Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of Premorbid Adjustment and Autistic Traits on Social Cognitive Dysfunction in Schizophrenia

Abstract Objectives: Premorbid dysfunction during childhood and adolescence is well documented in patients with schizophrenia. Literature pointed out multiple premorbid trajectories leading to different patients’ cognitive status, symptomatology, and global functioning after disease onset. This study aimed at identifying groups of premorbid trajectories and disentangling between group differences in clinical and cognitive measures, focusing on theory of mind (ToM) and autistic traits (ATs). Methods: Ninety-seven patients with schizophrenia were recruited and assessed for cognitive and ToM abilities, psychopathology, and ATs. A two-step cluster analysis identified three different groups of patients based on premorbid adjustment during childhood, adolescence, and late adolescence (i.e., stable-good, stable-poor, and “deteriorating”). Results: Compared to 66 healthy controls, results showed a widespread impairment in cognitive and ToM abilities among all groups of patients, except for affective ToM and executive functions in the stable-good group. Moreover, the stable-poor group exhibited more pronounced ATs and a more severe ToM impairment, compared to the other two groups of patients. Conclusions: Our findings highlight the existence of a group of patients with poor premorbid adjustment since childhood, more pronounced ATs and a severe ToM impairment affecting those basic mentalizing skills that are usually preserved in schizophrenia. Results might have intriguing implications in identifying underpinning endophenotypes and implementing cutting-edge rehabilitation programs.
PDLIM1 Inhibits Tumor Metastasis Through Activating Hippo Signaling in Hepatocellular Carcinoma

Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down‐regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis.
Coming to understand the child has autism: A process illustrating parents’ evolving readiness for engaging in care

We report results from a large qualitative study regarding the process of parents coming to understand the child has autism starting from the time of initial developmental concerns. Specifically, we present findings relevant to understanding how parents become motivated and prepared for engaging in care at this early stage. The study included primary data from 45 intensive interviews with 32 mothers and 9 expert professionals from urban and rural regions of Ontario, Canada. Grounded theory methods were used to guide data collection and analysis. Parents’ readiness (motivation and capacity) for engagement develops progressively at different rates as they follow individual paths of meaning making. Four optional steps account for their varied trajectories: forming an image of difference, starting to question the signs, knowing something is wrong, and being convinced it’s autism. Both the nature of the information and professional help parents seek, and the urgency with which they seek them, evolve in predictable ways depending on how far they have progressed in understanding their child has autism. Results indicate the need for sensitivity to parents’ varying awareness and readiness for involvement when engaging with them in early care, tailoring parent support interventions, and otherwise planning family-centered care pathways. Lay Abstract What is already known about the topic? Parents of children with autism often learn about their child’s autism before diagnosis and can spend long periods seeking care (including assessment) before receiving a diagnosis. Meanwhile, parents’ readiness to engage in care at this early stage can vary from parent to parent. What this paper adds? This study revealed how parents come to understand their child has autism—on their own terms, rather than from just talking to professionals. It also explained how parents’ growing awareness of their child’s autism leads them to feel more motivated to engage in care by seeking information and pursuing services. Four “optional steps” described how parents’ growing readiness to engage in care at this early stage can vary, depending on their personal process. Implications for practice, research, or policy The results suggest ways that professionals can be more sensitive (a) to parents’ varying awareness of autism and (b) to their varying readiness for being involved in early care. They also suggest ways to tailor parent supports to their individual situation and design care that is more family centered. Not all parents want high levels of involvement. Depending on their personal process, some parents may need care and support that is directed at them before feeling ready for professionals to engage them in care directed at the child.
Fast‐food restaurant, unhealthy eating, and childhood obesity: A systematic review and meta‐analysis

Excessive access to fast‐food restaurants (FFRs) in the neighbourhood is thought to be a risk factor for childhood obesity by discouraging healthful dietary behaviours while encouraging the exposure to unhealthful food venues and hence the compensatory intake of unhealthy food option. A literature search was conducted in the PubMed, Web of Science, and Embase for articles published until 1 January 2019 that analysed the association between access to FFRs and weight‐related behaviours and outcomes among children aged younger than 18. Sixteen cohort studies and 71 cross‐sectional studies conducted in 14 countries were identified. While higher FFR access was not associated with weight‐related behaviours (eg, dietary quality score and frequency of food consumption) in most studies, it was commonly associated with more fast‐food consumption. Despite that, insignificant results were observed for all meta‐analyses conducted by different measures of FFR access in the neighbourhood and weight‐related outcomes, although 17 of 39 studies reported positive associations when using overweight/obesity as the outcome. This systematic review and meta‐analysis revealed a rather mixed relationship between FFR access and weight‐related behaviours/outcomes among children and adolescents.
Hospital-based Surveillance for Pediatric Bacterial Meningitis in the Era of the 13-Valent Pneumococcal Conjugate Vaccine in Ghana

Abstract Background Global surveillance for vaccine preventable invasive bacterial diseases has been set up by the World Health Organization to provide disease burden data to support decisions on introducing pneumococcal conjugate vaccine (PCV). We present data from 2010 to 2016 collected at the 2 sentinel sites in Ghana. Methods Data were collected from children <5 years of age presenting at the 2 major teaching hospitals with clinical signs of meningitis. Cerebrospinal fluid specimens were collected and tested first at the sentinel site laboratory with conventional microbiology methods and subsequently with molecular analysis, at the World Health Organization Regional Reference Laboratory housed at the Medical Research Council Unit The Gambia, for identification of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, the 3 most common bacteria causing meningitis. Results There were 4008 suspected cases of meningitis during the surveillance period, of which 31 (0.8%) were laboratory confirmed. Suspected meningitis cases decreased from 923 in 2010 to 219 in 2016. Of 3817 patients with available outcome data, 226 (5.9%) died. S. pneumoniae was the most common bacterial pathogen, accounting for 68.5% of confirmed cases (50 of 73). H. influenzae and N. meningitidis accounted for 6.8% (5 of 73) and 21.9% (16 of 73), respectively. The proportion of pneumococcal vaccine serotypes causing meningitis decreased from 81.3% (13 of 16) before the introduction of 13-valent PCV (2010–2012) to 40.0% (8 of 20) after its introduction (2013–2016). Conclusions Cases of suspected meningitis decreased among children <5 years of age between 2010 and 2016, with declines in the proportion of vaccine-type pneumococcal meningitis after the introduction of 13-valent PCV in Ghana.
Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

Abstract Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. In this study, we characterize the mechanisms by which naïve mesenchymal stromal cells (MSCs) can acquire a CA-MSCs phenotype. Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells, resulting in the secretion of high levels of CXC chemokine receptors 1 and 2 (CXCR1/2) ligands such as chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and interleukin 8 (IL-8). CXCR1/2 ligands can also inhibit the immune response against ovarian tumor cells. Indeed, through their released factors, CA-MSCs promote the differentiation of monocytes towards M2 macrophages, which favors tumor progression. When CXCR1/2 receptors are inhibited, these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral phenotype. Both ex vivo and in vivo, we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of CA-MSCs. Since high concentrations of CXCR1/2 ligands in patients’ blood are associated with chemoresistance, CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.
Automatic detection of contouring errors using convolutional neural networks

Purpose To develop a head and neck normal structures autocontouring tool that could be used to automatically detect the errors in autocontours from a clinically validated autocontouring tool. Methods An autocontouring tool based on convolutional neural networks (CNN) was developed for 16 normal structures of the head and neck and tested to identify the contour errors from a clinically validated multiatlas‐based autocontouring system (MACS). The computed tomography (CT) scans and clinical contours from 3495 patients were semiautomatically curated and used to train and validate the CNN‐based autocontouring tool. The final accuracy of the tool was evaluated by calculating the Sørensen–Dice similarity coefficients (DSC) and Hausdorff distances between the automatically generated contours and physician‐drawn contours on 174 internal and 24 external CT scans. Lastly, the CNN‐based tool was evaluated on 60 patients' CT scans to investigate the possibility to detect contouring failures. The contouring failures on these patients were classified as either minor or major errors. The criteria to detect contouring errors were determined by analyzing the DSC between the CNN‐ and MACS‐based contours under two independent scenarios: (a) contours with minor errors are clinically acceptable and (b) contours with minor errors are clinically unacceptable. Results The average DSC and Hausdorff distance of our CNN‐based tool was 98.4%/1.23 cm for brain, 89.1%/0.42 cm for eyes, 86.8%/1.28 cm for mandible, 86.4%/0.88 cm for brainstem, 83.4%/0.71 cm for spinal cord, 82.7%/1.37 cm for parotids, 80.7%/1.08 cm for esophagus, 71.7%/0.39 cm for lenses, 68.6%/0.72 for optic nerves, 66.4%/0.46 cm for cochleas, and 40.7%/0.96 cm for optic chiasm. With the error detection tool, the proportions of the clinically unacceptable MACS contours that were correctly detected were 0.99/0.80 on average except for the optic chiasm, when contours with minor errors are clinically acceptable/unacceptable, respectively. The proportions of the clinically acceptable MACS contours that were correctly detected were 0.81/0.60 on average except for the optic chiasm, when contours with minor errors are clinically acceptable/unacceptable, respectively. Conclusion Our CNN‐based autocontouring tool performed well on both the publically available and the internal datasets. Furthermore, our results show that CNN‐based algorithms are able to identify ill‐defined contours from a clinically validated and used multiatlas‐based autocontouring tool. Therefore, our CNN‐based tool can effectively perform automatic verification of MACS contours.
Drug Metabolite Cluster-Based Data-Mining Method for Comprehensive Metabolism Study of 5-hydroxy-6,7,3′,4′-tetramethoxyflavone in Rats

The screening of drug metabolites in biological matrixes and structural characterization based on product ion spectra is among the most important, but also the most challenging due to the significant interferences from endogenous species. Traditionally, metabolite detection is accomplished primarily on the basis of predicted molecular masses or fragmentation patterns of prototype drug metabolites using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Although classical techniques are well-suited for achieving the partial characterization of prototype drug metabolites, there is a pressing need for a strategy to enable comprehensive drug metabolism depiction. Therefore, we present drug metabolite clusters (DMCs), different from, but complementary to, traditional approaches for mining the information regarding drugs and their metabolites on the basis of raw, processed, or identified tandem mass spectrometry (MS/MS) data. In this paper, we describe a DMC-based data-mining method for the metabolite identification of 5-hydroxy-6,7,3′,4′-tetramethoxyflavone (HTF), a typical hydroxylated-polymethoxyflavonoid (OH-PMF), which addressed the challenge of creating a thorough metabolic profile. Consequently, eight primary metabolism clusters, sixteen secondary metabolism clusters, and five tertiary metabolism clusters were proposed and 106 metabolites (19 potential metabolites included) were detected and identified positively and tentatively. These metabolites were presumed to generate through oxidation (mono-oxidation, di-oxidation), methylation, demethylation, methoxylation, glucuronidation, sulfation, ring cleavage, and their composite reactions. In conclusion, our study expounded drug metabolites in rats and provided a reference for further research on therapeutic material basis and the mechanism of drugs.
Experience with a “Feed and Swaddle” program in infants up to six months of age

Feed and swaddle is a technique in which an infant is fed and allowed to fall asleep to facilitate diagnostic imaging. This study reviews our experience and diagnostic success in premature and term infants up to 6 months old undergoing brain magnetic resonance imaging (MRI) using a feed and swaddle technique and with comparable patients imaged under anesthesia.
Substrate characteristic bacterial fatty acid production based on amino acid assimilation and transformation in marine sediments.

Polar lipid-derived fatty acids (PLFAs) and their stable carbon isotopes are frequently combined to characterize microbial populations involved in the degradation of organic matter, offering a link to biogeochemical processes and carbon sources used. However, PLFA patterns derive from multiple species and may be influenced by substrate types. Here we investigated such dependencies by monitoring the transformation of position-specifically 13C-labelled amino acids in coastal marine sediments dominated by heterotrophic bacteria. Alanine was assimilated into straight-chain FAs, while valine and leucine incorporation led to the characteristic production of even- and odd-numbered iso-series FAs. This suggests that identical microbial communities adjust lipid biosynthesis according to substrate availability. Transformation into precursor molecules for FA biosynthesis was manifested in increased 13C recoveries of the corresponding volatiles acetate, isobutyrate and isovalerate of up to 39.1%, much higher than for PLFAs (<0.9%). A significant fraction of 13C was found in dissolved inorganic carbon (up to 37.9%), while less was recovered in total organic carbon (up to 17.3%). We observed a clear discrimination against the carboxyl C, whereby C2 and C3 positions were preferentially incorporated into PLFAs. Therefore, position-specific labelling is an appropriate tool for reconstructing the metabolic fate of protein-derived AAs in marine environments.
Pharmacy Students’ Utilization of an Online Tool for Immediate Formative Feedback on Reflective Writing Tasks

Objective. To assess pharmacy students’ perceptions of the benefits and utility of a novel online reflective-writing tool. Methods. After completing a required Academic Writing Analytics (AWA) workshop, Master of Pharmacy students submitted a reflective writing assignment in the AWA web application. A six-item survey was administered to students prior to and immediately after using AWA. Results. Sixty students volunteered to participate in the study; however, only 39 students provided a pseudonym that allowed their pretest and posttest to be matched. A comparison of students’ responses on the pretest with those on the posttest, which was administered four weeks after the workshop, suggest a noticeable increase in agreement with AWA’s benefits as an effective, online tool for improving their reflective learning skills. Conclusion. This novel online tool has the potential to assist pharmacy students with self-critiquing and improving their reflective writing assignments prior to submission. Furthermore, as the elements of reflection are transferable, this tool has the potential to be used in other educational contexts.
Emulsion electrospun PLA/calcium alginate nanofibers for periodontal tissue engineering

Objective The regeneration of periodontal bone tissue is a major obstacle in tissue engineering. We have recently designed a compound nanofiber scaffold for the tissue repair of periodontal bone, which was composed of poly(lactic acid) (PLA) and calcium alginate (CA). The obtained improvements in both physical properties and biological effects on periodontal tissue were systematically evaluated and discussed. Method Neat PLA and PLA/CA nanofiber scaffolds were prepared by electrospinning technology. Scanning electron microscopy was applied for the observation of surface morphology. Their mechanical properties were evaluated in terms of elongation at break and elastic modulus. Hydrophilic/hydrophobic nature of the nanofibers was investigated by a stereomicroscope, and their vitro degradation was tested as well. Cell proliferation and adhesion were detected in order to evaluate the biocompatibility of nanofiber scaffolds. Expression of cell mineralization gene and formation of mineralization knots were examined so as to assess scaffolds’ capability of regenerating bone tissues. The expression of Toll-like receptor 4 (TLR4), IL-6, IL-8, and IL-1β was utilized to decide the possibility of tissue inflammation caused by the nanofibers with the assistance of reverse transcription-polymerase chain reaction (RT-PCR) assay. Results The obtained nanofibers possessed uniform surface morphology. The elongation at break and elastic modulus of PLA/CA nanofiber scaffolds were higher than those of neat PLA. CA could enhance the hydrophilicity of PLA fibers; in the meantime, it promoted cell adhesion of periodontal ligament cells (PDLCs) and bone marrow stromal cells (BMSCs). Addition of CA had raised the expression level of cell mineralization gene and the formation of mineralization knots (BMSCs). On the other hand, both neat PLA fibers and PLA/CA fibers could induce higher expression level of inflammatory mediators and TLR4 of human periodontal ligament cells (hPDLCs). Conclusions The introduction of CA enhanced the mechanical properties of neat PLA nanofibers and increased its hydrophilicity. Neat PLA nanofibers and PLA/CA scaffold could both facilitate BMSCs proliferation, while the addition of CA promoted BMSCs osteogenic differentiation. The improved (or enhanced) expression of inflammatory mediators caused by nanofibers might be regulated via TLR4 pathway.
Drosophila melanogaster Mutated in its GBA1b Ortholog Recapitulates Neuronopathic Gaucher Disease

Gaucher disease (GD) results from mutations in the GBA1 gene, which encodes lysosomal glucocerebrosidase (GCase). The large number of mutations known to date in the gene lead to a heterogeneous disorder, which is divided into a non-neuronopathic, type 1 GD, and two neurological, type 2 and type 3, forms. We studied the two fly GBA1 orthologs, GBA1a and GBA1b. Each contains a Minos element insertion, which truncates its coding sequence. In the GBA1am/m flies, which express a mutant protein, missing 33 C-terminal amino acids, there was no decrease in GCase activity or substrate accumulation. However, GBA1bm/m mutant flies presented a significant decrease in GCase activity with concomitant substrate accumulation, which included C14:1 glucosylceramide and C14:0 glucosylsphingosine. GBA1bm/m mutant flies showed activation of the Unfolded Protein Response (UPR) and presented inflammation and neuroinflammation that culminated in development of a neuronopathic disease. Treatment with ambroxol did not rescue GCase activity or reduce substrate accumulation; however, it ameliorated UPR, inflammation and neuroinflammation, and increased life span. Our results highlight the resemblance between the phenotype of the GBA1bm/m mutant fly and neuronopathic GD and underlie its relevance in further GD studies as well as a model to test possible therapeutic modalities.
Effects of pharmacologically induced Leydig cell testosterone production on intratesticular testosterone and spermatogenesis†

Abstract The Leydig cells of the mammalian testis produce testosterone (T) in response to luteinizing hormone (LH). In rats and men with reduced serum T levels, T replacement therapy (TRT) will raise T levels, but typically with suppressive effects on sperm formation. The rate-determining step in T formation is the translocation of cholesterol to the inner mitochondrial membrane, mediated by protein–protein interactions of cytosolic and outer mitochondrial membrane proteins. Among the involved proteins is cholesterol-binding translocator protein (TSPO) (18 kDa TSPO). We hypothesized that in contrast to TRT, the administration of the TSPO agonist N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide (FGIN-1-27), by stimulating the ability of the Leydig cells to produce T, would result in the elevation of serum T levels while maintaining intratesticular T concentration and therefore without suppression of spermatogenesis. Age-related reductions in both serum and intratesticular T levels were seen in old Brown Norway rats. Both exogenous T and FGIN-1-27 increased serum T levels. With exogenous T, serum LH and Leydig cell T formation were suppressed, and intratesticular T was reduced to below the concentration required to maintain spermatogenesis quantitatively. In contrast, FGIN-1-27 stimulated Leydig cell T formation, resulting in increased serum T without reductions in intratesticular T concentrations or in testicular sperm numbers. FGIN-1-27 also significantly increased serum and intratesticular T levels in rats made LH-deficient by treatment with the gonadotropin-releasing hormone antagonist cetrorelix. These results point to a possible approach to increasing serum T without negative effects on spermatogenesis, based upon stimulating T production by the Leydig cells themselves rather than administering T exogenously. Summary Sentence The TSPO agonist FGIN-1-27 stimulates the ability of the Leydig cells producing testosterone and results in elevating serum and intratesticular testosterone without negative effect on spermatogenesis.