Miracle-dz/UniFAR-FTUs huggingface dataset:
Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine

Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave of neuronal and glial depolarization originating in the occipital cortex, followed by temporary neuronal silencing. During a migraine attack, increased expression of inflammatory mediators, along with a decrease in the expression of anti-inflammatory genes, have been observed. The aim of this study was to evaluate the expression of inflammatory genes, in particular that of IL-1 receptor antagonist (IL-1RN), following CSD in a mouse model of familial hemiplegic migraine type 1 (FHM-1). We show here that the expression of IL-1RN was upregulated after the CSD, suggesting a possible attempt to modulate the inflammatory response. This study allows researchers to better understand the development of the disease and aids in the search for new therapeutic strategies in migraine.
Long‐term successful treatment of chronic inflammatory demyelinating polyneuropathy‐like polyneuropathy induced by levodopa‐carbidopa intestinal gel with intravenous immunoglobulin

Polyneuropathy (PNP) can develop in approximately 4.1% of patients treated with levodopa-carbidopa intestinal gel (LCIG)[1]. Almost all of these patients suffer from mild, chronic, progressive, axonal, predominantly sensory PNP, and only a few cases with acute-subacute demyelinating neuropathy resistant to immuno-modulatory treatments have been reported thus far[2-4]. However, a recent review recommended to consider these neuropathies axonal because they did not meet the electrodiagnostic criteria for demyelination[1]. Consequently, this may be the first report of a real LCIG-induced demyelinating PNP. This article is protected by copyright. All rights reserved.
Optogenetic stimulation of serotonin nuclei retrieve the lost memory in Alzheimer's disease

How are memories stored and retrieved? It was one of the most discussed questions in the past century by neuroscientists. Leading studies of the period brought two different explanations to this question: The first statement considers memory as a physiological change in the brain and suggest that the retrieval of memory is only occurred by the same physiologic changes observed during the memory formation, while the second suggests that memory is a psychic mood stored in mind and the retrieval of memory is occurred by mystical energy fluctuations. Although the exact reason and the pathogenesis of Alzheimer's disease have not yet been fully understood, the approaches that centered the retrieval strategy of lost memory constitutes the basis of the treatment strategies in Alzheimer's disease today. The majority of treatment studies has based on the manipulation of the cholinergic system; however, although serotonin has mnemonic effects, its role in the pathogenesis of Alzheimer's disease has not been investigated as much as the cholinergic system. Here we show how serotonin affects the pathogenesis of Alzheimer's disease in a comprehensive perspective and we suggest that the optogenetics manipulation of serotonin nuclei retrieve the lost memory by closing the inward‐rectifier potassium channel Kir2 on the memory engram cells. Also, we raise the possible effects of serotonin on the memory engram cells and the interactions between the amyloid‐centric hypothesis of Alzheimer's disease and the memory engram hypothesis to explain the pathophysiology of memory loss in Alzheimer's disease.
Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.

OBJECTIVE The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. RESULTS Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.
Pilot testing an app-based stress management intervention for cancer survivors

Abstract Psychosocial eHealth intervention programs for cancer survivors are still in their infancy, with inconsistent findings so far in the scientific literature. The aim of this study was to explore system use, usefulness, ease of use, and preliminary effects of Stress Proffen, an app-based cognitive-behavioral stress management intervention for patients with cancer. A feasibility pilot project tested the intervention with cancer survivors (N = 25). The intervention contained (a) one face-to-face introduction session, (b) 10 app-based modules with stress management educational material and exercises, and (c) one follow-up phone call. Post-intervention interviews were conducted and user log-data were extracted. Outcome measures—Perceived Stress Scale (PSS), Anxiety and Depression (Hospital Anxiety and Depression Scale [HADS]), Health-Related Quality of Life (HRQoL; SF-36), and Self-Regulatory Fatigue (SRF-18)—were completed at baseline and post-intervention. Participants were primarily women (84%), age 34–71 (mean 48) and represented a variety of cancer diagnoses (majority breast cancer: 40%). Twenty-two participants completed all (pre–post) questionnaires. Sixteen participants (67%) completed at least 7 of 10 modules within the 8-week study period. Post-intervention interviews described StressProffen as providing a new, appreciated, and easily accessible stress management tool for the cancer survivors. Dependent/paired t-tests showed significant pre–post intervention effects with significant decrease in stress (p = .008), anxiety (p = .019), and self-regulatory fatigue (p = .025), and improved HRQoL (Role Physical, General Health, Vitality, and Role Emotional, all p’s <.01). App-based stress management interventions such as StressProffen can provide appreciated support for cancer survivors, should be easy to use, can provide significant stress reduction, and improve emotional well-being. Further testing in a randomized controlled trial is warranted and is in progress. Clinicaltrials.gov: NCT0293961.
Effect of Ce Doping on the Structure and Chemical Stability of Nano-α-Fe2O3

Ce-doped nano-α-Fe2O3 was successfully synthesized via the hydrothermal method. The properties of the prepared particles were studied by X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and electrochemical methods. It was found that the Ce element can be doped into the α-Fe2O3 lattice resulting in lattice distortion, which can refine the grain and improve the crystal surface’s integrity significantly. In addition, doping of Ce element can shorten the Fe–O bond length in the α-Fe2O3 crystal, cause a blue shift of the stretching vibration band, enhance binding energy of Fe–O and the chemical stability of the α-Fe2O3 crystal.
Maternal hypertensive disorders in pregnancy and risk of hypoxic-ischemia encephalopathy

Abstract Background Hypoxic–ischemic encephalopathy (HIE) is one of the most serious birth complications for neonates. Few studies reported the relationship between maternal blood pressure disorders and risk of neonatal HIE. Objective This study was conducted to examine whether maternal hypertensive disorders in pregnancy increase the risk of HIE. Methods The analyses were performed using data from a large population-based cohort study aiming to prevent neural tube defects by supplementation with folic acid. The subjects comprised 183,981 women with singleton live births delivered at gestational ages of 32–42 weeks, who registered in two southern provinces in China. Blood pressure was measured by trained health care workers at each prenatal visit. Diagnosis information on HIE was recorded at the time of delivery. Results Totally 19,298 women (10.49%) were diagnosed with maternal hypertensive disorders in pregnancy and 255 infants (1.4 per 1000) with HIE, respectively. Compared with the normotensive group, a great increment in the risk of HIE was observed in women with hypertensive disorders (adjusted RR = 2.40, 95% confidence interval [CI]: 1.79–3.22) after adjusting for maternal confounding factors. A greater association was presented among preterm (32–36 weeks) infants with an adjusted RR of 5.45 (95% CI: 2.79, 10.65) compared to a RR of 2.09 (95% CI: 1.49, 2.92) among full-term (37–42 weeks) infants (p for heterogeneity < .05). Further stratification analyses showed that no matter with or without small for gestational age (SGA), maternal hypertensive disorders were associated with the increased risk for HIE. Sensitivity analyses excluding infants with low or high birth weight did not appreciably change the findings. Conclusions Our present study demonstrated a positive association of maternal hypertensive disorders in pregnancy with the risk of neonatal HIE.
Faster Gastric Emptying Is Unrelated to Feeding Success in Preterm Infants: Randomized Controlled Trial

Objectives: To evaluate the relationship between gastric emptying (GE) time and days to achievement of full enteral feeding (≥140 mL/kg/day) in preterm infants randomly assigned to receive one of two marketed study formulas for the first 14 feeding days: intact protein premature formula (IPF) or extensively hydrolyzed protein (EHF) formula. Methods: In this triple-blind, controlled, prospective, clinical trial, we report GE time (time to half-emptying, t1/2) by real-time ultrasonography on Study Day 14, in preterm infants receiving IPF or EHF formula. The association between GE time and achievement of full enteral feeding was evaluated by Pearson correlation. Per-protocol populations for analysis included participants who (1) completed the study (overall) and (2) who received ≥ 75% study formula intake (mL/kg/day). Results: Median GE time at Day 14 was significantly faster for the EHF vs. IPF group overall and in participants who received ≥ 75% study formula intake (p ≤ 0.018). However, we demonstrated GE time had no correlation with the achievement of full enteral feeding (r = 0.08; p = 0.547). Conclusion: Feeding IP premature formula vs. EH formula was associated with shorter time to full enteral feeding. However, faster GE time did not predict feeding success and may not be a clinically relevant surrogate for assessing feeding tolerance.
Aggravated effects of coexisting marginal thiamine deficits and zinc excess on SN56 neuronal cells

ABSTRACT Objectives: Zinc excitotoxicity and thiamine pyrophosphate deficiency (TD) are known pathogenic signals contributing to mechanism of different encephalopathies through inhibition of enzymes responsible for energy metabolism such as pyruvate dehydrogenase, aconitase or ketoglutarate dehydrogenase. The aim of this work was to investigate whether subclinical Zn excess and TD, frequent in aging brain, may combine yielding overt neuronal impairment. Results: Clonal SN56 cholinergic neuronal cells of septal origin were used as the model of brain cholinergic neurons, which are particularly susceptible to neurodegeneration in the course of Alzheimer’s disease, hypoxia and other dementia-linked brain pathologies. Neither subtoxic concentration of Zn (0.10 mM) nor mild 20–25% TD deficits alone caused significant negative changes in cultured cholinergic neurons viability and their acetyl-CoA/acetylcholine metabolism. However, cells with mild TD accumulated Zn in excess, which impaired their energy metabolism causing a loss of neurons viability and their function as neurotransmitters. These negative effects of Zn were aggravated by amprolium which is an inhibitor of thiamine intracellular transport. Conclusion: Our data indicate that TD may amplify otherwise non-harmful border-line Zn excitotoxic signals yielding progress of neurodegeneration.
A tel2 Mutation That Destabilizes the Tel2-Tti1-Tti2 Complex Eliminates Rad3ATR Kinase Signaling in the DNA Replication Checkpoint and Leads to Telomere Shortening in Fission Yeast

In response to perturbed DNA replication, ATR (ataxia telangiectasia and Rad3-related) kinase is activated to initiate the checkpoint signaling necessary for maintaining genome integrity and cell survival. To better understand the signaling mechanism, we carried out a large-scale genetic screen in fission yeast looking for mutants with enhanced sensitivity to hydroxyurea. ABSTRACT In response to perturbed DNA replication, ATR (ataxia telangiectasia and Rad3-related) kinase is activated to initiate the checkpoint signaling necessary for maintaining genome integrity and cell survival. To better understand the signaling mechanism, we carried out a large-scale genetic screen in fission yeast looking for mutants with enhanced sensitivity to hydroxyurea. From a collection of ∼370 primary mutants, we found a few mutants in which Rad3 (ATR ortholog)-mediated phospho-signaling was significantly compromised. One such mutant carried an uncharacterized mutation in tel2, a gene encoding an essential and highly conserved eukaryotic protein. Previous studies in various biological models have shown that Tel2 mainly functions in Tel2-Tti1-Tti2 (TTT) complex that regulates the steady-state levels of all phosphatidylinositol 3-kinase-like protein kinases, including ATR. We show here that although the levels of Rad3 and Rad3-mediated phospho-signaling in DNA damage checkpoint were moderately reduced in the tel2 mutant, the phospho-signaling in the DNA replication checkpoint was almost completely eliminated. In addition, the tel2 mutation caused telomere shortening. Since the interactions of Tel2 with Tti1 and Tti2 were significantly weakened by the mutation, destabilization of the TTT complex likely contributes to the observed checkpoint and telomere defects.
Avoidance of psychological pain and suicidal ideation in community samples: Replication across two countries and two languages.

OBJECTIVES A multidimensional psychological pain model of suicide has been developed that includes three dimensions: affective, cognitive, and avoidance. In the present research, we evaluated the relationships between the three dimensions of psychological pain and suicidal ideation. METHOD Two community samples from Portugal and the U.S. participated in the research. RESULTS Hierarchical multiple regression analysis demonstrated that when controlling for the effects of depressive symptoms and psychache, the avoidance dimension, but not the cognitive or affective dimension of psychological pain, explained significant, and unique variance in suicidal ideation in each sample. CONCLUSION Even when individuals perceive psychological pain, there may not be an elevated risk of suicide, provided that they do not consider suicide as a form of coping to decrease that pain.
Molecular Dynamics Simulation on Mechanical and Piezoelectric Properties of Boron Nitride Honeycomb Structures

Boron nitride honeycomb structure is a new three-dimensional material similar to carbon honeycomb, which has attracted a great deal of attention due to its special structure and properties. In this paper, the tensile mechanical properties of boron nitride honeycomb structures in the zigzag, armchair and axial directions are studied at room temperature by using molecular dynamics simulations. Effects of temperature and strain rate on mechanical properties are also discussed. According to the observed tensile mechanical properties, the piezoelectric effect in the zigzag direction was analyzed for boron nitride honeycomb structures. The obtained results showed that the failure strains of boron nitride honeycomb structures under tensile loading were up to 0.83, 0.78 and 0.55 in the armchair, zigzag and axial directions, respectively, at room temperature. These findings indicated that boron nitride honeycomb structures have excellent ductility at room temperature. Moreover, temperature had a significant effect on the mechanical and tensile mechanical properties of boron nitride honeycomb structures, which can be improved by lowering the temperature within a certain range. In addition, strain rate affected the maximum tensile strength and failure strain of boron nitride honeycomb structures. Furthermore, due to the unique polarization of boron nitride honeycomb structures, they possessed an excellent piezoelectric effect. The piezoelectric coefficient e obtained from molecular dynamics was 0.702 C/m2, which was lower than that of the monolayer boron nitride honeycomb structures, e=0.79 C/m2. Such excellent piezoelectric properties and failure strain detected in boron nitride honeycomb structures suggest a broad prospect for the application of these new materials in novel nanodevices with ultrahigh tensile mechanical properties and ultralight-weight materials.
Developmental topography of cortical thickness during infancy

Significance During the first 2 postnatal years, the human brain undergoes dynamic growth and shows rapid expansions in behavioral and cognitive abilities. Charting the developmental patterns of cortical thickness in healthy infants is important for understanding many neurodevelopmental disorders, which unfortunately remains unexplored. Therefore, we investigate the infantile developmental regionalization of cortical thickness, which describes regions naturally formed during the dynamic development of cortical thickness and differs markedly from conventional anatomical parcellations. Meanwhile, this study delineates the inverted U-shaped developmental trajectory and peak age of cortical thickness, which clarifies the previous ambiguity on the peaking time of cortical thickness during early brain development. During the first 2 postnatal years, cortical thickness of the human brain develops dynamically and spatially heterogeneously and likely peaks between 1 and 2 y of age. The striking development renders this period critical for later cognitive outcomes and vulnerable to early neurodevelopmental disorders. However, due to the difficulties in longitudinal infant brain MRI acquisition and processing, our knowledge still remains limited on the dynamic changes, peak age, and spatial heterogeneities of cortical thickness during infancy. To fill this knowledge gap, in this study, we discover the developmental regionalization of cortical thickness, i.e., developmentally distinct regions, each of which is composed of a set of codeveloping cortical vertices, for better understanding of the spatiotemporal heterogeneities of cortical thickness development. We leverage an infant-dedicated computational pipeline, an advanced multivariate analysis method (i.e., nonnegative matrix factorization), and a densely sampled longitudinal dataset with 210 serial MRI scans from 43 healthy infants, with each infant being scheduled to have 7 longitudinal scans at around 1, 3, 6, 9, 12, 18, and 24 mo of age. Our results suggest that, during the first 2 y, the whole-brain average cortical thickness increases rapidly and reaches a plateau at about 14 mo of age and then decreases at a slow pace thereafter. More importantly, each discovered region is structurally and functionally meaningful and exhibits a distinctive developmental pattern, with several regions peaking at varied ages while others keep increasing in the first 2 postnatal years. Our findings provide valuable references and insights for early brain development.
Review of Drug Development Guidance to Treat Chronic Obstructive Pulmonary Disease: US and EU Perspectives

Chronic obstructive pulmonary disease (COPD) remains a leading cause of death worldwide, yet only one new drug class has been approved in the last decade. However, resurgence in COPD treatment has been recently fueled by a greater understanding of the pathophysiology and natural history of the disease, as well as a growing prevalence and an aging population. Currently, there are nearly 25 novel drug targets in development. Furthermore, the indication has undergone some fundamental changes over the last couple of years, including an updated diagnosis paradigm, validation, and approval of patient‐reported outcome questionnaires for clinical trials, and drug development tools, such as a prognostic biomarker for patient selection. In the context of clinical trials, this review aims to summarize recent changes to the diagnosis and evaluation of COPD and to provide an overview of US and European regulatory guidance.
The Potential of Cannabidiol as a Treatment for Psychosis and Addiction: Who Benefits Most? A Systematic Review

The endogenous cannabinoid (eCB) system plays an important role in the pathophysiology of both psychotic disorders and substance use disorders (SUDs). The non-psychoactive cannabinoid compound, cannabidiol (CBD) is a highly promising tool in the treatment of both disorders. Here we review human clinical studies that investigated the efficacy of CBD treatment for schizophrenia, substance use disorders, and their comorbidity. In particular, we examined possible profiles of patients who may benefit the most from CBD treatment. CBD, either as monotherapy or added to regular antipsychotic medication, improved symptoms in patients with schizophrenia, with particularly promising effects in the early stages of illness. A potential biomarker is the level of anandamide in blood. CBD and THC mixtures showed positive effects in reducing short-term withdrawal and craving in cannabis use disorders. Studies on schizophrenia and comorbid substance use are lacking. Future studies should focus on the effects of CBD on psychotic disorders in different stages of illness, together with the effects on comorbid substance use. These studies should use standardized measures to assess cannabis use. In addition, future efforts should be taken to study the relationship between the eCB system, GABA/glutamate, and the immune system to reveal the underlying neurobiology of the effects of CBD.