Ben‐Shalom Roy , Guerrini Renzo , Specchio Nicola , George Alfred L. , Goldberg Ethan M.
Published: December 2024

Objective

SCN2A encodes the voltage‐gated sodium (Na+) channel α subunit NaV1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders. However, the mechanisms whereby variation in SCN2A leads to disease remains incompletely understood, and the full spectrum of SCN2A‐related disorders may not be fully delineated.

Methods

Here, we identified seven de novo heterozygous variants in SCN2A in eight individuals with developmental and epileptic encephalopathy (DEE) accompanied by prominent malformation of cortical development (MCD). We characterized the electrophysiological properties of Na + currents in human embryonic kidney (HEK) cells transfected with the adult (A) or neonatal (N) isoform of wild‐type (WT) and variant NaV1.2 using manual and automated whole‐cell voltage clamp recording.

Results

The neonatal isoforms of all SCN2A variants studied exhibit gain of function (GoF) with a large depolarized shift in steady‐state inactivation, creating a markedly enhanced window current common across all four variants tested. Computational modeling demonstrated that expression of the NaV1.2‐p.Met1770Leu‐N variant in a developing neocortical pyramidal neuron results in hyperexcitability.

Significance

These results support expansion of the clinical spectrum of SCN2A‐related disorders and the association of genetic variation in SCN2A with MCD, which suggests previously undescribed roles for SCN2A in fetal brain development.
Temporal ecological processes have different seasonal influences on multiple dimensions of riverine insect diversity in China
Authors: Lin Xiaowei , Zhang Xiaoguang , Tan Lu , Tian Zhen , Li Jingting , Luo Qingyi , Resh Vincent H. , Cai Qinghua , Chiu Ming‐Chih
Published: December 2024

An understanding of the relative importance of ecological processes affecting biological communities can assist in interpretations of biodiversity patterns. However, the mechanism behind temporal beta diversity, which refers to the dissimilarity between community structures at different times, remains unclear for aquatic insect communities.

Therefore, we collected monthly samples of aquatic insects at five sites in streams from July 2011 to June 2012 in Central China. The five sample sites were located in river sections with perennially flowing water, which were subject to little human disturbance. We examined taxonomic‐ and trait‐based temporal beta diversity patterns of riverine insects across seasons in sites.

Taxonomic‐ and trait‐based temporal beta diversity demonstrated a decline with species richness but an increase with the time between sampling dates. Taxonomic‐based temporal beta diversity was significantly higher than trait‐based temporal beta diversity. Turnover (i.e. species replacement) was the main driver of taxonomic‐based temporal beta diversity whereas nestedness (i.e. species gain or loss) contributed more to trait‐based temporal beta‐diversity values. In addition, the correlation between taxonomic‐ and trait‐based temporal beta diversity was weak.

Deterministic processes (i.e. operating through physico‐chemical factors and climate) and stochastic processes (i.e. operating through temporal variables) are distinct, but they can act together in influencing the temporal beta diversity of riverine insects. Taxonomic‐based temporal beta diversity was more sensitive to environmental changes than trait‐based temporal beta diversity, and taxonomic shift do not necessarily result in trait changes. The main driver of taxonomic‐based temporal beta diversity changed with the location and components analysed. In contrast, stochastic processes were the most dominant influence on trait‐based temporal beta diversity.

Results suggest that taxonomic‐ and trait‐based conservation measures should consider both turnover and nestedness patterns in the protection of riverine insects in China and elsewhere. Additionally, the development of integrated monitoring and management protocols that apply across seasons and life stages should be considered.
Evidence‐Based Leadership in Nursing: An Evolutionary Concept Analysis
Authors: Hu Shuang , Liu Siying , Li Xianfeng , Chen Wenjun , Li Jialin , Jiale Hu , Välimäki Maritta Anneli , Li Xianhong
Published: December 2024

Aim

To conduct a concept analysis of evidence‐based leadership in a nursing context.

Methods

Rodgers' evolutionary method was employed to identify attributes, antecedents, consequences, definitions and surrogate and related terms.

Data Source

We systematically searched three databases (PubMed, Cumulative Index to Nursing and Allied Health Literature and Scopus) for relevant publications. The databases were searched from their inception to 4 February 2024.

Results

We included 12 papers published between 2005 and 2022. The attributes include leadership attributes (personality, developing common goals and visions and influencing others) and evidence‐based attributes (valuing evidence‐based practice, integrating evidence and adapting evidence). The antecedents include individual internal factors (commitment to growth and proficiency in implementation science) and individual external factors (growing need for evidence‐based practice, training support and available resources), while the consequences are personal growth, organisational benefit and disciplinary development. Based on the concept analysis, evidence‐based leadership can be defined as a process whereby individuals, based on their personality and values towards evidence‐based practices, integrate the best evidence into practice, adapt the evidence integration process based on evaluations and influence others towards achieving a common goal and vision.

Conclusions

This concept analysis enhances our understanding of evidence‐based leadership, guiding nurses to integrate evidence into their leadership practices to achieve specific goals and visions within the healthcare context. Future studies could consider developing instruments to evaluate evidence‐based leadership based on this refined concept, ultimately promoting nurses' leadership competencies in real‐world settings.

Implication for Nursing Practice

This concept analysis not only raises awareness of the responsibilities of nurses as healthcare professionals, including the provision of evidence‐based practice, but also facilitates their effective execution of these responsibilities. Empowering nurses to actively incorporate evidence into their leadership practices can further enhance the quality of healthcare delivery.

Reporting Method

Not applicable.

Patient or Public Contribution

Not applicable.
Exploring the Prognostic Value of Tumour‐Associated Genes in Clear Cell Renal Cell Carcinoma Through Single‐Cell RNA Sequencing Insights
Authors: Fu Tongfei , Zhang Xinyi , Liu Yuedong , Wu Junsong , Liu Xuefeng , Lu Bichao , Huang Yi , Yang Liping , Zhan Yongli
Published: December 2024

Clear cell renal cell carcinoma (ccRCC) characterised by its diversity and a tendency to defy standard therapeutic approaches. Amidst the advent of immunotherapy, it has become imperative to pinpoint prognostic indicators of the tumour microenvironment (TME) influence the efficacy of treatments. Employing single‐cell RNA sequencing (scRNA‐seq), this research delved into the diverse landscape of ccRCC, uncovering its complex underpinnings and pinpointing molecular avenues for therapeutic intervention. We constructed a prognostic model using 101 machine learning algorithms and integrated data from multiple cohorts, including TCGA, ICGC, and microarray datasets. The model's efficacy was assessed using the Concordance Index (C‐index), and further analyses included pseudotime analysis of tumour cells, mutation analysis and correlation analysis between the prognostic model and tumour immunity. The prognostic model, combining Lasso regression and survival Support Vector Machine (SVM), demonstrated robust discrimination with a C‐index of 0.650. Investigation into the TME uncovered pronounced associations between the presence of immune cell infiltrates and patient outcomes, with a notable emphasis on the impact of CCL2‐expressing neoplastic cells. The GO Biological Processes (GOBP) encompass the regulation of endothelial cell maturation, the formation of endothelial layers, the enhancement of gene expression controlled by Notch receptors, and the development of endothelial barriers. The research effectively pinpointed critical prognostic markers and crafted a forecasting model that achieved a C‐index of 0.650, highlighting the significant impact of immune cell infiltration, especially CCL2+ neoplastic cells, on ccRCC patient prognosis.
MSA‐MaxNet: Multi‐Scale Attention Enhanced Multi‐Axis Vision Transformer Network for Medical Image Segmentation
Authors: Wu Wei , Huang Junfeng , Zhang Mingxuan , Li Yichen , Yu Qijia , Zhao Qi
Published: December 2024

Convolutional neural networks (CNNs) are well established in handling local features in visual tasks; yet, they falter in managing complex spatial relationships and long‐range dependencies that are crucial for medical image segmentation, particularly in identifying pathological changes. While vision transformer (ViT) excels in addressing long‐range dependencies, their ability to leverage local features remains inadequate. Recent ViT variants have merged CNNs to improve feature representation and segmentation outcomes, yet challenges with limited receptive fields and precise feature representation persist. In this work, we propose MSA‐MaxNet. Specifically, our model utilises an encoder–decoder structure, using MaxViT blocks that apply multi‐axis self‐attention (Max‐SA) as the encoder for local and global feature extraction. To restore the feature map's spatial resolution during upsampling operations, a symmetric MaxViT block–based decoder and upsampling layers are employed. To address the feature mismatches in the skip connections of UNet architecture, we introduce convolutional block attention module (CBAM). Furthermore, we design a multi‐scale convolutional block attention module (MCBAM) based on CBAM, which utilises multi‐scale features to enhance feature representation and refine the skip connection. We evaluate the segmentation performance of MSA‐MaxNet on three publicly available medical imaging datasets, including Synapse for multi‐organ segmentation, ACDC for cardiac analysis and Kvasir‐SEG for gastrointestinal polyp detection. Notably, MSA‐MaxNet achieves state‐of‐the‐art (SOTA) Dice scores of 85.59% and 95.26% on Synapse and Kvasir‐SEG datasets, respectively, with 40.28 M parameters. Additionally, we introduce two smaller versions of MSA‐MaxNet to meet the demands of various scenarios. In summary, our work provides a robust framework for diverse medical imaging tasks, offering potential applications in early cancer detection, cardiovascular disease diagnosis and comprehensive organ‐level assessments.
Association between infant feeding and ADHD development in childhood: a birth cohort study in Taiwan
Authors: Chen Chiu‐Ying , Shih Pin‐Yang , Su Chih‐Ting , Cheng Chi‐Fung , Lee Meng‐Chih , Lane Hsien‐Yuan
Published: December 2024

Background

Infant feeding plays a vital role in neurodevelopment, and a lack of breastfeeding and complementary feeding may increase the risk of developing attention‐deficit/hyperactivity disorder (ADHD). However, empirical evidence on this relationship remains uncertain, as most studies are based on cross‐sectional designs. Therefore, this study aimed to examine this temporal relationship using longitudinal data from a birth cohort.

Methods

A retrospective cohort study was conducted using data from Wave I (starting at 6 months old, 2005–2006) to Wave IV (up to 5 years old, 2010–2011) of the Taiwan Birth Cohort Study. A total of 19,721 pairs completed the four‐wave interviews and provided information on infant feeding, medical history, ADHD occurrence, and sociodemographic characteristics. An extended Cox model with time‐dependent covariates was used to examine this association.

Results

In total, 207 infants developed ADHD during the 54‐month observational period, with an estimated cumulative incidence of 5.56 per 1,000 person‐years. The average breastfeeding duration was approximately 2 months. With complementary feeding, rice solid food (HR = 0.73) was found to be a protective factor against developing ADHD. Significantly associated factors for increasing ADHD risk included males, lower family income, low birth weight, maternal weight, advanced maternal age, child gastrointestinal disease, child seizures, maternal heart disease, and paternal diabetes mellitus.

Conclusions

Complementary feeding within 6 months is important to protect infants from developing ADHD. The beneficial effect of breastfeeding within 6 months was not observed while controlling for other risk factors. However, owing to the limitation of a smaller number of ADHD cases, further studies should rely on larger observational periods.
Rapid Visual Detection of Red Sea Bream Iridovirus Using a Novel Cross‐Priming Amplification‐Based Lateral Flow Assay
Authors: Kim Guk Hyun , Shin Dong Jun , Choi Ji Yeong , Choi Hyun Deok , Min Joon Gyu , Kim Kwang Il
Published: December 2024

Red sea bream iridovirus (RSIV) occurs mainly at high water temperatures and infects more than 30 different species of fish. In Asia, infected fish cause mass mortality every year. Molecular diagnostics is a technology that efficiently detects and identifies a wide range of fish pathogens through rapid and sensitive analysis of their genetic material. Rapid viral detection is essential for effective disease control. In this study, we developed and validated a cross‐priming amplification‐based lateral flow assay (CPA‐LFA) suitable for field diagnosis owing to its short diagnostic time and simple diagnostic process. The CPA‐LFA achieved optimal performance with concentrations of 4 mM MgSO4, 1.2 mM dNTPs and 0.7 M betaine, with the reaction conducted at 60°C for 60 min. The developed CPA‐LFA could specifically identify RSIV without cross‐reactivity with several pathogens commonly reported in various fish cell lines and fish. The 95% limit of detection (LOD95%) of CPA‐LFA was 385.76 copies/μL, which was comparable to that of conventional polymerase chain reaction (PCR). Quantitative PCR (qPCR) was used to identify true‐positive and true‐negative samples from 210 fish samples (160 from cultured fish and 50 from artificially infected fish). Compared with qPCR, CPA‐LFA classified six positive samples as false positives. The viral load of these samples was determined to be less than 195.1 copies/μL. The diagnostic sensitivity and specificity of CPA‐LFA were 94.34% and 100%, respectively. Furthermore, inter‐operator reproducibility testing yielded a kappa value of 1.0, indicating perfect agreement. Therefore, the novel CPA‐LFA is especially well‐suited for field diagnostics owing to its straightforward diagnostic procedure and capability to quickly and accurately detect RSIV.
Transauricular vagal nerve stimulation suppresses inflammatory responses in the gut and brain in an inflammatory bowel disease model
Authors: Atalar Kerem , Alim Ece , Yigman Zeynep , Belen Hayrunnisa Bolay , Erten Fusun , Sahin Kazım , Soylu Ayse , Dizakar Saadet Ozen Akarca , Bahcelioglu Meltem
Published: December 2024

Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a major health problem on a global scale and its treatment is unsatisfactory. We aimed to investigate the effects of transauricular vagal nerve stimulation (tVNS) on inflammation in rats with IBD induced by trinitrobenzene sulfonic acid (TNBS). A total of 36 adult female Sprague–Dawley rats were given TNBS, or vehicle, and tVNS, or sham, every other day for 30 min for 10 days. Postmortem macroscopic and microscopic colon morphology were evaluated by histological staining. Additionally, IL‐1β, IL‐6, IL‐10, and TNF‐α cytokine levels in the colon and the brain were evaluated by immunohistochemistry and western blotting analysis. TNBS induced epithelial damage, inflammation, ulceration, and thickened mucosal layer in the colonic tissues. Administration of tVNS significantly ameliorated the severity of TNBS‐induced tissue damage and inflammatory response. TNBS also alters pro‐inflammatory and anti‐inflammatory balance in the brain tissue. TVNS application significantly suppressed the protein levels of pro‐inflammatory cytokines, namely IL‐1β, IL‐6, and TNF‐ α while augmenting the level of anti‐inflammatory cytokine IL‐10 in the colonic and the brain tissue. We have shown that TNBS‐mediated colonic inflammation and tissue damage are associated with neuroinflammatory responses in the brain tissue. Also demonstrated for the first time that neuroinflammatory response in the gut‐brain axis is suppressed by tVNS in the IBD model. Non‐invasive tVNS stands out as a new potential treatment option for types of IBD.
Cap‐to‐bell stage molar tooth morphogenesis occurs through proliferation‐independent sulcus sharpening and condensation‐associated tension in the dental papilla
Authors: Piper Claire , Green Jeremy B. A.
Published: December 2024

The anatomy of molar teeth is important both functionally for chewing food and in evolutionary studies as a well‐preserved species marker in the fossil record. Molar teeth begin to develop their characteristic biting‐surface shape of cusps (peaks) and sulci (valleys) at the bell stage, when corresponding folds in the dental epithelium become apparent. Theories about the developmental mechanisms of cusp and sulcus morphogenesis have hitherto largely focused on the non‐proliferating nature of the secondary enamel knots (EKs) at the cusp tips. EKs have been thought to direct cusp/sulcus formation by stimulating proliferative growth of the surrounding epithelium which, being confined within a capsule of condensed mesenchyme, bends by mechanical buckling. Here we show, using explant inhibition and cut‐and‐recoil experiments, that cap‐to‐bell morphogenesis is largely proliferation‐independent (sulcus sharpening entirely so) and that tension in the mesenchyme of the dental papilla, immediately sub‐adjacent to the cusps, rather than compression by the mesenchyme surrounding the whole structure, is what holds the structure in shape. Fine mapping of the degree of condensation shows that it is highest in the mesenchyme of the dental papilla and becomes progressively more focused to the cusp regions, consistent with a key role in cusp shaping. Together these findings overturn the prevailing models of molar morphogenesis, including both cusp and sulcus formation.
The osteohistology of gorgonopsian therapsids and implications for Permo‐Triassic theriodont growth
Authors: Botha Jennifer
Published: December 2024

During the Late Permian, saber‐toothed gorgonopsian therapsids were the dominant terrestrial predators, playing crucial roles as apex predators alongside therocephalian therapsids within Permian terrestrial ecosystems. The entire gorgonopsian clade went extinct during the Permo‐Triassic mass extinction, leaving other therapsids to continue into the Triassic. Gorgonopsians have not been well studied, particularly in terms of their growth patterns, with only a few genera having undergone osteohistological analysis. In this study, I present a thorough osteohistological examination of the most extensive collection of gorgonopsian specimens to date, spanning a diverse range of limb bones sourced from various species. The osteohistological analysis of gorgonopsian specimens reveals a trend of rapid growth characterized by a highly vascularized woven‐parallel complex. The abundance of growth marks and variable zone widths suggests a growth trajectory that could indicate longer lifespans and slower growth rates when compared to Early Triassic therapsids. The high vascularity, coupled with the observed growth patterns, implies that gorgonopsians experienced rapid growth during favorable conditions. However, the multiple growth marks indicate that they likely had the capacity for longer lifespans and more gradual maturation than their Early Triassic counterparts. Additionally, their ability to reach later ontogenetic stages supports the hypothesis that favorable environmental conditions facilitated larger body sizes. In contrast, Early Triassic therapsids primarily consisted of juveniles or individuals who reached reproductive maturity within a year, likely indicative of harsher conditions that contributed to higher mortality rates at younger ages. The onset of decreased growth rates, usually indicative of reproductive maturity, occurred later in gorgonopsians compared to Early Triassic therapsids and may have contributed to their decline, as the heightened juvenile mortality rates during the PTME would have limited the gorgonopsians' ability to reproduce effectively.
Use of blended feeds in children requiring tube feeding
Authors: Sun Jessica , Chuah Irene , Drobiszewski Alexandra , Arrowsmith Fiona , Low Rachel , Wong Wing Hei Valerie , Kaur Rajneesh , Dalby‐Payne Jacqueline
Published: December 2024

Aim

The use of blended tube feeding (BTF) in children is a controversial area with persistent concerns regarding the nutritional adequacy and risk of associated infections and equipment complications. Parents in Australia are electing to use BTF in their children despite local hospital guidelines, calling for further research to support its use.

Methods

A retrospective case‐series study was conducted at a tertiary paediatric hospital, to characterise the paediatric population electively using BTF and evaluate their clinical outcomes. Demographic, anthropometric and clinical data were collected from pre‐existing medical records.

Results

Data from 178 clinical visits of 26 participants were included in analysis. The median age of participants was 4.1 years (range 7 months −14 years). BTF was most commonly used for symptom control (n = 8, 30.8%). The most common cause of clinical presentation during the use of BTF was respiratory conditions (number of presentations = 60, 47.2%). There was no reported increase in hospital presentations, gastrointestinal infections or equipment complications with the use of BTF. BTF did not promote weight gain in this population of children, particularly those who were already underweight.

Conclusion

This case‐series found the use of BTF in a paediatric population with underlying complex medical conditions requiring enteral nutrition was driven by parental preference and the goals of symptomatic control. BTF did not demonstrate benefits of weight gain, though it was not associated with an increase in complications and hospital admission.