bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroanatomical evidence and a mouse calcitonin gene–related peptide model in line with human functional magnetic resonance imaging data support the involvement of peptidergic Edinger–Westphal nucleus in migraine
Authors: Al-Omari Ammar , Gaszner Balázs , Zelena Dóra , Gecse Kinga , Berta Gergely , Biró-Sütő Tünde , Szocsics Péter , Maglóczky Zsófia , Gombás Péter , Pintér Erika , Juhász Gabriella , Kormos Viktória 
Published: June 2024

Abstract
The urocortin 1 (UCN1)–expressing centrally projecting Edinger–Westphal (EWcp) nucleus is influenced by circadian rhythms, hormones, stress, and pain, all known migraine triggers. Our study investigated EWcp's potential involvement in migraine. Using RNAscope in situ hybridization and immunostaining, we examined the expression of calcitonin gene–related peptide (CGRP) receptor components in both mouse and human EWcp and dorsal raphe nucleus (DRN). Tracing study examined connection between EWcp and the spinal trigeminal nucleus (STN). The intraperitoneal CGRP injection model of migraine was applied and validated by light–dark box, and von Frey assays in mice, in situ hybridization combined with immunostaining, were used to assess the functional–morphological changes. The functional connectivity matrix of EW was examined using functional magnetic resonance imaging in control humans and interictal migraineurs. We proved the expression of CGRP receptor components in both murine and human DRN and EWcp. We identified a direct urocortinergic projection from EWcp to the STN. Photophobic behavior, periorbital hyperalgesia, increased c-fos gene–encoded protein immunoreactivity in the lateral periaqueductal gray matter and trigeminal ganglia, and phosphorylated c-AMP–responsive element binding protein in the STN supported the efficacy of CGRP-induced migraine-like state. Calcitonin gene–related peptide administration also increased c-fos gene–encoded protein expression, Ucn1 mRNA, and peptide content in EWcp/UCN1 neurons while reducing serotonin and tryptophan hydroxylase-2 levels in the DRN. Targeted ablation of EWcp/UCN1 neurons induced hyperalgesia. A positive functional connectivity between EW and STN as well as DRN has been identified by functional magnetic resonance imaging. The presented data strongly suggest the regulatory role of EWcp/UCN1 neurons in migraine through the STN and DRN with high translational value.
Illness perceptions and blood pressure control among hypertensive Filipino Americans: A cross-sectional study
Authors: dela Cruz Felicitas A. , Yu Chong Ho (Alex) , Lao Brigette T. 
Published: June 2024

ABSTRACT

Background:
Among Asian Americans, Filipino Americans (FAs)—who constitute the fourth largest US immigrant group and who fill in health care workforce shortages—experience high prevalence but low control rates of high blood pressure (HBP). Research reveals that patients' illness perceptions, their common-sense model (CSM) of the illness, influence treatment behaviors, and management outcomes. However, scarce information exists about FAs' perceptions about HBP.

Purpose:
To address this gap, we conducted a cross-sectional study to (a) identify the illness perceptions of hypertensive FAs, (b) classify these perceptions into clusters, and (c) determine the association between illness perceptions and BP control.

Methodology:
The responses of 248 FAs with HBP to the Brief Illness Perception Questionnaire were analyzed using JMP Pro version 17 to discover their CSMs or illness perceptions. We used iterative K means cluster analysis to classify variations in CSMs and analysis of means chart to determine the association of illness perceptions and BP control.

Results:
Hypertensive FAs expressed threatening (negative) views of HBP through their emotional perceptions of the illness and its chronic time line, whereas their positive views centered on their cognitive beliefs about understanding HBP and its controllability. Based on the biomedical model of HBP, the overall illness perceptions or CSMs encompassed three clusters. Generally, threatening illness perceptions were associated with stage 2 HBP.

Conclusions/Implications:
The findings underscore the need for nurse practitioners to elicit, listen, discern, and understand the illness perceptions or CSMs of hypertensive FAs to improve BP treatment and control with scientifically and culturally tailored interventions.
Reimagining the Future of Clinical Nursing Education: A Cohort Partnership Model
Authors: Buron Bill , Abbott Eng Cassy , Eagleton Alison 
Published: June 2024

Background:
As the demand for registered nurses increases, innovative methods for stabilizing, improving, and ensuring the longevity of quality clinical nursing education should be considered. Traditionally, full-time nursing faculty teach nursing students in clinical settings.

Problem:
Considering the impending nurse educator crisis, characterized by increasing demands on a dwindling nursing faculty, traditional approaches to clinical nursing education are no longer feasible.

Approach:
A new clinical cohort model (CCM), developed from an academic/health system partnership, is proposed as an innovative approach to future clinical nursing education.

Outcomes:
CCM implementation resulted in a significant reduction in the cost of educating nursing students. The health care system noted a 100% postgraduation 2-year retention rate among cohort students. Nursing students overwhelmingly expressed satisfaction, comfort, and new opportunities through participation in the CCM.

Conclusions:
This new CCM has significant benefits for schools of nursing, health care systems, and nursing students.
Implementing a Pediatric Escape Room Simulation to Improve Student Learning
Authors: Stanek Rachel J. , Montgomery Kathleen E. , Anibas Melissa 
Published: June 2024

Background:
Escape room simulations are an innovative teaching methodology that may be useful in addressing pediatric-specific content and clinical placement limitations of generalist nursing programs.

Problem:
This project studied if a pediatric escape room simulation improved students’ knowledge and confidence in pediatric nursing to support the development of the pediatric nursing workforce.

Approach:
A pediatric escape room simulation was developed for a large Midwestern university’s prelicensure nursing program. Students completed surveys to assess knowledge and confidence in pediatric nursing. Simulation quality was assessed using the Simulation Learning Effectiveness Inventory.

Outcomes:
Students’ (N = 37) knowledge and confidence in pediatric nursing concepts significantly increased after the simulation. Students responded positively to the simulation and recommended it be included in the undergraduate curriculum.

Conclusions:
The pediatric escape room simulation offers a promising alternative for students to gain pediatric-specific knowledge and confidence for prelicensure nursing programs in the context of limited pediatric clinical placements.
Risk Factors for Adverse Outcomes in Kidney Transplants From Donors After Circulatory Death With Normothermic Regional Perfusion: A Systematic Analysis
Authors: Savoye Emilie , Martin-Lefèvre Laurent , Dantal Jacques , Dorez Didier , Gaudez François , Drouin Sarah , Riou Bruno , Strecker Guillaume , Thierry Antoine , Legeai Camille , Bronchard Régis , Kerbaul François , Antoine Corinne ,   the Controlled Donation After the Circulatory Determination of Death National Steering Committee
Published: June 2024

Background.
This study examined 1071 adult primary kidney transplants from the French-controlled donation after the circulatory determination of death (cDCD) program, which uses normothermic regional perfusion (NRP), and involves short cold ischemia times (CIT) and constrained asystole times differing by donor age.

Methods.
Logistic regression identified risk factors for primary nonfunction (PNF), delayed graft function (DGF), and graft failure.

Results.
Risk factors for PNF included donor hypertension, admission for ischemic vascular stroke, and HLA DR mismatches. Risk factors for DGF included functional warm ischemia time >40 min, dialysis >2 y, recipient body mass index of 30 kg/m2 or higher, recipient diabetes, and CIT >10 h. Risk factors for 1-y graft failure included donor hypertension, donor lung recovery, ostial calcification, recipient cardiovascular comorbidities, and HLA DR mismatches. A high donor estimated glomerular filtration rate protected against DGF and graft failure at 1-y. After adjustment restricted to recipient and graft factors and donor age, the risks of PNF, DGF, and graft failure increased with donor age up to 65 y and then remained stable.

Conclusions.
The study suggests that cDCD kidney transplants are highly successful, but also that its outcomes are influenced by lung recovery, poor HLA DR matching, and warm ischemia times differing with donor age. Our study identified several risk factors for kidney transplantation failure after cDCD with systematic use of NRP and some of them seem as modifiable variables associated with cDCD transplant outcome.
An optimized and robust workflow for quantifying the canonical histone ubiquitination marks H2AK119ub and H2BK120ub by LC-MS/MS
Authors: Lopes Mariana , Lund Peder J. , Garcia Benjamin A. 
Published: June 2024

ABSTRACTThe eukaryotic genome is packaged around histone proteins, which are subject to a myriad of post-translational modifications. By controlling DNA accessibility and the recruitment of protein complexes that mediate chromatin-related processes, these modifications constitute a key mechanism of epigenetic regulation. Since mass spectrometry can easily distinguish between these different modifications, it has become an essential technique in deciphering the histone code. Although robust LC-MS/MS methods are available to analyze modifications on the histone N-terminal tails, routine methods for characterizing ubiquitin marks on histone C-terminal regions, especially H2AK119ub, are less robust. Here we report the development of a simple workflow for the detection and improved quantification of the canonical histone ubiquitination marks H2AK119ub and H2BK120ub. The method entails a fully tryptic digestion of acid-extracted histones followed by derivatization with heavy or light propionic anhydride. A pooled sample is then spiked into oppositely labeled single samples as a reference channel for relative quantification, and data is acquired using PRM-based nanoLC-MS/MS. We validated our approach with synthetic peptides as well as treatments known to modulate the levels of H2AK119ub and H2BK120ub. This new method complements existing histone workflows, largely focused on the lysine-rich N-terminal regions, by extending modification analysis to other sequence contexts.
Nitazoxanide ameliorates OVA-induced airway inflammation in asthmatic mice via p38-MAPK/NFkB and AMPK/STAT3 pathways
Authors: Huang Zhuyun , Zhang Yanwen , Sun Yudi , Wang Qian , Men Zhonglan , Chu Fuao , Sun Shuangyong 
Published: June 2024

AbstractNitazoxanide has an anti-inflammatory effect, we clarified the ameliorative effect of nitazoxanide on asthmatic airway inflammation by conducting in vitro and in vivo experiments. In vitro, we assessed the effect of nitazoxanide on cytokine production by lipopolysaccharide-stimulated RAW 264.7 cells, as well as the diastolic effect of nitazoxanide on isolated rat airways. Nitazoxanide was found to have a diastolic effect on isolated tracheal spasms caused by spasmogenic substances, and to inhibit IL-6 and IL-1β production by RAW 264.7 cells. Meanwhile, nitazoxanide can inhibit the proliferation and migration of human bronchial smooth muscle cells (HBSMCs). In vivo, an ovalbumin (OVA)-induced asthma model was established in mice, and the airway resistance was measured by Whole Body Plethysmography (WBP) after inhalation of acetylcholine in mice, and the levels of IL-4, IL-6, IL-12, and IL-17 were detected in bronchoalveolar lavage fluid (BALF) of mice by ELISA and the inflammatory cells were counted. H&E staining was used to observe the changes in lung histopathology, and the expression of NFkB, MAPK, AMPK, and STAT3 in lung tissues was quantified using Western-blot. Nitazoxanide reduced inflammatory cell infiltration and goblet cell proliferation in the lungs of asthmatic mice. Moreover, the expression of IL-4, IL-5, and IL-6 in BALF was down-regulated in asthmatic mice. In addition, nitazoxanide could inhibit the expression of NFkB, MAPK, STAT 3 proteins and ascend the expression of AMPK in lung tissues. In conclusion, nitazoxanide could diastole airway smooth muscle and ameliorate OVA-induced airway inflammation in asthmatic mice via NFkB/MAPK and AMPK/STAT3 pathways.
Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression
Authors: Ramage Dylan E. , Grant Drew W. , Timms Richard T. 
Published: June 2024

ABSTRACTThe 26S proteasome is a multi-catalytic protease that serves as the endpoint for protein degradation via the ubiquitin-proteasome system. Proteasome function requires the concerted activity of 33 distinct gene products, but how the expression of proteasome subunits is regulated in mammalian cells remains poorly understood. Leveraging coessentiality data from the DepMap project, here we characterize an essential role for the dystonia geneTHAP1in maintaining the basal expression ofPSMB5. PSMB5 insufficiency resulting from loss of THAP1 leads to defects in proteasome assembly, impaired proteostasis and cell death. Exploiting the fact that the toxicity associated with loss of THAP1 can be rescued upon exogenous expression of PSMB5, we define the transcriptional targets of THAP1 through RNA-seq analysis and perform a deep mutational scan to systematically assess the function of thousands of single amino acid THAP1 variants. Altogether, these data identify THAP1 as a critical regulator of proteasome function and suggest that aberrant proteostasis may contribute to the pathogenesis of THAP1 dystonia.
Development of a Time-Resolved Fluorescence Resonance Energy Transfer ultra-high throughput screening assay for targeting SYK and FCER1G interaction
Authors: Du Yuhong , Wang Dongxue , Katis Vittorio L. , Zoeller Elizabeth L. , Qui Min , Levey Allan I. , Gileadi Opher ,   Emory-SAGE-SGC TREAT-AD Center, Fu Haian 
Published: June 2024

AbstractThe spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) interaction has a major role in the normal innate and adaptive immune responses, but dysregulation of this interaction is implicated in several human diseases, including autoimmune disorders, hematological malignancies, and Alzheimer’s Disease. Development of small molecule chemical probes could aid in studying this pathway both in normal and aberrant contexts. Herein, we describe the miniaturization of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to measure the interaction between SYK and FCER1G in a 1536-well ultrahigh throughput screening (uHTS) format. The assay utilizes the His-SH2 domains of SYK, which are indirectly labeled with anti-His-terbium to serve as TR-FRET donor and a FITC-conjugated phosphorylated ITAM domain peptide of FCER1G to serve as acceptor. We have optimized the assay into 384-well HTS format and further miniaturized the assay into a 1536-well uHTS format. Robust assay performance has been achieved with a Z’ factor > 0.8 and signal-to-background (S/B) ratio > 15. The utilization of this uHTS TR-FRET assay for compound screening has been validated by a pilot screening of 2,036 FDA-approved and bioactive compounds library. Several primary hits have been identified from the pilot uHTS. One compound, hematoxylin, was confirmed to disrupt the SYK/FECR1G interaction in an orthogonal protein–protein interaction assay. Thus, our optimized and miniaturized uHTS assay could be applied to future scaling up of a screening campaign to identify small molecule inhibitors targeting the SYK and FCER1G interaction.
Mutual information for detecting multi-class biomarkers when integrating multiple bulk or single-cell transcriptomic studies
Authors: Zou Jian , Li Zheqi , Carleton Neil , Oesterreich Steffi , Lee Adrian V. , Tseng George C. 
Published: June 2024

AbstractMotivationBiomarker detection plays a pivotal role in biomedical research. Integrating omics studies from multiple cohorts can enhance statistical power, accuracy and robustness of the detection results. However, existing methods for horizontally combining omics studies are mostly designed for two-class scenarios (e.g., cases versus controls) and are not directly applicable for studies with multi-class design (e.g., samples from multiple disease subtypes, treatments, tissues, or cell types).ResultsWe propose a statistical framework, namely Mutual Information Concordance Analysis (MICA), to detect biomarkers with concordant multi-class expression pattern across multiple omics studies from an information theoretic perspective. Our approach first detects biomarkers with con-cordant multi-class patterns across partial or all of the omics studies using a global test by mutual information. A post hoc analysis is then performed for each detected biomarkers and identify studies with concordant pattern. Extensive simulations demonstrate improved accuracy and successful false discovery rate control of MICA compared to an existing MCC method. The method is then applied to two practical scenarios: four tissues of mouse metabolism-related transcriptomic studies, and three sources of estrogen treatment expression profiles. Detected biomarkers by MICA show intriguing biological insights and functional annotations. Additionally, we implemented MICA for single-cell RNA-Seq data for tumor progression biomarkers, highlighting critical roles of ribosomal function in the tumor microenvironment of triple-negative breast cancer and underscoring the potential of MICA for detecting novel therapeutic targets.Availabilityhttps://github.com/jianzou75/MICA
Dynamic changes in structure and function of brain mural cells around chronically implanted microelectrodes
Authors: Wellman Steven M. , Forrest Adam M. , Douglas Madeline M. , Subbaraman Ashwat , Zhang Guangfeng , Kozai Takashi D.Y. 
Published: June 2024

1.0ABSTRACTIntegration of neural interfaces with minimal tissue disruption in the brain is ideal to develop robust tools that can address essential neuroscience questions and combat neurological disorders. However, implantation of intracortical devices provokes severe tissue inflammation within the brain, which requires a high metabolic demand to support a complex series of cellular events mediating tissue degeneration and wound healing. Pericytes, peri-vascular cells involved in blood-brain barrier maintenance, vascular permeability, waste clearance, and angiogenesis, have recently been implicated as potential perpetuators of neurodegeneration in brain injury and disease. While the intimate relationship between pericytes and the cortical microvasculature have been explored in other disease states, their behavior following microelectrode implantation, which is responsible for direct blood vessel disruption and dysfunction, is currently unknown. Using two-photon microscopy we observed dynamic changes in the structure and function of pericytes during implantation of a microelectrode array over a 4-week implantation period. Pericytes respond to electrode insertion through transient increases in intracellular calcium and underlying constriction of capillary vessels. Within days following the initial insertion, we observed an influx of new, proliferating pericytes which contribute to new blood vessel formation. Additionally, we discovered a potentially novel population of reactive immune cells in close proximity to the electrode-tissue interface actively engaging in encapsulation of the microelectrode array. Finally, we determined that intracellular pericyte calcium can be modulated by intracortical microstimulation in an amplitude- and frequency-dependent manner. This study provides a new perspective on the complex biological sequelae occurring the electrode-tissue interface and will foster new avenues of potential research consideration and lead to development of more advanced therapeutic interventions towards improving the biocompatibility of neural electrode technology.
Improving the Reliability and Accuracy of Population Receptive Field Measures Using a Logarithmically Warped Stimulus
Authors: Chang Kelly , Fine Ione , Boynton Geoffrey M. 
Published: June 2024

AbstractThe population receptive field method, which measures the region in visual space that elicits a BOLD signal in a voxel in retinotopic cortex, is a powerful tool for investigating the functional organization of human visual cortex with fMRI (Dumoulin & Wandell, 2008). However, recent work has shown that population receptive field (pRF) estimates for early retinotopic visual areas can be biased and unreliable, especially for voxels representing the fovea. Here, we show that a ‘log-bar’ stimulus that is logarithmically warped along the eccentricity dimension produces more reliable estimates of pRF size and location than the traditional moving bar stimulus. The log-bar stimulus was better able to identify pRFs near the foveal representation, and pRFs were smaller in size, consistent with simulation estimates of receptive field sizes in the fovea.
Aerial litter mimicry: a novel form of floral deception mediated by a monoterpene synthase
Authors: Liu Ming-Fai , Chen Junhao , Goodrich Katherine R. , Chiu Sung Kay , Pang Chun-Chiu , Scharaschkin Tanya , Saunders Richard M. K. 
Published: June 2024

AbstractFloral mimics deceive their pollinators by developing visual and olfactory resemblance to their models. Our knowledge on the diversity of models is expanding rapidly. We report a system in which the flowers exhibit phenotypes similar to aerial litter and deceives an aerial litter specialist beetle to achieve pollination.We assessed the floral phenology and the effective pollinators of an Australian understorey treelet,Meiogyne heteropetala(Annonaceae). The similarities of morphology, colour and odour between the flowers and co-occurring aerial litter were investigated. The terpene synthase involved in floral scent emission was identified by expression patterns and product profile. The behavioural responses of the pollinator to various odours were assessed using bioassays.The erotylid beetleLoberus sharpiis the most likely effective pollinator ofM. heteropetala, and its eggs were found on the petals ofM. heteropetala.Loberus sharpiwas exclusively found in aerial litter andM. heteropetalaflowers. The morphology and spectral reflectance of the flowers overlap with aerial litter. The floral scent was dominated by monoterpenes, especially 1,8-cineole. The cineole synthase MhCINS was the only highly expressed floral terpene synthase and possessed a highly similar product profile to the floral scent composition. NMDS showed that the volatile composition ofM. heteropetalaflowers is distinct from other congeners and highly similar to aerial litter, indicating advergence to aerial litter. Visual and odour resemblance, coupled with the deposition of eggs on the flowers, provides evidence that the beetles were deceived into pollinating the flowers. Behavioural experiments showed that the pollinator was attracted to both aerial litter andM. heteropetalaflowers. The beetles were also attracted to 1,8-cineole and synthetic mixes of floral odour and MhCINS products. The beetles were unable to distinguish floral scent from MhCINS products, nor from 1,8-cineole, suggesting MhCINS alone sufficed to attract the pollinator olfactorily. The beetles, however, preferred aerial litter over flowers. The beetles likely categorised the flower as a general, but not the most preferred brood substrate.Synthesis.This study reports the first case of floral mimicry of aerial litter and characterises the biochemical process responsible for olfactory mimicry.