Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined Intrinsic Local Functional Connectivity With Multivariate Pattern Analysis to Identify Depressed Essential Tremor

Background Although depression is one of the most common neuropsychiatric symptoms in essential tremor (ET), the diagnosis biomarker and intrinsic brain activity remain unclear. We aimed to combine multivariate pattern analysis (MVPA) with local brain functional connectivity to identify depressed ET. Methods Based on individual voxel-level local brain functional connectivity (regional homogeneity, ReHo) mapping from 41 depressed ET, 43 non-depressed ET, and 45 healthy controls (HCs), the binary support vector machine (BSVM) and multiclass Gaussian Process Classification (MGPC) algorithms were used to identify depressed ET patients from non-depressed ET and HCs, the accuracy and permutations test were used to assess the classification performance. Results The MGPC algorithm was able to classify the three groups (depressed ET, non-depressed ET, and HCs) with a total accuracy of 84.5%. The BSVM algorithm achieved a better classification performance with total accuracy of 90.7, 88.64, and 90.48% for depressed ET vs. HCs, non-depressed ET vs. HCs, and depressed ET vs. non-depressed ET, and the sensitivity for them at 80.49, 76.64, and 80.49%, respectively. The significant discriminative features of depressed ET vs. HCs were primarily located in the cerebellar-motor-prefrontal gyrus-anterior cingulate cortex pathway, and for depressed ET vs. non-depressed ET located in the cerebellar-prefrontal gyrus-anterior cingulate cortex circuits. The partial correlation showed that the ReHo values in the bilateral middle prefrontal gyrus (positive) and the bilateral cerebellum XI (negative) were significantly correlated with clinical depression severity. Conclusion Our findings suggested that combined individual ReHo maps with MVPA not only could be used to identify depressed ET but also help to reveal the intrinsic brain activity changes and further act as the potential diagnosis biomarker in depressed ET patients.
Effectiveness of Transcranial Direct Current Stimulation and Monoclonal Antibodies Acting on the CGRP as a Combined Treatment for Migraine (TACTIC): Protocol for a Randomized, Double-Blind, Sham-Controlled Trial

Background Migraine is a recurrent headache disorder that has a still unclear pathophysiology, involving several circuits of both the central and peripheral nervous system. Monoclonal antibodies acting on the calcitonin gene-related (CGRP) pathway (CGRP-MAbs) are the first drugs specifically designed for migraine; those drugs act peripherally on the trigeminal ganglion without entering the blood-brain barrier. Conversely, neuromodulation techniques such as transcranial direct current stimulation (tDCS) act centrally by increasing or decreasing the neuronal firing rate of brain cortical areas. The aim of the study will be to evaluate whether tDCS, in addition to CGRP-MAbs, is an effective add-on treatment in reducing headache frequency, intensity and acute medication use in patients with migraine. To demonstrate the biological effects of tDCS, the electroencephalographic (EEG) power changes after tDCS will be assessed. Methods We will include patients with migraine on treatment with CGRP-MAbs and reporting ≥8 monthly migraine days. During a prospective 28-day baseline period, patients will fill in a headache diary and questionnaires to evaluate migraine-related disability, anxiety and depressive symptoms, sleep quality, and health-related quality of life. Subjects will be randomly assigned in a 1:1 ratio to active or sham tDCS. The stimulation protocol will consist in five daily sessions, the cathodes will be applied bilaterally above the occipital areas, with the reference anode electrodes positioned above the primary motor areas. Before the first, and immediately after the last stimulation session, patients will perform a 10-min resting EEG recording. During a 28-day follow-up period following tDCS, patients will have to fill in a headache diary and questionnaires identical to those of the baseline period. Discussion This trial will evaluate the efficacy of an add-on treatment acting on the brain in patients with migraine, who are already treated with peripherally acting drugs, showing how tDCS acts in restoring the dysfunctional brain networks typical of the migraine patient. Clinical Trial Registration NCT05161871.
Transcutaneous Electrical Cranial-Auricular Acupoint Stimulation vs. Escitalopram for Patients With Mild-to-Moderate Depression (TECAS): Study Design for a Randomized Controlled, Non-inferiority Trial

Background Previous studies in animals and humans indicated that transcutaneous vagus nerve stimulation (tVNS) and transcutaneous electrical acupoint stimulation (TEAS) on trigeminal nerve-innervated forehead acupoints can relief the symptoms of depression. However, due to the limited investigations on these two interventions, more research are needed to confirm their efficacy in depression. To improve the efficacy of the single treatment, we combined two treatments and created a novel non-invasive stimulation, transcutaneous electrical cranial-auricular acupoint stimulation (TECAS). To assess the efficacy and safety of TECAS, we compare it with a selective serotonin reuptake inhibitor (SSRI), escitalopram, for the treatment of depression. Methods/Design This is a multi-center, non-inferiority, randomized controlled trial that will involve 470 patients with mild to moderate depression. Patients will be randomly assigned to either the TECAS group or the escitalopram group in a 1:1 ratio. The TEAS group will receive two sessions of treatments per day for 8 consecutive weeks, and the escitalopram group will receive 8 weeks of oral escitalopram tablets prescribed by clinical psychiatrists as appropriate for their condition. The primary outcome is the clinical response as determined by Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week 8, with −10% as the non-inferior margin. The secondary outcomes include the response rate determined by 17-item Hamilton Depression Rating Scale (HAMD-17), remission rate, changes from baseline in the scores on the MADRS, the HAMD-17, the Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Short Form 36 Health Survey (SF-36). Discussion This will be the first randomized controlled trial to compare the efficacy of TECAS with escitalopram for depression. If effective, this novel intervention could have significant clinical and research implications for patients with depression. Clinical Trial Registration [ClinicalTrials.gov], identifier [NCT03909217].
Eosinophilic Granulomatosis With Polyangiitis Presenting With Oral Granuloma as the Initial Symptom: A Case Report

Antineutrophil cytoplasmic antibody associated vasculitis includes granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis. While EGPA has no specific symptoms, it usually presents as necrotizing vasculitis, eosinophil infiltration of the tissues and organs, and extravascular granuloma formation. Here, we report a patient who had a rare initial presentation of oral granuloma and had been previously misdiagnosed several times at other hospitals. He was finally diagnosed with EGPA and recovered after methylprednisolone and cyclophosphamide treatment. The disease EGPA can present with a rare initial presentation of oral granuloma, methylprednisolone, and cyclophosphamide can be a suitable choice of treatment.
Efficacy and Mechanism of Moxibustion Treatment on Mild Cognitive Impairment Patients: An fMRI Study Using ALFF

Background Mild Cognitive Impairment (MCI), as a high risk of Alzheimer’s disease (AD), represents a state of cognitive function between normal aging and dementia. Moxibustion may effectively delay the progression of AD, while there is a lack of studies on the treatments in MCI. This study aimed to evaluate the effect of moxibustion treatment revealed by the amplitude of low-frequency fluctuation (ALFF) in MCI. Method We enrolled 30 MCI patients and 30 matched healthy controls (HCs) in this study. We used ALFF to compare the difference between MCI and HCs at baseline and the regulation of spontaneous neural activity in MCI patients by moxibustion. The Mini-Mental State Examination and Montreal Cognitive Assessment scores were used to evaluate cognitive function. Results Compared with HCs, the ALFF values significantly decreased in the right temporal poles: middle temporal gyrus (TPOmid), right inferior temporal gyrus, left middle cingulate gyrus, and increased in the left hippocampus, left middle temporal gyrus, right lingual gyrus, and right middle occipital gyrus in MCI patients. After moxibustion treatment, the ALFF values notably increased in the left precuneus, left thalamus, right temporal poles: middle temporal gyrus, right middle frontal gyrus, right inferior temporal gyrus, right putamen, right hippocampus, and right fusiform gyrus, while decreased in the bilateral lingual gyrus in MCI patients. The Mini-Mental State Examination and Montreal Cognitive Assessment scores increased after moxibustion treatment, and the increase in Mini-Mental State Examination score was positively correlated with the increase of ALFF value in the right TPOmid, the right insula, and the left superior temporal gyrus. Conclusion Moxibustion treatment might improve the cognitive function of MCI patients by modulating the brain activities within the default mode network, visual network, and subcortical network with a trend of increased ALFF values and functional asymmetry of the hippocampus. These results indicate that moxibustion holds great potential in the treatment of MCI.
Associations Between Adult Triceps Skinfold Thickness and All-Cause, Cardiovascular and Cerebrovascular Mortality in NHANES 1999–2010: A Retrospective National Study

Background: The association between triceps skinfold (TSF) thickness and mortality in previous studies was controversial. This study aimed to explore how TSF thickness affects all-cause, cardiovascular, and cerebrovascular mortality among the United States (U.S.) general population. Methods Our research included 25,954 adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Participants were categorized by the baseline TSF quartiles [quartile 1 (Q1): < 11.8, (Q2): 11.8–17.4, (Q3): 17.4–25, and (Q4): ≥25; unit: millimeter (mm)]. Cox regression models were used to assess the association of TSF with all-cause, cardiovascular, and cerebrovascular mortality. The association between mid-arm muscle circumference (MAMC) and mortality was also explored. Subgroup analyses were conducted to assess heterogeneity in different subgroups. Results The highest TSF group (Q4) had the lowest risk to experience all-cause (HR, 0.46; 95% CI, 0.38–0.59; P < 0.001) and cardiovascular mortality (HR, 0.35; 95% CI, 0.23–0.54; P < 0.001) than the lowest TSF group (Q1) after multivariate adjustment. However, there was no relationship between TSF quartiles and cerebrovascular mortality (HR, 0.98; 95%CI, 0.42–2.30; P = 0.97). The protective effects of TSF thickness on mortality still existed after adjusting for BMI and MAMC. For every 1 mm increase in TSF thickness, the risk of all-cause and cardiovascular death decreased by 4% (HR, 0.96; 95% CI, 0.95–0.97; P < 0.001) and 6% (HR, 0.94; 95% CI, 0.93–0.96; P < 0.001), respectively. In the stratified analysis, the relationships between TSF and mortality risk were generally similar across all subgroups. Conclusions Higher TSF thickness was associated with lower all-cause and cardiovascular mortality, independent of BMI and MAMC. Our study revealed that the TSF thickness may be a convenient and credible indicator to predict mortality, especially in those with severe cardiovascular diseases.
Paraventricular Vitamin D Receptors Are Required for Glucose Tolerance in Males but Not Females

When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice’s paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance while female mice are unaffected. Weights were unaltered in both sexes by PVH VDR loss. Additionally, PVH VDR loss did not cause any glucose abnormalities in either sex when the mice were on a chow diet. Utilizing electrophysiology studies, we show PVH VDR loss resulted in decreased baseline firing frequency and resting membrane potential in males, but not females. Additionally, male mice with PVH VDR loss had impaired miniature excitatory postsynaptic currents (mEPSC), while females were unaffected. Interestingly, the PVH neurons of both sexes were activated by exogenous vitamin D (1,25-dihydroxyvitamin D3), an effect dependent upon the VDR. Thus, there is sexual dimorphism, for the actions of the PVH VDR on glucose regulation. PVH VDRs are necessary for normal glucose homeostasis in males but not females and this may be secondary to actions of the VDR on neuronal activity.
Altered White Matter Integrity at Illness Onset in Adolescents With a First Episode of Psychosis

Background Disruption in white matter integrity has been consistently observed in individuals with psychosis. However, whether such abnormalities are already present at illness onset or are related to downstream processes remains elusive. The study of adolescents with a recent onset of psychosis provides the opportunity to evaluate white matter integrity proximally to disease onset. Methods Twenty-six adolescents (aged 15.9 ± 1.3 years) with a first episode of psychosis (FEP) (less than 6 months duration) were compared with 26 age and sex-matched healthy controls (HC) (16.8 ± 2 years). In participants with a FEP, clinical diagnoses were confirmed after a minimum of 1 year follow-up (main categories: schizophrenia, bipolar disorder, or schizoaffective disorder). Anatomical images and diffusion tensor sequences were acquired using a 1.5T scanner. Whole brain, voxel-wise group differences in fractional anisotropy (FA) were investigated between participants with a FEP and controls. Results Relative to HC, FEP participants displayed decreased FA in the right posterior cingulate gyrus, encompassing the right superior and posterior corona radiata, and the right parahippocampal gyrus, including the cingulum and fornix. FEP patients showed no areas of increased FA relative to HC. The results remained significant after controlling for medication, cannabis use and intelligence. Conclusion Our findings indicate that adolescents with recent onset of psychotic disorders show decreased white matter integrity in circuits implicated in cognitive functions and emotion regulation.
Screen Time and Body Mass Index Among Children and Adolescents: A Systematic Review and Meta-Analysis

Background There is no summative quantitative study that report the difference in BMI in high screen user children and adolescents or give a difference in screen time in children and adolescents with obesity vs. children and adolescents without obesity. In the current meta-analysis we systematically summarized the association between obesity and screen time and meta-analyzed the results. Methods A systematic search from Scopus, PubMed and Embase electronic databases. Studies that evaluated the association between screen time and obesity up to June 2021. Results Results revealed that those at the highest screen time category had 0.7 kg/m2 higher BMI (WMD = 0.703; CI = 0.128, 1.278; P < 0.016; I2 = 95.8%). Moreover, children and adolescents with obesity had a mean value of 0.313 h higher screen time compared with children and adolescents without obesity (WMD: 0.313; OR = 0.219, 0.407; P < 0.001; I2 = 96%). The results of subgrouping showed that study quality, continent and sample size could reduce the heterogeneity values. No evidence of publication bias was reported according to visual asymmetry of funnel plots and the results of Begg’s and Egger’s tests. Conclusion For the first time, the current systematic review and meta-analysis revealed a positive association between screen time and obesity among children and adolescents. Due to the cross-sectional design of the included studies, causal inference is impossible, therefore, further studies in separate analysis of both genders are suggested to better elucidate gender-specific results. Systematic Review Registration [www.ClinicalTrials. gov], identifier [CRD4202123 3899].
A Double-Edged Sword: The Role of Prior Knowledge in Memory Aging

Introduction People accumulate knowledge throughout their lifespan and the accumulated knowledge influences how we encode and retrieve information in memory processing. This study aims to investigate the role of knowledge in associative memory across the adult lifespan, and specifically examines the effects of two material properties that interact with prior knowledge: congruency – whether the material is congruent with people’s prior knowledge, and ambiguity – whether the material is ambiguous to interpret based on prior knowledge. Method 273 participants (aged 22–70 years old) completed an incidental memory task online. Participants were shown pictures depicting an object in a scene and judged if the object was likely or unlikely to be in the particular scene. Later, in the recognition test, participants were asked to identify if the exact picture was presented earlier. The pictures were manipulated to have varying levels of congruency, meaning that some depicted likely object–scene pairs and some unlikely. We also measured how different the likely/unlikely judgment for each object–scene pair was across all participants to determine the ambiguity level of the object–scene pair: some were more likely to receive diverse responses across people, whereas others are unambiguously consistent (or inconsistent) with common knowledge shared by most people. We used mixed-effects logistic regressions to predict memory outcome for each trial as a function of age, age2, congruency/ambiguity, and their interactions. Results The object–scene pairs perceived as congruent had higher hit rates than incongruent ones, as well as higher false alarm rates, especially in middle-aged and older people. Higher ambiguity was also related to both greater true and false memory, independent of age. Finally, the effect of ambiguity only emerged when the object–scene pair was perceived incongruent. Discussion The results suggest that people rely on prior knowledge to process new information and that this reliance improves hit responses, but also induces false memories particularly for middle-aged and older people, suggesting a double-edged role of knowledge in associative memory and its disproportionate influence on memory aging. Over-reliance on knowledge in older adults, which has been suspected in other cognitive processes, may be one of the mechanisms underlying associative memory decrease in aging.
Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

Macrophages belong to a special phagocytic subgroup of human leukocytes and are one of the important cells of the human immune system. Small noncoding RNAs are a group of small RNA molecules that can be transcribed without the ability to encode proteins but could play a specific function in cells. SncRNAs mainly include microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs) and repeat RNAs. We used high-throughput sequencing analysis and qPCR to detect the expression changes of the small noncoding RNAome during macrophage polarization. Our results showed that 84 miRNAs and 47 miRNAs with were downregulated during M1 macrophage polarization and that 11 miRNAs were upregulated and 19 miRNAs were downregulated during M2 macrophage polarization. MiR-novel-3-nature and miR-27b-5p could promote expression of TNF-α which was marker gene of M1 macrophages. The piRNA analysis results showed that 69 piRNAs were upregulated and 61 piRNAs were downregulated during M1 macrophage polarization and that 3 piRNAs were upregulated and 10 piRNAs were downregulated during M2 macrophage polarization. DQ551351 and DQ551308 could promote the mRNA expression of TNF-α and DQ551351overexpression promoted the antitumor activity of M1 macrophages. SnoRNA results showed that 62 snoRNAs were upregulated and 59 snoRNAs were downregulated during M1 macrophage polarization, whereas 6 snoRNAs were upregulated and 10 snoRNAs were downregulated during M2 macrophage polarization. Overexpression of snoRNA ENSMUST00000158683.2 could inhibit expression of TNF-α. For snRNA, we found that 12 snRNAs were upregulated and 15 snRNAs were downregulated during M1 macrophage polarization and that 2 snRNAs were upregulated during M2 macrophage polarization. ENSMUSG00000096786 could promote expression of IL-1 and iNOS and ENSMUSG00000096786 overexpression promoted the antitumor activity of M1 macrophages. Analysis of repeat RNAs showed that 7 repeat RNAs were upregulated and 9 repeat RNAs were downregulated during M1 macrophage polarization and that 2 repeat RNAs were downregulated during M2 macrophage polarization. We first reported the expression changes of piRNA, snoRNA, snRNA and repeat RNA during macrophage polarization, and preliminarily confirmed that piRNA, snoRNA and snRNA can regulate the function of macrophages.
Site-Specific Regulation of Stress Responses Along the Rostrocaudal Axis of the Insular Cortex in Rats

The insular cortex (IC) has been described as a part of the central network implicated in the integration and processing of limbic information, being related to the behavioral and physiological responses to stressful events. Besides, a site-specific control of physiological functions has been reported along the rostrocaudal axis of the IC. However, a functional topography of the IC in the regulation of stress responses has never been reported. Therefore, this study aimed to investigate the impact of acute restraint stress in neuronal activation at different sites along the rostrocaudal axis of the IC. Furthermore, we evaluated the involvement of IC rostrocaudal subregions in the cardiovascular responses to acute restraint stress. We observed that an acute session of restraint stress increased the number of Fos-immunoreactive cells in the rostral posterior region of the IC, while fewer activated cells were identified in the anterior and caudal posterior regions. Bilateral injection of the non-selective synaptic inhibitor CoCl2 into the anterior region of the IC did not affect the blood pressure and heart rate increases and the sympathetically mediated cutaneous vasoconstriction to acute restraint stress. However, synaptic ablation of the rostral posterior IC decreased the restraint-evoked arterial pressure increase, whereas tachycardia was reduced in animals in which the caudal posterior IC was inhibited. Taken together, these pieces of evidence indicate a site-specific regulation of cardiovascular stress response along the rostrocaudal axis of the IC.