bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes and reinterventions following uterine artery embolization for the treatment of uterine leiomyomata
Authors: Martin Jonathan G. , Medema Alexis M. 
Published: February 2024

ABSTRACTPurposeUterine leiomyomas are common benign tumors that arise from smooth muscle and can significantly impact quality of life. Over the past two decades, uterine artery embolization has risen as a minimally invasive alternative treatment to hysterectomy or myomectomy for the management of leiomyomas. While prior work has established the safety of this procedure, there exist few reports quantifying sequelae, notably rates of subsequent treatment and primary ovarian insufficiency. The purpose of this study is to demonstrate the efficacy of uterine artery embolization as well as to investigate the frequency of gynecologic reintervention and primary ovarian insufficiency following treatment.MethodsThe study cohort consisted of patients (n=199) who presented with symptoms concerning for uterine pathology and with leiomyoma(s) confirmed by MRI. This cohort underwent embolization between January 2013 and December 2018 at a single academic institution. Data was collected from retrospective chart review and included demographics, symptomology, imaging, procedural details, and follow-up care. This data was subsequently analyzed to quantify the frequencies of various outcomes at 4–10 years following embolization.ResultsOf 199 symptomatic patients with confirmed leiomyomas, all underwent technically successful uterine artery embolization. At the time of follow-up, information was available for 188 (94.5%) patients, of which 145 (77.1%) reported significant symptomatic improvement while 34 required additional intervention—either medical (9%) or surgical (9%). The most common secondary medical management involved hormone therapy, while the most common subsequent gynecologic procedure was a hysterectomy. Additionally, there were seven (3.7%) cases of amenorrhea following embolization.ConclusionGiven its minimally invasive nature, rapid recovery time, and uterine-sparing capability, uterine artery embolization should be considered a frontline therapy for symptomatic leiomyomas. This study supports an overall low complication rate, limited hospitalization time, near-complete resolution of symptoms, and low risk of ovarian dysfunction for a majority of patients. Following embolization, only 9% of patients required additional medical management, and only 9% required a second procedural intervention.
Perspectives of Osteopathic Medical Students on Preclinical Urology Exposure: A Single Institution Cross Sectional Survey
Authors: Wong Ryan , Mayrovitz Harvey N. 
Published: February 2024

ABSTRACTContextThere is an increasing number of medical school graduates opting for surgical specialties and the osteopathic applicant match rate for urology is lower than that of allopathic applicants. Factors influencing this may include a lack of interest, perceived challenges in matching into urology, insufficient urology mentorship, limited research opportunities, and inadequate osteopathic representation in urology.ObjectiveTo assess osteopathic medical students’ perspectives on pursuing urology and enhancing preclinical exposure to and knowledge of urology.MethodsA 20-question survey addressing experiences and the factors influencing osteopathic medical students’ specialty selection and their interest in and perception of urology was designed by the investigators on Research Electronic Data Capture software. This survey was distributed via email listserv to all current osteopathic medical students attending Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine over two months. Responses were collected and analyzed using Fisher’s exact test.ResultsOf 150 respondents, 91% found mentors crucial in selecting a medical specialty, 95% emphasized the importance of early exposure, and 68% lacked familiarity with urology, with more M1 students unfamiliar compared to M2 (70.37% vs. 59.02%). A larger proportion of combined M1 and M2 (preclinical) students are considering urology as a specialty compared to M3 and M4 (clinical) students who are actively on rotations (56.52% vs. 28.57%;p= 0.0064). Also, a greater percentage of males are considering urology compared to females (64.15% vs. 42.71%;p= 0.0164). Among those considering urology (n = 75), 57.3% lack awareness of urology’s scope, and 84% report no preclinical discussions with urologists. Those students who report they are considering urology value early exposure significantly more than others (98.67% vs. 78.67%;p= 0.0001). They also express greater interest in having a core urology course (73.33% vs. 38.67%;p< 0.0001). More urology considering students are interested in extracurricular urology-related workshops, seminars, or conferences (61.33% vs. 17.33%;p<0.0001). Students who are considering urology as a specialty show greater interest in having a mentorship program (85.33% vs. 28%;p< 0.0001).ConclusionResults suggested that increased urology exposure during the preclinical years is important. Urology elective offerings and urology mentorship are of high interest among those considering urology. However, additional investigation is needed to determine the impact of preclinical urology curricula implementation on urology match outcomes.
Deep Learning Prediction of Glycopeptide Tandem Mass Spectra Powers Glycoproteomics
Authors: Zong Yu , Wang Yuxin , Qiu Xipeng , Huang Xuanjing , Qiao Liang 
Published: February 2024

AbstractProtein glycosylation plays a significant role in numerous physiological and pathological cellular functions. Glycoproteomics based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) studies the protein glycosylation on a proteome-wide scale to get combinational information on glycosylation site, glycosylation level and glycan structure. However, the current sequence searching-based methods for glycoproteomics often fall short in glycan structure determination due to the limited occurrence of structure-determining ions. While spectral searching methods can utilize fragment intensity information to facilitate the identification of glycopeptides, its application is hindered by the difficulties in spectral library construction. In this work, we present DeepGP, a hybrid deep learning framework based on Transformer and graph neural network (GNN), for the prediction of MS/MS spectra and retention time of glycopeptides. Two GNN modules are utilized to capture the branched glycan structure and predict glycan ions intensity, respectively. Additionally, a pre-training strategy is implemented to alleviate the insufficiency of glycoproteomics data. Testing on multiple biological datasets, we demonstrate that DeepGP can predict MS/MS spectra and retention time of glycopeptides closely aligning with the experimental results. Comprehensive benchmarking of DeepGP on synthetic and biological datasets validates its effectiveness in distinguishing similar glycoforms. Remarkably, DeepGP can differentiate isomeric glycopeptides using MS/MS spectra without diagnostic ions. Based on various decoy methods, we demonstrated that DeepGP in combination with database searching can significantly increase the detection sensitivity of glycopeptides. We outlook that DeepGP can inspire extensive future work in glycoproteomics.
Structural insights into agonist binding and activation of succinate receptor 1
Authors: Liu Aijun , Liu Yezhou , Zhang Weijia , Ye Richard D. 
Published: February 2024

AbstractSuccinate is an intermediate of the citric acid cycle and serves important functions in energy homeostasis and metabolic regulation. Extracellular accumulation of succinate acts as a stress-induced signal through its G protein-coupled receptor, SUCNR1. Research on succinate signaling is hampered by the lack of high-resolution structures of the agonist-bound receptor. Here we present cryo-EM structures of SUCNR1-Gi complexes with the receptor bound to succinate and its non-metabolite derivative epoxysuccinate. Structural analysis of SUCNR1 identified key determinants for recognition of the dicarboxylate agonists incisconformation. R2817.39and Y832.64are critical to ligand binding, but Y301.39and R993.29also participate in binding of succinate and epoxysuccinate, respectively. The extracellular loop 2, through F175ECL2in its β-hairpin, forms a hydrogen bond with one of the carboxyl groups and serves as a lid to cap the binding pocket for succinate. At the receptor-Gi protein interface, agonist binding induces the rearrangement of a hydrophobic network on TM5 and TM6, leading to transmembrane signaling through TM3 and TM7. The agonist-bound SUCNR1 structures shed light on molecular recognition of succinate for receptor signaling, that may promote further development of novel agonists, antagonists and biased agonists targeting SUCNR1.
Attractor-like circuits improve visual decoding and behavior in zebrafish
Authors: Privat Martin , Hansen Enrique Carlos Arnoldo , Pietri Thomas , Marachlian Emiliano , Uribe-Arias Alejandro , Duchemin Auriane , Candat Virginie , Nourin Sarah , Sumbre Germán 
Published: February 2024

ABSTRACTAttractor networks are neural circuits with stable states that represent information or memories. They play a crucial role in memory retrieval, decision-making and integrating noisy cues. In zebrafish larvae, the spontaneous dynamics of the optic tectum is structured according to topographically organized neuronal assemblies exhibiting attractor-like behavior.Here, we took advantage of the Methyl-CpG-binding protein 2 (MeCP2) deficient zebrafish mutant, which displays perturbed tectal dynamics, to study the functional role of the attractor-like circuits in visual processing.In comparison to wild-type larvae, themecp2-mutant showed reduced functional connectivity in the optic tectum. This abnormal connectivity significantly affected the visual response, and the ability to discriminate between visual stimuli. Finally, the mutant larvae where less efficient in hunting paramecia. We argue that the attractor dynamics of the tectal assemblies improve stimulus discrimination, visual resolution, and increase the sensitivity to behaviorally relevant visual stimuli.
The co-receptor Tetraspanin12 directly captures Norrin to promote ligand-specific β-catenin signaling
Authors: Bruguera Elise S. , Mahoney Jacob P. , Weis William I. 
Published: February 2024

AbstractWnt/β-catenin signaling directs animal development and tissue renewal in a tightly controlled, cell- and tissue- specific manner. In the mammalian central nervous system, the atypical ligand Norrin controls angiogenesis and maintenance of the blood-brain barrier and blood-retina barrier through the Wnt/β-catenin pathway. Like Wnt, Norrin activates signaling by binding and heterodimerizing the receptors Frizzled (Fzd) and Low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6), leading to membrane recruitment of the intracellular transducer Dishevelled (Dvl) and ultimately stabilizing the transcriptional coactivator β-catenin. Unlike Wnt, the cystine-knot ligand Norrin only signals through Fzd4 and additionally requires the co-receptor Tetraspanin12 (Tspan12); however, the mechanism underlying Tspan12-mediated signal enhancement is unclear. It has been proposed that Tspan12 integrates into the Norrin-Fzd4 complex to enhance Norrin-Fzd4 affinity or otherwise allosterically modulate Fzd4 signaling. Here, we measure direct, high-affinity binding between purified Norrin and Tspan12 in a lipid environment and use AlphaFold models to interrogate this interaction interface. We find that Tspan12 and Fzd4 can simultaneously bind Norrin and that a pre-formed Tspan12/Fzd4 heterodimer, as well as cells co-expressing Tspan12 and Fzd4, more efficiently capture low concentrations of Norrin than Fzd4 alone. We also show that Tspan12 competes with both heparan sulfate proteoglycans and LRP6 for Norrin binding and that Tspan12 does not impact Fzd4-Dvl affinity in the presence or absence of Norrin. Our findings suggest that Tspan12 does not allosterically enhance Fzd4 binding to Norrin or Dvl, but instead functions to directly capture Norrin upstream of signaling.
Chronic IL-1-induced DNA double-strand break response in hippocampal neurons drives cognitive deficits
Authors: Marcy Belloy , Schmitt Benjamin A. M. , Marty Florent H. , Charlotte Paut , Emilie Bassot-Parra , Amel Aïda , Marine Alis , Romain Ecalard , Raphaël Boursereau , Daniel Gonzalez-Dunia , Nicolas Blanchard , Elsa Suberbielle 
Published: February 2024

ABSTRACTChronic inflammation characterized by increased cytokine levels, such as interleukin-1 (IL-1), accompanies many neurological diseases but little is known about IL-1 contribution to cognitive impairment and its interplay with epigenetic processes, including the DNA double-strand break (DSB) response.Here, we demonstrate that H2A.X-dependent DSB signaling in hippocampal neurons drives cognitive deficits upon chronically elevated IL-1. Mice persistently and latently infected withToxoplasma gondiidisplay impaired spatial memory consolidation along with elevated IL-1β in the hippocampus. We find that neuronal IL-1 signaling in excitatory neurons is required for the spatial memory deficits caused byT. gondiiinfection and by chronic systemic infusion of IL-1β. In both cases, the deficit in spatial memory was prevented by the abrogation of neuronal H2A.X-dependent signaling.Our results highlight the instrumental role of cytokine-induced DSB-dependent signaling in spatial memory defects. This novel pathological mechanism in inflammation control of neuronal function may extend to several neurological diseases.
Automated neuropil segmentation of fluorescent images for Drosophila brains
Authors: Hsu Kai-Yi , Shih Chi-Tin , Chen Nan-Yow , Lo Chung-Chuan 
Published: February 2024

AbstractThe brain atlas, which provides information about the distribution of genes, proteins, neurons, or anatomical regions in the brain, plays a crucial role in contemporary neuroscience research. To analyze the spatial distribution of those substances based on images from different brain samples, we often need to warp and register individual brain images to a standard brain template. However, the process of warping and registration often leads to spatial errors, thereby severely reducing the accuracy of the analysis. To address this issue, we develop an automated method for segmenting neuropils in theDrosophilabrain using fluorescence images from theFlyCircuitdatabase. This technique allows future brain atlas studies to be conducted accurately at the individual level without warping and aligning to a standard brain template.Our method, LYNSU (Locating by YOLO and Segmenting by U-Net), consists of two stages. In the first stage, we use the YOLOv7 model to quickly locate neuropils and rapidly extract small-scale 3D images as input for the second stage model. This stage achieves a 99.4% accuracy rate in neuropil localization. In the second stage, we employ the 3D U-Net model to segment neuropils. LYNSU can achieve high accuracy in segmentation using a small training set consisting of images from merely 16 brains. We demonstrate LYNSU on six distinct neuropils or structure, achieving a high segmentation accuracy, which was comparable to professional manual annotations with a 3D Intersection-over-Union(IoU) reaching up to 0.869.Most notably, our method takes only about 7 seconds to segment a neuropil while achieving a similar level of performance as the human annotators. The results indicate the potential of the proposed method in high-throughput connectomics construction forDrosophilabrain optical imaging.
Neonatal Amygdala Mean Diffusivity: A Potential Predictor of Emotional Face Perception
Authors: Hashempour Niloofar , Tuulari Jetro J. , Merisaari Harri , Lewis John D. , Häikiö Tuomo , Scheinin Noora M. , Nolvi Saara , Korja Riikka , Karlsson Linnea , Karlsson Hasse , Kataja Eeva-Leena 
Published: February 2024

AbstractThe ability to differentiate between different facial expressions is an important part of human social and emotional development that begins in infancy. Studies have shown that within the first year of life, infants develop a distinctive attentional bias towards fearful facial expressions. Investigations into the neural basis for this bias have highlighted the significance of the amygdala. The amygdala’s role in directing attention towards fearful facial expressions underscores its importance in early emotional development, significantly influencing how infants interpret and react to facial expressions. To date, no studies have been conducted to investigate the associations between the amygdala microstructure and infants’ perception of emotional faces. This study aimed to elucidate this relationship while also investigating whether this association is sex specific. We measured the amygdala microstructural properties using diffusion tensor imaging mean diffusivity (MD) measurements in 40 healthy infants aged 2 to 5 weeks. Eye tracking was used to assess attention disengagement from fearful vs. non-fearful (happy and neutral) facial expressions as well as scrambled non-face control picture at 8 months. Generally, infants were age-typically less likely to disengage from fearful faces than from non-fearful faces towards salient distractors. A significant negative association was observed between the right amygdala MD measures and disengagement probability from fearful faces in the overall sample. Moreover, there was a positive association between the bilateral amygdala MD measures and the disengagement probability from scrambled non-face control picture in girls. These results indicate that the amygdala MD is associated with attention disengagement processes already in infancy, both in fear processing and in non-emotional conditions. Specifically, these findings highlight the role of the amygdala microstructure in modulating attentional processes, which may have implications for emotional regulation and susceptibility to emotional dysregulation later in life.
Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles
Authors: Rogers Sophie A. , Heller Elizabeth A. , Corder Gregory 
Published: February 2024

AbstractThe serotonin 2 receptor (5HT2R) agonist psilocybin displays rapid and persistent therapeutic efficacy across neuropsychiatric disorders characterized by cognitive inflexibility. However, the impact of psilocybin on patterns of neural activity underlying sustained changes in behavioral flexibility has not been characterized. To test the hypothesis that psilocybin enhances behavioral flexibility by altering activity in cortical neural ensembles, we performed longitudinal single-cell calcium imaging in the retrosplenial cortex across a five-day trace fear learning and extinction assay. A single dose of psilocybin induced ensemble turnover between fear learning and extinction days while oppositely modulating activity in fearand extinctionactive neurons. The acute suppression of fear-active neurons and delayed recruitment of extinction-active neurons were predictive of psilocybin-enhanced fear extinction. A computational model revealed that acute inhibition of fear-active neurons by psilocybin is sufficient to explain its neural and behavioral effects days later. These results align with our hypothesis and introduce a new mechanism involving the suppression of fear-active populations in the retrosplenial cortex.
Vagus nerve damage increases alcohol intake and preference in a nonpreferring rat line: Relationship to vagal regulation of the hypothalamic–pituitary–adrenal axis
Authors: Keller Bailey N. , Snyder Angela E. , Coker Caitlin R. , Aguilar Elizabeth A. , O'Brien Mary K. , Lookfong Nicole A. , Bingaman Sarah S. , Arnold Amy C. , Hajnal Andras , Silberman Yuval 
Published: February 2024

AbstractBackgroundClinical and preclinical research indicates that gastric weight loss surgeries, such as Roux‐en‐Y gastric bypass surgery, can induce alcohol use disorder (AUD). While numerous mechanisms have been proposed for these effects, one relatively unexplored potential mechanism is physical damage to the gastric branch of the vagus nerve, which can occur during bypass surgery. Therefore, we hypothesized that direct damage to the gastric branch of the vagus nerve, without altering other aspects of gastric anatomy, could result in increased alcohol intake.MethodsTo test this hypothesis, we compared alcohol intake and preference in multiple models in male Sprague–Dawley rats that received selective gastric branch vagotomy (VX) with rats who underwent sham surgery. Because the vagus nerve regulates hypothalamic‐pituitary‐adrenal (HPA) axis function, and alterations to HPA function are critical to the escalation of non‐dependent alcohol intake, we also tested the hypothesis that gastric VX increases HPA function.ResultsWe found that VX increases alcohol intake and preference in the every‐other‐day, two‐bottle choice test and increases preference for 1 g/kg alcohol in the conditioned place preference test. The effects were selective for alcohol, as sucrose intake and preference were not altered by VX. We also found that VX increases corticotropin releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN), increases putative PVN CRF neuronal action potential firing, and increases corticosterone levels.ConclusionsOverall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of PVN CRF mRNA expression and putative PVN CRF neuronal activity. Furthermore, disruptions to vagal regulation of HPA axis function may increase alcohol intake and preference.
Longitudinal stability of reward and relief drinking phenotypes in community and treatment‐seeking individuals who engage in heavy drinking
Authors: Hebden Hanna M. , Swan Julia E. , Claus Eric D. , Pentkowski Nathan S. , Witkiewitz Katie 
Published: February 2024

AbstractBackgroundPrecision medicine approaches aim to improve treatment outcomes by identifying which treatments work best for specific individual phenotypes. In the treatment of alcohol use disorder (AUD), precision medicine approaches have been proposed based on phenotypes characterized by individuals who drink primarily to enhance rewarding experiences (i.e., reward drinking) or those who drink primarily to relieve negative states (i.e., relief drinking). This study examined these phenotypes across treatment‐ and nontreatment‐seeking individuals and the stability of the phenotypes over time.MethodsWe used latent profile and latent transition analyses to identify and assess longitudinal stability (over 3 or 4 months) of reward and relief drinking subgroups within a nontreatment‐seeking community sample that engaged in hazardous drinking (n = 189) and two treatment‐seeking samples of individuals with AUD enrolled in two large clinical trials (n = 1726, n = 1383). We examined prospective associations with alcohol consumption and consequences at long‐term follow‐up (15 or 18 months).ResultsResults supported four subgroups: low reward/low relief, low reward/high relief, high reward/low relief, and high reward/high relief. The community sample contained more individuals classified within the high reward/low relief subgroup than treatment‐seeking samples. Subgroups were generally more stable over time in the community sample than in the treatment‐seeking samples. Alcohol consumption and consequences decreased over time for the treatment‐seeking samples, with consequences and drinking frequency decreasing for the community sample. Participants classified within the high reward/high relief and low reward/high relief groups reported the most consequences and consumption at long‐term follow‐up.ConclusionReward and relief drinking phenotypes can be identified within community and treatment‐seeking samples of individuals who drink heavily. The phenotypic subgroups appear to be stable over time in the absence of treatment, change somewhat during treatment, and provide utility in predicting alcohol consumption and consequences.