Miracle-dz/UniFAR-FTUs huggingface dataset:
Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4‐AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4‐AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4‐AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4‐AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4‐AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4‐AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221‐3.760). In this study, a genome‐wide RNA sequencing dataset was used to identify 927 genes co‐expressing with FOXP4‐AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4‐AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome‐wide RNA sequencing dataset was done. We have found that FOXP4‐AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor‐related pathways such as NF‐kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4‐AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4‐AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome‐wide approaches, we identified the potential molecular mechanisms of FOXP4‐AS1 in PDAC and two targeted therapeutic drugs for it.
Direct evidence that tumor cells soften when navigating confined spaces

The mechanical properties of cells strongly regulate many physiological and pathological processes. For example, in cancer, invasive and metastatic tumor cells have often been reported to be softer than nontumor cells, raising speculation that cancer cells might adaptively soften to facilitate migration through narrow tissue spaces. Despite growing interest in targeting cell softening to impede invasion and metastasis, it remains to be directly demonstrated that tumor cells soften as they migrate through confined spaces. Here, we address this open question by combining topographically patterned substrates with atomic force microscopy (AFM). Using a polydimethylsiloxane open-roof microdevice featuring tapered, fibronectin-coated channels, we followed the migration of U2OS cells through various stages of confinement while simultaneously performing AFM indentation. As cells progress from unconfined migration to fully confined migration, cells soften and exclude Yes-associated protein from the nucleus. Superresolution imaging reveals that confinement induces remodeling of actomyosin stress fiber architecture. Companion studies with flat one-dimensional microlines indicate that the changes in cytoarchitecture and mechanics are intrinsically driven by topographical confinement rather than changes in cellular aspect ratio. Our studies represent among the most direct evidence to date that tumor cells soften during confined migration and support cell softening as a mechanoadaptive mechanism during invasion.
Robust Collaborative Clustering of Subjects and Radiomic Features for Cancer Prognosis

Feature dimensionality reduction plays an important role in radiomic studies with a large number of features. However, conventional radiomic approaches may suffer from noise, and feature dimensionality reduction techniques are not equipped to utilize latent supervision information of patient data under study, such as differences in patients, to learn discriminative low dimensional representations. To achieve robustness to noise and feature dimensionality reduction with improved discriminative power, we develop a robust collaborative clustering method to simultaneously cluster patients and radiomic features into distinct groups respectively under adaptive sparse regularization. Our method is built upon matrix tri-factorization enhanced by adaptive sparsity regularization for simultaneous feature dimensionality reduction and denoising. Particularly, latent grouping information of patients with distinct radiomic features is learned and utilized as supervision information to guide the feature dimensionality reduction, and noise in radiomic features is adaptively isolated in a Bayesian framework under a general assumption of Laplacian distributions of transform-domain coefficients. Experiments on synthetic data have demonstrated the effectiveness of the proposed approach in data clustering, and evaluation results on an FDG-PET/CT dataset of rectal cancer patients have demonstrated that the proposed method outperforms alternative methods in terms of both patient stratification and prediction of patient clinical outcomes.
Cardiovascular health and menopause in aging women with polycystic ovary syndrome

ABSTRACT Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with heterogeneous clinical manifestations. Current evidence suggests that women with PCOS exhibit an unfavorable metabolic profile which may pose them at increased risk for cardiovascular events later in life. Areas covered: Herein, we present a review of the existing literature relating to PCOS and long-term cardiovascular (CV) health risks in women after menopause. We performed an electronic-based search with the use of PubMed from 1990 to August 2019 and systematically reviewed studies assessing CV events in women with PCOS. We aimed to outline the gaps in the current evidence and suggest areas for future research. Expert opinion: Although there is a clear association between PCOS and cardiometabolic dysfunction, data on actual cardiovascular disease (CVD) events are conflicting. Additional large, prospective cohort studies of well-phenotyped women with PCOS and long-term follow-up into the late menopause are needed to elucidate the true CVD risk in this population.
Perceived abortion stigma and psychological well-being over five years after receiving or being denied an abortion

Objective To prospectively assess perceptions of abortion stigma after receiving or being denied an abortion over 5 years, the factors associated with perceived abortion stigma, and the effects of perceived abortion stigma on psychological well-being. Methods We recruited people seeking abortion from 30 facilities across the US, and interviewed them by phone one week post-abortion seeking, then semiannually for 5 years. We used adjusted mixed effects regression analyses to examine the abortion stigma trajectories of those who obtained an abortion near a facility’s gestational age limit (Near-limits) compared to those denied an abortion because they were just over the limit and carried their pregnancies to term (Turnaway-births). Results Of the 956 people recruited, we removed 28 due to ineligibility or missing data, leaving a final sample of 928. In unadjusted analyses, at one-week post-abortion seeking, over half of those seeking abortion perceived that if others knew they had sought an abortion, they would be looked down upon at least “a little bit” by people close to them (60%) or by people in their community (56%). In longitudinal adjusted analyses, people denied an abortion and who carried their pregnancies to term (Turnaway-birth group) reported significantly lower baseline perceived abortion stigma from people close to them (-0.38; 95% CI, -0.59, -0.16) and from people in their community (0.30; 95% CI, -0.52, -0.08), than Near-limits, differences that remained statistically significant for 1.5 years. Overall perceived abortion stigma declined significantly (p < .001) for both study groups. High perceived abortion stigma at baseline was associated with higher odds of experiencing psychological distress years later (adjusted Odds Ratio, 3.98; 95% CI, 1.39, 11.37). Conclusions Most people considering abortion perceive some abortion stigma, which is associated with psychological distress years later.
Crystal structure of the mineralocorticoid receptor ligand‐binding domain in complex with a potent and selective nonsteroidal blocker, esaxerenone (CS‐3150)

Activation of the mineralocorticoid receptor (MR) has long been considered a risk factor for cardiovascular diseases. It has been reported that the novel MR blocker esaxerenone shows high potency and selectivity for MR in vitro as well as great antihypertensive and renoprotective effects in salt‐sensitive hypertensive rats. Here, we determined the cocrystal structure of the MR ligand‐binding domain (MR‐LBD) with esaxerenone and found that esaxerenone binds to MR‐LBD in a unique manner with large side‐chain rearrangements, distinct from those of previously published MR antagonists. This structure also displays an antagonist form that has not been observed for MR previously. Such a unique binding mode of esaxerenone provides great insight into the novelty, potency, and selectivity of this novel antihypertensive drug.
RUNX1 Dosage in Development and Cancer

The transcription factor RUNX1 first came to prominence due to its involvement in the t(8;21) translocation in acute myeloid leukemia (AML). Since this discovery, RUNX1 has been shown to play important roles not only in leukemia but also in the ontogeny of the normal hematopoietic system. Although it is currently still challenging to fully assess the different parameters regulating RUNX1 dosage, it has become clear that the dose of RUNX1 can greatly affect both leukemia and normal hematopoietic development. It is also becoming evident that varying levels of RUNX1 expression can be used as markers of tumor progression not only in the hematopoietic system, but also in non-hematopoietic cancers. Here, we provide an overview of the current knowledge of the effects of RUNX1 dosage in normal development of both hematopoietic and epithelial tissues and their associated cancers.
EWSR1 fusions: Ewing sarcoma and beyond

Vickie Y. Jo received a BA at Williams College in Williamstown, Massachusetts, and an MD at the University of Virginia in Charlottesville, Virginia, where she also completed her Anatomic and Clinical Pathology residency. She did her fellowship training in soft-tissue pathology and cytopathology at Brigham and Women’s Hospital (BWH) in Boston, Massachusetts, and joined the BWH faculty in 2012 and is currently an Assistant Professor at Harvard Medical School. She is active in the head and neck, soft-tissue, and cytopathology services at BWH and Dana-Farber Cancer Institute, with research interests in the clinicopathologic characterization of soft-tissue and head and neck neoplasms and the development of diagnostic biomarkers in surgical pathology and cytopathology.
Prevalence of Thyroid Incidentalomas from 1995 to 2016: A Single-Center, Retrospective Cohort Study.

Background Incidental detection of thyroid nodules on nonthyroid imaging may contribute to increased diagnosis of thyroid cancer. We investigated the prevalence of thyroid incidentalomas across imaging modalities among a predominately male veteran population. Methods Thyroid nodules were identified on nonthyroid-directed radiology reports using natural language processing. All reports from 1995 to 2016 for chest computed tomography (CT), carotid ultrasound (US), and neck magnetic resonance imaging (MRI) were reviewed. Individuals with multiple studies were included at their initial study and duplicates removed. Results A total of 25 763 carotid US, 23 526 chest CTs with contrast, 39 262 noncontrast chest CTs, and 9503 MRIs were reviewed. With duplicates removed, 14 642 carotid US, 12 923 chest CTs with contrast, 17 416 noncontrast chest CTs, and 6926 MRIs were included. Mean age was 66.2 years and 1834 were female (3.53%). Thyroid nodules were reported on 0.84% carotid US, 3.45% MRIs, 5.84% chest CTs with contrast, and 5.14% noncontrast chest CTs. Women had a higher rate of thyroid nodules on MRI (6.46% vs 3.20%, P = .003), chest CT with contrast (9.80% vs 5.72%, P = .007), and noncontrast chest CT (8.77% vs 5.02%, P = .002), but not on carotid US (1.99% vs 0.81%, P = .12). Incidentaloma prevalence increased with age on MRI, chest CT with or without contrast, but not on carotid US, and were more commonly reported from 2007 to 2016 compared to before 2007 across all modalities. Conclusions Thyroid incidentalomas are commonly reported, are more common among women, and increase with age. The rate of reported incidental thyroid nodules is increasing, likely contributing to the increase in thyroid cancer.
Moderate prenatal stress may buffer the impact of Superstorm Sandy on placental genes: Stress in Pregnancy (SIP) Study

The placenta plays a central role in the epigenetic programming of neurodevelopment by prenatal stress (PS), but this pathway is not fully understood. It difficult to study in humans because the conditions for intense, traumatic PS are almost impossible to create ethically. This study was able to capitalize on a 2012 disaster that hit New York, Superstorm Sandy, to examine the impact of traumatic stress on placental gene expression while also examining normative PS, and compare the two. Of the 303 expectant mothers participating in the Stress in Pregnancy Study, 95 women were pregnant when Superstorm Sandy struck. During their pregnancy, participants completed self-report measures of PS and distress that were combined, using latent profile analysis, into one global indicator of normative PS. Placental tissue was collected at delivery and frozen for storage. RNA expression was assessed for 40 placental genes known to associate with the stress response system and neurodevelopment in offspring. Results showed that normative PS increased expression of just MECP2, HSD11B2, and ZNF507, whereas Superstorm Sandy PS decreased expression of CDKL5, CFL1, DYRK1A, HSD11B2, MAOA, MAOB, NCOR1, and ZNF507. Interaction analyses indicated that Superstorm Sandy PS was associated with decreased gene expression for the low and high PS group for CFL1, DYRK1A, HSD11B2, MAOA, and NCOR1 and increased expression for the moderate PS group for FOXP1, NR3C1, and NR3C2. This study supports the idea that a moderate amount of normative PS may buffer the impact of traumatic PS, in this case caused by Superstorm Sandy, on placental gene expression, which suggests that the placenta itself mirrors the organism’s ability to develop an epigenetic resilience to, and inoculation from, stress.
Modification of tubular chitosan-based peripheral nerve implants: applications for simple or more complex approaches

Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic. Up to now, none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve function. This restriction is also effective for novel clinically approved artificial nerve guides. In this review, we compare surgical repair techniques primarily for digital nerve injuries reported with relatively high prevalence to be valuable attempts in clinical digital nerve repair and point out their advantages and shortcomings. We furthermore discuss the use of artificial nerve grafts with a focus on chitosan-based nerve guides, for which our own studies contributed to their approval for clinical use. In the second part of this review, very recent future perspectives for the enhancement of tubular (commonly hollow) nerve guides are discussed in terms of their clinical translatability and ability to form three-dimensional constructs that biomimick the natural nerve structure. This includes materials that have already shown their beneficial potential in in vivo studies like fibrous intraluminal guidance structures, hydrogels, growth factors, and approaches of cell transplantation. Additionally, we highlight upcoming future perspectives comprising co-application of stem cell secretome. From our overview, we conclude that already simple attempts are highly effective to increase the regeneration supporting properties of nerve guides in experimental studies. But for bringing nerve repair with bioartificial nerve grafts to the next level, e.g. repair of defects > 3 cm in human patients, more complex intraluminal guidance structures such as innovatively manufactured hydrogels and likely supplementation of stem cells or their secretome for therapeutic purposes may represent promising future perspectives.
Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico.

INTRODUCTION Tyrosinase is a multifunctional copper-containing oxidase enzyme that catalyses the first steps in the formation of melanin pigments. Identification of tyrosinase inhibitors is of value for applications in cosmetics, medicine and agriculture. OBJECTIVE To develop an analytical method that allows identification of drug-like natural products that can be further developed as tyrosinase inhibitors. Results of in vitro and in silico studies will be compared in order to gain a deeper insight into the mechanism of action of enzyme inhibition. METHOD Using an in vitro assay we tested tyrosinase inhibitor effects of five structurally related flavones, i.e. luteolin (1), eupafolin (2), genkwanin (3), nobiletin (4), and chrysosplenetin (5). The strongest inhibitors were further investigated in silico, using enzyme docking simulations. RESULTS All compounds tested showed modest tyrosinase inhibitory effect compared to the positive control, kojic acid. The polymethoxy flavones 4 and 5 exhibited the strongest tyrosinase inhibitory effect with the half maximal inhibitory concentration (IC50 ) values of 131.92 ± 1.75 μM and 99.87 ± 2.38 μM respectively. According to kinetic analysis 2, 4 and 5 were competitive inhibitors, whereas 1 and 3 were non-competitive inhibitors of tyrosinase. Docking studies indicated that methoxy groups on 4 and 5 caused steric hindrance which prevented alternative binding modes in the tyrosinase; the methoxy groups on the B-ring of these flavones faced the catalytic site in the enzyme. CONCLUSIONS The docking simulations nicely complemented the in vitro kinetic studies, opening the way for the development of predictive models for use in drug design.
Intellectual Property and the Organization of the Global Value Chain

This paper introduces the concept of intangible assets in a property rights model of sequential supply chains. Firms transmit knowledge to their suppliers to facilitate input customization. Yet, to avoid knowledge dissipation, they must protect the transmitted intangibles, the cost of which depends on the knowledge intensity of inputs and the quality of institutions protecting intellectual property rights (IPR) in supplier locations. When input knowledge intensity increases (decreases) downstream and suppliers' investments are complements, the probability of integrating a randomly selected input is decreasing (increasing) in IPR quality and increasing (decreasing) in the relative knowledge intensity of downstream inputs. Opposite but weaker predictions hold when suppliers' investments are substitutes. Comprehensive trade and FDI data on Slovenian firms' value chains provide evidence in support of our model's predictions. They also suggest that, in line with our model, better institutions may have very different effects on firm organization depending on whether they improve the protection of tangible or intangible assets.
Determinant of Corporate Turnaround: A Review Study

The aim of this research is to discuss about factors that affect corporate turnaround with literature study. Corporate turnaround become a treasure to a company that had financial distress which can cause a company have bankruptcy. This literature study discusses some past research about factors can affect corporate turnaround. In this research we select the factors such as firm size, free asset and assets retrenchment as they represent from each corporate turnaround dimension Keywords—corporate turnaround, corporate distress, firm size,free assets, assets retrenchment.
CHEMICAL MODIFICATIONS OF ALGINATE AND ITS DERIVATIVES

Alginate is a polysaccharide obtained from seaweeds that are abundantly available and have shown great potential for diverse industrial applications. However, alginate lacks properties such as stability under aqueous conditions and it is difficult to control the rate of degradation of alginate-based materials, crucial for various medical applications. Therefore, researchers have modified alginate using physical or chemical approaches to enhance physical properties, biocompatibility, solubility and also to control the biodegradability of alginate-based materials. Crosslinking using ionic, covalent, photo and enzymatic approaches are one of the preferred methods for modifying the properties of alginates and its derivatives. Crosslinking binds the individual polymer chains with one another to form a network that enhances mechanical properties and stability. Among the different crosslinking approaches, ionic crosslinking provides biomaterials with limited stability whereas biomaterials with high mechanical stability can be prepared by covalent crosslinking. Although a wide variety of crosslinking chemicals and approaches are available to make alginate suitable for various applications, the methods used, properties and applications of the cross-linked materials vary significantly between studies. There are very few reports that have compared and evaluated the benefits of using different crosslinking approaches and the properties and applications of cross-linked alginate. In this review, the various methods of crosslinking alginates, their advantages, and limitations have been reviewed with particular emphasis on medical applications of alginate. The data for writing the review was obtained using search engines like Google scholar, Sci-hub and Sci finder and the keywords used include alginate, crosslinking, ionic, covalent, photo, enzymatic, biomedical applications.
Forward Guidance Without Common Knowledge

How does the economy respond to news about future policies or future fundamentals? Standard practice assumes that agents have common knowledge of such news and face no uncertainty about how others will respond. Relaxing this assumption attenuates the general-equilibrium effects of news and rationalizes a form of myopia at the aggregate level. We establish these insights within a class of games which nests, but is not limited to, the New Keynesian model. Our results help resolve the forward-guidance puzzle, offer a rationale for the front-loading of fiscal stimuli, and illustrate more broadly the fragility of predictions that rest on long series of forward-looking feedback loops.