bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Medical Error Attitudes of Surgical Nurses and Evidence-Based Work Environment
Authors: Gökçe Esma , Doğan Aysel , Özer Demet
Published: January 2025

Background:

It is important for health care professionals to use evidence-based practice during ﻿ surgical procedures to ensure patient safety and prevent medical errors.

Aims:

The aim of this study was to examine the relationship between surgical nurses’ perceptions of their work environment’s support for evidence-based practice and their attitudes toward medical errors.

Methods:

The descriptive cross-sectional study was conducted between February and May 2023. A total of 105 nurses participated in the study. A personal information form, a medical errors attitude scale, and an evidence-based practice work environment scale were used to collect the data.

Results:

It was determined that 92 (87.6%) of the participants used evidence-based practice. It was determined that the answers given by the nurses to the scales had very high reliability, and the mean score of the attitude scale in medical errors was 3.90 (Cronbach-α coefficient 0.770), and the mean score of the evidence-based practice work environment scale was 2.90 (Cronbach-α coefficient 0.840). In addition, according to the correlation, a positive, weak, and statistically significant correlation was found between the total scores of the attitude scale in medical errors and the evidence-based practice work environment scale (P<0.05).

Conclusion:

As a result of the study, it was determined that nurses’ attitudes toward preventing medical errors were positive and their perceptions of support for evidence-based practice work environments were high. In this direction, it can be said that the attitudes toward preventing medical errors of nurses whose working environment is supported by evidence-based practice can be positively affected and error tendencies in surgical clinics can be reduced.
EFFICACY AND SAFETY OF DOLUTEGRAVIR/LAMIVUDINE IN ANTIRETROVIRAL THERAPY-NAIVE PEOPLE LIVING WITH HIV-1 AND WITH HIGH-LEVEL VIREMIA
Authors: Calza Leonardo , Colangeli Vincenzo , Giglia Maddalena , Rigamonti Claudio , Bon Isabella , Cretella Silvia , Viale Pierluigi
Published: January 2025

Background.

Dual regimen dolutegravir/lamivudine (DOL/3TC) showed potent efficacy and favourable safety in both antiretroviral therapy-naïve and -experienced patients, but data from real life about naive people with high-level viremia are still lacking.

Methods.

We performed a retrospective cohort study of people living with HIV (PLWH) who were naive to antiretroviral therapy, had baseline HIV-1 RNA ranging from 100000 to 500000 copies/mL, and initated DOL/3TC. Virological efficacy and changes in immunological parameters after 12 months of treatment were evaluated and compared with highly viremic PLWH who started a triple antiretroviral combination.

Results.

Inclusion criteria were met by 58 patients with median age of 43.4 years. At baseline, mean HIV RNA was 5.4 log10 and mean CD4 T lymphocyte count was 488 cells/mm3. HIV RNA <50 copies/mL was obtained in 45 patients (77.6% in the intention-to-treat analysis) after 6 months and in 53 (91.4%) after 12 months. Reasons for treatment failure were virological failure in two cases and adverse events in three. No significant changes in median value of lipids were reported, while there was a not significant increase in body weight (+1.18 Kg). Virological and immunological response at month 12 in patients on DOL/3TC was comparable to that observed in 50 naive patients with high-level viremia and starting a triple antiretroviral therapy.

Conclusion.

In this real-life cohort of naive patients with high-level viremia, DOL/3TC was associated with high virological efficacy and good tolerability after 12 months, supporting use of this dual regimen also in persons with high initial viremia.
Incidentally Diagnosed Endolymphatic Sac Tumor on 68Ga-DOTA-TATE PET/CT in a Suspected Case of Pheochromocytoma
Authors: Koorma Harini , Jayanthi Mohan Roop , Vengala Sudhakar , Reddy Ajay Varun
Published: January 2025

Endolymphatic sac tumors (ELSTs) are rare, slow-growing, and locally aggressive neoplasms that originate from the epithelial lining of the endolymphatic duct and sac. These are characterized by their infiltrative growth pattern and the potential for local destruction of surrounding structures, including the inner ear and temporal bone. We report a case of an incidentally diagnosed sporadic ELST. The article provides an overview of the relevant literature on this topic and discusses the clinical, radiological, and surgical findings pertaining to this particular ELST case. Given their indolent growth pattern and lack of significant changes on interval imaging, surgical intervention is often deferred for these lesions.
Gastrin-Releasing Peptide Receptor Targeting PET/CT With 68Ga-NOTA-RM26 in the Assessment of Glioma and Combined Multiregional Biopsies
Authors: Wang Rongxi , Li Yilin , Li Ziyang , Wang Jiarou , Li Linlin , Xiang Jialin , Jia Chenhao , Peng Xingtong , Wang Yu , Ma Wenbin , Wang Li'ao , Jia Wang , Chen Xiaoyuan , Li Deling , Zhu Zhaohui , Zhang Jingjing
Published: January 2025

Purpose

The aim of this study was to investigate the value of 68Ga-NOTA-RM26 (68Ga-RM26), a gastrin-releasing peptide receptor–targeting antagonist labeled with the radionuclide 68Ga, in the diagnosis of high-grade gliomas and in combination with multiregional biopsies using PET/CT.

Patients and Methods

After institutional review board approval and informed consent, a total of 35 patients with suspected glioma lesions were enrolled in this study. All patients underwent 68Ga-RM26 PET/CT scans within 2 weeks before surgery.

Results

There were 8 grade II gliomas, 6 grade III gliomas, and 18 grade IV gliomas in a total of 32 glioma lesions. 68Ga-RM26 PET/CT diagnosed 74.4% of lesions (27/32) of all glioma tumor types, and almost all high-grade gliomas were successfully diagnosed (23/24, 95.8%). Among the 9 negative glioma lesions, there were 8 low-grade gliomas (grade II). There was a significantly higher SUVmax, SUVmean, and the lesion-to-background ratio (T/B ratio) in high-grade gliomas compared with low-grade gliomas (P < 0.001). In addition, there was a high correlation between the immunohistochemical staining score of gliomas and parameters (SUVmax, SUVmean, and T/B ratio) on 68Ga-RM26 PET/CT (P < 0.001), and verified by immunohistochemical staining on multiple-point samples of glioma lesions guided by 68Ga-RM26 PET/CT.

Conclusions

68Ga-RM26 could noninvasively diagnose high-grade gliomas and be a promising PET tracer for predicting glioma grading before surgery. This pilot study indicated that the uptake of 68Ga-RM26 correlates with WHO grade in glioma, and preoperative 68Ga-RM26 PET/CT may be helpful to guide multiple-point biopsy of gliomas.
Education on the Importance of Doctor-patient Communication in Orthodontic Clinical Teaching
Authors: Zhou Shan , Qu Yun , Song Yu-Jia , Wang Jing-Chao , Zhao Ling-Bo , Hu Na-Ri-Su
Published: January 2025

In the process of orthodontic clinical teaching, it is very important to teach medical students how they are expected to communicate effectively with patients and their families, as this has a direct impact on patient compliance throughout the process of diagnosis and treatment and on patient satisfaction after treatment. Doctor-patient communication is therefore an essential skill for medical students to gain before taking up clinical work. In view of the problems that are often encountered in each stage of orthodontic treatment, the present paper discusses the specific content of doctor-patient communication education in clinical teaching. The discussion is given in both theoretical and practical terms to lay a solid foundation for improving the overall quality of medical service provided by medical students in teaching hospitals and establishing a harmonious medical environment.
Clinical Reference Strategy for the Selection of Surgical Treatment for Nonsyndromic Sagittal Craniosynostosis: A Systematic Review and Network Meta-Analysis
Authors: Duan Jing , Yang Bin
Published: January 2025

Objective:

There is a lack of comprehensive comparative evidence regarding the effectiveness, intraoperative management, and safety of different surgical procedures for treating nonsyndromic sagittal synostosis. This study aims to evaluate existing clinical studies to provide evidence-based guidance for clinical practice.

Methods:

The authors performed a comprehensive search of 5 databases up to August 2024. Key outcomes included clinical effectiveness, measured by cephalic index (CI), and intraoperative management and safety indicators, such as intraoperative blood loss, operative time, and length of hospital stay. Direct and indirect effects, along with treatment rankings, were assessed using Bayesian pairwise and network meta-analysis models.

Results:

Fifteen studies with 1436 patients were included, and 4 network meta-analysis models were used to compare 5 surgical techniques: open strip craniectomy (OSS), calvarial vault remodeling (CVR), spring-mediated cranioplasty (SMC), endoscopic strip craniectomy (ESC), and endoscopic spring-mediated cranioplasty (ESMC). No significant differences in postoperative CI were found between the surgical methods. However, CVR was associated with significantly greater blood loss, longer operative time, and longer hospital stays compared with OSS, SMC, and ESC.

Conclusions:

Current evidence does not demonstrate a clear superiority of one surgical method over another, with comparable treatment outcomes overall. However, CVR carries higher risks, and the choice of surgical approach should be individualized based on patient-specific factors and clinical judgment.
Association between Deficient MSH2/MSH6 vs MLH1/PMS2 Status and Survival Rates in Localized Colorectal Cancer
Authors: Justesen Tobias Freyberg , Orhan Adile , Rosen Andreas Weinberger , Gögenur Mikail , Krarup Peter-Martin , Qvortrup Camilla , Gögenur Ismail
Published: January 2025

Objective:

This study investigated the association between loss of MSH2/MSH6 versus loss of MLH1/PMS2 expression and overall survival and disease-free survival in patients with localized colorectal cancer.

Background:

The risk of developing colorectal cancer varies depending on the expression of mismatch repair proteins. However, it is unknown if the prognosis differs accordingly.

Methods:

In this retrospective study, we included a Danish cohort of patients who underwent surgery for colorectal cancer between 2009 and 2020. The Danish Colorectal Cancer Group database was used to identify patients, and patient-level data were extracted from six registries. Subsequently, patients with proficient mismatch repair status, with metastatic disease, who underwent emergency surgery, or who received neoadjuvant therapy were excluded. Patients were then propensity score matched in a 1:1 ratio.

Results:

A total of 3,625 patients with localized deficient mismatch repair colorectal cancer were included in the study. Patients had a median age of 75 years and a median follow-up of 4.3 years. Before matching, the MSH2/MSH6 versus MLH1/PMS2 groups differed in age, gender, and comorbidities. After matching, 556 patients were included and loss of MSH2/MSH6 was significantly associated with better overall survival (hazard ratio 0.60; 95% CI, 0.37-0.94); however, not disease-free survival (hazard ratio 0.84; 95% CI, 0.54-1.30).

Conclusions:

In patients with localized deficient mismatch repair colorectal cancer who underwent surgery, a significant association was found between loss of MSH2/MSH6 versus loss of MLH1/PMS2 expression and overall survival. Thus, these patients may be a target for a differentiated follow-up strategy.
COVID-19 pandemic and changes in urban-rural inequalities of suicide in the Province of Buenos Aires-Argentina, 2017-2021
Authors: Leveau Carlos M. , Velázquez Guillermo A.
Published: January 2025

Introduction

Our objective was to analyze the urban-rural inequalities of suicide between the pre-pandemic and pandemic periods in the Province of Buenos Aires (PBA), during 2017-2021.

Methods

Data regarding sex, age and municipality of occurrence of suicides were used, provided by the Ministry of Health (MSAL) of the PBA and the National Criminal Information System (SNIC). Municipalities were divided into four urbanization categories according to their population density. Annual variations in suicide were analyzed and through two periods: pre-pandemic (2017-2019) and pandemic (2020-2021). Negative binomial regressions were calculated to estimate suicide inequalities between urbanization categories.

Results

Men, people 60+ years old, residents of municipalities with high social fragmentation, and with low levels of poverty presented a higher risk of suicide. The year 2020 recorded the lowest risk of suicide. The most urbanized municipalities had a lower risk of suicide compared to the most rural municipalities. With data from the MSAL, these inequalities were similar comparing between the pre-pandemic and pandemic periods. The SNIC data showed some differences possibly attributable to under-reporting of suicides in 2020.

Conclusion

Analysis of both data sources suggest that the social and economic effects of the COVID-19 pandemic did not lead to an increase in urban-rural suicide gaps.
WARMING AND INCREASED RAINFALL REDUCE BUMBLEBEE QUEEN FITNESS
Authors: Archer C. Ruth , Schmid-Hempel Paul , Schmid-Hempel Regula , Wilfert Lena
Published: January 2025

How populations respond to climatic change depends on how climate affects individual growth, survival and reproduction – traits that ultimately shape population dynamics. However, climate can have complex effects on these traits and long-term data linking insect life-histories and climatic variation are rare.

Here, we test how climate affects health, survival and reproduction in wildBombus terrestrisqueens caught over 15 years after emerging from hibernation. We relate climate variation experienced by queens as they developed in their natal colonies and entered hibernation, to fitness traits assayed under constant lab conditions.

We show that wet years consistently reduced queen fitness, while warm temperatures had positive and negative impacts. Behind these annual effects, lies strong seasonality. In particular, climatic conditions experienced by young queens as they forage, mate and enter hibernation are vital in determining whether they reproduce the following spring.

Results suggest that these climate effects are partly due to resources: climatic drivers that reduce resource acquisition prior to hibernation, or disrupt diapause and thus accelerate resource loss over winter, are especially detrimental to spring queen fitness. While results show potential for increasingly negative effects of climate change on bumblebees, they also inform mitigation strategies; providing high-quality forage in late summer, before queens enter diapause.
Protein stability is determined by single-site bias rather than pairwise covariance
Authors: Sternke Matt , Tripp Katherine W. , Barrick Doug
Published: January 2025

The biases revealed in protein sequence alignments have been shown to provide information related to protein structure, stability, and function. For example, sequence biases at individual positions can be used to design consensus proteins that are often more stable than naturally occurring counterparts. Likewise, correlations between pairs of residue can be used to predict protein structures. Recent work using Potts models show that together, single-site biases and pair correlations lead to improved predictions of protein fitness, activity, and stability. Here we use a Potts model to design groups of protein sequences with different amounts of single-site biases and pair correlations, and determine the thermodynamic stabilities of a representative set of sequences from each group. Surprisingly, sequences excluding pair correlations maximize stability, whereas sequences that maximize pair correlations are less stable, suggesting that pair correlations contribute to another aspect of protein fitness. Consistent with this interpretation, we find that for adenylate kinase, enzyme activity is greatly increased by maximizing pair correlations. The finding that elimination of covariant residue pairs increases protein stability suggests a route to enhance stability of designed proteins; indeed, this strategy produces hyperstable homeodomain and adenylate kinase proteins that retain significant activity.

Significance statement

Recent methods for protein structure analysis and design have used sequence covariance to help predict protein structure, stability, and function. Here, by designing homeodomain and adenylate kinase sequences with different amounts of single-site bias and pairwise covariance, we find that stability is solely determined by single-site bias but not pairwise covariance. However, pairwise covariance makes an important contribution to catalysis in adenylate kinase. Our findings suggest a new way to generate highly stable proteins: by separating single-site biases from pairwise covariance, the single-site coefficients can be used to design proteins with stabilities even higher than those obtained by consensus design.
TOC1 phosphorylation disproportionally enhances chromatin binding at rhythmic gene promoters
Authors: Yan Jiapei , Zhang Ying , Chen Guoting , Gui Cuilin , Tu Zhangli , Cao Donglin , Li Xingwang , Somers David E
Published: January 2025

Protein phosphorylation is a key regulatory mechanism in circadian systems. TIMING OF CAB EXPRESSION 1(TOC1) is a core element in the plant circadian system that is phosphorylated near its N-terminus. We establish that TOC1 phosphorylation (particularly at S175) is necessary for optimal interaction with FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and PHYTOCHROME INTERACTING FACTOR 5 (PIF5) at theCIRCADIAN CLOCK-ASSOCIATED 1 (CCA1)promoter to downregulateCCA1expression. At the same time, expression of the closely relatedLATE ELONGATED HYPOCOTYL (LHY)also requires TOC1, but is independent of the TOC1 phosphorylation state. We additionally show how phosphorylation-dependent interactions of TOC1 at specific clock gene promoters selectively regulate these circadian system components more acutely than non-rhythmic genes. Our genome-wide analysis shows that the phosphostate of TOC1 is important for optimal chromatin presence and robust rhythmic gene expression.
MicroRNA-502-3p modulates the GABA A subunits, synaptic proteins and mitochondrial morphology in hippocampal neurons
Authors: Sharma Bhupender , Rodarte Daniela , Goyal Gunjan , Rodriguez Sheryl , Kumar Subodh
Published: January 2025

MicroRNA-502-3p (MiR-502-3p), a synapse enriched miRNA is considerably implicated in Alzheimer’s disease (AD). Our previous study found the high expression level of miR-502-3p in AD synapses relative to controls. Further, miR-502-3p was found to modulate the GABAergic synapse function via modulating the GABA A receptor subunit α-1 (GABRA1) protein. The current study is attempted to examine the impact of miR-502-3p on other GABA subunit proteins, synaptic proteins, mitochondrial morphology and other hippocampal neuron genes. Mouse hippocampal neuronal (HT22) cells were transfected with miR-502-3p overexpression (OE) vector, miR-502-3p sponge (suppression) vector and scramble control vector. MiR-502-3p vectors transfection was confirmed by fluorescence microscopy. MiR-502-3p expression andGABRA1expression was confirmed by qRT-PCR and miRNAScopein-situhybridization. GABA A subunit and synaptic proteins were studied by immunoblotting analysis and mitochondrial morphology was analyzed by transmission electron microscopy (TEM) analysis. Further, Affymetrix gene array analysis was conducted in miR-502-3p overexpressed and suppressed cells. Our results observed that elevated miR-502-3p, negatively modulates the GABRA1 level. The levels of GABA A subunit and synaptic proteins were reduced by ectopic expression of miR-502-3p and increase by miR-502-3p suppression. The mitochondrial morphology was found to be improved in-terms of their number and length in miR-502-3p suppressed cells. Further, Gene array analysis unveiled the deregulation of several genes by miR-502-3p, which are associated with oxidative stress, immune response and synaptic function. These results provide new insights and an update to understand the biological roles of miR-502-3p in regulation of neuron function and synaptic activity.
Real-time Color Flow Mapping of Ultrasound Microrobots
Authors: Dillinger Cornel , Rasaiah Ahilan , Vogel Abigail , Ahmed Daniel
Published: January 2025

Visualization and tracking of microrobots in real-time pose key challenges for surgical microrobotic systems, as existing imaging modalities like MRI, CT, and X-ray are unable to monitor microscale items with real-time resolution. Ultrasound imaging-guided drug administration represents a significant advancement in this respect, offering real-time visual feedback on invasive medical procedures. However, ultrasound imaging still faces substantial inherent limitations in spatial resolution and signal attenuation, which hinder extending this method to microrobot visualization. Here, we introduce an approach for visualizing individual microrobots in real-time with Color Flow Mapping ultrasound imaging, based on acoustically induced structural oscillations of the microrobot generating a pseudo-Doppler signal. This approach enables the simultaneous localization and activation of bubble-based microrobots using two ultrasound sources operating at distinct frequency bandwidths. Our successful capture of microrobots measuring 60–80 micrometers in diameter reveals the potential of real-time ultrasonic imaging at the microscale.

One-sentence Summary

Advancing ultrasound imaging for real-time, microscale visualization—a critical breakthrough for therapeutic microrobots.
Entrenchment and contingency in neutral protein evolution with epistasis
Authors: Schmelkin Lisa , Carnevale Vincenzo , Haldane Allan , Townsend Jeffrey P. , Chung Sarah , Levy Ronald M. , Kumar Sudhir
Published: January 2025

Protein sequence evolution in the presence of epistasis makes many previously acceptable amino acid residues at a site unfavorable over time. This phenomenon of entrenchment has also been observed with neutral substitutions using Potts Hamiltonian models. Here, we show that simulations using these models often evolve non-neutral proteins. We introduce a Neutral-with-Epistasis (N×E) model that incorporates purifying selection to conserve fitness, a requirement of neutral evolution. N×E protein evolution revealed a surprising lack of entrenchment, with site-specific amino-acid preferences remaining remarkably conserved, in biologically realistic time frames despite extensive residue coupling. Moreover, we found that the overdispersion of the molecular clock is caused by rate variation across sites introduced by epistasis in individual lineages, rather than by historical contingency. Therefore, substitutional entrenchment and rate contingency may indicate that adaptive and other non-neutral evolutionary processes were at play during protein evolution.
Phylogenetic biome niche conservatism underlies the evolution of forest paleoendemic legume trees in tropical Africa
Authors: Ojeda Dario I. , Gorel Anaïs-Pasiphae , Dauby Gilles , Cervantes Sandra , Pan Aaron D. , Marcussen Thomas , Vanden Abeele Samuel , Boom Arthur , Forest Félix , de la Estrella Manuel , Hardy Olivier J.
Published: January 2025

Niche conservatism is prevalent during the evolution of plant lineages. However, inferring biome niche lability and its impact on tropical tree species diversification is currently limited. To better understand biome niche lability and its effect on diversification rates, we analyzed an endemic lineage of African tropical trees, testing whether biome niche type (forest vs savanna) and biome lability are non-randomly distributed. We reconstructed a time-calibrated phylogeny of the Berlinia clade (16 genera, ca 201 species) using 140 nuclear genes, 75% of its extant species, and eight fossil calibrations. We also analyzed the phylogenetic signal of biome shifts across the group and its effect on diversification and extinction rates. We found the forest biome as the ancestral condition and a directional shift from forest to savanna (no reversals). The forest biome type is conserved in the Berlinia clade, but the lability to shift biomes is randomly distributed in the group. We did not find evidence that biome shift was associated with higher diversification or lower extinction rates. Our analyses identified five paleoendemic genera that have persisted solely in the forest biome since the Eocene. These paleoendemic and forest-restricted lineages are potentially more susceptible to habitat alterations of human related activities and future climate change, due to perhaps an innate limitation to adapt to new habitat types.
Antibody affinity engineering using antibody repertoire data and machine learning
Authors: Erlach Lena , Friedensohn Simon , Neumeier Daniel , Mason Derek M. , Reddy Sai T.
Published: January 2025

Advanced antibody discovery and engineering workflows take advantage of the combination of high-throughput screening, deep sequencing and machine learning (ML). Most high-throughput methods, however, lack the resolution to provide absolute affinity values of antibody-antigen interactions, limiting their utility for precise engineering of binding kinetics. In this study, we utilize antibody repertoire data, affinity characterization and ML for antibody affinity engineering. Leveraging natural antibody sequence information from repertoires of immunized mice, we identified and experimentally measured affinities for 35 antigen-specific variants. Supervised ML models trained on these sequences achieved remarkable accuracy in predicting affinity, despite the limited dataset size. We utilized the trained ML model toin silico-design eight synthetic antibody variants, of which seven exhibited the desired affinities. Our study illustrates the potential of this streamlined and efficient approach for precise engineering of the affinity of antibodies while reducing extensive experimental screening.
The secreted redox sensor roGFP2-Orp1 reveals oxidative dynamics in the plant apoplast
Authors: Ingelfinger Julian , Zander Lisa , Seitz Patricia L. , Trentmann Oliver , Tiedemann Sophie , Sprunck Stefanie , Dresselhaus Thomas , Meyer Andreas J. , Müller-Schüssele Stefanie J.
Published: January 2025

Specific generation of reactive oxygen species (ROS) is important for signalling and defence in many organisms. In plants, different types of ROS perform useful biological functions in the extracellular space (apoplast) supporting processes such as polymerisation and cell wall remodelling. In addition, increased formation of extracellular superoxide and hydrogen peroxide occurs during immune responses. Our current knowledge of apoplastic ROS dynamics is based on luminescence assays, ROS staining methods and indirect evidence via changes to intracellular redox balance. However, dynamic monitoring of extracellular redox processesin vivoremains difficult.

Using two evolutionary distant land plant model species, the mossPhyscomitrium patensand the flowering plantArabidopsis thaliana, we test whether the genetically encoded redox biosensor roGFP-Orp1 can be used to assess extracellular redox dynamics. We found that secreted roGFP-Orp1 can inform about local diffusion barriers, as well as protein cysteinyl oxidation rate in the apoplast after pre-reduction. Observed re-oxidation rates were surprisingly slow within the range of hours. ComparingA. thalianatoP. patens, we found faster sensor re-oxidation that increased after triggering an immune response. Our data indicate differences in extracellular oxidative processes between species and within a species, depending on immune signalling.
Effects of elevation and microclimatic temperatures on butterfly-flower interaction networks in a Mediterranean mountain range
Authors: Alamo Mario , Álvarez Hugo Alejandro , Mingarro Mario , Wilson Robert J.
Published: January 2025

Researching the properties of mutualistic networks over environmental gradients is a promising but underexplored means to test how global change can affect ecosystem assembly and functioning. We examined how elevation and microclimate influenced butterfly-flower interaction networks at the hottest time of year in a Mediterranean mountain range.

Throughout July 2023, we recorded weekly butterfly-flower interaction networks from 36 transects in nine sites, across an 800 m elevation gradient in the Sierra de Guadarrama (Central Spain). We quantified the connectance, nestedness, modularity and robustness to species loss of networks, and related these descriptors using Generalized Additive Mixed Models to elevation, microclimate temperature (modelled using Microclima), date and time of day.

The networks were dominated at all sites by one or two abundant butterfly and flower species, but these varied with elevation. Butterfly networks were more robust to plant species loss at higher elevations, where communities showed increased linkage density. Butterfly-plant networks became less nested at higher microclimatic temperatures in July. Network properties also varied through the day, with connectance decreasing markedly from morning to afternoon.

In the Mediterranean mountains studied, summer butterfly-flower interaction networks were more resilient to disturbance at high elevations and in cooler microclimates. Nectar availability could become an important limiting factor for insects in a warming climate, and understanding the mechanisms influencing the properties of flower visitor networks is therefore likely to become increasingly important for adapting the conservation of insects to climate change.
Generation of a T cell receptor, cytokine and cell repertoire synovial fluid atlas to define commonalities and dissimilarities between arthritic diseases through systems immunology approaches
Authors: Ha My K. , Deuren Vincent Van , de Carvalho Fraga Carlos Alberto , Hotterbeekx An , Dehoorne Joke , Renson Thomas , Geens Elke , Aerts Nicolaas , Heusdens Christiaan , Kuznetsova Maria , Mechelen Margot Van , Bulcke Michaël Vanden , Hoffman Ilse , Wittoek Ruth , Wachter Eva De , Andrzejewski Aurelie , Bartholomeus Esther , de Vrij Nick , Suls Arvid , Lion Eva , Vanhee Stijn , Adriaensen Wim , Mullan Kerry , Nakaya Helder , Kumar-Singh Samir , Laukens Kris , Joos Rik , Meysman Pieter , Ogunjimi Benson
Published: January 2025

Although different chronic arthritic diseases are defined by clinical factors like gender, psoriasis and auto-antibodies, the biology of inflamed joints while comparing the different diseases remains neglected. Here, after curating an inflamed joint derived T-cell receptor (TCR) database, our new TRIASSIC tool identified 66303 significantly convergent TCR clonotypes. Clustering TCR clonotypes showed that synovial fluid convergence clusters (SFCCs) characterized HLA-B27+ mediated diseases (spondyloarthritis, SpA, and enthesitis-related juvenile idiopathic arthritis, JIA-ERA), Lyme arthritis and oligoarticular JIA. Single-cell transcriptomics and bulk proteomics showed upregulated interferon type I and II and TNF-α pathways in oJIA. Adult and juvenile psoriatic arthritis, (JIA-)PsA, was characterized by upregulated HSP expression in monocytes and TXNIP in T-cells. We discovered an abundance of CCL5 expressing CD8+ T-cells in SF from HLA-B27+ JIA-ERA and SpA patients. JIA-ERA patients showed upregulation of CD74 and LGALS1 in Th1 and Th17 cells and IGHV7-4.1 in B-cells. oJIA patients shared a TRBV28 RG-motif on CXCL13 producing helper T-cells. Rheumatoid arthritis and (JIA-)PsA patients carried EBV-reactive cytotoxic CD8+ T-cells. Annexin signalling was shown to be important in the intercellular communication for all arthritis groups. Collectively, our work showed that chronic arthritis is characterized by both disease-specific and broadly shared mechanisms.
Larger larval sea lamprey (Petromyzon marinus)have longer survival times when exposed to the lampricide 3-trifluoromethyl-4-nitrophenol
Authors: Nalesnik Allison M. , Martin Emily L. , Kovacs Ian S. , Johnson Connor S. , Carroll Emma I. , Jubar Aaron , Hemstrom William , Wilkie Michael P. , Dunlop Erin S. , Sepulveda Maria S. , Johnson Nicholas S. , Christie Mark R.
Published: January 2025

Invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes have negatively impacted ecological and economically important fishes for nearly a century. To mitigate these negative effects, the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) is applied annually to Great Lakes tributaries to kill larval lampreys before they become juveniles, out-migrate to the lakes, and parasitize other fishes. It has been hypothesized that larval size (e.g., mass, length, condition) may affect survival time in response to TFM. To test this hypothesis, we conducted an experiment with 8,611 larvae across four temporal replicates, in which TFM concentrations like those used in present-day stream treatments were applied for up to 18 hours. We found a significant, positive correlation between the total length and mass of larval sea lamprey and their survival times to TFM. Specifically, there was a 4.56 minute increase in survival time for each one centimeter increase in total length after accounting for the effect of mass. We also identified a phenotypic trade-off where the survival time of heavier larvae decreased with an increase in total length and vice versa. The changes in total length and mass of larval sea lamprey stored in ethanol for four months was also quantified. The observation that five larvae survived well past the 12-hour time window of a typical TFM field treatment highlights the need for continuous monitoring and the development of new control strategies to ensure the continued effective management of this invasive species.
Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA
Authors: Tanu Tanzina , Cox Anna M. , Karlow Jennifer , Sharma Priyanka , He Xueyang , Wu Constance , Babu Swathy , Brown Jared , Brown Kevin M. , Chanock Stephen J. , Liu David , Zhang Tongwu , Burns Kathleen H. , Boutz Paul L. , Insco Megan L.
Published: January 2025

Endogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear RNA surveillance complexes, has recurrent truncating mutations in cancer. We show that Z18truncmutations are oncogenic and that Z18 plays an evolutionarily conserved role in nuclear RNA surveillance of ERV RNA. In zebrafish, Z18truncexpedited melanoma onset and promoted a specific accumulation of ERV RNA. Z18 mutant human cell lines from the Cancer Cell Line Encyclopedia also expressed higher levels of ERV RNA. In engineered human melanoma cells, Z18truncenhanced ERV RNA accumulation more than loss of one Z18 copy, indicating dominant negative activity. Z18truncdirectly bound and stabilized ERV RNA. Notably, expression of ERV RNA was sufficient to expedite oncogenesis in a zebrafish model, which is the first evidence of which we are aware that ERV transcripts can play a functional role in cancer. Our work illuminates a mechanism for elevated ERV transcripts in cancer and supports that aberrant RNA accumulation is broadly oncogenic.
A genealogy-based approach for revealing ancestry-specific structures in admixed populations
Authors: Tang Ji , Chiang Charleston W. K.
Published: January 2025

Elucidating ancestry-specific structures in admixed populations is crucial for comprehending population history and mitigating confounding effects in genome-wide association studies. Existing methods for elucidating the ancestry-specific structures generally rely on frequency-based estimates of genetic relationship matrix (GRM) among admixed individuals after masking segments from ancestry components not being targeted for investigation. However, these approaches disregard linkage information between markers, potentially limiting their resolution in revealing structure within an ancestry component. We introduce ancestry-specific expected GRM (as-eGRM), a novel framework for elucidating the relatedness within ancestry components between admixed individuals. The key design of as-eGRM consists of defining ancestry-specific pairwise relatedness between individuals based on genealogical trees encoded in the Ancestral Recombination Graph (ARG) and local ancestry calls and computing the expectation of the ancestry-specific relatedness across the genome. Comprehensive evaluations using both simulated stepping-stone models of population structure and empirical datasets based on three-way admixed Latino cohorts showed that analysis based on as-eGRM robustly outperforms existing methods in revealing the structure in admixed populations with diverse demographic histories. Taken together, as-eGRM has the promise to better reveal the fine-scale structure within an ancestry component of admixed individuals, which can help improve the robustness and interpretation of findings from association studies of disease or complex traits for these understudied populations.
Overexpression of the MADS-box geneCRM3in the fernCeratopteris richardiiaffects sporophyte development
Authors: Schulz Robin , Theißen Günter
Published: January 2025

MADS-box genes encode MADS-domain transcription factors that play important roles in the development and evolution of land plants. Especially well-characterized is their role as organ identity genes during flower development of angiosperms. Even though the first MADS-box genes have been molecularly cloned from ferns almost 30 years ago, little is known about their function, mainly due to a lack of mutants. Also their quite broad expression domain, often comprising both the gametophytic and the sporophytic phase of the life cycle of ferns, provide few specific clues concerning gene function. However, as sister group of seed plants monilophytes (ferns and their allies such as horsetails) are of great interest in many attempts to understand both MADS-box gene and land plant evolution. Here we report, to the best of our knowledge, the first mutant phenotype based on transgenic overexpression of a fern MADS-box gene. Transgenic plants of the fern model systemCeratopteris richardiioverexpressing the MIKCC-type MADS-box geneCRM3under control of the Cauliflower Mosaic Virus (CaMV) 35S promoter show a significant reduction of the length of sporophylls. This finding reveals that overexpression ofCRM3affects sporophyll development inC. richardii, possibly by inhibiting cell proliferation or elongation.
Psychometric and biomedical outcomes of glycated haemoglobin target-setting in adults with type 1 and type 2 diabetes: A mixed-methods parallel-group randomised feasibility study
Authors: Westall Samuel J , Watmough Simon , Narayanan Ram Prakash , Irving Greg , Hardy Kevin
Published: January 2025

Background

Glycated haemoglobin (HbA1c) targets are commonly used to guide patient management in diabetes to reduce future risk of diabetes complications, but little is known of the psychological impact of HbA1ctarget-setting. We explored the feasibility of undertaking a conclusive study evaluating the impact of setting explicit HbA1ctargets in adults with diabetes.

Methods

A randomised, mixed-methods study design was used to quantitatively and qualitatively evaluate the psychometric and biomedical impact of intensified or relaxed glycaemic targets in adults with diabetes. Alongside baseline measurement of HbA1c, blood pressure and body mass index, patients completed baseline validated psychometric questionnaires (EuroQoL-5D-5L, Problem Areas In Diabetes, Summary of Diabetes Self-Care Activities, Well-Being Quetionnaire-12, Diabetes Empowerment Scale-Long Form) and were randomised 1:1. Participants in group A received explicit HbA1ctarget intervention targets 5 mmol/mol above current HbA1c. Participants in group B received explicit HbA1ctargets 5 mmol/mol below current HbA1c. Rates of eligibility, recruitment, retention and questionnaire response were recorded. Outcomes were re-measured 3-months post-intervention. Patients and healthcare professionals attended semi-structured interviews for qualitative evaluation.

Results

Fifty participants were recruited. Withdrawal rate was 34% (n=17). Endpoint evaluation revealed no significant between-group differences in patient-reported outcome measures or HbA1clevels. Overall, levels of distress (-4.4, p=.009), self-efficacy (.25 [.09–.41], p=.004) and subsequent HbA1creadings (-2.8 [-5.0–-.7], p=.012) improved, with non-significant changes seen in health-related quality of life, wellbeing, and self-care. Patients and healthcare professional interviews demonstrated study acceptability alongside specific motivators (e.g., target achievability, hypoglycaemia avoidance) and demotivators (e.g., lack of understanding, lack of target achievability) for striving to reach glycaemic targets. Combined qualitative data from patient and healthcare professional interviews and quantitative study aspects triangulated, enhancing data trustworthiness, and informing future hypotheses and methodologies.

Discussion

This mixed-methods study demonstrates feasibility and provides a novel insight into the psychological implications of HbA1ctarget-setting.

Trial registration

The study is registered with the ISRCTN (registration number:12461724; date registered: 11thJune 2021).
Anticancer synthetic arylsulfonamides with Wnt1-modulating activity
Authors: Gutti Mihira , Luo Jennifer , Sharma Vihaan , Lee Emilia , Desarkar Arshia , Raval Rushika , Soedarmono Augustus , Zhu Joy , Njoo Edward
Published: January 2025

Dysregulation of the Wnt1/β-catenin signaling pathway has been demonstrated to be a driving factor in the propagation of several human cancers. Previous studies have discovered methyl 3-{[(4-methylphenyl)sulfonyl]amino}benzoate (MSAB) as a selective inhibitor of the Wnt1/β-catenin signaling pathway, which putatively functions through direct engagement of β-catenin. To understand how changes to the identity and position of the methyl ester affect thein vitropotency of this compound in Wnt1-driven mammalian cell lines, we prepared and evaluated three analogs of MSAB with 3- and 4-substituted methyl and ethyl esters. In MTT assays, analogs with methyl esters showed significantly more activity than their ethyl ester counterparts and both 4-substituted esters exhibited significantly attenuated antiproliferative activity, with MSAB exhibiting dose-dependent activity across cancerous cell lines. Further analysis by flow cytometry reveals low-Annexin V signal, suggesting that these compounds do not function via a pro-apoptotic pathway. Additionally, through a TCF/LEF-activated luciferase reporter cell assay, we observe that the 4-substituted methyl ester analogous to MSAB exhibits slightly diminished Wnt1-inhibitory activity, while 3- and 4-substituted ethyl esters exhibit minimal Wnt1-inhibitory activity. This difference in potency with a simple ester substitution might be attributed to several factors that ultimately drive antiproliferative activity, prompting the investigation of other potential substituents to further investigate the structure-activity relationship of these compounds as Wnt1-based antiproliferative agents.
BicD and MAP7 collaborate to activate homodimericDrosophilakinesin-1 by complementary mechanisms
Authors: Ali M Yusuf , Lu Hailong , Fagnant Patricia M. , Macfarlane Jill E. , Trybus Kathleen M.
Published: January 2025

The folded auto-inhibited state of kinesin-1 is stabilized by multiple weak interactions and binds weakly to microtubules. Here we investigate the extent to which homodimericDrosophilakinesin-1 lacking light chains is activated by the dynein activating adaptorDrosophilaBicD. We show that one or two kinesins can bind to the central region of BicD (CC2), a region distinct from that which binds dynein-dynactin (CC1) and cargo-adaptor proteins (CC3). Kinesin light chain significantly reduces the amount of kinesin bound to BicD and thus regulates this interaction. Binding of kinesin to BicD increases the number of motors bound to the microtubule, the fraction moving processively and the run length, suggesting that BicD relieves kinesin auto-inhibition. In contrast, microtubule-associated protein 7 (MAP7) has minimal impact on the percentage of motors moving processively but enhances both kinesin-1 recruitment to microtubules and run length. BicD relieves auto-inhibition of kinesin, while MAP7 enables activated motors to engage productively with microtubules. When BicD and MAP7 are combined, the most robust activation of kinesin-1 occurs, highlighting the crosstalk between adaptors and microtubule associated proteins in regulating transport. These observations imply that when both dynein and kinesin-1 are simultaneously bound to BicD, the direction the complex moves on MTs will be influenced by MAP7 and the number of bound kinesins.
FGFR1 inhibition improves therapy efficacy and prevents metabolic adaptation associated with temozolomide resistance in glioblastoma
Authors: Zarzuela Laura , López-Cepero Ignacio G. , Rattigan Kevin M. , Sánchez-Escabias Elena , Morillo-Huesca Macarena , Reina-Bando Ana , Oltra Sara S. , Sierra-Párraga Jesús M. , Ceballos-Chávez María , Capilla-González Vivian , Moreno-Bueno Gema , Murdoch Piedad del Socorro , Reyes José C. , Helgason G. Vignir , Tomé Mercedes , Durán Raúl V.
Published: January 2025

Recurrent therapy resistance is a major limitation in clinical efficacy and for the outcome of glioblastoma (GBM) patients, positioning GBM among the tumor types with the poorest survival outcomes. In this work, we dissected resistance mechanisms in GBM, which resulted in the identification of FGFR1 pathway as a major regulator of the signaling and metabolic rewiring associated with temozolomide (TMZ) resistance in GBM. Hence, we described a mechanism of resistance that operates at two major levels. First, a p53-mediated regulation of cell cycle inducing cell cycle arrest to allow DNA repair in response to TMZ. And second, a complete metabolic rewiring promoting lipid catabolism and preventing lipid peroxidation. Both the p53-mediated response and the metabolic adaptation are controlled by FGFR1, as inhibition of the FGFR1 pathway completely abolishes this signaling and metabolic reprograming, restoring sensitivity to TMZ. Our results also indicated a correlation of FGFR1 levels with poor prognosis in GBM patients, and validated the treatment of TMZ in combination with FGFR1 inhibitors as an efficient strategy to induce tumor cell death in pre-clinical animal models. This data position the receptor FGFR1 as a very promising candidate for evaluation in future clinical approaches to limit the development of therapy resistance to TMZ in GBM patients.
Biosynthesis and Bioactivity of Anti-Inflammatory Triterpenoids inCalendula officinalis(pot marigold)
Authors: Golubova D , Salmon M , Su H , Tansley C , Kaithakottil GG , Linsmith G , Schudoma S , Swarbreck D , O’Connell MA , Patron NJ
Published: January 2025

Plants have been central to traditional medicine for millennia, yet the precise metabolites responsible for their therapeutic properties often remain unidentified. Moreover, the low natural abundance and structural complexity of bioactive molecules can hinder their accessibility and chemical synthesis. Here, we investigate the widely reported anti-inflammatory properties ofCalendula officinalis(pot marigold), an ancient medicinal herb. We confirm C16-hydroxylated triterpenoids as key contributors to the anti-inflammatory activity ofC. officinalisfloral extracts and uncover a novel mechanism by which they act in modulating interleukin 6 release. Through biosynthetic pathway elucidation, we demonstrate that the oxidosqualene synthase catalysing the first committed step emerged early in Asteraceae evolution and identify residues governing product specificity. Further, we functionally characterise cytochrome P450s and acyltransferases responsible for downstream modifications. By reconstructing the complete biosynthetic pathway in the heterologous plant chassisNicotiana benthamiana, we provide a platform for production of the anti-inflammatory components. Our work highlights how integrated studies of bioactivity and biosynthesis can unlock the therapeutic potential of medicinal plants.