Miracle-dz/UniFAR-FTUs huggingface dataset:
De Novo Variants in EEF2 Cause a Neurodevelopmental Disorder with Benign External Hydrocephalus.

Eukaryotic translation elongation factor 2 (eEF2) is a key regulatory factor in gene expression that catalyzes the elongation stage of translation. A functionally impaired eEF2, due to a heterozygous missense variant in the EEF2 gene, was previously reported in one family with spinocerebellar ataxia-26 (SCA26), an autosomal dominant adult-onset pure cerebellar ataxia. Clinical exome sequencing identified de novo EEF2 variants in three unrelated children presenting with a neurodevelopmental disorder. Individuals shared a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly. Populational data and bioinformatic analysis underscored the pathogenicity of all de novo missense variants. eEF2 yeast model strains demonstrated that patient-derived variants affect cellular growth, sensitivity to translation inhibitors and translational fidelity. Consequently, we propose that pathogenic variants in the EEF2 gene, so far exclusively associated with late-onset SCA26, can cause a broader spectrum of neurologic disorders, including childhood-onset neurodevelopmental disorders and benign external hydrocephalus.
APC Promoter Hypermethylation as a Prognostic Marker in Breast Cancer Patients

Background: Adenomatous polyposis coli (APC) promoter hypermethylation implicated in breast cancer development through Wnt signaling pathway, hypermethylation may result in inactivation of APC expression. This study aimed to investigated whether hypermethylation of APC promoter, the aggressive behavior of breast cancer cells, and correlated them with clinicopathological parameters and survival. Methods: Sixty-one fresh tissues of breast tumor were evaluated for APC promoter hypermethylation with methylation-specific PCR techniques (MS-PCR) and APC mRNA expression level analysis by quantitative real-time reverse transcription-PCR. Results: Our results show aberrant APC hypermethylation status was founded in 27 of 61 cases (44%), and significantly associated with chemotherapy treatment (OR= 6.9, 95%CI=1.5-31.01, P = 0.01), distant metastasis (OR = 5.52, 95%CI = 1.27-24.08, P = 0.04) as well as APC methylated status also associated with shorter overall survival than those without (8.4 and 11.0 years respectively, P = 0.02). Conclusion: The findings indicated hypermethylation of APC promoter may be used as a useful prognostic biomarker in breast cancer patients.
Multivariate Base Rates of Low Scores on Tests of Executive Functions in a Multi-Country Latin American Sample

ABSTRACT The objective of the study was to determine the prevalence of low scores in a diverse Latin American population for two neuropsychological commonly used tests to evaluate executive functions and to compare the number of low scores obtained using normative data from a Spanish-speaking population from Latin America versus an English-speaking population from U.S.A. Healthy adults (N = 5402) were administered the Modiﬁed Wisconsin Card Sorting Test and Stroop Color-Word. Low scores on measures of executive functioning are common. Clinicians working with Spanish-speaking adults should take into account the higher probability of low scores on these measures to reduce false-positive diagnoses of cognitive deficits in an individual.
Chorion and amnion/chorion membranes in oral and periodontal surgery: A systematic review.

The aim of this study was to perform a systematic review on the clinical applications where chorion membrane (CM) and amnion/chorion membrane (ACM) were used for oral tissue regeneration procedures. Selection of articles was carried out by two evaluators in Pubmed and Scopus databases, and Outcomes (PICO) method was used to select the relevant articles. Clinical studies reporting the use of CM or ACM for oral soft and hard tissue regeneration were included. The research involved 21 studies conducted on 375 human patients. Seven clinical applications of CM and ACM in oral and periodontal surgery were identified: gingival recession treatment, intrabony and furcation defect treatment, alveolar ridge preservation, keratinized gum width augmentation around dental implants, maxillary sinus membrane repair, and large bone defect reconstruction. CM and ACM were compared to negative controls (conventional surgeries without membrane) or to the following materials: collagen membranes, dense polytetrafluoroethylene membranes, platelet-rich fibrin membranes, amnion membranes, and to a bone substitute. Several studies support the use of CM and ACM as an efficient alternative to current techniques for periodontal and oral soft tissue regeneration procedures. However, further studies are necessary to increase the level of evidence and especially to demonstrate their role for bone regeneration.
Different DOACs Control Inflammation in Cardiac Ischemia-Reperfusion Differently.

Rationale: While thrombin is the key protease in thrombus formation, other coagulation proteases, such as fXa or activated protein C (aPC), independently modulate intracellular signaling via partially distinct receptors. Objective: To study the differential effects of fXa or fIIa inhibition on gene expression and inflammation in myocardial ischemia-reperfusion injury (IRI). Methods and Results: Mice were treated with a direct fIIa inhibitor (fIIai) or direct fXa inhibitor (fXai) at doses that induced comparable anticoagulant effects ex vivo and in vivo (tail bleeding assay and FeCl3-induced thrombosis). Myocardial IRI was induced via LAD ligation. We determined infarct size and in vivo aPC generation, analyzed gene expression by RNAseq, and performed immunoblotting and ELISA. The signaling-only 3K3A-aPC variant and inhibitory antibodies that blocked all or only the anticoagulant function of aPC were used to determine the role of aPC. Doses of fIIai and fXai that induced comparable anticoagulant effects resulted in a comparable reduction in infarct size. However, unbiased gene expression analyses revealed marked differences, including pathways related to sterile inflammation and inflammasome regulation. fXai but not fIIai inhibited sterile inflammation by reducing the expression of proinflammatory cytokines (IL-1beta, IL-6, and TNFalpha) as well as NF-κB and inflammasome activation. This anti-inflammatory effect was associated with reduced myocardial fibrosis 28 days post myocardial IRI. Mechanistically, in vivo aPC generation was higher with fXai than with fIIai. Inhibition of the anticoagulant and signaling properties of aPC abolished the anti-inflammatory effect associated with fXai, while inhibiting only the anticoagulant function of aPC had no effect. Combining 3K3A-aPC with fIIai reduced the inflammatory response, mimicking the fXai-associated effect. Conclusions: We showed that specific inhibition of coagulation via DOACs had differential effects on gene expression and inflammation, despite comparable anticoagulant effects and infarct sizes. Targeting individual coagulation proteases induces specific cellular responses unrelated to their anticoagulant effect.
PyTHang: an open-source wearable sensor system for real-time monitoring of head-torso angle for ambulatory applications

Abstract This article presents the realization of a low-cost wearable sensor system and its Python-based software that can measure and record relative head-torso angle, especially in sagittal plane. The system is mainly developed to track head-torso angle during walk in a clinical study. The open-hardware part of the system is composed of a pair of triaxial digital accelerometers, a microprocessor, a Bluetooth module and a rechargeable battery unit. The reception of the transmitted acceleration data, visualization, interactive sensor alignment, angle estimation and data-logging are realized by the developed open-source graphical user interface. The system is tested on a tripod for verification and on a subject for practical demonstration. Developed system can be constructed and used for ambulatory monitoring and analysis of relative head-torso angle. Open-source user interface can be downloaded and developed for further (different) algorithms and device hardware.
Fluoride-assisted galvanic replacement synthesis of Ag and Au dendrites on aluminum foil with enhanced SERS and catalytic activities

Although Al has a lower redox potential [Al3+/Al, −1.67 V vs. SHE] than most metallic ions, metal galvanic replacement reactions on pure aluminum foil can be hardly observed because of the existence of the thin layer of aluminum oxide, In this work, we develop a facile, economical and general approach to achieve large-scale production of silver and gold dendrites as well as other metal hierarchical micro/nanostructures (Cu, Pt, Pd, Ni, Co and Zn) on commercial aluminum foil in the presence of NaF or NH4F. Studies of the galvanic replacement reaction by open circuit potential–time (OCP–t) measurements demonstrate that fluoride plays an important role in etching the alumina layer and thus induces the continuous proceeding of the galvanic replacement reaction. The synthesis process is carried out at room temperature and without any templates, surfactants, or special reagents. The obtained silver and gold dendrites show significantly enhanced SERS signals of a self-assembled monolayer of 2-naphthalenethiol and 4-mercaptobenzoic acid, and also could effectively catalyze the reduction reaction of 4-nitrophenol and 2-nitrophenol at room temperature.
Acute Δ9‐tetrahydrocannabinol prompts rapid changes in cannabinoid CB1 receptor immunolabeling and subcellular structure in CA1 hippocampus of young adult male mice

The use and abuse of cannabis can be associated with significant pathophysiology, however, it remains unclear whether (1) acute administration of Δ‐9‐tetrahydrocannabinol (THC) during early adulthood alters the cannabinoid type 1 (CB1) receptor localization and expression in cells of the brain, and (2) THC produces structural brain changes. Here we use electron microscopy and a highly sensitive pre‐embedding immunogold method to examine CB1 receptors in the hippocampus cornu ammonis subfield 1 (CA1) 30 min after male mice were exposed to a single THC injection (5 mg/kg). The findings show that acute exposure to THC can significantly decrease the percentage of CB1 receptor immunopositive terminals making symmetric synapses, mitochondria, and astrocytes. The percentage of CB1 receptor‐labeled terminals forming asymmetric synapses was unaffected. Lastly, CB1 receptor expression was significantly lower at terminals of symmetric and asymmetric synapses as well as in mitochondria. Structurally, CA1 dendrites were significantly larger, and contained more spines and mitochondria following acute THC administration. The area of the dendritic spines, synaptic terminals, mitochondria, and astrocytes decreased significantly following acute THC exposure. Altogether, these results indicate that even a single THC exposure can have a significant impact on CB1 receptor expression, and can alter CA1 ultrastructure, within 30 min of drug exposure. These changes may contribute to the behavioral alterations experienced by young individuals shortly after cannabis intoxication.
Biosynthetic Activity Differs Between Islet Cell Types and in Beta Cells Is Modulated by Glucose and Not by Secretion

Abstract A correct biosynthetic activity is thought to be essential for the long-term function and survival of islet cells in culture and possibly also after islet transplantation. Compared to the secretory activity, biosynthetic activity has been poorly studied in pancreatic islet cells. Here we aimed to assess biosynthetic activity at the single cell level to investigate if protein synthesis is dependent on secretagogues and increased as a consequence of hormonal secretion. Biosynthetic activity in rat islet cells was studied at the single cell level using O-propargyl-puromycin (OPP) that incorporates into newly translated proteins and chemically ligates to a fluorescent dye by “click” reaction. Heterogeneous biosynthetic activity was observed between the four islet cell types, with delta cells showing the higher relative protein biosynthesis. Beta cells protein biosynthesis was increased in response to glucose while 3-isobutyl-1-methylxanthine and phorbol-12-myristate-13-acetate, 2 drugs known to stimulate insulin secretion, had no similar effect on protein biosynthesis. However, after several hours of secretion, protein biosynthesis remained high even when cells were challenged to basal conditions. These results suggest that mechanisms regulating secretion and biosynthesis in islet cells are different, with glucose directly triggering beta cells protein biosynthesis, independently of insulin secretion. Furthermore, this OPP labeling approach is a promising method to identify newly synthesized proteins under various physiological and pathological conditions.
Mental health shame, self‐compassion and sleep in UK nursing students: Complete mediation of self‐compassion in sleep and mental health

To explore relationships between mental health problems, mental health shame, self‐compassion and average length of sleep in UK nursing students. The increasing mental health problems in nursing students may be related to a strong sense of shame they experience for having a mental health problem. Self‐compassion has been identified as a protective factor for mental health and shame in other student populations. Further, studies highlight the importance of sleep relating to mental health.
A systematic review of randomized controlled trials of dietary interventions for weight loss in adults in the Middle East and north Africa region

The prevalence and incidence of obesity, and associated complications, such as type 2 diabetes, in the Middle East and north Africa (MENA) region rank among the highest in the world. Little is known about the effectiveness of dietary weight loss interventions conducted in the MENA region. We conducted a systematic review of randomized clinical trials aiming to assess the effectiveness of dietary interventions for weight loss in the adult population originating from and residing in the MENA region. In accordance with PRISMA guidelines, PubMed, CINAHL, Cochrane, and EMBASE were systematically searched for randomized controlled trials (RCT) using dietary interventions for weight loss conducted in the MENA region. RCTs examining weight loss as an outcome in adults (≥ 18 years old) were included. The Cochrane Collaboration tool for assessing risk of bias was used to ascertain the quality of the eligible RCTs and the Template for Intervention Description and Replication for population health and policy interventions (TIDieR‐PHP) checklist was used to evaluate the reporting of the interventions. Twenty‐nine RCTs including 2792 adults from five countries in the MENA region met the search criteria. Study participants were predominantly middle‐aged females. Duration of follow up was mostly 3 months or less. Weight loss ranged from −0.7 to 16 kg across all intervention groups and the average weight loss was 4.8 kg. There was paucity of description of the weight loss interventions and variations amongst studies did not allow a meta‐analysis of findings. It was not possible to draw firm conclusions on the effectiveness of dietary weight loss interventions in the region. High quality studies using more structured interventions of longer duration with standardized outcome measures are needed in the MENA region to support clinical practice with evidence‐based interventions for obesity.
Frequency and Correlation of Common Genes Copy Number Alterations in Childhood Acute Lymphoblastic Leukemia with Prognosis

Objective: It was shown by genomic profiling that despite no detectable chromosomal abnormalities a proportion of children with pre-B acute lymphoblastic leukemia harbors copy number alterations (CNA) of genes playing role in B-cell development and function. The aim of the study was to determine the frequency of CNA in pediatric acute lymphoblastic leukemia and correlate these findings with clinical outcome. Methods: DNA extracted from peripheral blood or bone marrow at diagnosis/relapse of fifty newly diagnosed children with precursor B-cell acute lymphoblastic leukemia was analyzed for CNA with multiplex ligation-dependent probe amplification. Results: The analysis revealed 76 CNA in 24 patients most frequently found in PAR1 (17%), CDKN2A/B (15.7%) and PAX5 (14.4%) genes. There were significant CNA co-occurrences between PAX5, CDKN2A/B, BTG1, ETV6, PAR1 or XP22 genes, (p<0.020) and the high-risk group. There was a significant correlation between EBF1, RB1, and IKZF1 alterations and bone marrow relapse. Patients with CNA in screened genes are more likely to succumb to their disease except for those with PAR1 or XP22 genes (p<0.050). Conclusion: The multiplex ligation-dependent probe amplification could be considered as an independent diagnostic tool allowing prompt identification of patients at high risk of treatment failure and, subsequently, a more adequate treatment approach.
TMEM173 protects against pressure overload‐induced cardiac hypertrophy by modulating autophagy

TMEM173 has been reported to participate in endoplasmic reticulum stress, inflammation and immunology, all of which closely involved with cardiac hypertrophy. But its role in autophagy is not fully figured out. In our research, Tmem173 global knockout (KO) mice manifested more deteriorated hypertrophy, fibrosis, inflammatory infiltration and cardiac malfunction compared with wild type C57BL/6 mice after 6 weeks of transverse aortic constriction. And KO mice showed inhibited autophagosome degradation in myocardium observed under transmission electron microscope and in protein level. In in vitro experiments conducted in neonatal rat cardiomyocytes under phenylephrine treatment, the abundance of Tmem173 gene was negatively related to the abundance of LC3‐Ⅱ and the number of red and yellow fluorescent dots, of which reflected the capacity of autophagosome degradation. These results indicated that TMEM173 might be a promoter of autophagic flux and protected against pressure overload‐induced cardiac hypertrophy. It may serve as a potential therapeutic target for cardiac hypertrophy in the future.
A patient–clinician James Lind Alliance partnership to identify research priorities for hyperemesis gravidarum

Objective There are many uncertainties surrounding the aetiology, treatment and sequelae of hyperemesis gravidarum (HG). Prioritising research questions could reduce research waste, helping researchers and funders direct attention to those questions which most urgently need addressing. The HG priority setting partnership (PSP) was established to identify and rank the top 25 priority research questions important to both patients and clinicians. Methods Following the James Lind Alliance (JLA) methodology, an HG PSP steering group was established. Stakeholders representing patients, carers and multidisciplinary professionals completed an online survey to gather uncertainties. Eligible uncertainties related to HG. Uncertainties on nausea and vomiting of pregnancy and those on complementary treatments were not eligible. Questions were verified against the evidence. Two rounds of prioritisation included an online ranking survey and a 1-hour consensus workshop. Results 1009 participants (938 patients/carers, 118 professionals with overlap between categories) submitted 2899 questions. Questions originated from participants in 26 different countries, and people from 32 countries took part in the first prioritisation stage. 66 unique questions emerged, which were evidence checked according to the agreed protocol. 65 true uncertainties were narrowed via an online ranking survey to 26 unranked uncertainties. The consensus workshop was attended by 19 international patients and clinicians who reached consensus on the top 10 questions for international researchers to address. More patients than professionals took part in the surveys but were equally distributed during the consensus workshop. Participants from low-income and middle-income countries noted that the priorities may be different in their settings. Conclusions By following the JLA method, a prioritised list of uncertainties relevant to both HG patients and their clinicians has been identified which can inform the international HG research agenda, funders and policy-makers. While it is possible to conduct an international PSP, results from developed countries may not be as relevant in low-income and middle-income countries.
Omics Integration Analysis Unravel the Landscape of Driving Mechanisms of Colorectal Cancer

Colorectal cancer (CRC) is one of the most malignant cancers and results in a substantial rate of morbidity and mortality. Diagnosis of this malignancy in early stages increases the chance of effective treatment. High-throughput data analyses reveal omics signatures and also provide the possibility of developing computational models for early detection of this disease. Such models would be able to use as complementary tools for early detection of different types of cancers including CRC. In this study, using gene expression data, the Flux balance analysis (FBA) applied to decode metabolic fluxes in cancer and normal cells. Moreover, transcriptome and genome analyses revealed driver agents of CRC in a biological network scheme. By applying comprehensive publicly available data from TCGA, different aspect of CRC regulome including the regulatory effect of gene expression, methylation, microRNA, copy number aberration and point mutation profile over protein levels investigated and the results provide a regulatory picture underlying CRC. Compiling omics profiles indicated snapshots of changes in different omics levels and flux rate of CRC. In conclusion, considering obtained CRC signatures and their role in biological operating systems of cells, the results suggest reliable driver regulatory modules that could potentially serve as biomarkers and therapeutic targets and furthermore expand our understanding of driving mechanisms of this disease.
Diketopiperazine and enterotoxin analogues from the mangrove derived-soil Streptomyces sp. SCSIO 41400 and their biological evaluation

Abstract A new diketopiperazine, cyclo-( d -8-acetoxyl-Pro- l -Leu) (1), together with eight known compounds (2–9) including three enterotoxins (2–4), four diketopiperazines (5–8) and maltol (9), were isolated from the mangrove derived-soil Streptomyces sp. SCSIO 41400. The planar structures of all compounds were determined from analysis of NMR spectra, MS, optical rotation and comparing with literature data. The absolute configuration of compound 1 was assigned by electronic circular dichroism (ECD). The isolated compounds (1–9) were tested for their acetyl cholinesterase (AChE) and pancreatic lipase (PL) enzyme inhibitory activities. Among them, the new diketopiperazine (1) displayed preferable PL enzyme inhibitory activity with IC50 value of 27.3 μg/mL, while compounds 2, 5 and 6 showed weak PL enzyme inhibitory activity. Further molecular docking simulation exhibited that compound 1 could be well bind with the catalytic pocket of the PL. Besides, compound 9 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with MIC value of 12.5 μg/mL, which was comparable to that of the positive control ampicillin with MIC value of 3.125 μg/mL.