Miracle-dz/UniFAR-FTUs huggingface dataset:
Heat Shock Protein 27 Phosphorylation Regulates Tumor Cell Migration under Shear Stress

Heat shock protein 27 (HSP27) is a multifunctional protein that undergoes significant changes in its expression and phosphorylation in response to shear stress stimuli, suggesting that it may be involved in mechanotransduction. However, the mechanism of HSP27 affecting tumor cell migration under shear stress is still not clear. In this study, HSP27-enhanced cyan fluorescent protein (ECFP) and HSP27-Ypet plasmids are constructed to visualize the self-polymerization of HSP27 in living cells based on fluorescence resonance energy transfer technology. The results show that shear stress induces polar distribution of HSP27 to regulate the dynamic structure at the cell leading edge. Shear stress also promotes HSP27 depolymerization to small molecules and then regulates polar actin accumulation and focal adhesion kinase (FAK) polar activation, which further promotes tumor cell migration. This study suggests that HSP27 plays an important role in the regulation of shear stress-induced HeLa cell migration, and it also provides a theoretical basis for HSP27 as a potential drug target for metastasis.
Vomiting and Dehydration in a 2-Year-Old

In this article, we detail the diagnostic dilemma of a young child with vomiting and dehydration. A 2-year-old girl with a past medical history of cutaneous mastocytosis and eczema presented with 1 day of yellow-green, nonbloody vomiting, bradycardia, and listlessness. She was evaluated by her pediatrician and sent to the emergency department because of concern for dehydration. In the emergency department, she improved with fluid rehydration but still had decreased energy and bradycardia. Her electrocardiogram revealed sinus bradycardia, and laboratory results did not reveal any electrolyte abnormalities. Glucose levels were normal. An abdominal radiograph revealed a moderate-to-large stool burden, and the results of a computed tomography scan of the head were normal. An abdominal ultrasound was obtained to evaluate for intussusception. The ultrasound revealed a blind-ending tubular structure in the right-lower quadrant with adjacent free fluid, which was concerning for appendicitis. The patient was admitted to the surgical service for further management and was taken to the operating room, where a definitive diagnosis was made.
Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid[S]

All-trans retinoic acid (atRA) is used to treat certain cancers and dermatologic diseases. A common adverse effect of atRA is hypercholesterolemia; cytochrome P450 (CYP) 7A repression is suggested as a driver. However, the underlying molecular mechanisms remain unclear. We investigated CYP7A1 expression in the presence of atRA in human hepatocytes and hepatic cell lines. In HepaRG cells, atRA increased cholesterol levels dose-dependently alongside dramatic decreases in CYP7A1 expression. Lentiviral-mediated CYP7A1 overexpression reversed atRA-induced cholesterol accumulation, suggesting that CYP7A1 repression mediated cholesterol accumulation. In CYP7A1 promoter reporter assays and gene-knockdown studies, altered binding of hepatocyte nuclear factor 4 α (HNF4α) to the proximal promoter was essential for atRA-mediated CYP7A1 repression. Pharmacologic inhibition of c-Jun N-terminal kinase (JNK) and ERK pathways attenuated atRA-mediated CYP7A1 repression and cholesterol accumulation. Overexpression of AP-1 (c-Jun/c-Fos), a downstream target of JNK and ERK, repressed CYP7A1 expression. In DNA pull-down and chromatin immunoprecipitation assays, AP-1 exhibited sequence-specific binding to the proximal CYP7A1 promoter region overlapping the HNF4α binding site, and atRA increased AP-1 but decreased HNF4α recruitment to the promoter. Collectively, these results indicate that atRA activates JNK and ERK pathways and the downstream target AP-1 represses HNF4α transactivation of the CYP7A1 promoter, potentially responsible for hypercholesterolemia.
Hierarchical Surface Prediction

Recently, Convolutional Neural Networks have shown promising results for 3D geometry prediction. They can make predictions from very little input data such as a single color image. A major limitation of such approaches is that they only predict a coarse resolution voxel grid, which does not capture the surface of the objects well. We propose a general framework, called hierarchical surface prediction (HSP), which facilitates prediction of high resolution voxel grids. The main insight is that it is sufficient to predict high resolution voxels around the predicted surfaces. The exterior and interior of the objects can be represented with coarse resolution voxels. This allows us to predict significantly higher resolution voxel grids around the surface, from which triangle meshes can be extracted. Additionally it allows us to predict properties such as surface color which are only defined on the surface. Our approach is not dependent on a specific input type. We show results for geometry prediction from color images and depth images. Our analysis shows that our high resolution predictions are more accurate than low resolution predictions.
Group leader and participant perceptions of Balancing Everyday Life, a group-based lifestyle intervention for mental health service users

Abstract Background: There exist few recovery and occupation-based interventions for mental health service users. Balancing Everyday Life (BEL) is a new occupation-based lifestyle intervention that was created to fill this need. Aim: To gain group leaders’ and participants’ perspectives of the BEL intervention content and format, including factors that helped, hindered, and could be improved. Methods: A constructivist grounded theory method guided data collection and analysis. Interviews took place with 12 BEL group leaders and 19 BEL participants from out-patient psychiatry settings and community-based day centers in Sweden. Results: BEL’s structure and content were appreciated, yet flexibility was desired to adapt to participant needs. BEL could act as a bridge, helping participants connect with others, and to a more engaged and balanced everyday life. Facilitating factors included a person-focused (versus illness-focused) approach, physical and emotional environments, and connection. Barriers included room resources. More sessions were desired for the intervention. Conclusion: Group leaders and participants experienced BEL as a useful tool to instigate meaningful change and connection in the participants’ lives. The combination of a positive person-focused approach and group support was appreciated. These results could inform future research, evaluation, and development of occupation-focused lifestyle interventions for mental health service users.
Functional Workspace Optimization via Learning Personal Preferences from Virtual Experiences

The functionality of a workspace is one of the most important considerations in both virtual world design and interior design. To offer appropriate functionality to the user, designers usually take some general rules into account, e.g., general workflow and average stature of users, which are summarized from the population statistics. Yet, such general rules cannot reflect the personal preferences of a single individual, which vary from person to person. In this paper, we intend to optimize a functional workspace according to the personal preferences of the specific individual who will use it. We come up with an approach to learn the individual's personal preferences from his activities while using a virtual version of the workspace via virtual reality devices. Then, we construct a cost function, which incorporates personal preferences, spatial constraints, pose assessments, and visual field. At last, the cost function is optimized to achieve an optimal layout. To evaluate the approach, we experimented with different settings. The results of the user study show that the workspaces updated in this way better fit the users.
Microvesicle Proteomic Profiling of Uterine Liquid Biopsy for Ovarian Cancer Early Detection*

High-grade ovarian cancer accounts for higher mortality rates because of ineffective biomarkers for early diagnosis. Deep proteome profiling of the microvesicles from a total of 187 liquid biopsies of Utero-tubal Lavage, combined with support vector machine algorithms, extracted a 9-protein classifier with high accuracy. The signature predicted all the early stage lesions, and outperformed the known markers CA125 and HE4 with 70% sensitivity and 76.2% specificity. Our study reveals UtL-microvesicle proteomics as the potential biomarker source for early diagnosis of HGOC. Graphical Abstract Highlights Microvesicle proteomics of 187 utero-tubal lavage samples for early diagnosis of HGOC. Machine learning-based classification of a 9-protein signature with high predictive power. Signature has 70% sensitivity and 76.2% specificity, predicting stage I lesions. High-grade ovarian cancer (HGOC) is the leading cause of mortality from gynecological malignancies, because of diagnosis at a metastatic stage. Current screening options fail to improve mortality because of the absence of early-stage-specific biomarkers. We postulated that a liquid biopsy, such as utero-tubal lavage (UtL), may identify localized lesions better than systemic approaches of serum/plasma analysis. Further, while mutation-based assays are challenged by the rarity of tumor DNA within nonmutated DNA, analyzing the proteomic profile, is expected to enable earlier detection, as it reveals perturbations in both the tumor as well as in its microenvironment. To attain deep proteomic coverage and overcome the high dynamic range of this body fluid, we applied our method for microvesicle proteomics to the UtL samples. Liquid biopsies from HGOC patients (n = 49) and controls (n = 127) were divided into a discovery and validation sets. Data-dependent analysis of the samples on the Q-Exactive mass spectrometer provided depth of 8578 UtL proteins in total, and on average ∼3000 proteins per sample. We used support vector machine algorithms for sample classification, and crossed three feature-selection algorithms, to construct and validate a 9-protein classifier with 70% sensitivity and 76.2% specificity. The signature correctly identified all Stage I lesions. These results demonstrate the potential power of microvesicle-based proteomic biomarkers for early cancer diagnosis.
Characterization of a metazoan ADA acetyltransferase complex

Abstract The Gcn5 acetyltransferase functions in multiple acetyltransferase complexes in yeast and metazoans. Yeast Gcn5 is part of the large SAGA (Spt-Ada-Gcn5 acetyltransferase) complex and a smaller ADA acetyltransferase complex. In flies and mammals, Gcn5 (and its homolog pCAF) is part of various versions of the SAGA complex and another large acetyltransferase complex, ATAC (Ada2A containing acetyltransferase complex). However, a complex analogous to the small ADA complex in yeast has never been described in metazoans. Previous studies in Drosophila hinted at the existence of a small complex which contains Ada2b, a partner of Gcn5 in the SAGA complex. Here we have purified and characterized the composition of this complex and show that it is composed of Gcn5, Ada2b, Ada3 and Sgf29. Hence, we have named it the metazoan ‘ADA complex’. We demonstrate that the fly ADA complex has histone acetylation activity on histones and nucleosome substrates. Moreover, ChIP-Sequencing experiments identified Ada2b peaks that overlap with another SAGA subunit, Spt3, as well as Ada2b peaks that do not overlap with Spt3 suggesting that the ADA complex binds chromosomal sites independent of the larger SAGA complex.
Immunotoxicity of poly (lactic-co-glycolic acid) nanoparticles: influence of surface properties on dendritic cell activation

Abstract Modified nanoparticles (NPs) can interact with the immune system by causing its activation to fight tumors or for vaccination. During this activation, dendritic cells (DCs) are effective in generating robust immune response. However, the effect of nanomaterials on dendritic cell (DC) maturation, and the associated adjuvant effect, should be assessed as a novel biocompatibility criteria for biomaterials since immune consequences may constitute potential complications in nanomedicine. Among emerging biomaterials, poly(lactic-co-glycolic acid) NPs (PLGA NPs) are widely explored for various applications in which the degree of desired adjuvant effect may vary. As contradictory results are reported regarding their effects on DCs, we aimed at clarifying this point with particular emphasis on the relative impact of particle surface properties. To that end, NP uptake and effects on the viability, phenotype, and secretory activity of DC primary cultures. Intracellular signaling pathways were explored and evaluated. Immature human and murine DCs were exposed to cationic, neutral, or anionic PLGA NPs. Particle uptake was assessed by both confocal microscopy and flow cytometry. Cell viability was then evaluated prior to the study of maturation by examination of both surface marker expression and cytokine release. Our results demonstrate that PLGA NPs are rapidly engulfed by DCs and do not exert cytotoxic effects. However, upon exposure to PLGA NPs, DCs showed phenotypes and cytokine secretion profiles consistent with maturation which resulted, at least in part, from the transient intracellular activation of mitogen-activated protein kinases (MAPKs). Interestingly, NP-specific stimulation patterns were observed since NP surface properties had a sensible influence on the various parameters measured.
Perceived stress and psychosis: The effect of perceived stress on psychotic‐like experiences in a community sample of adolescents

Psychotic‐like experiences (PLE) are sub‐threshold, non‐clinical forms of psychosis which can place an individual at greater risk of development of a psychotic disorder. Subtypes of PLE have also been shown to exist (bizarre experiences, persecutory ideation, perceptual abnormalities and magical thinking). Perceived stress relates to how two individuals may deal with the same objectively stressful event in different ways. The objective of our study was to investigate the extent to which perceived stress is associated with PLE in a community sample of adolescents, whether certain subtypes of PLE correlate more with perceived stress than others and to explore the role of depression with these associations.
Reduced Neuroinflammation and Improved Functional Recovery after Traumatic Brain Injury by Prophylactic Diet Supplementation in Mice

Currently, there are no approved therapeutic drugs for the treatment of traumatic brain injury (TBI), and new targets and approaches are needed to provide relief from the long-term effects of TBI. Recent studies suggest that nutrition plays a critical role in improving the outcome from TBI in both civilians and military personnel. We have previously shown that GrandFusion® (GF) diets improved recovery from cerebral ischemia and enhanced physical activity and endurance in rodent models. We, therefore, sought to determine the impact of a prophylactic diet enriched in fruits and vegetables on recovery from TBI in the controlled cortical impact rodent model. Results demonstrated that mice fed the diets had improved neuromotor function, reduced lesion volume, increased neuronal density in the hippocampus and reduced inflammation. As previously shown, TBI increases cathepsin B as part of the inflammasome complex resulting in elevated inflammatory markers like interleukin-1β (IL-1β). Consumption of the GF diets attenuated the increase in cathepsin B levels and prevented the increase in the proapoptotic factor Bax following TBI. These data suggest that prior consumption of diets enriched in fruits and vegetables either naturally or through powdered form can provide protection from the detrimental effects of TBI.
Relationships of Mean Platelet Volume and Plasma Thrombopoietin with Glycocalicin Levels in Thrombocytopenic Patients

Backgrounds/Aims: Relationships of mean platelet volume (MPV) and thrombopoietin (TPO) with platelet turnover assessed by glycocalicin measurement were evaluated in thrombocytopenic patients. Methods: MPV, glycocalicin and platelet-associated IgG (PA-IgG) were measured in 107 patients with idiopathic thrombocytopenic purpura (ITP) and 19 patients with hypoproductive thrombocytopenia (HPT; aplastic anemia or leukemia), and TPO was measured in 53 ITP and 12 HPT patients. All the included ITP patients had PA-IgG ≥300% and glycocalicin ≥50% of control values, and HPT patients had PA-IgG <300% and glycocalicin <50% of control values. Results and Conclusions: MPV was higher in ITP than in HPT patients: 9.56 ± 1.69 and 7.59 ± 0.90 fl (p < 0.001). In the ITP group a direct correlation was detected between MPV and glycocalicin (r = 0.344, p < 0.001). This interaction was essentially expressed in patients with normal/increased glycocalicin (≥100% of control; r = 0.470, p < 0.001, n = 64). TPO was greatly enhanced in HPT in comparison with ITP patients (958 ± 659 and 11 ± 27 pg/ml, p < 0.001). In the ITP group a reverse correlation was detected between TPO and glycocalicin (r = -0.373, p = 0.006). © 2014 S. Karger AG, Basel
Use of PHQ-9 scores to guide treatment decisions in primary care.

Shaw and colleagues stated no changes in depression management were seen in studies they reviewed of using patient health questionnaire (PHQ-9) scores to guide primary care treatment.1 This statement is an inaccurate reflection of the literature they reviewed and cannot go unchallenged. The observational study conducted in Southampton practices, in the year following the introduction of the DEP3 QOF indicator rewarding the use of symptom questionnaires at follow-up of depressed patients between 5 and 12 weeks, showed that follow-up scores …
Two novel genetic variants in the STK38L and RAB27A genes are associated with glioma susceptibility

Glioma is the most common malignant primary brain tumors with poor prognosis. Genome wide association studies (GWAS) of glioma in populations with Western European ancestry were completed in the US and UK. However, our previous results strongly suggest the genetic heterogeneity could be important in glioma risk. To systematically investigate glioma risk–associated variants in Chinese population, we performed a multistage GWAS of glioma in the Han Chinese population, with a total of 3,097 glioma cases and 4,362 controls. In addition to confirming two associations reported in other ancestry groups, this study identified one new risk‐associated locus for glioma on chromosome 12p11.23 (rs10842893, pmeta = 2.33x10‐12, STK38L) as well as a promising association at 15q15‐21.1 (rs4774756, pmeta = 6.12x10‐8, RAB27A) in 3,097 glioma cases and 4,362 controls. Our findings demonstrate two novel association between the glioma risk region marked by variant rs10842893 and rs4774756) and glioma risk. These findings may advance the understanding of genetic susceptibility to glioma.
Does fecal calprotectin equally and accurately measure disease activity in small bowel and large bowel Crohn’s disease?: a systematic review

Fecal calprotectin (FC) is a highly sensitive disease activity biomarker in inflammatory bowel disease. However, there are conflicting reports on whether the diagnostic accuracy in Crohn’s disease is influenced by disease location. The aim of this study was to undertake a systematic review of the published literature. Relevant databases were searched from inception to November 8, 2016 for cohort and case control studies which had data on FC in patients with isolated small bowel (SB) and large bowel (LB) Crohn’s disease. Reference standards for disease activity were endoscopy, magnetic resonance imaging, computed tomography or a combination of these. The QUADAS-2 research tool was used to assess the risk of bias. There were 5,619 records identified at initial search. The 2,098 duplicates were removed and 3,521 records screened. Sixty-one full text articles were assessed for eligibility and 16 studies were included in the final review with sensitivities and specificities per disease location available from 8 studies. Sensitivities of FC at SB and LB locations ranged from 42.9% to 100% and 66.7% to 100% respectively while corresponding specificities were 50% to 100% and 28.6% to 100% respectively. The sensitivities and specificities of FC to accurately measure disease activity in Crohn’s disease at different disease locations are diverse and no firm conclusion can be made. Better studies need to be undertaken to categorically answer the effect of disease location on the diagnostic accuracy of FC.
Relationship of fatigue with cognitive performance in women with early‐stage breast cancer over 2 years

Fatigue and cognitive dysfunction are major concerns for women with early‐stage breast cancer during treatment and into survivorship. However, interrelationships of these phenomena and their temporal patterns over time are not well documented, thus limiting the strategies for symptom management interventions. In this study, changes in fatigue across treatment phases and the relationship among fatigue severity and its functional impact with objective cognitive performance were examined.
Whole-Genome Sequence Data Uncover Widespread Heterothallism in the Largest Group of Lichen-Forming Fungi

Abstract Fungal reproduction is regulated by the mating-type (MAT1) locus, which typically comprises two idiomorphic genes. The presence of one or both allelic variants at the locus determines the reproductive strategy in fungi—homothallism versus heterothallism. It has been hypothesized that self-fertility via homothallism is widespread in lichen-forming fungi. To test this hypothesis, we characterized the MAT1 locus of 41 genomes of lichen-forming fungi representing a wide range of growth forms and reproductive strategies in the class Lecanoromycetes, the largest group of lichen-forming fungi. Our results show the complete lack of genetic homothallism suggesting that lichens evolved from a heterothallic ancestor. We argue that this may be related to the symbiotic lifestyle of these fungi, and may be a key innovation that has contributed to the accelerated diversification rates in this fungal group.
Electroporated GLUT4‐7myc‐GFP detects in vivo glucose transporter 4 translocation in skeletal muscle without discernible changes in GFP patterns

What is the central question of this study? Resolving the mechanism(s) leading to glucose transporter 4 (GLUT4) translocation to the muscle surface membrane has great therapeutic potential. However, the measurement of GLUT4 translocation is technically challenging. Here, we asked whether electroporation of GLUT4‐7myc‐GFP into skeletal muscle could be used as a tool to study GLUT4 translocation in vivo. What is the main finding and its importance? By acutely inducing GLUT4‐7myc‐GFP expression in skeletal muscle, we verified that in vivo exercise and AICAR stimulation increased the GLUT4 presence in the sarcolemma measured as myc signal. Importantly, the increased myc signal in the sarcolemma was not accompanied by major visual changes in the distribution of the GFP signal.