bluuebunny/crossref_metadata_2025_split huggingface dataset:
NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice
Authors: Fotio Yannick , Mabou Tagne Alex , Squire Erica , Lee Hye-lim , Phillips Connor M. , Chang Kayla , Ahmed Faizy , Greenberg Andrew S. , Villalta S. Armando , Scarfone Vanessa M. , Spadoni Gilberto , Mor Marco , Piomelli Daniele 
Published: February 2024

AbstractCirculating monocytes participate in pain chronification but the molecular events that cause their deployment are unclear. Using a mouse model of hyperalgesic priming (HP), we show that monocytes enable progression to pain chronicity through a mechanism that requires transient activation of the hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting NAAA in the 72 hours following administration of a priming stimulus prevented HP. This effect was phenocopied by NAAA deletion and depended on PPAR-α recruitment. Mice lacking NAAA in CD11b+ cells – monocytes, macrophages, and neutrophils – were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. Depletion of monocytes, but not resident macrophages, generated mice that were refractory to HP. The results identify NAAA-regulated signaling in monocytes as a control node in the induction of HP and, potentially, the transition to pain chronicity.
How probiotics, prebiotics, synbiotics, and postbiotics prevent dental caries: an oral microbiota perspective
Authors: Luo Si-Chen , Wei Si-Min , Luo Xin-Tao , Yang Qiong-Qiong , Wong Ka-Hing , Cheung Peter C. K. , Zhang Bo-Bo 
Published: February 2024

AbstractDental caries, a highly prevalent oral disease, impacts a significant portion of the global population. Conventional approaches that indiscriminately eradicate microbes disrupt the natural equilibrium of the oral microbiota. In contrast, biointervention strategies aim to restore this balance by introducing beneficial microorganisms or inhibiting cariogenic ones. Over the past three decades, microbial preparations have garnered considerable attention in dental research for the prevention and treatment of dental caries. However, unlike related pathologies in the gastrointestinal, vaginal, and respiratory tracts, dental caries occurs on hard tissues such as tooth enamel and is closely associated with localized acid overproduction facilitated by cariogenic biofilms. Therefore, it is insufficient to rely solely on previous mechanisms to delineate the role of microbial preparations in the oral cavity. A more comprehensive perspective should involve considering the concepts of cariogenic biofilms. This review elucidates the latest research progress, mechanisms of action, challenges, and future research directions regarding probiotics, prebiotics, synbiotics, and postbiotics for the prevention and treatment of dental caries, taking into account the unique pathogenic mechanisms of dental caries. With an enhanced understanding of oral microbiota, personalized microbial therapy will emerge as a critical future research trend.
Synaptic loss and its association with symptom severity in Parkinson’s disease
Authors: Holmes Sophie E. , Honhar Praveen , Tinaz Sule , Naganawa Mika , Hilmer Ansel T. , Gallezot Jean-Dominique , Dias Mark , Yang Yanghong , Toyonaga Takuya , Esterlis Irina , Mecca Adam , Van Dyck Christopher , Henry Shannan , Ropchan Jim , Nabulsi Nabeel , Louis Elan D. , Comley Robert , Finnema Sjoerd J. , Carson Richard E. , Matuskey David 
Published: February 2024

AbstractParkinson’s disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [11C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain. We also examined a measure of relative brain perfusion from the early part of the same PET scan. Our results provide evidence for synaptic density loss in the substantia nigra that had been previously reported, but also extend this to other early-Braak stage regions known to be affected in PD (brainstem, caudate, olfactory cortex). Importantly, we also found a direct association between synaptic density loss in the nigra and severity of symptoms in patients. A greater extent and wider distribution of synaptic density loss in PD patients with longer illness duration suggests that [11C]UCB-J PET can be used to measure synapse loss with disease progression. We also demonstrate lower brain perfusion in PD vs. HC groups, with a greater extent of abnormalities in those with longer duration of illness, suggesting that [11C]UCB-J PET can simultaneously provide information on changes in brain perfusion. These results implicate synaptic imaging as a useful PD biomarker for future disease-modifying interventions.
A history of avoidance does not impact extinction learning in male rats
Authors: López-Moraga Alba , Luyten Laura , Beckers Tom 
Published: February 2024

AbstractPervasive avoidance is one of the central symptoms of all anxiety-related disorders. In treatment, avoidance behaviors are typically discouraged because they are assumed to maintain anxiety. Yet, it is not clear if engaging in avoidance is always detrimental. In this study, we used a platform-mediated avoidance task to investigate the influence of avoidance history on extinction learning in male rats. Our results show that having the opportunity to avoid during fear acquisition training does not significantly influence the extinction of auditory-cued fear in rats subjected to this platform-mediated avoidance procedure, which constitutes a realistic approach/avoidance conflict. This holds true irrespective of whether or not avoidance was possible during the extinction phase. This suggests that imposing a realistic cost on avoidance behavior prevents the adverse effects that avoidance has been claimed to have on extinction. However, avoidance does not appear to have clear positive effects on extinction learning nor on retention either.
Remote Sensing-Based Extension of GRDC Discharge Time Series - A Monthly Product with Uncertainty Estimates
Authors: Elmi Omid , Tourian Mohammad J. , Saemian Peyman , Sneeuw Nico 
Published: February 2024

AbstractThe Global Runoff Data Center (GRDC) data set has faced a decline in the number of active gauges since the 1980s, leaving only 14% of gauges active as of 2020. We develop the Remote Sensing-based Extension for the GRDC (RSEG) data set that can ingest legacy gauge discharge and remote sensing observations. We employ a stochastic nonparametric mapping algorithm to extend the monthly discharge time series for inactive GRDC stations, benefiting from satellite imagery- and altimetry-derived river width and water height observations. After a rigorous quality assessment of our estimated discharge, involving statistical validation, tests and visual inspection, results in the extension of discharge records for 3377 out of 6015 GRDC stations. The quality of discharge estimates for the rivers with a large or medium mean discharge is quite satisfactory (average KGE value > 0.5) however for river reaches with a low mean discharge the average KGE value drops to 0.33.The RSEG data set regains monitoring capability for 83% of total river discharge measured by GRDC stations, equivalent to 7895 km3/month.
Ocular microvascular alteration in patients with myocardial infarction—a new OCTA study
Authors: Wu Jun-Yi , Hu Jin-Yu , Ge Qian-Min , Xu San-Hua , Zou Jie , Kang Min , Ying Ping , Wei Hong , Ling Qian , He Liang-Qi , Chen Cheng , Shao Yi 
Published: February 2024

AbstractMyocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.
In vivo imaging of cathepsin B in activated glia in the brain after orofacial formalin test
Authors: McIlwrath Sabrina L. , Carroll-Portillo Amanda C. , Lin Henry C. , Westlund Karin N. 
Published: February 2024

AbstractPURPOSE Cathepsin B (Cat B) is a cysteine lysosomal protease that is upregulated in many inflammatory diseases and widely expressed in the brain. Here, we used a Cat B activatable near-infrared (NIR) imaging probe to measure glial activation in vivo in the formalin test, a standard orofacial inflammatory pain model. The probe’s efficacy was quantified with immunohistochemical analysis of the somatosensory cortex. PROCEDURES Three different concentrations of Cat B imaging probe (30, 50, 100 pmol/200 g bodyweight) were injected intracisternally into the foramen magnum of rats under anesthesia. Four hours later formalin (1.5%, 50 μl) was injected into the upper lip and the animal’s behaviors recorded for 45 min. Subsequently, animals were repeatedly scanned using the IVIS Spectrum (8, 10, and 28 h post imaging probe injection) to measure extracellular Cat B activity. Aldehyde fixed brain sections were immunostained with antibodies against microglial marker Iba1 or astrocytic GFAP and detected with fluorescently labeled secondary antibodies to quantify co-localization with the fluorescent probe. RESULTS The Cat B imaging probe only slightly altered the formalin test results. Nocifensive behavior was only reduced in phase 1 in the 100 pmol group. In vivo measured fluorescence efficiency was highest in the 100 pmol group 28 h post imaging probe injection. Post-mortem immunohistochemical analysis of the somatosensory cortex detected the greatest amount of NIR fluorescence localized on microglia and astrocytes in the 100 pmol imaging probe group. Sensory neuron neuropeptide and cell injury marker expression in ipsilateral trigeminal ganglia was not altered by the presence of fluorescent probe. CONCLUSIONS These data demonstrate a concentration- and time-dependent visualization of extracellular Cat B in activated glia in the formalin test using a NIR imaging probe. Intracisternal injections are well suited for extracellular CNS proteinase detection in conditions when the blood–brain barrier is intact.
Alcohol consumption as a socially contagious phenomenon in the Framingham Heart Study social network
Authors: van den Ende Maarten W. J. , van der Maas Han L. J. , Epskamp Sacha , Lees Mike H. 
Published: February 2024

AbstractWe use longitudinal social network data from the Framingham Heart Study to examine the extent to which alcohol consumption is influenced by the network structure. We assess the spread of alcohol use in a three-state SIS-type model, classifying individuals as abstainers, moderate drinkers, and heavy drinkers. We find that the use of three-states improves on the more canonical two-state classification, as the data show that all three states are highly stable and have different social dynamics. We show that when modelling the spread of alcohol use, it is important to model the topology of social interactions by incorporating the network structure. The population is not homogeneously mixed, and clustering is high with abstainers and heavy drinkers. We find that both abstainers and heavy drinkers have a strong influence on their social environment; for every heavy drinker and abstainer connection, the probability of a moderate drinker adopting their drinking behaviour increases by $$40\%$$

40
%

and $$18\%$$

18
%

, respectively. We also find that abstinent connections have a significant positive effect on heavy drinkers quitting drinking. Using simulations, we find that while both are effective, increasing the influence of abstainers appears to be the more effective intervention compared to reducing the influence of heavy drinkers.
Development of a CD8+ T cell associated signature for predicting the prognosis and immunological characteristics of gastric cancer by integrating single-cell and bulk RNA-sequencing
Authors: Li Jianxin , Han Ting , Wang Xin , Wang Yinchun , Yang Rui , Yang Qingqiang 
Published: February 2024

AbstractThe universally poor clinical outcome makes gastric cancer (GC) still a significant public health threat, the main goal of our research is to develop a prognostic signature that can forecast the outcomes and immunological characteristics of GC via integrating single-cell and bulk RNA-sequencing. The CD8+ T cell feature genes were screened out by exploring single-cell RNA-sequencing (scRNA-seq) profiles retrieved from the TISCH2 database. Then, Cox and LASSO regressions were exploited for constructing a prognostic model in TCGA cohort based on these CD8+ T cell feature genes. Survival analysis was conducted to investigate the predictive capability of the signature for the clinical outcome of GC patients in TCGA and GEO cohorts. Additionally, we further examined the correlations between the risk signature and tumor immunotherapeutic response from the perspectives of immune infiltration, tumor mutation burden (TMB), immune checkpoint biomarker (ICB) expression, tumor microenvironment (TME), microsatellite instability (MSI), TIDE, and TCIA scores. In total, 703 CD8+ T cell feature genes were identified, eight of which were selected for constructing a prognostic signature. GC patients who possess high-risk score had significantly poorer survival outcomes than those who possess low-risk score in TCGA and GEO cohorts. Immune infiltration analysis proved that the risk score was negatively connected with the infiltration abundance of CD8+ T cells. Then, our findings demonstrated that GC patients in the high-risk subgroup possess a higher proportion of MSI-L/MSS, lower immune checkpoint biomarker expression, lower TMB, higher TIDE scores and lower TCIA scores compared to those in the low-risk subgroup. What’s more, immunotherapy cohort analysis confirmed that patients who possess high-risk score are not sensitive to anti-cancer immunotherapy. Our study developed a reliable prognostic signature for GC that was significantly correlated with the immune landscape and immunotherapeutic responsiveness. The risk signature may guide clinicians to adopt more accurate and personalized treatment strategies for GC patients.
Hippocampal volume changes after (R,S)-ketamine administration in patients with major depressive disorder and healthy volunteers
Authors: Evans Jennifer W. , Graves Morgan C. , Nugent Allison C. , Zarate Carlos A. 
Published: February 2024

AbstractThe hippocampus and amygdala have been implicated in the pathophysiology and treatment of major depressive disorder (MDD). Preclinical models suggest that stress-related changes in these regions can be reversed by antidepressants, including ketamine. Clinical studies have identified reduced volumes in MDD that are thought to be potentiated by early life stress and worsened by repeated depressive episodes. This study used 3T and 7T structural magnetic resonance imaging data to examine longitudinal changes in hippocampal and amygdalar subfield volumes associated with ketamine treatment. Data were drawn from a previous double-blind, placebo-controlled, crossover trial of healthy volunteers (HVs) unmedicated individuals with treatment-resistant depression (TRD) (3T: 18 HV, 26 TRD, 7T: 17 HV, 30 TRD) who were scanned at baseline and twice following either a 40 min IV ketamine (0.5 mg/kg) or saline infusion (acute: 1–2 days, interim: 9–10 days post infusion). No baseline differences were noted between the two groups. At 10 days post-infusion, a slight increase was observed between ketamine and placebo scans in whole left amygdalar volume in individuals with TRD. No other differences were found between individuals with TRD and HVs at either field strength. These findings shed light on the timing of ketamine’s effects on cortical structures.
Spectrofluorimetric determination of butylated hydroxytoluene and butylated hydroxyanisole in their combined formulation: application to butylated hydroxyanisole residual analysis in milk and butter
Authors: Galal Sara Abdel Basset , Elzanfaly Eman Saad , Hussien Emad Mohamed , Amer Enas Abdel Hakim , Zaazaa Hala Elsayed 
Published: February 2024

AbstractButylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) are two antioxidants that have been extensively used in many applications. Both are well known for their debatable health risks due to their multiple intake sources. Therefore, conservative limits are set for them in different regulations adapted to the matrices in which they exist. Here we present a simple spectrofluorimetric method for the determination of BHT and BHA based on their native fluorescence and synchronous scanning mode. The type of solvent and the interval between emission and excitation wavelengths were carefully optimized. Under the optimized conditions, good linearities were obtained between the emission intensity and the corresponding concentrations of BHT and BHA over the range of 3–18 µg/mL and 0.1–7 µg/mL, respectively with a good correlation coefficient (r > 0.99). The limits of detection were 0.9 and 0.02 µg/mL, and the quantification limits were 3 and 0.05 µg/mL for BHT and BHA, respectively. The suggested procedure was validated according to ICH guidelines Q2 (R1). Furthermore, the method’s greenness was assessed by three different methods, and it proved to be eco-reasonable. The method was successfully applied to the determination of BHT and BHA in pharmaceutical formulations. We also applied the suggested method for monitoring the residual BHA in conventional, powdered milk and butter, with good recovery in spiked samples.
Fibroblast mediated dynamics in diffusively uncoupled myocytes: a simulation study using 2-cell motifs
Authors: Sridhar S. , Clayton Richard H. 
Published: February 2024

AbstractIn healthy hearts myocytes are typically coupled to nearest neighbours through gap junctions. Under pathological conditions such as fibrosis, or in scar tissue, or across ablation lines myocytes can uncouple from their neighbours. Electrical conduction may still occur via fibroblasts that not only couple proximal myocytes but can also couple otherwise unconnected regions. We hypothesise that such coupling can alter conduction between myocytes via introduction of delays or by initiation of premature stimuli that can potentially result in reentry or conduction blocks. To test this hypothesis we have developed several 2-cell motifs and investigated the effect of fibroblast mediated electrical coupling between uncoupled myocytes. We have identified various regimes of myocyte behaviour that depend on the strength of gap-junctional conductance, connection topology, and parameters of the myocyte and fibroblast models. These motifs are useful in developing a mechanistic understanding of long-distance coupling on myocyte dynamics and enable the characterisation of interaction between different features such as myocyte and fibroblast properties, coupling strengths and pacing period. They are computationally inexpensive and allow for incorporation of spatial effects such as conduction velocity. They provide a framework for constructing scar tissue boundaries and enable linking of cellular level interactions with scar induced arrhythmia.
Splenectomy has opposite effects on the growth of primary compared with metastatic tumors in a murine colon cancer model
Authors: Kaneko Yuki , Miyato Hideyo , Tojo Mineyuki , Futoh Yurie , Takahashi Kazuya , Kimura Yuki , Saito Akira , Ohzawa Hideyuki , Yamaguchi Hironori , Sata Naohiro , Kitayama Joji , Hosoya Yoshinori 
Published: February 2024

AbstractThe spleen is a key source of circulating and tumor-infiltrating immune cells. However, the effect of splenectomy on tumor growth remains unclear. At 3 weeks after splenectomy, we subcutaneously injected LuM1 cells into BALB/c mice and evaluated the growth of primary tumors and lung metastases at 4 weeks after tumor inoculation. In addition, we examined the phenotypes of immune cells in peripheral blood by using flow cytometry and in tumor tissue by using multiplex immunohistochemistry. The growth of primary tumors was reduced in splenectomized mice compared with the sham-operated group. Conversely, splenectomized mice had more lung metastases. Splenectomized mice had fewer CD11b+cells, especially monocytic MDSCs (CD11b+Gr-1neg-lowLy6chigh), and NK cells (CD49b+CD335+). The proportion of NK cells was inversely correlated with the number of lung metastases. In splenectomized mice, the density of CD3+ and granzyme B+ CD8+ T cells was increased, with fewer M2-type macrophages in primary tumors, but NK cells were decreased markedly in lung. Splenectomy concurrently enhances T cell-mediated acquired immunity by reducing the number of monocytic MDSCs and suppresses innate immunity by decreasing the number of NK cells. Splenectomy has opposite effects on primary and metastatic lesions through differential regulation on these two immune systems.