bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Early Growth Response 3 in Skin Cancers
Authors: Zhou Kai-Yi , Deng Li-Jia , Luo Si-Yu , Wang Qin-Xiao , Fang Sheng 
Published: March 2024

Objective:
To assess the expression of early growth response 3 (EGR3) in normal skin and different types of skin tumors: cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), melanoma (MM), and cutaneous adnexal tumors containing sebaceous carcinoma (SC), trichoepithelioma (TE) and clear cell hidradenoma (CCH).

Background:
EGR3, expressed in multiple organs, including skin, plays an important role in cell differentiation and tumor growth. Previous studies have shown that EGR3 suppresses tumor growth and is downregulated in various malignancies. However, its distribution in normal skin and its expression especially in skin tumors have not been studied.

Materials and Methods:
Samples of normal cases (n = 4), cSCC (n = 12), BCC (n = 12), MM (n = 12), SC (n = 4), TE (n = 4), and CCH (n = 4) were collected from patients treated in our department between 2018 and 2023. Immunohistochemistry was used to investigate the expression of EGR3. The results were analyzed with the description of the staining pattern and the histochemical score.

Results:
Immunohistochemical staining showed that EGR3 was uniquely expressed in normal skin in the granular layer and upper part of the stratum spinosum, as well as in sebaceous glands and hair follicles, but not in sweat glands. In skin cancers, BCC, SC, and TE showed positive EGR3 staining, whereas cSCC, MM, and CCH were negative.

Conclusions:
EGR3 has a specific expression pattern in normal skin and in skin tumors, which is important for the differential diagnosis of skin tumors, in particular for cSCC and sebaceous gland carcinoma.
Methylene Blue in Metformin Intoxication
Authors: Katlan Banu 
Published: March 2024

Abstract
Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes.
Characteristics and Risk Factors of Central Nervous System Infection in Children With Febrile Seizures
Authors: do Valle Daniel Almeida , Costa Luisa Carolina Vinhal , Fregonese Amanda Perin , da Silva Dannyelle Heloize Leite , Maldonado Giovana Kellen Souza , da Silva Letícia Tozzini Tavares , Couto Mylena da Silva 
Published: March 2024

Objective
The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific to Brazil.

Methods
A retrospective cross-sectional study was performed from January 2017 to December 2021.

Results
A total of 469 children with seizure and fever were analyzed. The identified event was the first in 65.9% (n = 309). A total of 54.2% (n = 254) of patients had a simple febrile seizure. Infectious focus, excluding previous central nervous system (CNS) infection, was identified in 35.6% (n = 167) patients. Meningitis was identified in 7.7% (n = 36) patients, all of them were viral. Patients with CNS infection had a higher frequency of symptoms such as nausea and vomiting, drowsiness, headache, and higher level of leukocytosis. A longer duration of fever was found to be more strongly associated with CNS infection.

Conclusions
When considering the use of lumbar puncture in febrile seizure, it is important to conduct a comprehensive evaluation that considers multiple factors, including clinical signs, symptoms, and the overall clinical context. Meningeal signs may be less prominent, and other symptoms such as lethargy, irritability, and vomiting may serve as more reliable indicators. Although clinical examination suggestive of meningitis remains an important factor, the recurrence of febrile seizures and a longer length of fever can provide additional insights and aid in decision-making regarding lumbar puncture.
Use of Donor-derived Cell-free DNA to Inform Tapering of Immunosuppression Therapy in Kidney Transplant Recipients: An Observational Study
Authors: Osuchukwu George , Trevino Alexa , McCormick Sarah , Kaur Navchetan , Prigmore Brittany , Al Haj Baddar Nour , Bloom Michelle S. , Demko Zachary , Gauthier Philippe 
Published: March 2024

Background.
Immunosuppression therapy (IST) is required for allograft survival but can cause significant adverse effects. Donor-derived cell-free DNA (dd-cfDNA) is a validated noninvasive biomarker for active rejection in kidney transplant (KTx). Evidence supporting dd-cfDNA testing use in IST management is limited.

Methods.
In this single-center observational study, dd-cfDNA testing was performed in 21 KTx patients considered good candidates for mycophenolic acid (MPA) reduction. Patients with dd-cfDNA <1% at the first visit (enrollment) had their MPA dosage reduced; those with dd-cfDNA ≥1% had their MPA dosage maintained. Patients were monitored with dd-cfDNA for 6 additional visits.

Results.
Of 21 patients enrolled in the study, 17 were considered low risk for rejection by dd-cfDNA and underwent MPA reduction; 4 patients were considered high risk for rejection by dd-cfDNA and had their initial MPA dosage maintained. Of the 4 patients considered high risk for rejection by dd-cfDNA, 1 experienced chronic allograft nephropathy and graft loss, and another received an indication biopsy that showed no evidence of rejection. Of the 17 patients considered low risk for rejection by dd-cfDNA, none experienced allograft rejection. dd-cfDNA was used for surveillance in a 6-mo period following MPA reduction; no untoward results were noted.

Conclusions.
This proof-of-concept study reports the use of dd-cfDNA to directly inform IST management in a cohort of KTx who were candidates for IST reduction.
Composite material in the sea urchin
Cidaris
rugosa
: ordered and disordered micrometre-scale bicontinuous geometries
Authors: Jessop Anna-Lee , Millsteed Allan J. , Kirkensgaard Jacob J. K. , Shaw Jeremy , Clode Peta L. , Schröder-Turk Gerd E. 
Published: March 2024

The sponge-like biomineralized calcite materials found in echinoderm skeletons are of interest in terms of both structure formation and biological function. Despite their crystalline atomic structure, they exhibit curved interfaces that have been related to known triply periodic minimal surfaces. Here, we investigate the endoskeleton of the sea urchin
Cidaris rugosa
that has long been known to form a microstructure related to the Primitive surface. Using X-ray tomography, we find that the endoskeleton is organized as a composite material consisting of domains of bicontinuous microstructures with different structural properties. We describe, for the first time, the co-occurrence of ordered single Primitive and single Diamond structures and of a disordered structure within a single skeletal plate. We show that these structures can be distinguished by structural properties including solid volume fraction, trabeculae width and, to a lesser extent, interface area and mean curvature. In doing so, we present a robust method that extracts interface areas and curvature integrals from voxelized datasets using the Steiner polynomial for parallel body volumes. We discuss these very large-scale bicontinuous structures in the context of their function, formation and evolution.
Interaction of MLE with CLAMP zinc finger is involved in proper MSL proteins binding to chromosomes in
Drosophila
Authors: Tikhonova Evgeniya , Revel-Muroz Anastasia , Georgiev Pavel , Maksimenko Oksana 
Published: March 2024

The
Drosophila
male-specific lethal (MSL) complex binds to the male X chromosome to activate transcription. It comprises five proteins (MSL1, MSL2, MSL3, male absent on the first (MOF), and maleless (MLE)) and two long noncoding RNAs (lncRNAs; roX1 and roX2). The MLE helicase remodels the roX lncRNAs, enabling the lncRNA-mediated assembly of the
Drosophila
dosage compensation complex. MSL2 is expressed only in males and interacts with the N-terminal zinc finger of the transcription factor chromatin-linked adapter for MSL proteins (CLAMP), which is important for the specific recruitment of the MSL complex to the male X chromosome. Here, we found that MLE's unstructured C-terminal region interacts with the sixth zinc-finger domain of CLAMP.
In vitro
, 4–5 zinc fingers are critical for the specific DNA-binding of CLAMP with GA repeats, which constitute the core motif at the high affinity binding sites for MSL proteins. Deleting the CLAMP binding region in MLE decreases the association of MSL proteins with the male X chromosome and increases male lethality. These results suggest that interactions of unstructured regions in MSL2 and MLE with CLAMP zinc finger domains are important for the specific recruitment of the MSL complex to the male X chromosome.
Reduction in activity and abundance of mitochondrial electron transport chain supercomplexes in pulmonary hypertension-induced right ventricular dysfunction
Authors: Ma Wenzhuo , Zhang Peng , Vang Alexander , Zimmer Alexsandra , Huck Scarlett , Nicely Preston , Wang Eric , Mancini Thomas J , Owusu-Sarfo Joseph , Cavarsan Clarissa F. , Belyvech Andriy E. , Campbell Kenneth S. , Terentyev Dmitry , Choudhary Gaurav , Clements Richard T. 
Published: March 2024

AbstractPulmonary hypertension (PH) results in RV hypertrophy, fibrosis and dysfunction resulting in RV failure which is associated with impaired RV metabolism and mitochondrial respiration. Mitochondrial supercomplexes (mSC) are assemblies of multiple electron transport chain (ETC) complexes that consist of physically associated complex I, III and IV that may enhance respiration and lower ROS generation. The goal of this study was to determine if mSCs are reduced in RV dysfunction associated with PH. We induced PH in Sprague-Dawley rats by Sugen/Hypoxia (3 weeks) followed by normoxia (4 weeks). Control and PH rats were subjected to echocardiography, blue and clear native-PAGE to assess mSC abundance and activity, and cardiomyocyte isolation to assess mitochondrial reactive oxygen species (ROS). mSC formation was also assessed in explanted human hearts with and without RV dysfunction. RV activity of CI and CIV and abundance of CI, CIII and CIV in mitochondrial mSCs was severely reduced in PH rats compared to control. There were no differences in total CI or CIV activity or abundance in smaller ETC assemblies. There were no changes in both RV and LV of expression of representative ETC complex subunits. PAT, TAPSE and RV Wall thickness significantly correlated with CIV and CI activity in mSC, but not total CI and CIV activity in the RV. Consistent with reduced mSC activity, isolated PH RV myocytes had increased mitochondrial ROS generation compared to control. Reduced mSC activity was also demonstrated in explanted human RV tissue from patients undergoing cardiac transplant with RV dysfunction. The right atrial pressure/pulmonary capillary wedge pressure ratio (RAP/PCWP, an indicator of RV dysfunction) negatively correlated with RV mSC activity level. In conclusion, reduced assembly and activity of mitochondrial mSC is correlated with RV dysfunction in PH rats and humans with RV dysfunction.
Activation of the mPFC-NAc pathway reduces motor impulsivity but does not affect risk-related decision-making in innately high-impulsive rats
Authors: Arrondeau Chloé , Urueña-Méndez Ginna , Marchessaux Florian , Goutaudier Raphaël , Ginovart Nathalie 
Published: March 2024

AbstractAttention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are characterized by exacerbated motor and risk-related impulsivities, which are associated with decreased cortical activity. In rodents, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been separately implicated in impulsive behaviors, but studies on the specific role of the mPFC-NAc pathway in these behaviors are limited. Here, we investigated whether heightened impulsive behaviors are associated with reduced mPFC activity in rodents, and determined the involvement of the mPFC-NAc pathway in motor and risk-related impulsivities. We used the Roman High- (RHA) and Low-Avoidance (RLA) rat lines, which display divergent phenotypes in impulsivity. To investigate alterations in cortical activity in relation to impulsivity, regional brain glucose metabolism was measured using positron emission tomography and [18F]-fluorodeoxyglucose ([18F]FDG). Using chemogenetics, the activity of the mPFC-NAc pathway was either selectively activated in high-impulsive RHA rats or inhibited in low-impulsive RLA rats, and the effects of these manipulations on motor and risk-related impulsivity were concurrently assessed using the rat gambling task. We showed that basal [18F]FDG uptake was lower in the mPFC and NAc of RHA compared to RLA rats. Activation of the mPFC-NAc pathway in RHA rats reduced motor impulsivity, without affecting risk-related decision-making. Conversely, inhibition of the mPFC-NAc pathway had no effect in RLA rats. Our results suggest that the mPFC-NAc pathway controls motor impulsivity, but has limited involvement in risk-related decision-making. Our findings suggest that reducing fronto-striatal activity may help attenuate motor impulsivity in patients with impulse control dysregulation like ADHD or SUD.
Functions ofC. elegansneurons from synaptic connectivity
Authors: Emmons Scott W. 
Published: March 2024

AbstractDespite decades of research on theC. elegansnervous system based on an anatomical description of synaptic connectivity, the circuits underlying behavior remain incompletely described and the functions of many neurons are still unknown. Updated and more complete chemical and gap junction connectomes of both adult sexes covering the entire animal including the muscle end organ have become available recently. Here these are analyzed to gain insight into the overall structure of the connectivity network and to suggest functions of individual neuron classes. Modularity analysis divides the connectome graph into ten communities that can be correlated with broad categories of behavior. A significant role of the body wall musculature end organ is emphasized as both a site of significant information convergence and as a source of sensory input in a feedback loop. Convergence of pathways for multisensory integration occurs throughout the network — most interneurons have similar indegrees and outdegrees and hence disperse information as much as they aggregate it. New insights include description of a set of high degree interneurons connected by many gap junctions running through the ventral cord that may represent a previously unrecognized locus of information processing. There is an apparent mechanosensory and proprioceptive field covering the entire body formed by connectivity of the many mechanosensory neurons of multiple types to two interneurons with output connections across the nervous system. Several additional significant, previously unrecognized circuits and pathways are uncovered, some involving unstudied neurons. The insights are valuable for guiding theoretical investigation of network properties as well as experimental studies of the functions of individual neurons, groups of neurons, and circuits.
Transcriptional bursting, gene activation, and roles of SAGA and Mediator Tail measured using nucleotide recoding single cell RNA-seq
Authors: Schofield Jeremy A , Hahn Steven 
Published: March 2024

AbstractA time resolved nascent single-cell RNA-seq approach was developed to dissect gene-specific transcriptional bursting and the roles of SAGA and Mediator Tail (the activator-binding module). Most yeast genes show near-constitutive behavior while only a subset of genes show high mRNA variance suggestive of transcription bursting. Bursting behavior is highest in the coactivator redundant (CR) gene class (dependent on both SAGA and TFIID) and is strongest in TATA-containing CR genes. Applying this approach to analyze gene activation, we found that basal histone gene transcription is in a low level, low-noise constitutive mode while the activated state unexpectedly shows an increase in both the fraction of active promoters and a switch to a noisy and bursty transcription mode. Rapid depletion of either SAGA or Mediator Tail suggests that both factors play an important role in stimulating the fraction of active promoters at CR genes, with a variable gene-specific role in transcriptional bursting.
An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning
Authors: Lv Mingyue , Cai Ruyi , Zhang Renzimo , Xia Xiju , Li Xuelin , Wang Yipan , Wang Huan , Zeng Jianzhi , Xue Yifei , Mao Lanqun , Li Yulong 
Published: March 2024

ABSTRACTOctopamine (OA), analogous to norepinephrine in vertebrates, is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various biological functions, including olfactory associative learning. However, the spatial and temporal dynamics of OAin vivoremain poorly understood due to limitations associated with the currently available methods used to detect it. To overcome these limitations, we developed a genetically encodedGPCRactivation-based (GRAB) OA sensor called GRABOA1.0. This sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular OA. Using GRABOA1.0, we monitored OA release in theDrosophilamushroom body (MB), the fly’s learning center, and found that OA is released in response to both odor and shock stimuli in an aversive learning model. This OA release requires acetylcholine (ACh) released from Kenyon cells, signaling via nicotinic ACh receptors. Finally, we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Octβ1R in dopaminergic neurons, leading to alterations in synaptic plasticity within the MB. Thus, our new GRABOA1.0sensor can be used to monitor OA release in real-time under physiological conditions, providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.
Advancements in Cardiovascular Disease Detection: Leveraging Data Mining and Machine Learning
Authors: Hossain Md. Sahadat , Talukder Md. Alamin , Mahmud Md. Zulfiker 
Published: March 2024

AbstractCardiovascular disease (CVD) is a significant global health concern, requiring early detection and accurate prediction for effective intervention. Machine learning (ML) offers a data-driven approach to analyzing patient data, identifying complex patterns and predicting CVD risk factors like blood pressure (BP), cholesterol levels, and genetic predispositions. Our research aims to predict CVD presence using ML algorithms, leveraging the Heart Disease UCI dataset with 14 attributes and 303 instances. Extensive feature engineering enhanced model performance. We developed five models using Logistic Regression, K-Nearest Neighbors (KNN), Decision Tree Classifier, Support Vector Machine (SVM), and Random Forest Classifier, refining them with hyperparameter tuning. Results show substantial accuracy improvements post-tuning and feature engineering. ‘Logistic Regression’ achieved the highest accuracy at 93.44%, closely followed by ‘Support Vector Machine’ at 91.80%. Our findings emphasize the potential of ML in early CVD prediction, underlining its value in healthcare and proactive risk management. ML’s utilization for CVD risk assessment promises personalized healthcare, benefiting both patients and healthcare providers. This research showcases the practicality and effectiveness of ML-based CVD risk assessment, enabling early intervention, improving patient outcomes, and optimizing healthcare resource allocation.
Forest and Biodiversity 2: a tree diversity experiment to understand the consequences of multiple dimensions of diversity and composition for long-term ecosystem function and resilience
Authors: Cavender-Bares Jeannine , Grossman Jake J. , Guzmán Q. J. Antonio , Hobbie Sarah E. , Kaproth Matthew A. , Kothari Shan , Lapadat Cathleen , Montgomery Rebecca , Park Maria 
Published: March 2024

AbstractWe introduce a new “low-density” tree diversity experiment at the Cedar Creek Ecosystem Science Reserve in central Minnesota, USA aimed at testing long-term ecosystem consequences of tree diversity and composition. The experiment was designed to provide guidance on forest restoration efforts that will simultaneously advance carbon sequestration goals and contribute to biodiversity conservation and sustainability.The new Forest and Biodiversity (FAB2) experiment uses native tree species in varying levels of species richness, phylogenetic diversity, and functional diversity to test the mechanisms and processes that contribute to forest stability and ecosystem productivity in the face of global change. FAB2 was designed and established in conjunction with a prior experiment (FAB1) in which the same set of twelve species was planted in 16 m2plots at high density (0.5 m spacing). In addition to lower density plantings (1 m spacing), FAB2 also has larger plots (100 m2and 400 m2) appropriate for testing long-term ecosystem consequences of species composition and diversity.Within the first six years, mortality in the 400 m2monoculture plots was significantly higher than in the 100 m2plots. The highest mortality among any treatments occurred inTilia americanaandAcer negundomonocultures, but mortality for both species decreased with increasing plot diversity. These results highlight the importance of forest diversity in reducing mortality in some species and point to potential mechanisms, including light and drought stress, that cause tree mortality in vulnerable monocultures. The experiment highlights challenges to maintaining monoculture and low-diversity treatments in tree mixture experiments of large extent.The FAB2 experiment provides a long-term platform for discerning the importance of species and lineage effects and of multiple dimensions of diversity in restoring ecosystem functions and services provided by forests. It also provides a platform for improving remote sensing approaches, including Uncrewed Aerial Vehicles (UAVs) equipped with LiDAR, multispectral, and hyperspectral sensors, to complement ground-based monitoring of forest function and diversity. We aim for the experiment to contribute to international efforts to monitor and manage forests in the face of global change.