Miracle-dz/UniFAR-FTUs huggingface dataset:
Polarization of human gingival fibroblasts by Th1-, Th2-, Th17-, and Treg-derived cytokines.

BACKGROUND AND OBJECTIVE The purpose of this study was to evaluate whether gingival fibroblasts (GFs) can be differently activated and polarized into distinct functional subtypes by T-helper (Th) cytokines. METHODS Gingival fibroblasts were stimulated with interferon (IFN)-γ, interleukin (IL)-4, IL-17, and transforming growth factor (TGF)-β, representative cytokines of Th1, Th2, Th17, and regulatory T cells, respectively, and the gene expression profiles were analyzed by microarray. Differentially expressed genes (DEGs) in GFs stimulated by 4 cytokines were screened, and a gene ontology (GO) analysis of the DEGs was conducted. To confirm the reliability of the microarray results, the DEGs that showed the largest differences compared with non-stimulated GFs were further analyzed by RT-PCR. To evaluate the effect of polarization on GFs responses to lipopolysaccharide (LPS), GFs stimulated by 4 cytokines were further stimulated with Escherichia coli LPS and mRNA levels of several genes were analyzed using RT-PCR. RESULTS Differentially expressed genes by 4 Th cytokines were enriched in different GO terms, and the patterns of gene expression on GFs were shown functionally different. GFs stimulated with IFN-γ (GF(IFN-γ)) up-regulated the expression of chemokines (chemokine (C-X-C motif) ligand (CXCL)9, -10, -11, chemokine (C-C motif) ligand (CCL)8), molecules involved in antigen presentation, complement component 3 (C3), and other immune response-related molecules, whereas they down-regulated the expression of several types of collagen, extracellular matrix (ECM) components, and DNA replication and nuclear protein-related molecules. By contrast, GF(IL-4) up-regulated the expression of ECM components, cell adhesion molecules, and tissue development-related molecules and down-regulated the expression of chemokines (CXCL10 and CXCL8) and adaptive immune response-related molecules. GF(IL-17) up-regulated the expression of chemokines and other molecules for neutrophil infiltration and activation, the pro-inflammatory cytokine IL-6, and C3. GF(TGF-β) up-regulated the expression of cell growth-related molecules, ECM components, several types of collagen, and cell adhesion molecules and down-regulated the expression of molecules related to complement activation and bacterial recognition. GFs stimulated by 4 cytokines responded differently to LPS. CONCLUSION These results show that Th cytokines can polarize GFs into cells with functionally distinct features: immune-activating but tissue-destructive GF(IFN-γ), tissue-reparative, and immune-inhibiting GF(IL-4), highly pro-inflammatory GF(IL-17), and potent tissue-reparative GF(TGF-β).
Single-cell genome-wide concurrent haplotyping and copy-number profiling through genotyping-by-sequencing

Abstract Single-cell whole-genome haplotyping allows simultaneous detection of haplotypes associated with monogenic diseases, chromosome copy-numbering and subsequently, has revealed mosaicism in embryos and embryonic stem cells. Methods, such as karyomapping and haplarithmisis, were deployed as a generic and genome-wide approach for preimplantation genetic testing (PGT) and are replacing traditional PGT methods. While current methods primarily rely on single-nucleotide polymorphism (SNP) array, we envision sequencing-based methods to become more accessible and cost-efficient. Here, we developed a novel sequencing-based methodology to haplotype and copy-number profile single cells. Following DNA amplification, genomic size and complexity is reduced through restriction enzyme digestion and DNA is genotyped through sequencing. This single-cell genotyping-by-sequencing (scGBS) is the input for haplarithmisis, an algorithm we previously developed for SNP array-based single-cell haplotyping. We established technical parameters and developed an analysis pipeline enabling accurate concurrent haplotyping and copy-number profiling of single cells. We demonstrate its value in human blastomere and trophectoderm samples as application for PGT for monogenic disorders. Furthermore, we demonstrate the method to work in other species through analyzing blastomeres of bovine embryos. Our scGBS method opens up the path for single-cell haplotyping of any species with diploid genomes and could make its way into the clinic as a PGT application.
Workplace greenspace exposure and the change in dimensions of mood states: an experimental study in Taiwan

ABSTRACT Changes in the dimensions of psychological health in relation to workplace greenspace exposure and its relationship with job stress was not yet fully revealed. A neighboring park of the workplace and a forest were chosen to represent experimental stimuli and the control, respectively. The experiment was conducted in March 2021 in Taiwan, using a virtual reality. Results show that negative emotions decreased in the post-test in both environment settings. However, positive emotion increased only after exposure to the forest (t=-3.88, p < .001). After virtually visiting the workplace greenspace, depression in the high stress group decreased significantly (t = 3.48 , p < .01) while the counterpart did not exhibit any significant change. Based on the interviews, participants only indicated stressful elements of the workplace greenspace video, despite the video also contained natural elements. Topics related to work decreased feelings of being away. Greenspace in a work context should be carefully designed to avoid the stressful elements.
An opinion piece: the evolutionary and ecological consequences of changing selection pressures on marine migration in Atlantic salmon

Abstract There are strong signals that the selection forces favouring the expression of long‐distance sea migration by Atlantic salmon (Salmo salar) are changing. Unlike many other behavioural traits, the costs of migration are incurred before any fitness benefits become apparent to the migrant. The expression of this behaviour has thus been shaped by selection forces over multiple generations and cannot respond to short interval (within a single generation) environmental change as many other behavioural traits can. Here we provide a framework to examine the evolutionary and ecological consequences of a sustained increase in migration cost. We argue that Atlantic salmon may have entered an evolutionary trap, where long‐distance sea migration has become maladaptive because of shifting environmental conditions. We predict that if higher migration costs (affecting survivorship and ultimately fitness) persist, then shifting selection pressures will result in continuing declines in population size. We suggest, however, that in some populations there is demonstrable capacity for evolutionary rescue responses within the species which is to be found in the variation in the expression of migration. Under a scenario of low to moderate change in the selection forces that previously promoted migration, we argue that disruptive, sex‐based selection would result in partial migration, where females retain sea migration but with anadromy loss predominantly in males. With more acute selection forces, anadromy may be strongly selected against, under these conditions both sexes may become freshwater resident. We suggest that as the migration costs appear to be higher in catchments with standing waters, then this outcome is more likely in such systems. We also speculate that as a result of the genetic structuring in this species, not all populations may have the capacity to respond adequately to change. The consequences of this for the species and its management are discussed.
Research on Processing Technology of Multi-Layer Heterogeneous Material Composite Micron Cantilever Beam Structure

In order to overcome the simplicity and instability of micron cantilever membrane structure, sacrificial layer technology and multi-layer heterogeneous material composite stacking technology were designated. Based on the research with respect to a multi-layer heterogeneous cantilever beam structure, multi-layer heterogeneous material composite, and sacrificial layer release craft, different characteristics of sacrificial layer material and film preparation craft were analyzed. According to these results, the suitable film preparation craft was generated to reduce the stress between materials and to improve the reliability and percentage of finished products. Our work put multi-layer material composite micro-cantilever beam structure into practice, and accelerated the manufacturing of a micro-acceleration sensor and vibration sensor in the future.
Sentinel Events and Miscommunication What do we know in 2021: A Language and Social Psychology Framework

ABSTRACT The paper explored the extent to which hospital appointed official root cause analysis (RCA) panels consider antecedent and proximal events when they investigate communication related sentinel events (CRSEs) in hospitals. It also explored which CRSEs are most common in the hospital setting in Hong Kong and the communication modes most commonly associated with CRSEs. The data consisted of Risk Alert and Annual Report on SEs issued by the Hong Kong Hospital Authority from October 2007 to September 2017. Over the period studied, there were 379 reported sentinel events (SEs). In 186 of these SEs we identified communication as a contributing factor. We examined the RCA panels’ reports on contributing factors and subsequent recommendations in these 186 SEs and found that their recommendations only highlighted the proximal contributing factors and not antecedent factors that may be relevant. RCA panels most often recommended that communication should be enhanced or documentation improved. We propose that it is time to review the RCA process to recognize that many CRSEs may occur because of antecedent factors that result from the complex hospital organizational structure and its associated hierarchical culture. We suggest two ways forward, 1) applying a language and social psychology perspective to the investigations of CRSEs and, 2) the involvement of experts from different disciplines who can work with clinicians during RCA investigations.
Burned-Out Classroom Climate, Intrinsic Motivation, and Academic Engagement: Exploring Unresolved Issues in the Job Demand-Resource Model

This study aimed to test the multilevel mediating effect of intrinsic motivation on the relationship between burned-out classroom climate and academic engagement and theoretically investigate the unresolved issues in the Job Demands-Resources model. Data were collected from 1015 high school students from 43 classes. Multilevel structural equation modeling indicated that a high level of burned-out classroom climate was related to a low level of academic engagement. In addition, intrinsic motivation mediated the path from burned-out classroom climate to academic engagement. Practical implications to improve classroom climate and academic engagement are discussed.
Heterointerface Created on Au‐Cluster‐Loaded Unilamellar Hydroxide Electrocatalysts as a Highly Active Site for the Oxygen Evolution Reaction

The oxygen evolution reaction (OER) is a critical element for all sorts of reactions that use water as a hydrogen source, such as hydrogen evolution and electrochemical CO2 reduction, and novel design principles that provide highly active sites on OER electrocatalysts push the limits of their practical applications. Herein, Au‐cluster loading on unilamellar exfoliated layered double hydroxide (ULDH) electrocatalysts for the OER is demonstrated to fabricate a heterointerface between Au clusters and ULDHs as an active site, which is accompanied by the oxidation state modulation of the active site and interfacial direct OO coupling (“interfacial DOOC”). The Au‐cluster‐loaded ULDHs exhibit excellent activities for the OER with an overpotential of 189 mV at 10 mA cm−2. X‐ray absorption fine structure measurements reveal that charge transfer from the Au clusters to ULDHs modifies the oxidation states of trivalent metal ions, which can be active sites on the ULDHs. The present study, supported by highly sensitive spectroscopy combining reflection absorption infrared spectroscopy and modulation‐excitation spectroscopy and density functional theory calculations, indicates that active sites at the interface between the Au clusters and ULDHs promote a novel OER mechanism through interfacial DOOC, thereby achieving outstanding catalytic performance.
Understanding weight stigma in eating disorder treatment: Development and initial validation of a treatment-based stigma scale

Weight stigma is a well-established risk factor for eating disorder pathology, and it is prevalent among healthcare professionals. The current investigation developed and psychometrically validated the Scale for Treatment-based Experiences of Weight Stigma (STEWS) for patient-centered assessment of weight-stigmatizing experiences in eating disorder treatment. Former eating disorder patients (N = 142) with a body-mass-index greater than 25.0 were recruited via Amazon Mechanical Turk. The STEWS demonstrated good internal consistency, convergent validity with widely used weight stigma scales, and incremental validity in predicting eating disorder symptomatology. The STEWS is the first psychometrically sound instrument for treatment-based weight stigma in eating disorder recovery.
ADC Histogram Analysis of Pediatric Low-Grade Glioma Treated with Selumetinib: A Report from the Pediatric Brain Tumor Consortium

ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas. BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging–derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549–BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1–associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1–associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1–associated OPHG. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.
Cepharanthine hydrochloride inhibits the Wnt/β-catenin/Hedgehog signaling axis in liver cancer

Cepharanthine, a biscoclaurine alkaloid isolated from the roots of Stephania cephalantha Hayata, has been reported to demonstrate antitumor activity across multiple cancer types; however, the mechanisms are still under investigation. High transcriptional responses by both the Hedgehog and Wnt pathways are frequently associated with specific human cancers, including liver cancer. To investigate whether these signaling pathways are involved in the pharmaceutical action of cepharanthine, we investigated Hedgehog and Wnt signaling in models of liver cancer treated with a semi-synthetic cepharanthine derivative, cepharanthine hydrochloride (CH), in vitro and in vivo. By using MTT cytotoxic, scratch, Transwell, colony formation and flow cytometry assays, the pharmaceutical effect of CH was assessed. The compound was found to inhibit cellular proliferation and invasion, and promote apoptosis. Subsequent mechanistic investigations revealed that CH suppressed the Hedgehog/Gli1 signaling pathway by inhibiting Gli1 transcription and its transcriptional activity. CH also inhibited Wnt/β-catenin signaling, and the pathway was found to be an upstream regulator of Hedgehog signaling in CH-treated liver cancer cells. Finally, the antitumor effects of CH were demonstrated in an in vivo xenograft tumor model. Immunohistochemical analysis indicated that Gli1 protein levels were diminished in CH-treated xenografts, compared with that noted in the controls. In summary, our results highlight a novel pharmaceutical antitumor mechanism of cepharanthine and provide support for CH as a clinical therapy for refractory liver cancer and other Wnt/Hedgehog-driven cancers.
A Multipronged, Evidence-Based Approach to Improving Mental Health Among Transgender and Gender-Diverse Youth.

A growing body of research indicates that transgender and gender-diverse (TGD) youth experience considerable mental health disparities when compared with their cisgender peers, including higher rates of depression, anxiety, and suicidality. 1 These disparities have been attributed to two processes: gender dysphoria and gender minority stress. 1 Gender dysphoria refers to distress related to one’s body developing in a way that is incongruent with one’s gender identity. It is important to note that not all TGD youth experience gender dysphoria, but that this can be a substantial source of distress for many. Gender minority stress refers to the ways in which society’s mistreatment of TGD people negativelyimpactsmentalandphysicalhealth. 1 Thegenderminoritystressmodeloutlinesbothdistal “external” factors (experiences of discrimination, rejection, and violence on the basis of gender identity) as well as subsequent proximal “internal” factors (expectations of rejection, concealment of one’s gender identity, and internalized transphobia). of the multifactorial contributions to disparities for TGD youth, reducing these disparities requires a multipronged approach, working on both gender dysphoria and gender minority stress. In this issue of JAMA Network Open we find two excellent studies—one examining the treatment of physical gender dysphoria through gender-affirming medical care, and a second that aims to lessen stigma against TGD youth, with the greater goal of lessening the impact of gender minority stress.
Contextual uncertainty of visual scene modulates object-based attention

Contextual information involves invariant properties that are critical in selective attention. There is no direct evidence showing the effect of contextual information on object-based selective attention. The current study aimed to investigate the role of contextual uncertainty on object-based effect using a flanker task and to clarify the contradictory results obtained in previous studies. Herein, contextual uncertainty specifically referred to the configurations of the stimuli presented randomly as vertical or horizontal displays (high contextual uncertainty) that was reduced by showing consistent configurations within a block, via implicit learning of configuration (low contextual uncertainty). In Experiment 1, the object-based effect was observed under the high uncertainty condition and disappeared under the low uncertainty condition, demonstrating that contextual uncertainty modulated object-based attention. Experiment 2 provided explicit knowledge of the configural orientations, which can be utilised to sufficiently guide subsequent perception with increase in cueing interval, and therefore, affected contextual uncertainty. Relative to a short cueing interval, the long cueing interval enabled the participants to utilise the contextual knowledge for guiding visual attention and reducing uncertainty. Consistent with the finding in Experiment 1, the explicit manipulation of contextual uncertainty affected the object-based effect. The results proved that the contextual uncertainty played an important role in prioritisation in the object-based attentional selection. The mechanism of the interplay between contextual uncertainty and object-based attention was discussed.
Relationship between Epicardial and Coronary Adipose Tissue and the Expression of Adiponectin, Leptin, and Interleukin 6 in Patients with Coronary Artery Disease

Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest to researchers, owing to their potential effects on the myocardium and blood vessels. The aim of the study was to assess the expression and secretion of adipocytokine genes in the AT of patients with coronary artery disease (CAD) and patients with aortic or mitral valve replacement. This study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous, epicardial (EAT), and perivascular AT (PVAT), and were cultured for 24 h. EAT exhibited the lowest level of adiponectin gene expression and secretion, regardless of nosology, and high expression levels of the leptin gene and interleukin-6 (IL-6). However, EAT adipocytes in patients with CAD were characterized by more pronounced changes in comparison with the group with heart defects. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with CAD. Therefore, our results revealed the pathogenetic significance of alterations in the adipokine and cytokine status of adipocytes of EAT and PVAT in patients with CAD.
Quantification of Neurite Degeneration with Enhanced Accuracy and Efficiency in an In Vitro Model of Parkinson’s Disease

Abstract Neurite degeneration is associated with early stages of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease (PD), and amyotrophic lateral sclerosis. One method that is commonly used to analyze neurite degeneration involves calculation of a Degeneration Index (DI) following utilization of the Analyze Particles tool of ImageJ to detect neurite fragments in micrographs of cultured cells. However, DI analyses are prone to several types of measurement error, can be time consuming to perform, and are limited in application. Here, we describe an improved method for performing DI analyses. Accuracy of measurements was enhanced through modification of selection criteria for detecting neurite fragments, removal of image artifacts and non-neurite materials from images, and optimization of image contrast. Such enhancements were implemented into an ImageJ macro that enables rapid and fully automated DI analysis of multiple images. The macro features operations for automated removal of cell bodies from micrographs, thus expanding the application of DI analyses to use in experiments involving dissociated cultures. We present experimental findings supporting that, compared with the conventional method, the enhanced analysis method yields measurements with increased accuracy and requires significantly less time to perform. Furthermore, we demonstrate the utility of the method to investigate neurite degeneration in a cell culture model of PD by conducting an experiment revealing the effects of c-Jun N-terminal kinase (JNK) on neurite degeneration induced by oxidative stress in human mesencephalic cells. This improved analysis method may be used to gain novel insight into factors underlying neurite degeneration and the progression of neurodegenerative disorders.