bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of Plasma Melatonin in Medication-Overuse Headache: A Cross-Sectional Study
Authors: Tao Huimin , Wan Qi , Sun Mei , Cai Kefu , Song Yan , He Mingqing , Shen Jiabing 
Published: October 2023

Objectives
Patients with medication-overuse headache (MOH) are often complicated with anxiety, depression, and sleep disorders and are associated with dependence behavior and substance abuse. Melatonin has physiological properties including analgesia, regulation of circadian rhythms, soporific, and antidepressant and affects drug preference and addiction. This study aimed to investigate the role of melatonin in MOH compared with episodic migraine (EM) and healthy controls and to verify the relationship between plasma melatonin levels and psychiatric symptoms.

Methods
Thirty patients affected by MOH, 30 patients with EM, and 30 matched healthy controls were enrolled. All subjects completed a detailed headache questionnaire and scales including the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index, the Leeds Dependence Questionnaire. Melatonin levels in plasma samples were measured by enzyme immunoassay method.

Results
The levels of plasma melatonin were significantly different among 3 groups of subjects (MOH, 7.74 [5.40–9.89]; EM, 9.79 [8.23–10.62]; Control, 10.16 [8.60–17.57]; H = 13.433; P = 0.001). Significantly lower levels of melatonin were found in MOH patients compared with healthy controls (P = 0.001). The level of plasma melatonin inversely correlated with the scores of HADS-Anxiety (r = −0.318, P = 0.002), HADS-Depression (r = −0.368, P < 0.001), Pittsburgh Sleep Quality Index (r = −0.303, P = 0.004), and Leeds Dependence Questionnaire (r = −0.312, P = 0.003).

Conclusions
This study innovatively detects the plasma melatonin levels in MOH patients and explores the association between melatonin levels and psychiatric symptoms. Melatonin may be potential complementary therapy in the treatment of MOH considering its comprehensive role in multiple aspects of MOH.
A 5-structured visits multidisciplinary clinical care approach to optimize the care of patients with type 2 diabetes: a pilot study
Authors: Allam Magdy Mohamed , Younan Mariam , Abdelhamid Mohamed , Khan Muhammad , Elshafee Mohamed , Nada Aml Mohamed 
Published: October 2023

Introduction
Multidisciplinary coordinated care has been associated with improvement of diabetes care.

Aim and methods
This is a retrospective cohort analysis aimed to assess the effect of application of the five-structured visits Multi-disciplinary Clinical Care Approach (FMCA) on each of T2DM control, complications and comorbidities. The patients’ records were assessed for one year of regular diabetes care followed with a year after implementation of FMCA for patients attending the diabetes clinic at Zulekha hospital. The patients were divided according to HbA1c (cutoff 7%) at the end of the FMCA year of follow-up into a group of controlled and another group of uncontrolled diabetes designated CDM and UCDM, respectively.

Results
49% of patients were males and the mean age was 44.22 years. HbA1c levels, LDL and urinary albumin/creatinine ratio (UACR) showed a marked decrease among the patients after implementation of FMCA (P = 0.02, P = 0.04, P = 0.003, respectively). Compared with an increase in the atherosclerotic cardiovascular risk score (ASCVD) during the regular period, exposure to FMCA significantly decreased the cardiovascular risk score (0.17%, 11.41%, P = 0.001, P = 0.001, respectively). A self-management score was significantly higher in CDM patients. After a multivariate regression analysis of factors affecting DM control, we detected that baseline HbA1c, UACR, self-management score and hospital admission rate were the most important factors to predict diabetes control.

Conclusion
The implementation of FMCA has shown a significant improvement in clinical and humanistic aspects of individuals with T2DM with a better outcome, more control and less complications.
Abrogation and Homeostatic Restoration of IgE Responses by a Universal IgE Allergy CTL Vaccine—The Three Signal Self/Non-Self/Self (S/NS/S) Model
Authors: Chen Swey-Shen , Zhang Hailan 
Published: October 2023

AbstractNatural IgE cytotoxic peptides (nECPs), which are derived from the constant domain of the heavy chain of human IgE producing B cells via endoplasmic reticulum (ER) stress, are decorated onto MHC class 1a molecules (MHCIa) as unique biomarkers for CTL (cytotoxic T lymphocyte)-mediated immune surveillance. Human IgE exhibits only one isotype and lacks polymorphisms; IgE is pivotal in mediating diverse, allergen-specific allergies. Therefore, by disrupting self-IgE tolerance via costimulation, the cytotoxic T lymphocytes (CTLs) induced by nECPs can serve as universal allergy vaccines (UAVs) in humans to dampen IgE production mediated by diverse allergen-specific IgE- secreting B cells and plasma cells expressing surface nECP-MHCIa as targets. The study herein has enabled the identification of nECPs produced through the correspondence principle1, 2. Furthermore, nECP-tetramer-specific CTLs were found to be converted into CD4 Tregs that restored IgE competence via the homeostatic principle, mediated by SREBP-1c suppressed DCs. Thus, nECPs showed causal efficacy and safety as UAVs for treating type I hypersensitivity IgE-mediated allergies. The applied vaccination concept presented provides the foundation to unify, integrate through a singular class of tetramer-specific TCR clonotypes. The three signal model is proposed on the mechanisms underlying central tolerance, breaking tolerance and regaining peripheral tolerance via homeostasis concerning nECP as an efficacious and safe UAV to treat type I IgE-mediated hypersensitivity.One Sentence SummaryHuman IgE self-peptides are identified as universal allergy vaccines that inhibit IgE synthesis while allowing homeostatic IgE recovery.Graphic abstract textThree cell S/NS/S model of Universal Allergy Vaccines (UAV): Natural IgE peptides (nECPs) presented by enabler DCs break central IgE tolerance (Self), leading to CTLs that inhibit IgE production (Non-self). Generative DCs converted by the metabolic milieu transform the pre-existing nECP-specific CTLs into nECP-specific Tregs leading to homeostatic recovery of IgE competence (S).
CD1d-dependent neuroinflammation impairs tissue repair and functional recovery following a spinal cord injury
Authors: Wu Xiangbing , Liu Jianyun , Li Wei , Khan Mohammad Faizan , Dai Heqiao , Tian Jeremy , Priya Raj , Tian Daniel J. , Wu Wei , Yaacoub Alan , Gu Jun , Syed Fahim , Yu Christopher H. , Gao Xiang , Yu Qigui , Xu Xiao-Ming , Brutkiewicz Randy R. 
Published: October 2023

AbstractTissue damage resulting from a spinal cord injury (SCI) is primarily driven by a robust neuroimmune/neuroinflammatory response. This intricate process is mainly governed by a multitude of cytokines and cell surface proteins in the central nervous system (CNS). However, the critical components of the neuroimmune/neuroinflammatory response during SCI are still not well-defined. In this study, we investigated the impact of CD1d, an MHC class I-like molecule mostly known for presenting lipid antigens to natural killer T (NKT) cells and regulating immune/inflammatory responses, on neuroimmune/neuroinflammatory responses induced by SCI. We observed an increased expression of CD1d on various cell types within the spinal cord, including microglia/macrophages, oligodendrocytes (ODCs), and endothelial cells (DCs), but not on neurons or astrocytes post-SCI. In comparison to wildtype (WT) mice, a T10 contusive SCI in CD1d knockout (CD1dKO orCd1d-/-) mice resulted in markedly reduced proinflammatory cytokine release, microglia/macrophage activation and proliferation. Following SCI, the levels of inflammatory cytokines and activation/proliferation of microglia/macrophages were dramatically reduced, while anti-inflammatory cytokines such as IL-4 and growth factors like VEGF were substantially increased in the spinal cord tissues of CD1dKO mice when compared to WT mice. In the post-acute phase of SCI (day 7 post-SCI), CD1dKO mice had a significantly higher frequency of tissue-repairing macrophages, but not other types of immune cells, in the injured spinal cord tissues compared to WT mice. Moreover, CD1d-deficiency protected spinal cord neuronal cells and tissue, promoting functional recovery after a SCI. However, the neuroinflammation in WT mouse spinal cords was independent of the canonical CD1d/NKT cell axis. Finally, treatment of injured mice with a CD1d-specific monoclonal antibody significantly enhanced neuroprotection and improved functional recovery. Therefore, CD1d promotes the proinflammatory response following a SCI and represents a potential therapeutic target for spinal cord repair.Significance StatementThe cell surface molecule, CD1d, is known to be recognized by cells of the immune system. To our knowledge, this is the first observation that the CD1d molecule significantly contributes to neuroinflammation following a spinal cord injury (SCI) in a manner independent of the CD1d/NKT cell axis. This is important, because this work reveals CD1d as a potential therapeutic target following an acute SCI for which there are currently no effective treatments.
Homogenization of taxonomic, phylogenetic, and functional characteristics of bumble bee communities at regional scales in anthropogenic landscapes
Authors: Perry Kayla I , Gratton Claudio , Tai Taylor , Strange James P 
Published: October 2023

ABSTRACTBiotic homogenization has been documented following extensive anthropogenic landscape change such as urbanization and agriculture, but diverse native communities also have been reported in these ecosystems. Understanding the influence of landscape-level characteristics on processes of community assembly can inform how human-dominated landscapes shape the structure and composition of local communities, including important pollinators such as bumble bees (Bombusspp.). The objective of this study was to investigate multi-scale patterns of taxonomic, phylogenetic, and functional beta- diversity of bumble bees in greenspaces along an urban-agricultural gradient to understand landscape- scale constraints on processes of community assembly. Bumble bees were collected in greenspaces along an urban-agricultural gradient in Madison, WI, USA. Patterns of biotic homogenization were investigated using measures of beta-diversity and null models relative to a regional bumble bee species pool in a 100 km area surrounding the city. Nine of the expected 13 species from the regional pool were collected in greenspaces in urban and agricultural landscapes. At the regional scale, we found evidence of taxonomic, phylogenetic, and functional homogenization among bumble bee communities in urban and agricultural landscapes, with species that were smaller in size, had shorter wings, were less hairy, but had larger eyes and longer setae on the corbicula (pollen-carrying hind legs) being more common than expected based on null models. When we evaluated filtering from the anthropogenic species pools (i.e., urban and agricultural) to local greenspaces, we found nuanced differences among land cover types, wherein agricultural landscapes supported higher beta-diversity of bumble bee communities than expected while urban landscapes continued to show signals of homogenization. Overall, anthropogenic landscapes acted as a strong filter for bumble bees, broadly selecting for a subset of functionally similar and phylogenetically related species that resulted in homogenization of communities within the region. Our findings support a landscape-level approach to biodiversity conservation that promotes diversifying landscapes to support diverse pollinator populations.OPEN RESEARCH STATEMENTData and novel code associated with this submission are provided in an external repository to be evaluated during the peer review process and are available athttps://github.com/kiperry/WI_Bumble_Bees. If this paper is accepted for publication, data and code will be permanently archived within a linked Zenodo repository.
Immediate and Long-Term Electrophysiological Biomarkers of Antidepressant Behavioral Effects After Subanesthetic Ketamine and Medial Prefrontal Cortex Deep Brain Stimulation Treatment
Authors: Bergosh Matthew , Medvidovic Sasha , Zepeda Nancy , Crown Lindsey , Ipe Jennifer , Debattista Lauren , Romero Luis , Amjadi Eimon , Lam Tian , Hakopian Erik , Choi Wooseong , Wu Kevin , Lo Yu Tung Jack , Lee Darrin Jason 
Published: October 2023

1AbstractKetamine and medial prefrontal cortex (mPFC) deep brain stimulation (DBS) are emerging depression treatments, however their mechanisms and efficacy biomarkers have not been established. This study investigates immediate and long-term mPFC electrophysiological correlates of their antidepressant effects, and explores the effects of combinatorial treatment. Local field potential electrodes were implanted into the mPFC of male Sprague Dawley rats, then corticosterone was administered for 21 days, except in the control group (n = 8). In the last week of depression induction, the remaining groups received mPFC DBS (n = 8), ketamine (n = 9), both (n = 9), or neither (n = 8). All groups then performed a behavioral assay. We found that DBS treatment immediately suppressed relative low gamma power and improved cognition in the long-term, which correlated with rescued apathy-like behavior in the Groom Test (GT). In contrast, ketamine treatment suppressed sample entropy in the long-term, which correlated with its immediate decrease in sample entropy as well as rescued GT behavior. In the combinatorial group these changes were inhibited, which correlated with a failure to fully rescue GT behavior. Despair-like behavior in the Forced Swim Test was rescued by all three treatments, which correlated with increased relative high frequency oscillation (HFO) power immediately after ketamine and combinatorial treatment. Our findings support the utility of low gamma and HFO power, sample entropy, and cognitive tests in the search for mechanisms and biomarkers of depression and novel treatments.2Significance StatementThere is growing interest in psychedelic pharmacological agents, such as ketamine, and direct neurostimulation techniques, like deep brain stimulation, as treatments for depression. However, their mechanisms are poorly understood, particularly those underlying their sustained benefits. Our study addresses this by correlating behavioral rescue with immediate and long-term changes in the function of the medial prefrontal cortex. These antidepressant correlates may represent therapeutically relevant functional changes, and therefore also have potential as biomarkers. Clinically, such biomarkers enable predicting and monitoring of treatment efficacy, and thereby contribute to the personalization of care. In research, utilizing these translatable biomarkers enhances the etiological validity of disease models, and enables the development of more targeted, next-generation treatment strategies.
Negative Binomial Mixture Model for Identification of Noise in Antigen-Specificity Predictions by LIBRA-seq
Authors: Wasdin Perry T. , Abu-Shmais Alexandra A. , Irvin Michael W. , Vukovich Matthew J. , Georgiev Ivelin S. 
Published: October 2023

Structured AbstractMotivationLIBRA-seq (linking B cell receptor to antigen specificity by sequencing) provides a powerful tool for interrogating the antigen-specific B cell compartment and identifying antibodies against antigen targets of interest. Identification of noise in LIBRA-seq antigen count data is critical for improving antigen binding predictions for downstream applications including antibody discovery and machine learning technologies.ResultsIn this study, we present a method for denoising LIBRA-seq data by clustering antigen counts into signal and noise components with a negative binomial mixture model. This approach leverages the VRC01 negative control cells included in a recent LIBRA-seq study(Abu-Shmaiset al.) to provide a data-driven means for identification of technical noise. We apply this method to a dataset of nine donors representing separate LIBRA-seq experiments and show that our approach provides improved predictions for in vitro antibody-antigen binding when compared to the standard scoring method used in LIBRA-seq, despite variance in data size and noise structure across samples. This development will improve the ability of LIBRA-seq to identify antigen-specific B cells and contribute to providing more reliable datasets for future machine learning based approaches to predicting antibody-antigen binding as the corpus of LIBRA-seq data continues to grow.Availability and ImplementationJupyter notebooks detailing model fitting and figure generation in Python are available athttps://github.com/perrywasdin/mixture_model_denoising.ContactEmail:Ivelin.Georgiev@Vanderbilt.eduSupplementary InformationSupplementary figures are provided in the attached PDF.
Conscious and unconscious perception of errors in auditory feedback during vocalization: Behavioral functions and event-related potential correlates
Authors: Suchý Daniel , Behroozmand Roozbeh , Railo Henry 
Published: October 2023

AbstractDuring vocalization, errors in the auditory feedback are processed rapidly and automatically, suggesting that feedback control of vocalization operates unconsciously. Humans are also able to consciously detect errors in their auditory feedback during vocalization, but the question whether consciousness modulates speech feedback control remains little studied. To address this question, we concurrently measured behavioral vocal responses and electroencephalography (EEG) in 30 participants while their online auditory feedback was altered using individually calibrated threshold-level pitch-shift perturbations (i.e., errors). Following each vocalization trial, participants rated if they consciously detected pitch errors in their auditory feedback. We analyzed the data on a trial-by-trial basis to test if vocal responses to pitch perturbations are modulated by conscious perception. Our results revealed that even on trials where participants reported not noticing the perturbation at all, a vocal compensation to the altered auditory feedback was generated. Conscious error detection was associated with increased magnitude of vocal responses roughly 500-700 ms after the altered feedback compared to the unconscious trials. Conscious detection of the altered feedback correlated with early (Auditory awareness negativity) and late (Late positivity) neural activity responses as indexed by the modulation of event-related potentials (ERPs). Source localization of ERP responses suggested that conscious error detection was attributed to increased neural activity within the temporal, frontal and parietal cortical networks known to be involved in speech motor control. These findings emphasize the importance of investigating the role of higher-level conscious processing mechanisms in regulating speech feedback control, and their effect on the underlying neural and behavioral functions.
Recommendations For a Standardized Approach to Histopathologic Evaluation of Synovial Membrane in Murine Models of Experimental Osteoarthritis
Authors: Obeidat Alia M , Kim Sung Yeon , Burt Kevin G , Hu Baofeng , Li Jun , Ishihara Shingo , Xiao Rui , Miller Rachel E , Little Christopher , Malfait Anne-Marie , Scanzello Carla R 
Published: October 2023

ABSTRACTBackgroundSynovial pathology has been linked to osteoarthritis (OA) pain in patients. Microscopic grading systems for synovial changes in human OA have been described, but a standardized approach for murine models of OA is needed. We sought to develop a reproducible approach and set of minimum recommendations for synovial histopathology in mouse models of OA.MethodsCoronal and sagittal sections from male mouse knee joints subjected to destabilization of medial meniscus (DMM) or partial meniscectomy (PMX) were collected as part of other studies. Stains included Hematoxylin and Eosin (H&E), Toluidine Blue (T- Blue) and Safranin O/Fast Green (Saf-O). Four blinded readers graded pathological features (hyperplasia, cellularity, and fibrosis) at specific anatomic locations in the medial and lateral compartments. Inter-reader reliability of each feature was determined.ResultsThere was acceptable to very good agreement between raters. After DMM, increased hyperplasia and cellularity and a trend towards increased fibrosis were observed 6 weeks after DMM in the medial locations, and persisted up to 16 weeks. In the PMX model, cellularity and hyperplasia were evident in both medial and lateral compartments while fibrotic changes were largely seen on the medial side. Synovial changes were consistent from section to section in the mid-joint area mice. H&E, T-blue, and Saf-O stains resulted in comparable reliability.ConclusionsTo allow for a standard evaluation that can be implemented and compared across labs and studies, we recommend using 3 readers to evaluate a minimum set of 3 pathological features at standardized anatomic areas. Pre-defining areas to be scored, and reliability for each pathologic feature should be considered.
Evolution of novel sensory organs in fish with legs
Authors: Allard Corey AH , Herbert Amy L , Krueger Stephanie P , Liang Qiaoyi , Walsh Brittany L , Rhyne Andrew L , Gourlay Allex N , Seminara Agnese , Baldwin Maude W , Kingsley David M , Bellono Nicholas W 
Published: October 2023

SummaryHow do animals evolve new traits? Sea robins are unusual “walking” fishes that use leg-like appendages to navigate the seafloor. Here, we show that legs arebona fidesense organs that mediate the unique ability to localize and uncover buried prey. We then probe the developmental and physiological basis of these novel sense organs as a striking example of a major trait gain in evolution. We find certain sea robin species have legs with unique end-organs called papillae that mediate enhanced mechanical and chemical sensitivity to enable predatory digging behavior. Papillae exhibit dense innervation from touch-sensitive neurons, noncanonical epithelial taste receptors, and chemical sensitivity that drives predatory digging behavior. Using a combination of developmental analyses, crosses between species with and without papillae, and interspecies comparisons of sea robins from around the world, we demonstrate that papillae represent a key evolutionary innovation associated with behavioral niche expansion on the seafloor. These discoveries provide a conceptual framework for understanding how molecular, cellular, and tissue-scale adaptations integrate to produce novel organismic traits and behavior.