Miracle-dz/UniFAR-FTUs huggingface dataset:
A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice

Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal degenerative disorder. A number of pathological mechanisms that lead to motor neuron death have been identified, although there are many unknowns in the disease aetiology of ALS. Alterations in lipid metabolism are well documented in the progression of ALS, both at the systemic level and in the spinal cord of mouse models and ALS patients. The origin of these lipid alterations remains unclear. This study aims to identify early lipid metabolic pathways altered before systemic metabolic symptoms in the spinal cord of mouse models of ALS. To do this, we performed a transcriptomic analysis of the spinal cord of SOD1G93A mice at an early disease stage, followed by a robust transcriptomic meta-analysis using publicly available RNA-seq data from the spinal cord of SOD1 mice at early and late symptomatic disease stages. The meta-analyses identified few lipid metabolic pathways dysregulated early that were exacerbated at symptomatic stages; mainly cholesterol biosynthesis, ceramide catabolism, and eicosanoid synthesis pathways. We present an insight into the pathological mechanisms in ALS, confirming that lipid metabolic alterations are transcriptionally dysregulated and are central to ALS aetiology, opening new options for the treatment of these devastating conditions.
PtII Phosphors with Click-Derived 1,2,3-Triazole-Containing Tridentate Chelates

A series of PtII complexes featuring 1,2,3-triazole-derived N∧N∧N-, N∧C∧N- and C∧N∧C-coordinating ligands were studied both experimentally and computationally aiming at the design of new PtII phosphors. By virtue of click chemistry, the new complexes were readily functionalized, e.g., with bulky groups in order to suppress aggregation of the complexes. For a N∧C∧N-type cyclometalated PtII complex, the high energy of the π* orbitals of the 1,2,3-triazole units gave rise to deep-blue phosphorescence; the poor luminescence quantum yield was attributed to an inadequate energy separation between the emissive state and the d–d states. However, when the 1,2,3-triazole donor moiety acted as a spectator/ancillary ligand only, an intense green emission could be achieved (ΦPL = 0.57, τ = 4.6 μs).
Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes

The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c. 3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), while T-T-G-T-wt and C-C-G-T-wt were prevalent only in CD children (OR = 29.36, and 12.93, respectively; p-value = 0.001). In conclusion, the presence of c. 3019_3020insC along with c.802C>T occurred as the most fundamental contributing diplotype in late-onset CD form, while in CD children, the mutual allele in all predisposing haplotypes was the c.2798 + 158T. Identifying the unique, high-impact haplotypes supports further studies of the NOD2 gene, including haplotypic backgrounds.
Effects of β-Phenylethylamine on Psychomotor, Rewarding, and Reinforcing Behaviors and Affective State: The Role of Dopamine D1 Receptors

Beta-phenylethylamine (β-PEA) is a well-known and widespread endogenous neuroactive trace amine found throughout the central nervous system in humans. In this study, we demonstrated the effects of β-PEA on psychomotor, rewarding, and reinforcing behaviors and affective state using the open-field test, conditioned place preference (CPP), self-administration, and ultrasonic vocalizations (USVs) paradigms. We also investigated the role of the dopamine (DA) D1 receptor in the behavioral effects of β-PEA in rodents. Using enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting, we also determined the DA concentration and the DA-related protein levels in the dorsal striatum of mice administered with acute β-PEA. The results showed that acute β-PEA increased stereotypic behaviors such as circling and head-twitching responses in mice. In the CPP experiment, β-PEA increased place preference in mice. In the self-administration test, β-PEA significantly enhanced self-administration during a 2 h session under fixed ratio (FR) schedules (FR1 and FR3) and produced a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement in rats. In addition, acute β-PEA increased 50-kHz USV calls in rats. Furthermore, acute β-PEA administration increased DA concentration and p-DAT and TH expression in the dorsal striatum of mice. Finally, pretreatment with SCH23390, a DA D1 receptor antagonist, attenuated β-PEA-induced circling behavior and β-PEA-taking behavior in rodents. Taken together, these findings suggest that β-PEA has rewarding and reinforcing effects and psychoactive properties, which induce psychomotor behaviors and a positive affective state by activating the DA D1 receptor in the dorsal striatum.
Correlations between Physical Activity Participation and the Environment in Children and Adolescents: A Systematic Review and Meta-Analysis Using Ecological Frameworks

Physical activity (PA) and sports are efficient ways to promote the young generation’s physical and mental health and development. This study expected to demonstrate the complexity of correlates associated with children’s and adolescents’ non-organized PA participation. Following the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA), a systematic review and meta-analysis were applied. Seven electronic databases were systematically searched to identify eligible articles based on a series of inclusion and exclusion criteria. The internal validity of the systematic reviews thus identified was evaluated using a validated quality instrument. Calculations were produced in SPSS 27.0 and Comprehensive Meta-Analysis 3.3. Thirty-nine eligible studies (N = 324,953) with moderate to high quality were included. No potential publication bias was detected using statistical analyses. The meta-analysis revealed that the overall ecological factors correlated positively with children and adolescents’ PA; the meta-analytic average of the correlations was (′r = 0.32, p < 0.001). Results from subgroup analysis indicated that theory-based influence factors achieved moderate effect with boys (′r = 0.37, p < 0.001) and girls (′r = 0.32, p < 0.001) in PA participation. Interestingly, higher correlations were found between ecological factors and twins’ PA participation (′r = 0.61, p = 0.001). Further, individual (′r = 0.32, p < 0.001), macro-, and chronosystems factors (′r = 0.50, p < 0.001) appeared slightly more influential than microsystems factors (′r = 0.28, p < 0.001) on children and adolescents’ PA participation. Although findings from the included studies covered were to some extent heterogeneous, it is possible to identify consistent correlates of PA in children and adolescents. The results supported that PA is a complex and multi-dimensional behavior, which is determined by numerous biological, psychological, sociocultural, and environmental factors. Future studies that focus on the integration effect of macrosystem and chronosystem environmental factors, and apply longitudinal designs and objective measurements are encouraged to further unfold the complexity of the ecological system and its implications in promoting children and adolescents’ PA participation.
Probing Biomolecular Interactions with Gold Nanoparticle-Decorated Single-Walled Carbon Nanotubes

Hybrid nanomaterials comprising metal–graphitic interfaces are uniquely suitable to probe molecular interactions and the associated phenomena such as charge transfer and adsorbate spillover effects. Herein, we study the modulation of the electronic and chemical properties of gold nanoparticle-decorated single-walled carbon nanotubes (SWCNT) using Raman spectroscopy and measurements of field-effect transistor (FET) characteristics. SWCNT are extremely sensitive to changes in the local electronic environment and therefore gold-analyte interactions may be probed both through changes in FET characteristics (as an electrical transducer) and in surface-enhanced Raman scattering (as a chromophore). We study these changes both experimentally and theoretically in order to elucidate the electronic structure of complex nanocomposites, and the information gathered from these experiments is applied to the study of biomolecular interactions with gold nanoparticle-decorated SWCNT. This study, in addition to providing de.
Tailoring the Structural and Electronic Properties of Graphene through Ion Implantation

Ion implantation is a superior post-synthesis doping technique to tailor the structural properties of materials. Via density functional theory (DFT) calculation and ab-initio molecular dynamics simulations (AIMD) based on stochastic boundary conditions, we systematically investigate the implantation of low energy elements Ga/Ge/As into graphene as well as the electronic, optoelectronic and transport properties. It is found that a single incident Ga, Ge or As atom can substitute a carbon atom of graphene lattice due to the head-on collision as their initial kinetic energies lie in the ranges of 25–26 eV/atom, 22–33 eV/atom and 19–42 eV/atom, respectively. Owing to the different chemical interactions between incident atom and graphene lattice, Ge and As atoms have a wide kinetic energy window for implantation, while Ga is not. Moreover, implantation of Ga/Ge/As into graphene opens up a concentration-dependent bandgap from ~0.1 to ~0.6 eV, enhancing the green and blue light adsorption through optical analysis. Furthermore, the carrier mobility of ion-implanted graphene is lower than pristine graphene; however, it is still almost one order of magnitude higher than silicon semiconductors. These results provide useful guidance for the fabrication of electronic and optoelectronic devices of single-atom-thick two-dimensional materials through the ion implantation technique.
Epilepsy in prolonged disorders of consciousness: a systematic review

ABSTRACT To date, no guideline exists for the management of epilepsy in patients with prolonged Disorders of Consciousness (DoC). This review aimed to assess the occurrence of epilepsy and epileptic abnormalities (EA) in these patients, to determine their impact on recovery; and to review the effect of antiepileptic drugs (AED) and therapeutic interventions on seizure occurrence and consciousness recovery. A structured search for studies on prolonged DoC and epilepsy was undertaken following PRISMA guidelines. From an initial search resulting in 5,775 titles, twelve studies met inclusion criteria. The occurrence of epilepsy and EA in DoC was poorly and inconsistently reported across studies. The results estimated a seizure prevalence of 27% in DoC. No conclusive data were found for the effects of AED on recovery nor on the influence of any therapeutic interventions on seizure occurrence. Given the scarcity of data, it is premature to make evidence-based recommendations on epilepsy in prolonged DoC. Based on this review and current clinical practices the following are recommended: (1) repeated standard EEG for detecting seizures and EA; (2) treating epilepsy while avoiding AEDs with sedating or cognitive side-effects. Future research should use standardized classification systems for seizures and EA.
Adaptation and Psychometric Validation of the EMPOWER-SUSTAIN Usability Questionnaire (E-SUQ) among Patients with Metabolic Syndrome in Primary Care

Self-management support is one of the most important components of the Chronic Care Model (CCM). The EMPOWER-SUSTAIN Global Cardiovascular Risks Self-Management Booklet© was developed for patients with Metabolic Syndrome (MetS), inspired by the CCM. Assessing usability of a self-management tool is important in chronic disease management. However, there was no available instrument to assess usability of a self-management booklet, as most instruments were developed to assess usability of mobile application. Therefore, this study aimed to adapt Skala Kebolehgunaan Aplikasi Mudah Alih (SKAMA) into the EMPOWER-SUSTAIN Usability Questionnaire (E-SUQ) and to determine its validity and reliability in assessing usability of a self-management booklet. A cross-sectional validation study was conducted among patients with MetS attending a university primary care clinic in Selangor, Malaysia. Content validation, adaptation and face validation of E-SUQ were performed according to recommended guidelines. It underwent two rounds of content validation as major revision was required for item 5. Subsequently, the revised E-SUQ was face-validated by 10 participants. Psychometric evaluation was conducted using principal component analysis with varimax rotation to determine the underlying structure of E-SUQ. Internal consistency reliability was assessed using Cronbach’s α coefficient and the test-retest reliability was assessed using intraclass correlation coefficient (ICC (2,k)). A total of 205 patients participated in the study. The item-level content-validity-index (I-CVI) for item 5 improved from 0.57 to 1.0 after the second round of content validation. The final S-CVI/Ave value for ESUQ was >0.90. The item-level face-validity-index (I-FVI) ranged between 0.9 and 1.0. Kaiser-Meyer-Olkin value of 0.871 and Bartlett’s test of sphericity p-value of <0.05 indicated good sample adequacy for factor analysis. Two factors with eigenvalues of >1 were extracted according to the Kaiser’s Criteria. The two extracted factors explained 60.6% of the cumulative percentage of variance. The elbow of the scree plot occurred between the second and third component, suggesting two factors to be retained. The two factors were consistent with “Positive” and “Negative” tone model. The overall Cronbach’s α coefficient was 0.77, indicating good internal reliability. The overall ICC was 0.85, indicating good reproducibility. The E-SUQ is shown to be valid, reliable and stable to measure the usability of a self-management booklet among patients with MetS in a university primary care clinic in Malaysia.
MicroRNA Let-7e in the Mouse Prefrontal Cortex Differentiates Restraint-Stress-Resilient Genotypes from Susceptible Genotype

Three strains of mice with various susceptibilities to restraint stress (RS), i.e., mice with a knocked out norepinephrine transporter gene (NET-KO), SWR/J and C57BL/6J (WT) mice were shown to serve as a good model to study the molecular mechanisms underlying different stress-coping strategies. We identified 14 miRNAs that were altered by RS in the PFC of these mice in a genotype-dependent manner, where the most interesting was let-7e. Further in silico analysis of its potential targets allowed us to identify five mRNAs (Bcl2l11, Foxo1, Pik3r1, Gab1 and Map2k4), and their level alterations were experimentally confirmed. A next-generation sequencing (NGS) approach, which was employed to find transcripts differentially expressed in the PFC of NET-KO and WT mice, showed that, among others, two additional mRNAs were regulated by mmu-let-7e, i.e., mRNAs that encode Kmt2d and Inf2. Since an increase in Bcl2l11 and Pik3r1 mRNAs upon RS in the PFC of WT mice resulted from the decrease in mmu-let-7e and mmu-miR-484 regulations, we postulated that MAPK, FoxO and PI3K-Akt signaling pathways were associated with stress resilience, although via different, genotype-dependent regulation of various mRNAs by let-7e and miR-484. However, a higher level of Kmt2d mRNA (regulated by let-7e) that was found with NGS analysis in the PFC of NET-KO mice indicated that histone methylation was also important for stress resilience.
Inhibition of Pro-Inflammatory Cytokine TNF-α by Boerhaavia diffusa (L.) in Liposaccharide stimulated Human THP-1 cells

http://dx.doi. org/10.21276/IJRDPL.227 8-0238.2017. 6(6). 2820-2823 ABSTRACT: The production and release of proinflammatory cytokines such as Tumor necrotic factor-α (TNFα), Interleukin-1β and Iinterleukin-6 from monocytes/macrophages play critical role in the pathogenesis of chronic inflammatory diseases and immune response. Boerhaavia diffusa L is a medicinal plant in the Indian traditional system known as Rasayana (Indigenous plants with immunomodulatory activity) and an important source of immunomodulators. In present study, the antiinflammatory activity of herbal immune modulator Boerhaavia diffusa L was studied by evaluating the inhibition of Lipopolysaccharide stimulated TNF-α secretion using human Monocytic THP-1 cells. Differentiation of the human monocytic cell THP-1 into macrophage-like cells was induced by exposure of the cells to Phorbol Myristate Acetate. When cells were pre-incubated with Methanolic extract of Boerhaavia diffusa L for 4 hrs and then stimulated with lipopolysaccharide for 12 hrs, secretion of tumor necrosis factorα was significantly decreased compared to control. The present study has shown that the Boerhaavia diffusa L inhibits the production and release of proinflammatory cytokines, TNF-α from monocytes/macrophages which play critical role in the pathogenesis of chronic inflammatory diseases and hence this could be the probable mechanism, by which this immunomodulatory herbal plant extracts possess anti-inflammatory activity. ⇑ Corresponding author at: Jay H. Shah, Faculty of Pharmacy, Hemchandracharya North Gujarat University, Patan,, India E-mail address: jay.mpharm. mba@gmail.com
Heterogeneous side effects of cortical inactivation in behaving animals

Cortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation studies is that the neurons in the target area become silent while the surrounding cortical tissue is only negligibly impacted. However, individual neurons are embedded in complex local circuits composed of excitatory and inhibitory cells with connections extending hundreds of microns. This raises the possibility that silencing one part of the network could induce complex, unpredictable activity changes in neurons outside the targeted inactivation zone. These off-target side effects can potentially complicate interpretations of inactivation manipulations, especially when they are related to changes in behavior. Here, we demonstrate that optogenetic inactivation of glutamatergic neurons in the superficial layers of monkey primary visual cortex (V1) induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified four types of stimulus-evoked neuronal responses within a cortical column, ranging from full suppression to facilitation, and a mixture of both. Mixed responses were most prominent in middle and deep cortical layers. These results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Importantly, consistent behavioral changes induced by optogenetic inactivation were only achieved when cumulative network activity was homogeneously suppressed. Therefore, careful consideration of the full range of network changes outside the inactivated cortical region is required, as heterogeneous side effects can confound interpretation of inactivation experiments.
Penetration and Displacement Behavior of N2 in Porous Interlayer Structures Containing Water/Salt Component by Molecular Dynamics Simulation

The penetration and displacement behavior of N2 molecules in porous interlayer structures containing a water/salt component with porosities of 4.29%, 4.73%, 5.17%, 7.22%, and 11.38% were explored using molecular dynamics simulations. The results demonstrated that the large porosity of the interlayer structures effectively enhanced the permeation and diffusion characteristics of N2. The water and salt in the interlayer structures were displaced during the injection of N2 in the porosity sequence of 4.29% < 4.73% < 5.17% < 7.22% < 11.38%. The high permeance of 7.12 × 10−6 indicated that the interlayer structures with a porosity of 11.38% have better movability. The strong interaction of approximately 15 kcal/mol between N2 and H2O had a positive effect on the diffusion of N2 and the displacement of H2O before it reached a stable equilibrium state. The distribution of N2 in porous interlayer structures and the relationship between the logarithm of permeability and breakthrough pressure were presented. This work highlighted the effects of porosity on the permeability and diffusion of N2/H2O in the interlayer, thus providing theoretical guidance for the development of petroleum resources.
Remote Virtual Reality Teaching: Closing an Educational Gap During a Global Pandemic.

OBJECTIVE Resident physicians are expected to recognize patients requiring escalation of care on day 1 of residency, as outlined by the Association of American Medical Colleges. Opportunities for medical students to assess patients at the bedside or through traditional simulation-based medical education have decreased because of coronavirus disease 2019 restrictions. Virtual reality (VR) delivered remotely via video teleconferencing may address this educational gap. METHODS A prospective pilot study targeting third-year pediatric clerkship students at a large academic children's hospital was conducted from April to December 2020. Groups of 6 to 15 students participated in a 1.5-hour video teleconferencing session with a physician facilitator donning a VR headset and screen sharing interactive VR cases of a hospitalized infant with respiratory distress. Students completed surveys assessing the immersion and tolerability of the virtual experience and reported its perceived effectiveness to traditional educational modalities. Comparisons were analyzed with binomial testing. RESULTS Participants included third-year medical students on their pediatric clerkship. A total of 140 students participated in the sessions, with 63% completing the survey. A majority of students reported VR captured their attention (78%) with minimal side effects. Students reported remote VR training as more effective (P < .001) than reading and online learning and equally or more effective (P < .001) than didactic teaching. Most students (80%) rated remote VR as less effective than bedside teaching. CONCLUSIONS This pilot reveals the feasibility of remote group clinical training with VR via a video conferencing platform, addressing a key experience gap while navigating coronavirus disease 2019 limitations on training.