Miracle-dz/UniFAR-FTUs huggingface dataset:
The antidepressant-like activity of chiral xanthone derivatives may be mediated by 5-HT1A receptor and β-arrestin signalling

Background: Our previous studies showed that xanthone derivatives with N-(2-methoxyphenyl)piperazine fragment have an affinity to the 5-HT1A receptor and show antidepressant-like properties in rodents. In this study, we tested three xanthone derivatives, HBK-1 (R, S) and its enantiomers, in which we increased the distance between the piperazine and xanthone fragments by using a hydroxypropoxy linker. We hypothesized that this would increase the binding to the 5-HT1A receptor and consequently, pharmacological activity. Aims: We aimed to assess the in vitro and in vivo pharmacological activity of the xanthone derivatives. Methods: We evaluated the in vitro affinity for serotonin 5-HT1A and 5-HT2A receptors and serotonin transporter. We also determined the intrinsic activity at the 5-HT1A receptor. We investigated the antidepressant-like properties and safety after acute administration (dose range: 1.25–20 mg/kg) using the forced swim, tail suspension, locomotor activity, rotarod and chimney tests in mice. We also evaluated the basic pharmacokinetic parameters. Results: Our results indicated that the compounds showed a high affinity for the 5-HT1A receptor but very weak antagonistic properties in the Ca2+ mobilization assay; however, they showed significant agonistic properties in the β-arrestin recruitment assay. In both behavioural tests the studied xanthone derivatives showed antidepressant-like activity. Pre-treatment with p-chlorophenylalanine or WAY-100635 abolished their antidepressant-like activity. None of the compounds caused motor impairments at antidepressant-like doses. The racemate penetrated the blood–brain barrier and had a relatively high bioavailability after intraperitoneal administration. Conclusions: Xanthone derivatives with N-(2-methoxyphenyl)piperazine fragment and hydroxypropoxy linker show increased binding to the 5-HT1A receptor and may represent an attractive putative treatment candidate for depression.
The intestinal quorum sensing 3-oxo-C12:2 Acyl homoserine lactone limits cytokine-induced tight junction disruption

ABSTRACT The intestine is home to the largest microbiota community of the human body and strictly regulates its barrier function. Tight junctions (TJ) are major actors of the intestinal barrier, which is impaired in inflammatory bowel disease (IBD), along with an unbalanced microbiota composition. With the aim to identify new actors involved in host-microbiota interplay in IBD, we studied N-acyl homoserine lactones (AHL), molecules of the bacterial quorum sensing, which also impact the host. We previously identified in the gut a new and prominent AHL, 3-oxo-C12:2, which is lost in IBD. We investigated how 3-oxo-C12:2 impacts the intestinal barrier function, in comparison to 3-oxo-C12, a structurally close AHL produced by the opportunistic pathogen P. aeruginosa. Using Caco-2/TC7 cells as a model of polarized enterocytes, we compared the effects on paracellular permeability and TJ integrity of these two AHL, separately or combined with pro-inflammatory cytokines, Interferon-γ and Tumor Necrosis Factor-α, known to disrupt the barrier function during IBD. While 3-oxo-C12 increased paracellular permeability and decreased occludin and tricellulin signal at bicellular and tricellular TJ, respectively, 3-oxo-C12:2 modified neither permeability nor TJ integrity. Whereas 3-oxo-C12 potentiated the hyperpermeability induced by cytokines, 3-oxo-C12:2 attenuated their deleterious effects on occludin and tricellulin, and maintained their interaction with their partner ZO-1. In addition, 3-oxo-C12:2 limited the cytokine-induced ubiquitination of occludin and tricellulin, suggesting that this AHL prevented their endocytosis. In conclusion, the role of 3-oxo-C12:2 in maintaining TJ integrity under inflammatory conditions identifies this new AHL as a potential beneficial actor of host–microbiota interactions in IBD.
The dual function of OsSWEET3a as a gibberellin and glucose transporter is important for young shoot development in rice.

Translocation and long-distance transport of phytohormones are considered important processes for phytohormone responses as well as their synthesis and signaling. Here, we report on the dual function of OsSWEET3a, a bidirectional sugar transporter from Clade I of the rice SWEET family of proteins, as both a gibberellin (GA) and a glucose transporter. OsSWEET3a efficiently transports GAs in the C13-hydroxylation pathway of GA biosynthesis. Both knockout and overexpression lines of OsSWEET3a showed defects in germination and early shoot development, which were partially restored by GA, especially GA20. Quantitative reverse transcription PCR, GUS staining, and in situ hybridization revealed that OsSWEET3a was expressed in vascular bundles in basal parts of the seedlings. OsSWEET3a expression co-localized with OsGA20ox1 expression in the vascular bundles but not with OsGA3ox2, whose expression was restricted to leaf primordia and young leaves. These results suggest that OsSWEET3a is expressed in the vascular tissue of basal parts of seedlings and is involved in the transport of both GA20 and glucose to young leaves, where GA20 is possibly converted to the bioactive GA1 form by OsGA3ox2, during early plant development. We also indicated that such GA transport activities of SWEET proteins have sporadically appeared in the evolution of plants: GA transporters in Arabidopsis evolved from sucrose transporters, while those in rice and sorghum have evolved from glucose transporters.
Osteohistology and microanatomy of a new specimen of Cearachelys placidoi (Testudines: Pleurodira) a side‐necked turtle from the lower Cretaceous of Brazil

Pelomedusoides had a recognised diverse Early Cretaceous fauna of turtles in Northeast Brazil. Within them, the bothremydid Cearachelys placidoi has a relatively abundant record. This diversity contrasts with the scarcity of osteohistological studies in this group. The relatively well‐preserved shell of C. placidoi (UFRPE 5600), from the Aptian age of Araripe Basin, is studied here for the purpose of filling this gap. We performed the osteohistological description of the plastron of a new specimen of C. placidoi. Also, to conduct a comparative study, we carried out histological sections in bones of the recent chelid Phrynops sp. Our histological findings indicate similarities between the histological pattern of freshwater turtles and the coastal marine C. placidoi. Moreover, osteohistological features imply metaplastic incorporation of dermal interwoven structural fiber bundles. Lastly, the xiphiplastron of C. placidoi shows an increase of bone compactness over its craniocaudal axis. This microanatomical feature is exclusive to Cearachelys so far.
Graphene‐Based Biomaterials for Bone Regenerative Engineering: A Comprehensive Review of the Field and Considerations Regarding Biocompatibility and Biodegradation

Graphene and its derivatives have continued to garner worldwide interest due to their unique characteristics. Having expanded into biomedical applications, there have been efforts to employ their exceptional properties for the regeneration of different tissues, particularly bone. This article presents a comprehensive review on the usage of graphene‐based materials for bone regenerative engineering. The graphene family of materials (GFMs) are used either alone or in combination with other biomaterials in the form of fillers in composites, coatings for both scaffolds and implants, or vehicles for the delivery of various signaling and therapeutic agents. The applications of the GFMs in each of these diverse areas are discussed and emphasis is placed on the characteristics of the GFMs that have implications in this regard. In tandem and of importance, this article evaluates the safety and biocompatibility of the GFMs and carefully elucidates how various factors influence the biocompatibility and biodegradability of this new class of nanomaterials. In conclusion, the challenges and opportunities regarding the use of the GFMs in regenerative engineering applications are discussed, and future perspectives for the developments in this field are proposed.
Flourishing at work: Nurses' motivation through daily communication – An ethnographic approach

Abstract Shortage and turnover of registered nurses are worldwide challenges, and work motivation is one factor in retaining staff in the healthcare sector. The aim of this study was to explore registered nurses' motivation expressed in daily communication, using the basic needs in self‐determination theory as a framework. A secondary analysis of ethnographic data, collected through participant observations, informal interviews during observations, and individual interviews, was used. A total sample of all registered nurses employed at a hospital unit in Sweden (n = 10) participated. The data were analyzed thematically through the lens of the basic needs in self‐determination theory: autonomy, competence, and relatedness. Self‐regulation of learning, the possibilities to discuss work‐related challenges with colleagues, and having registered nurses lead dialogues with physicians were factors connected to autonomy. Having a registered nurse and physician solve problems together was a factor connected to competence. A sense of belonging and security in a permissive climate between registered nurses was connected to relatedness. This paper has implications for increased awareness of the three basic motivational needs, which could be used in the development of attractive workplaces.
Evaluation of Arylsulfatase D (ARSD) and long noncoding RNA ARSD-AS1 gene expression in breast cancer patients and their association with oncogenic transcription factors.

PURPOSE Long non-coding RNAs (LncRNAs) are thought as tumorigenic factors in cancer progression. We investigated the clinical significance of arylsulfatase D (ARSD) and ARSD antisense in breast cancer patients. METHODS Eighty breast cancer tumors were obtained from the Tumor Bank of Cancer Institute, Imam Khomeini Hospital. The expression level of ARSD and ARSD-AS1 were examined in breast tumors in comparison to the margin of normal tissues using quantitative real-time PCR. Demographic information and the clinicopathologic characteristics including tumor grade, presence of cell receptors, lymph node and vascular invasion were also evaluated. Bioinformatics databases were used for identification of ARSD and ARSD-AS1 molecular targets and their association with cancer. RESULTS Significant up-regulation of ARSD was observed in tumor tissues in comparison with its antisense (p<0.05). Both ARSD and ARSD-AS1 expression in tumor specimens were notably lower than those in adjacent normal tissue. High expression of ARSD was associated to lower tumor grade (p<0.05). Bioinformatics results revealed the interaction of ARSD with STS and SUMF1 proteins was attributed to the inhibiting of sulfates activity. Also, ARSD co-expressed genes were associated with oncogenic transcription factors, MAF and GATA. TP53 transcription factor site was identified as a target of ARSD-AS1 mRNA. The interaction of this antisense with microRNA (miR-618) could explain its participation in tumor cell proliferation. CONCLUSION Low expression of ARSD was associated with higher tumor grade. The evidence from this study enhance our understanding of ARSD and ARSD-AS1 function in cancer gene therapy. Accordingly, they could be introduced as great potential targets for breast cancer treatment.
Skull diversity and evolution in miniaturized amphibians, genus Brachycephalus (Anura: Brachycephalidae)

Miniaturized amphibians of the genus Brachycephalus are phenotypically diverse. The species of Brachycephalus have bufoniform or leptodactyliform Baupläne and any of three skeletal states: nonhyperossified, hyperossified without dorsal shield, and hyperossified with dorsal shield. We integrate high‐resolution microcomputed tomography, geometric morphometrics, and an estimate of molecular phylogenetic relationships to investigate skull diversity in shape and size‐shape space in selected species of Brachycephalus. Skull diversity amongst species of Brachycephalus can be partitioned into shape and size‐shape space according to the four conditions of skeletal states‐Baupläne, namely, nonhyperossified leptodactyliform, nonhyperossified bufoniform, hyperossified bufoniform without dorsal shield, and hyperossified bufoniform with dorsal shield. Skull diversity in shape and size‐shape space in nonhyperossified leptodactyliform species of Brachycephalus is markedly larger, when compared to skull diversity in species of the three other conditions of skeletal states‐Baupläne. Variation in skull shape scales with size across Brachycephalus and, therefore, can be explained by allometry. Skull diversity, Baupläne, and skeletal states covary to a large extent with monophyletic lineages of Brachycephalus, as revealed by a mitochondrial DNA species tree. Nonhyperossified bufoniform species and hyperossified bufoniform species with or without dorsal shield are monophyletic lineages, as inferred from a mitochondrial DNA species tree. Nonhyperossified leptodactyliform species of Brachycephalus do not share, however, a most recent common ancestor. The nonhyperossified leptodactyliform species of Brachycephalus, due to their marked skull diversity and lack of monophyly, emerge as evolutionarily complex. Therefore, further sampling of the nonhyperossified leptodactyliform condition of skeletal states‐Baupläne will be necessary to further understand the evolutionary history of Brachycephalus.
Cross-Domain Authorship Verification Based on Topic Agnostic Features

Authorship veriﬁcation (AV) is a research branch in digital text forensics that deals with the problem to determine whether two documents were written by the same author. Research activities in the context of AV have steadily increased in recent years, which have led to a variety of approaches trying to solve this problem. Many of these approaches, however, make use of features that are related to or inﬂuenced by the topic of the documents. Therefore, it may accidentally happen that their veriﬁcation results are based not on the writing style alone (the actual focus of AV), but on the topic of the documents. To address this problem, we propose in the context of the AV shared task at the PAN 2020 work-shop an alternative approach, which considers only topic-agnostic features in its classiﬁcation decision. On the ofﬁcial test set, our approach was ranked third out of all submitted approaches.
Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model

Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract‐based‐spatial‐statistics of fractional anisotropy (FA), mean‐ (MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model‐derived parameters. Case–control comparisons revealed widespread ALS‐related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel‐wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS.
BROADLY NEUTRALIZING ANTI- HIV-1 ANTIBODIES DO NOT INHIBIT HIV-1 ENV-MEDIATED CELL-CELL FUSION

PG9, PG16, PGT121, and PGT145 antibodies were identified from culture media of activated memory B-cells of an infected donor and shown to neutralize many HIV-1 strains. Since HIV-1 spreads via both free virions and cell-cell fusion, we examined the effect of the antibodies on HIV-1 Env-mediated cell-cell fusion. Clone69TRevEnv cells that express Env in the absence of tetracycline were labeled with Calcein-AM Green, and incubated with CD4+ SupT1 cells labeled with CellTrace™ Calcein Red-Orange, with or without antibodies. Monoclonal antibodies PG9, PG16, 2G12, PGT121, and PGT145 (at up to 50 μg/mL) had little or no inhibitory effect on fusion between HIV-Env and SupT1 cells. By contrast, Hippeastrum hybrid agglutinin completely inhibited fusion. Our results indicate that transmission of the virus or viral genetic material would not be inhibited by these broadly neutralizing antibodies. Thus, antibodies generated by HIV-1 vaccines should be screened for their inhibitory effect on Env-mediated cell-cell fusion.
Impact of a family-centred early intervention programme in South India on caregivers of children with developmental delays

Abstract Background This study evaluated the impact on caregiver strain and family empowerment among caregivers of children with disabilities who received training and education as part of a family-centred community-based early intervention programme in South India. Methods This prospective open cohort longitudinal study compared change from baseline to two years post-intervention among caregivers of the first cohort of children who were enrolled in the programme. Paired t-tests determined effect on the Modified Caregiver Strain Index (MCSI) and Family Empowerment Scale (FES), and p-values were adjusted for multiple comparisons using the False Discovery Rate approach. Results Of the 308 caregivers (91% women), 44% provided care to children with cerebral palsy and 56% to children with other developmental delays. The mean age of the children at baseline was 3.3 (±1.5 years). The overall mean change from baseline in the FES was 4.1 (95% CI: 3.3, 4.9; p < 0.001) representing improved empowerment. The mean change for the MCSI score was −3.7 (95% CI: −4.5, −2.9; p < 0.001) representing reduced caregiver strain. Conclusions A family-centred early intervention programme that provides training and education to caregivers of children with developmental delays demonstrated positive change in caregiver strain and family empowerment. Implications for Rehabilitation The well-being of a child is influenced by the well-being of their caregiver. Improving caregiver well-being can help improve care and support for children with developmental delays. A family-centred early intervention therapy programme that includes training and education to caregivers can reduce strain and improve family empowerment.
Depression, Alcoholics Anonymous Involvement, and Daily Drinking Among Patients with Cooccurring Conditions: A Longitudinal Parallel Growth Mixture Model.

BACKGROUND Patients with cooccurring mental health and substance use disorders often find it difficult to sustain long-term recovery. One predictor of recovery may be how depression symptoms and Alcoholics Anonymous (AA) involvement influence alcohol consumption during and after inpatient psychiatric treatment. This study utilized a parallel growth mixture model to characterize the course of alcohol use, depression, and AA involvement in patients with cooccurring diagnoses. METHODS Participants were adults with cooccurring disorders (n = 406) receiving inpatient psychiatric care as part of a telephone monitoring clinical trial. Participants were assessed at intake, 3-, 9-, and 15-month follow-up. RESULTS A 3-class solution was the most parsimonious based upon fit indices and clinical relevance of the classes. The classes identified were high AA involvement with normative depression (27%), high stable depression with uneven AA involvement (11%), and low AA involvement with normative depression (62%). Both the low and high AA classes reduced their drinking across time and were drinking at less than half their baseline levels at all follow-ups. The high stable depression class reported an uneven pattern of AA involvement and drank at higher daily frequencies across the study timeline. Depression symptoms and alcohol use decreased substantially from intake to 3 months and then stabilized for 90% of patients with cooccurring disorders following inpatient psychiatric treatment. CONCLUSIONS These findings can inform future clinical interventions among patients with cooccurring mental health and substance use disorders. Specifically, patients with more severe symptoms of depression may benefit from increased AA involvement, whereas patients with less severe symptoms of depression may not.
Prognostic Factors of Patients with Stercoral Perforation of the Colon.

Background/Aims The incidence of stercoral perforation of the colon (SPC) is expected to rise, given the increased life expectancy and the aging population. On the other hand, the prognostic factors of mortality after surgery for SPC remain unclear. This study examined the prognostic factors of patients with SPC after surgery. Methods The medical records of 145 patients who underwent surgery for colonic perforation between April 2010 and May 2019 were reviewed retrospectively. In 145 patients, 22 patients who underwent SPC surgery were categorized into the following two groups according to in-hospital survival after surgery: alive (group A, n=15) and dead (group B, n=7). Results In all enrolled patients, the mean age was 75.7±9.0 years, with a female predominance (female patients, n=19, 86.4%). Sixteen patients (72.7%) had chronic constipation with medications, and five patients (22.7%) were bedridden. The rate of preoperative bedridden status was significantly higher in group B than group A (6.7% vs. 57.1%; p=0.021). Univariate analysis revealed immobility, a sequential organ failure assessment (SOFA) score, and lactate levels of more than 2.0 mmol/L to be factors associated with increased mortality rates in the postoperative period. Multivariate analysis revealed abnormal lactate levels to be the only factor related to mortality (hazard ratio 16.50, 95% CI 1.48-183.07, p=0.022). Conclusions Preoperative abnormal serum lactate levels may be a risk factor for mortality after surgery in patients with stercoral perforation. Further research will be needed to identify the postoperative prognostic SPC factors.