Miracle-dz/UniFAR-FTUs huggingface dataset:
Facilitating factors and barriers in help-seeking behaviour in adolescents and young adults with depressive symptoms: A qualitative study

Objective Despite the availability of mental health care, only a minority of depressed adolescents and young adults receive treatment. This study aimed to investigate facilitating factors and barriers in help-seeking behaviour of adolescents and young adults with depressive symptoms, using qualitative research methods. Methods In-depth, semi-structured interviews with 32 participants with current or previous depressive symptoms aged 16 to 24 years using thematic content analysis. Findings Our sample consisted mainly of adolescents who eventually found their way to professional help. Five main themes in help-seeking by adolescents and young adults were identified: (I) Individual functioning and well-being, (II) Health literacy, (III) Attitudinal aspects, (IV) Surroundings, and (V) Accessibility. Prompts to seek treatment were disease burden and poor academic performance. Health illiteracy negatively influenced treatment-seeking behaviour. Attitudinal aspects either hampered (shame, wanting to handle the problem oneself, negative attitudes towards treatment) or facilitated (positive attitudes towards treatment) help-seeking. Furthermore, adolescents’ surroundings (school, family, and peers) appeared to play a critical role in the recognition of depressive symptoms and encouragement to seek help. Barriers regarding accessibility of mental health care were found, whereas direct and easy access to treatment greatly improved mental health care use. Conclusion Facilitating factors can play a critical role in the help-seeking process of depressed adolescents and young adults, and may guide efforts to increase access to mental health care of this vulnerable age group. In particular, recognition and encouragement from school personnel and peers and easy access to care providers positively influenced help-seeking in our sample. Health illiteracy and attitudinal aspects appeared to be important barriers to seeking treatment and public/school campaigns aimed at reducing health illiteracy and stigma might be necessary to improve treatment-seeking and health care utilization in this age group.
Association of metabolic syndrome with the incidence of low-grade albuminuria: a cohort study in middle-aged and elderly Chinese adults

Background: Individuals with metabolic syndrome have elevated risks of micro- and macro-albuminuria as well as chronic kidney disease (CKD). Objective: To assess the influence of metabolic abnormalities on the presence of low-grade albuminuria (below the threshold for microalbuminuria). Design, participants, and main outcome measures: This community-based cohort study included 3,935 eligible individuals aged 40 years or older. The presence of low-grade albuminuria was detected in those without micro- or macro-albuminuria and analyzed according to the highest quartile of the baseline urinary albumin-to-creatinine ratio (ACR ≥11.13 mg/g). CKD was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the new presence of albuminuria (ACR ≥30 mg/g). Results: Overall, 577 (14.7%) participants developed low-grade albuminuria and 164 (4.2%) participants developed CKD during a mean follow-up period of 3.6 years. Compared with participants without metabolic syndrome, those with metabolic syndrome had greater risks of low-grade albuminuria [adjusted odd ratio (OR) and 95% confidence interval (95% CI): 1.30 (1.05–1.61)] and CKD [1.71 (1.20–2.44)]. Moreover, the incidence rates of low-grade albuminuria and CKD increased as the number of metabolic syndrome components increased (P for trend <0.0001). Conclusions: The presence of metabolic syndrome is associated with increased incidence rates of low-grade albuminuria and CKD the middle-aged and elderly Chinese populations.
A QSAR for Baseline Toxicity: Validation, Domain of Application, and Prediction

The interest in modeling and application of structure-activity relationships has steadily increased in recent decades. It is generally acknowledged that these empirical relationships are valid only within the same domain for which they were developed. However, model validation is sometimes neglected, and the application domain is not always well-defined. The purpose of this paper is to outline how validation and domain definition can facilitate the modeling and prediction of baseline toxicity for a large database. A large number of theoretical descriptors (867) were generated from two-dimensional molecular structures for compounds present in the U.S. EPA's Fathead Minnow Database (611) and the Syracuse Research Corporation's PhysProp Database (25,000+). A quantitative structure-activity relationship model was developed for baseline toxicity (narcosis) toward the fathead minnow (Pimephales promelas) using a projection-based regression technique, PLSR (partial least squares regression). The PLSR model was subsequently validated with an external test set. The main factors of variation were related to size/shape and polar interactions. The prediction error was comparable to, or slightly better than, the ECOSAR procedures. A set of 16,805 compounds, drawn from the PhysProp Database, was projected onto the PLSR model. More than 90% (15,597) of the compounds fall within the valid model domain, defined by the residual standard deviation and the leverage. The predicted baseline toxicity indicates an acute hazard for two-thirds of these compounds, classes I-III in the OECD Globally Harmonized Classification System (LC50 < or = 100 mg L(-1)). Finally, the mode of action assigned in the U.S. EPA Fathead Minnow Database was investigated. Reclassification to narcosis as the mode of action is suggested for 92 compounds, mostly from the groups "unsure" and "mixed". The present classification into specific modes of action seems to be further strengthened by the findings in this investigation.
Spatial profiling technologies and applications for brain cancers

ABSTRACT Introduction Malignant primary and secondary brain tumors pose a major health challenge, and the incidence of these tumors is rising. The brain tumor microenvironment (TME) is highly complex and thought to impact treatment resistance and failure. To enable a greater understanding of the milieu of cells in the brain TME, advances in imaging and sequential profiling of proteins/mRNA have given rise to the field of spatial transcriptomics. These technologies provide a greater depth of understanding of the tissue architecture, cellular and spatial profiles, including cellular activation status, which may provide insights into effective therapies for brain cancers. Areas Covered In this review, we provide an overview of spatial profiling technologies at the forefront in the field and describe the applications for brain cancer. Expert opinion Brain tumors are often resistant to treatment, and display both an immunosuppressive and heterogeneous tumor microenvironment. Next-generation imaging and multi-omics technologies are providing a tool for intricately characterizing their tissue biology. This information will aid in the design of effective therapies and begin to provide an understanding of therapy resistance.
Complementation in trans of Porphyromonas gingivalis Lipopolysaccharide Biosynthetic Mutants Demonstrates Lipopolysaccharide Exchange

Porphyromonas gingivalis is a keystone pathogen contributing to periodontitis in humans, leading to tooth loss. The oral microbiota is essential in this pathogenic process and changes from predominantly Gram-positive (health) to predominantly Gram-negative (disease) species. P. gingivalis uses its type IX secretion system (T9SS) to secrete and conjugate virulence proteins to anionic lipopolysaccharide (A-LPS). ABSTRACT Porphyromonas gingivalis, a bacterial pathogen contributing to human periodontitis, exports and anchors cargo proteins to its surface, enabling the production of black pigmentation using a type IX secretion system (T9SS) and conjugation to anionic lipopolysaccharide (A-LPS). To determine whether T9SS components need to be assembled in situ for correct secretion and A-LPS modification of cargo proteins, combinations of nonpigmented mutants lacking A-LPS or a T9SS component were mixed to investigate in trans complementation. Reacquisition of pigmentation occurred only between an A-LPS mutant and a T9SS mutant, which coincided with A-LPS modification of cargo proteins detected by Western blotting and coimmunoprecipitation/quantitative mass spectrometry. Complementation also occurred using an A-LPS mutant mixed with outer membrane vesicles (OMVs) or purified A-LPS. Fluorescence experiments demonstrated that OMVs can fuse with and transfer lipid to P. gingivalis, leading to the conclusion that complementation of T9SS function occurred through A-LPS transfer between cells. None of the two-strain crosses involving only the five T9SS OM component mutants produced black pigmentation, implying that the OM proteins cannot be transferred in a manner that restores function and surface pigmentation, and hence, a more ordered temporal in situ assembly of T9SS components may be required. Our results show that LPS can be transferred between cells or between cells and OMVs to complement deficiencies in LPS biosynthesis and hemin-related pigmentation to reveal a potentially new mechanism by which the oral microbial community is modulated to produce clinical consequences in the human host. IMPORTANCE Porphyromonas gingivalis is a keystone pathogen contributing to periodontitis in humans, leading to tooth loss. The oral microbiota is essential in this pathogenic process and changes from predominantly Gram-positive (health) to predominantly Gram-negative (disease) species. P. gingivalis uses its type IX secretion system (T9SS) to secrete and conjugate virulence proteins to anionic lipopolysaccharide (A-LPS). This study investigated whether components of this secretion system could be complemented and found that it was possible for A-LPS biosynthetic mutants to be complemented in trans both by strains that had the A-LPS on the cell surface and by exogenous sources of A-LPS. This is the first known example of LPS exchange in a human bacterial pathogen which causes disease through complex microbiota-host interactions.
Fecal Mycobiota Combined with Host Immune Factors Distinguish Clostridioides difficile Infection from Asymptomatic Carriage.

BACKGROUND & AIMS Although the role of gut microbiota in Clostridioides difficile infection (CDI) has been well established, little is known about the role of mycobiota in CDI. Here, we performed mycobiome data analysis in a well-characterized human cohort to evaluate the potential of using gut mycobiota features for CDI diagnosis. METHODS Stool samples were collected from 118 hospital patients, divided into three groups: CDI (n = 58), asymptomatic carriers (Carrier, n = 28) and Control (n = 32). The nuclear ribosomal DNA internal transcribed spacer 2 was sequenced using the Illumina HiSeq platform to assess the fungal composition. Downstream statistical analyses (including Alpha diversity analysis, ordination analysis, differential abundance analysis, fungal correlation network analysis, and classification analysis) were then performed. RESULTS Significant differences were observed in alpha and beta diversity between CDI patients and Carrier (P < .05). Differential abundance analysis identified two genera (Cladosporium and Aspergillus) enriched in Carrier. The ratio of Ascomycota to Basidiomycota was dramatically higher in CDI patients than in Carrier and Control (P < .05). Correlations between host immune factors and mycobiota features were weaker in CDI patients than in Carrier. Using 4 fungal OTUs combined with 6 host immune markers in the random forest classifier can achieve very high performance (AUC∼92.38%) in distinguishing CDI patients from Carrier. CONCLUSIONS Our study provides specific markers of stool fungi combined with host immune factors to distinguish CDI patients from Carrier. It highlights the importance of gut mycobiome in CDI, which may have been underestimated. Further studies on the diagnostic applications and therapeutic potentials of these findings are warranted.
WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms

ABSTRACT Autophagosome formation requires PROPPIN/WIPI proteins and monophosphorylated phosphoinositides, such as phosphatidylinositol-3-phosphate (PtdIns3P) or PtdIns5P. This process occurs in association with mammalian endosomes, where the PROPPIN WIPI1 has additional, undefined roles in vesicular traffic. To explore whether these functions are interconnected, we dissected routes and subreactions of endosomal trafficking requiring WIPI1. WIPI1 specifically acts in the formation and fission of tubulo-vesicular endosomal transport carriers. This activity supports the PtdIns(3,5)P2-dependent transport of endosomal cargo toward the plasma membrane, Golgi, and lysosomes, suggesting a general role of WIPI1 in endosomal protein exit. Three features differentiate the endosomal and macroautophagic/autophagic activities of WIPI1: phosphoinositide binding site II, the requirement for PtdIns(3,5)P2, and bilayer deformation through a conserved amphipathic α-helix. Their inactivation preserves autophagy but leads to a strong enlargement of endosomes, which accumulate micrometer-long endosomal membrane tubules carrying cargo proteins. WIPI1 thus supports autophagy and protein exit from endosomes by different modes of action. We propose that the type of phosphoinositides occupying its two lipid binding sites, the most unusual feature of PROPPIN/WIPI family proteins, switches between these effector functions. Abbreviations: EGF: epidermal growth factorEGFR: epidermal growth factor receptorKD: knockdownKO: knockoutPtdIns3P: phosphatidylinositol-3-phosphatePtdIns5P: phosphatidylinositol-5-phosphatePtdIns(3,5)P2: phosphatidylinositol-3,5-bisphosphateTF: transferrinTFRC: transferrin receptorWT: wildtype
Molecular Actions Underlying Wolffian Duct Regression in Sexual Differentiation of Murine Reproductive Tracts

Sexually dimorphic establishment of the reproductive tract system requires sex-specific regression of the Wolffian duct and Müllerian duct in the mesonephros. In an XX embryo, the Wolffian duct regresses under the control of the mesenchymal transcription factor COUP-TFII. To understand cellular and molecular actions underlying Wolffian duct regression, we performed transcriptomic analyses of XX mesonephroi with or without Coup-tfII and genome-wide analysis of COUP-TFII chromatin occupancy in XX mesonephroi. The integrative analysis of COUP-TFII genome-wide binding and transcriptomic analysis revealed the suppression of muscle differentiation and extracellular matrix genes by COUP-TFII and identified a group of potential transcriptional partners of COUP-TFII in the mesenchyme that potentially facilitate Wolffian duct regression. These findings provide insights into the molecular action of COUP-TFII in the Wolffian duct mesenchyme and identify a list of biologically relevant candidate genes and pathways for future functional analyses in sexual differentiation of reproductive tracts.
Kola nut from Cola nitida vent. Schott administered to pregnant rats induces histological alterations in pups’ cerebellum

Kola nut (from Cola nitida) is popular in Nigeria and West Africa and is commonly consumed by pregnant women during the first trimester to alleviate morning sickness and dizziness. There is, however, a dearth of information on its effects on the developing brain. This study, therefore, investigated the potential effects of kola nut on the structure of the developing neonatal and juvenile cerebellum in the rat. Pregnant Wistar rats were administered water (as control) or crude (aqueous) kola nut extract at 400, 600, and 800 mg/kg body weight orally, from pregnancy to day 21 after birth. On postnatal days 1, 7, 14, 21 and 28, the pups were weighed, anaesthetised, sacrificed and perfused with neutral buffered formalin. Their brains were dissected out, weighed and the cerebellum preserved in 10% buffered formalin. Paraffin sections of the cerebellum were stained with haematoxylin and eosin for cerebellar cytoarchitecture, cresyl violet stain for Purkinje cell count, Glial Fibrillary Acidic Protein (GFAP) immunohistochemistry (IHC) for estimation of gliosis, and B-cell lymphoma 2 (Bcl-2) IHC for apoptosis induction. The kola nut-treated rats exhibited initial reduction in body and brain weights, persistent external granular layer, increased molecular layer thickness, and loss of Bergmann glia. Their Purkinje cells showed reduction in density, loss of dendrites and multiple layering, and their white matter showed neurodegeneration (spongiosis) and GFAP and Bcl-2 over-expression, with evidence of reactive astrogliosis. This study, therefore, demonstrates that kola nut, administered repeatedly at certain doses to pregnant dams, could disrupt normal postnatal cerebellar development in their pups. The findings suggest potential deleterious effects of excessive kola nut consumption on human brain and thus warrant further studies to understand the wider implications for human brain development.
Structural, electronic and elastic properties of FeBO3 (B = Ti, Sn, Si, Zr) ilmenite: a density functional theory study

FeBO3 (B = Ti, Sn, Si, Zr) materials were simulated from Density Functional Theory (DFT) with the B3LYP hybrid functional to investigate the B-site replacement effect on the ilmenite structure. Lattice parameters, bond distances, bulk-modulus, density of states (DOS), Mulliken population analysis and charge density maps were examined. Calculated structural parameters were in agreement with experimental results and revealed that the unit cell volume was controlled by the ionic radius of the B-site metals. The bulk-modulus obtained indicated that these results were influenced by different material densities. The electronic results showed that the band-gap and structural stability were influenced by the energy levels and electronegativity of the metals occupying the B-site, as shown in the literature. Mulliken population analysis and charge density maps show the magnetic property for a Fe atom in the d6 configuration and charge corridor formation in the [001] direction due to the intermetallic connection.
Missense Mutations in the CrrB Protein Mediate Odilorhabdin Derivative Resistance in Klebsiella pneumoniae

NOSO-502 is a preclinical antibiotic candidate of the odilorhabdin class. This compound exhibits activity against Enterobacteriaceae pathogens, including carbapenemase-producing bacteria and most of the colistin (CST)-resistant strains. ABSTRACT NOSO-502 is a preclinical antibiotic candidate of the odilorhabdin class. This compound exhibits activity against Enterobacteriaceae pathogens, including carbapenemase-producing bacteria and most of the colistin (CST)-resistant strains. Among a collection of CST-resistant Klebsiella pneumoniae strains harboring mutations in the genes pmrAB, mgrB, phoPQ, and crrB, only those bearing mutations in the gene crrB were found to be resistant to NOSO-502. CrrB is a histidine kinase which acts with the response regulator CrrA to modulate the PmrAB system, which induces the restructuring of lipopolysaccharide on the outer membrane and thus leads to CST resistance. Moreover, crrB mutations also enhance the transcription of neighboring genes, such as H239_3063, encoding an ABC transporter transmembrane region, H239_3064, encoding a putative efflux pump also known as KexD, and H239_3065, encoding an N-acetyltransferase. To elucidate the mechanism of resistance to NOSO-502 induced by CrrB missense mutations in K. pneumoniae, mutants of NCTC 13442 and ATCC BAA-2146 strains resistant to NOSO-502 and CST with single amino acid substitutions in CrrB (S8N, F33Y, Y34N, W140R, N141I, P151A, P151L, P151S, P151T, or F303Y) were selected. Full susceptibility to NOSO-502 was restored in crrA- or crrB-deleted K. pneumoniae NCTC 13442 CrrB (P151L) mutants, confirming the role of CrrAB in controlling this resistance pathway. Deletion of kexD (but not other neighboring genes) in the same mutant also restored NOSO-502-susceptibility. Upregulation of the kexD gene expression was observed for all CrrB mutants. Finally, plasmid expression of kexD in a K. pneumoniae strain missing the locus crrABC and kexD significantly increased resistance to NOSO-502.
Microbiota functional activity biosensors for characterizing nutrient metabolism in vivo

Methods for measuring gut microbiota biochemical activities in vivo are needed to characterize its functional states in health and disease. To illustrate one approach, an arabinan-containing polysaccharide was isolated from pea fiber, its structure defined, and forward genetic and proteomic analyses used to compare its effects, versus unfractionated pea fiber and sugar beet arabinan, on a human gut bacterial strain consortium in gnotobiotic mice. We produced ‘Microbiota Functional Activity Biosensors’ (MFABs) consisting of glycans covalently linked to the surface of fluorescent paramagnetic microscopic glass beads. Three MFABs, each containing a unique glycan/fluorophore combination, were simultaneously orally gavaged into gnotobiotic mice, recovered from their intestines, and analyzed to directly quantify bacterial metabolism of structurally distinct arabinans in different human diet contexts. Colocalizing pea-fiber arabinan and another polysaccharide (glucomannan) on the bead surface enhanced in vivo degradation of glucomannan. MFABs represent a potentially versatile platform for developing new prebiotics and more nutritious foods.
Identification and validation of a two-gene metabolic signature for survival prediction in patients with kidney renal clear cell carcinoma

Metabolic reprogramming contributes to the high mortality of advanced stage kidney renal clear cell carcinoma (KIRC), the most common renal cancer subtype. This study aimed to identify a metabolism-related gene (MRG) signature to improve survival prediction in KIRC patients. We downloaded RNA sequencing data and corresponding clinical information for KIRC and control samples from The Cancer Genome Atlas database and identified, based on an MRG dataset in the Molecular Signatures Database, 123 MRGs with differential expression in KIRC. Following Cox regression analysis and least absolute shrinkage and selection operator selection, RRM2 and ALDH6A1 were identified as prognosis-related genes and used to construct a prognostic signature with independent prognostic significance. After risk score-based patient separation, stratified survival analysis indicated that high-risk patients showed poorer overall survival than low-risk patients. We then constructed a clinical nomogram that showed a concordance index of 0.774 and good performance based upon calibration curves. Gene set enrichment analysis revealed several metabolic pathways significantly enriched in the target genes. The two-gene metabolic signature identified herein may represent a highly valuable tool for KIRC prognosis prediction, and might also help identify new metabolism-related biomarkers and therapeutic targets for KIRC.