Miracle-dz/UniFAR-FTUs huggingface dataset:
STAT3 Targets ERR-α to Promote Epithelial–Mesenchymal Transition, Migration, and Invasion in Triple-Negative Breast Cancer Cells

STAT3 is constitutively activated in many malignant tumor types and plays an important role in multiple aspects of cancer aggressiveness. In this study, we found that estrogen-related receptor α (ERR-α) correlating with STAT3 was highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues, which was associated with both the pathologic stage and prognosis of patients with TNBC. In vitro studies showed that ERR-α promoted TNBC cell migration and invasion, which was regulated by STAT3. Phosphorylated STAT3 (p-STAT3, Tyr 705) could bind to the promotor of ERR-α, and activate its transcription, which was suggested by luciferase assay and chromatin immunoprecipitation assay. We also found that ERR-α was the key target gene regulated by STAT3 in promoting epithelial–mesenchymal transition (EMT), migration, and invasion. ERR-α upregulated the expression of ZEB1, N-cadherin, and vimentin while downregulated the expression of E-cadherin. Furthermore, in vivo studies showed that ERR-α could increase the metastasis ability of TNBC. Our finding demonstrated that ERR-α was a direct regulatory gene target of p-STAT3, which was enriched for processes involving invasion and metastasis in TNBC and provided insight into TNBC pathogenesis, as well as a potential therapeutic option against TNBC metastasis. Implications: Our research first showed that p-STAT3 (Tyr 705) could bind to the promotor region of ERR-α and promote EMT in TNBC by ZEB1 pathways, thus providing a potential clinical target for TNBC.
A Hypoxia-Inducible HIF1–GAL3ST1-Sulfatide Axis Enhances ccRCC Immune Evasion via Increased Tumor Cell–Platelet Binding

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and the major cause of mortality for individuals with von Hippel-Lindau (VHL) disease. ccRCC is characterized most frequently by inactivation of VHL tumor suppressor protein that mediates degradation of the alpha subunit of the hypoxia-inducible factor (HIF) transcription factor family. HIF has been implicated in disease progression and the aim of this study was to identify novel HIF target genes that may contribute to ccRCC. We show that GAL3ST1, an enzyme that catalyzes the sulfonation of the plasma membrane sulfolipid sulfatide, is among the top 50 upregulated genes in ccRCC tissue relative to matched normal tissue. Increased expression of GAL3ST1 in primary ccRCC correlates with decreased survival. We show that GAL3ST1 is a HIF target gene whose expression is induced upon VHL loss leading to the accumulation of its enzymatic product sulfatide. Notably, platelets bind more efficiently to renal cancer cells with high GAL3ST1-sulfatide expression than to GAL3ST1-sulfatide–negative counterparts, which protects ccRCC cells against natural killer cell–mediated cytotoxicity. These results suggest that GAL3ST1 is a HIF-responsive gene that may contribute to ccRCC development via promoting cancer cell evasion of immune surveillance. Implications: Cancer development is in part dependent on evasion of immune response. We identify a HIF target gene product GAL3ST1 that may play a role in this critical process.
Primordial black holes and induced gravitational waves from double-pole inflation

The primordial black hole (PBH) productions from the inflationary potential with an inflection point usually rely heavily on the fine-tuning of the model parameters. We propose in this work a new kind of the α-attractor inflation with asymmetric double poles that naturally and easily lead to a period of non-attractor inflation, during which the PBH productions are guaranteed with less fine-tuning the model parameters. This double-pole inflation can be tested against the observational data in the future with rich phenomenological signatures: (1) the enhanced curvature perturbations at small scales admit a distinctive feature of ultraviolet oscillations in the power spectrum; (2) the quasi-monochromatic mass function of the produced PBHs can be made compatible to the asteroid-mass PBHs as the dominant dark matter component, the planet-mass PBHs as the OGLE ultrashort-timescale microlensing events, and the solar-mass PBHs as the LIGO-Virgo events; (3) the induced gravitational waves can be detected by the gravitational-wave detectors in space and Pulsar Timing Array/Square Kilometer Array.
Vitreoschisis‐induced vitreous cortex remnants: missing link in proliferative vitreoretinopathy

caine in the presence of P. aeruginosa and S. marcescens (MIC > 2000 mg/l). However, a MIC was determined for all the other microbes, from 250 mg/l for M. catarrhalis up to 2000 mg/l for S. aureus and S. epidermidis. Finally, a MIC was determined for all the microbes in the presence of Tetracaine . These MIC were systematically lower than with Oxybuprocaine , ranging from 312 mg/l for C. macginleyi and M. catarrhalis up to 2500 mg/l for P. aeruginosa. The MIC results are summarized in Table 1. This is the first study to evaluate the antibacterial activity of Fluorescein . OurMIC results for the local anaesthetics were similar to those of previous studies (Kleinfeld & Ellis 1966; Labetoulle et al. 2002; Pelosini et al. 2009). It should be noted that in clinical practice, Fluorescein is very often used in combination with a local anaesthetic (Darugar et al. 2011). An additional analysis was therefore carried out using the combinations of Fluorescein -Oxybuprocaine and Fluorescein -Tetracaine (Table 1). No interaction was detected for the Fluorescein -Tetracaine combination. However, the Fluorescein Oxybuprocaine combination appeared to have a synergistic effect on Gram-positive cocci (Staphylococci and Pneumococci). Finally, with any cases of severe CA, the patient’s eye should be routinely rinsed with sterile saline solution before samples are taken, in order to remove the fluorescein and local anaesthetic and avoid producing a negative culture.
The change in quality of life for older Australians: A rural and urban comparison.

OBJECTIVE To assess the quality of life of older Australians living in rural and urban communities over time. DESIGN Panel survey conducted in 2012-2013 and 2014-2015. SETTING Participants lived in metropolitan Melbourne (urban sample, N = 279), rural Victoria (N = 98) or Tasmania (N = 47). PARTICIPANTS All participants (N = 424) were clients of aged care providers or residents in retirement housing or residential care. MAIN OUTCOME MEASURES Quality of life. RESULT A repeated-measures analysis of variance showed a decrease in quality of life over time. There was no difference in change in quality of life over time by location of participants (urban vs rural). Multiple regression analysis showed that resilience predicted baseline quality of life in all three locations. CONCLUSION These findings generally did not support significant differences between geographic locations in trajectories of older adults' quality of life over time. Instead, individuals' resilience appears to be the strongest predictor of quality of life.
Histochemical and immunohistochemical detection of pathogenic leptospires serovars in tissues of some captive wildlife from a University zoo in Nigeria

ABSTRACT The detection and documentation of pathogenic Leptospira serovars in wild captive and zoological garden animals are scarce in literature from Nigeria. The knowledge of the prevalence of prevalence of pathogenic Leptospira serovars in these animals as a zoonotic risk to workers, zoo visitors and the general public is essential. This investigation was carried out on archival kidney and liver samples of captive and Zoological Garden animals (66) of an institutional facility, submitted for necropsy to the Department of Veterinary Pathology between the periods of 2010–2015. The gross diagnosis reports were obtained from the necropsy records, detection of pathogenic Leptospira serovars was by Warthin Starry silver staining and immunohistochemistry techniques using standard methods. Six samples out of the sixty-six samples were positive for leptospira four samples were positive by silver stain method, while two samples were positive by immunohistochemistry. In this study, serovar Pomona and grippotyphosa were detected in the foxes while serovar Pomona was detected in the horse. This study has revealed the presence of pathogenic leptospires in some captive wild and zoological garden animals.
Co-ordination Assisted Self-assembled Polypeptide Nanogel to Selectively Combat Bacterial Infection.

In the present scenario, the invention of bacteria selective antimicrobial agent comprising negligible toxicity and hemolytic effect is a great challenge. To surmount this challenge, here a series of polypeptide nanogel (PNG) has been fabricated by co-ordination assisted self-assembly of mannose conjugated antimicrobial polypeptide, poly(arginine-r-valine)-mannose (poly(Arg-r-Val)-M2) with Zn2+ ion. Fabricated PG's are spherical in shape with a unique structural appearance similar to Taxus baccata fruits. PNG, with a unique structural arrangement and threshold surface charge density, selectively interacts with bacterial membrane and exhibits potent antimicrobial activity as reflected in their lower minimum inhibitory concentration (MIC) values (varies from 2 to 16 µg/mL). PNG shows a remarkably high binding constant, 6.02×105 M-1 (from isothermal titration calorimetry, ITC) with the bacterial membrane which manifests its potent bactericidal effect. PNG's are non-toxic against mammalian and red blood cells as reflected from their higher cell viability and insignificant hemolytic effect. PNG is taken up by the bacterial membrane and selectively undergoes structural deformation (scrutinized by ITC) followed by exposure of free poly(Arg-r-Val)-M2 molecules. The free poly(Arg-r-Val)-M2 molecules are enforced to lysis the bacterial membrane (visualized by cryo-TEM) followed by diffusion of the cytoplasmic component out of the membrane which culminates in final death of the bacterium.
Antigen Complexed with a TLR9 Agonist Bolsters c-Myc and mTORC1 Activity in Germinal Center B Lymphocytes

The germinal center (GC) is the anatomical site where humoral immunity evolves. B cells undergo cycles of proliferation and selection to produce high-affinity Abs against Ag. Direct linkage of a TLR9 agonist (CpG) to a T-dependent Ag increases the number of GC B cells. We used a T-dependent Ag complexed with CpG and a genetic model for ablating the TLR9 signaling adaptor molecule MyD88 specifically in B cells (B-MyD88− mice) together with transcriptomics to determine how this innate pathway positively regulates the GC. GC B cells from complex Ag-immunized B-MyD88− mice were defective in inducing gene expression signatures downstream of c-Myc and mTORC1. In agreement with the latter gene signature, ribosomal protein S6 phosphorylation was increased in GC B cells from wild-type mice compared with B-MyD88− mice. However, GC B cell expression of a c-Myc protein reporter was enhanced by CpG attached to Ag in both wild-type and B-MyD88− mice, indicating a B cell–extrinsic effect on c-Myc protein expression combined with a B cell–intrinsic enhancement of gene expression downstream of c-Myc. Both mTORC1 activity and c-Myc are directly induced by T cell help, indicating that TLR9 signaling in GC B cells either enhances their access to T cell help or directly influences these pathways to further enhance the effect of T cell help. Taken together, these findings indicate that TLR9 signaling in the GC could provide a surrogate prosurvival stimulus, “TLR help,” thus lowering the threshold for selection and increasing the magnitude of the GC response.
Development of a comprehensive protein microarray for immunoglobulin E profiling in horses with severe asthma

Abstract Background Severe asthma in horses, known as severe equine asthma (SEA), is a prevalent, performance‐limiting disease associated with increased allergen‐specific immunoglobulin E (IgE) against a range of environmental aeroallergens. Objective To develop a protein microarray platform to profile IgE against a range of proven and novel environmental proteins in SEA‐affected horses. Animals Six SEA‐affected and 6 clinically healthy Warmblood performance horses. Methods Developed a protein microarray (n = 384) using protein extracts and purified proteins from a large number of families including pollen, bacteria, fungi, and arthropods associated with the horses, environment. Conditions were optimized and assessed for printing, incubation, immunolabeling, biological fluid source, concentration techniques, reproducibility, and specificity. Results This method identified a number of novel allergens, while also identifying an association between SEA and pollen sensitization. Immunolabeling methods confirmed the accuracy of a commercially available mouse anti‐horse IgE 3H10 source (R 2 = 0.91). Biological fluid source evaluation indicated that sera and bronchoalveolar lavage fluid (BALF) yielded the same specific IgE profile (average R 2 = 0.75). Amicon centrifugal filters were found to be the most efficient technique for concentrating BALF for IgE analysis at 40‐fold. Overnight incubation maintained the same sensitization profile while increasing sensitivity. Reproducibility was demonstrated (R 2 = 0.97), as was specificity using protein inhibition assays. Arthropods, fungi, and pollens showed the greatest discrimination for SEA. Conclusions and Clinical Importance We have established that protein microarrays can be used for large‐scale IgE mapping of allergens associated with the environment of horses. This technology provides a sound platform for specific diagnosis, management, and treatment of SEA.
Bioactivity of Methoxylated and Methylated 1-Hydroxynaphthalene-2-Carboxanilides: Comparative Molecular Surface Analysis †

A series of twenty-six methoxylated and methylated N-aryl-1-hydroxynaphthalene- 2-carboxanilides was prepared and characterized as potential anti-invasive agents. The molecular structure of N-(2,5-dimethylphenyl)-1-hydroxynaphthalene-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. All the analysed compounds were tested against the reference strain Staphylococcus aureus and three clinical isolates of methicillin-resistant S. aureus as well as against Mycobacterium tuberculosis and M. kansasii. In addition, the inhibitory profile of photosynthetic electron transport in spinach (Spinacia oleracea L.) chloroplasts was specified. In vitro cytotoxicity of the most effective compounds was tested on the human monocytic leukaemia THP-1 cell line. The activities of N-(3,5-dimethylphenyl)-, N-(3-fluoro-5-methoxy-phenyl)- and N-(3,5-dimethoxyphenyl)-1-hydroxynaphthalene-2-carbox- amide were comparable with or even better than the commonly used standards ampicillin and isoniazid. All promising compounds did not show any cytotoxic effect at the concentration >30 µM. Moreover, an in silico evaluation of clogP features was performed for the entire set of the carboxamides using a range of software lipophilicity predictors, and cross-comparison with the experimentally determined lipophilicity (log k), in consensus lipophilicity estimation, was conducted as well. Principal component analysis was employed to illustrate noticeable variations with respect to the molecular lipophilicity (theoretical/experimental) and rule-of-five violations. Additionally, ligand-oriented studies for the assessment of the three-dimensional quantitative structure–activity relationship profile were carried out with the comparative molecular surface analysis to determine electron and/or steric factors that potentially contribute to the biological activities of the investigated compounds.
Diagnostic accuracy of Bilateral Inferior Petrosal Sinus Sampling: The Experience of a Tertiary Centre.

PURPOSE To assess the accuracy of bilateral inferior petrosal sinus sampling both in the differential diagnosis of adrenocorticotrophic hormone dependent Cushing's syndrome and predicting the localization on the pituitary. METHODS The authors evaluated all patients that undergone bilateral inferior petrosal sinus sampling in a tertiary centre, between January 1995 and March 2018. The probable diagnosis of Cushing's disease was made when the basal central/peripheral gradient was>2 and/or>3 after stimulation with corticotrophin releasing hormone. The localization was suggested when the inter-sinus gradient was>1.4. The results obtained were compared with the post operatory results: compatible histology and positive immunohistochemistry to adrenocorticotrophic hormone and/or the presence of criteria of cure. Sensitivity, specificity and predictive positive value were calculated. RESULTS A total of 49 patients were evaluated (75.5% female; mean age 45.4±16.3 years old). Bilateral inferior petrosal sinus sampling was compatible with Cushing's disease in 27 out of 28 confirmed cases in histology or by criteria of cure, and was compatible with ectopic secretion in the 2 cases confirmed as ectopic secretion of adrenocorticotrophic hormone (sensitivity 96.4%; specificity 100%). The lateralization calculated was concordant with the results after surgery in 17 out of 27 patients with Cushing's disease - predictive positive value of 63%. Magnetic resonance had a higher predictive value to lateralization - 70.0%. CONCLUSIONS Bilateral inferior petrosal sinus sampling is a safe and reliable procedure to diagnose Cushing's disease, with great sensitivity and specificity. Nevertheless, the capacity of this procedure to lateralize the lesion inside the pituitary is limited.
Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25–29 years to 5.1% for women aged 50–60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25–29) to 76.3% (for women 40–49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.
Is Antipsychotic Treatment Associated With Risk of Pneumonia in People With Serious Mental Illness?: The Roles of Severity of Psychiatric Symptoms and Global Functioning.

BACKGROUND Most pneumonia-related researches in people with severe mental illness were based on insurance claims data. This study aimed for a comprehensive analysis of factors potentially associated with risk of pneumonia in psychiatric inpatients. METHODS Inpatients at a large psychiatric hospital diagnosed with pneumonia during the course of hospitalization were enrolled as cases. Controls were matched by ward and date. The diagnosis of pneumonia was confirmed by physicians based on clinical features, chest radiographs, and blood tests. A stepwise conditional logistic regression model was used to identify potential risk factors for pneumonia. RESULTS Seventy-five pneumonia cases and 436 matched controls were enrolled. Conditional logistic regression revealed 3 variables significantly associated with an increased risk of pneumonia: a higher score on the Clinical Global Impression-Severity scale (adjusted odds ratio [aOR], 3.7; 95% confidence interval [CI]. 1.5-9.1), a higher score on the Charlson comorbidity index (aOR, 2.2; 95% CI, 1.5-3.2), and a longer duration of antipsychotic treatment (aOR, 1.0; 95% CI, 1.0-1.0). Two variables were significantly associated with a decreased risk of pneumonia: a higher score on the Global Assessment of Functioning scale (aOR, 0.9; 95% CI, 0.8-0.9) and an older age of onset (aOR, 0.9; 95% CI, 0.9-1.0). After adjusting for potential confounders, use of antipsychotic or other psychotropic medications was not found to be a significant risk factor for pneumonia. CONCLUSIONS Physical comorbidities, long duration of antipsychotic treatment, early onset, severe psychiatric symptoms, and poor global functioning are associated with pneumonia in people with serious mental illness.
The Snapdragon LATE ELONGATED HYPOCOTYL Plays A Dual Role in Activating Floral Growth and Scent Emission

The plant circadian clock controls a large number of internal processes, including growth and metabolism. Scent emission displays a circadian pattern in many species such as the snapdragon. Here we show that knocking down LATE ELONGATED HYPOCOTYL in Antirrhinum majus affects growth and scent emission. In order to gain an understanding of the growth kinetics, we took a phenomic approach using in-house artificial vision systems, obtaining time-lapse videos. Wild type flowers showed a higher growth speed than knockdown plants. The maximal growth rate was decreased by 22% in plants with lower LHY expression. Floral volatiles were differentially affected as RNAi plants showed advanced emission of compounds synthesized from cinnamic acid and delayed emission of metabolites of benzoic acid. The monoterpenes myrcene and ocimene were delayed, whereas the sesquiterpene farnesene was advanced. Overall, transgenic lines showed an altered volatile emission pattern and displayed a modified scent profile. Our results show that AmLHY plays an important role in the quantitative and qualitative control of floral growth and scent emission.