bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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.
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

AbstractIntroductionOur 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.MethodsData 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.ResultsMen, 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.ConclusionAnalysis 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

ABSTRACTHow 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

AbstractThe 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 statementRecent 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

AbstractProtein 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

ABSTRACTMicroRNA-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

AbstractVisualization 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 SummaryAdvancing 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

AbstractProtein 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

SummaryNiche 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

AbstractAdvanced 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

AbstractSpecific 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.