Miracle-dz/UniFAR-FTUs huggingface dataset:
TP53 missense mutations in PDAC are associated with enhanced fibrosis and an immunosuppressive microenvironment

Significance Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, which is presently refractory to all available therapeutic strategies. PDAC tumors are characterized by a high degree of fibrosis, believed to be a major contributor to their therapy resistance. Mutations in theTP53 tumor suppressor gene are very frequent in PDAC. We now report that TP53 missense mutations, which lead to production of mutant p53 proteins, increase the extent of fibrosis and reduce the infiltration of cytotoxic CD8+ T cells. The inhibition of CD8+ T cell infiltration may augment the ability of PDAC tumors to evade the immune system. Hence, inhibition of the activities of mutant p53 may potentially sensitize PDAC tumors to anticancer treatments, including immunotherapy. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, which is refractory to all currently available treatments and bears dismal prognosis. About 70% of all PDAC cases harbor mutations in the TP53 tumor suppressor gene. Many of those are missense mutations, resulting in abundant production of mutant p53 (mutp53) protein in the cancer cells. Analysis of human PDAC patient data from The Cancer Genome Atlas (TCGA) revealed a negative association between the presence of missense mutp53 and infiltration of CD8+ T cells into the tumor. Moreover, CD8+ T cell infiltration was negatively correlated with the expression of fibrosis-associated genes. Importantly, silencing of endogenous mutp53 in KPC cells, derived from mouse PDAC tumors driven by mutant Kras and mutp53, down-regulated fibrosis and elevated CD8+ T cell infiltration in the tumors arising upon orthotopic injection of these cells into the pancreas of syngeneic mice. Moreover, the tumors generated by mutp53-silenced KPC cells were markedly smaller than those elicited by mutp53-proficient control KPC cells. Altogether, our findings suggest that missense p53 mutations may contribute to worse PDAC prognosis by promoting a more vigorous fibrotic tumor microenvironment and impeding the ability of the immune system to eliminate the cancer cells.
Thermal and Radiation Stability of Nanomaterials

The kinetic/thermodynamic stabilization recent results of grain growth in nanomaterials (NMs)-based metals, alloys, and compounds are generalized. Due to their large share of interfaces which can act as the sinks for radiation defects, NMs show improved irradiation resistance such as the resistance to amorphization, hardening and swelling. Radiation defects will tend also to the nanostructure annihilation and transformation into amorphous state. Some unsolved problems are emphasized.
Parental Satisfaction With Autonomous Pediatric Ambulatory Surgery Units

Background and Objectives: Ambulatory surgery is much favored in children, as they are usually healthy with no major comorbidities. Obvious benefits are minimization of health costs, optimal utilization of resources, decreased exposure to infections, and psychological and emotional advantages of avoiding admission of the patient, especially for the family. Parental satisfaction is a challenge in pediatric surgery processes. The objective of this study was to compare satisfaction in parents whose children underwent surgery without overnight stays with parents whose children were operated on in an autonomous major ambulatory surgery unit (hospital isolated). Methods: This was a prospective observational study of 200 children who received surgery on an outpatient basis (133 were included in an outpatient unit and 67 in a hospital setting). Different variables were collected, including sex, age, type of surgery, and length of stay in the hospital and location, and a telephone perception survey was conducted (questionnaire of satisfaction of 14 questions with possible answers from 1 to 4 on a Likert scale and a 15th question on global satisfaction, with an answer from 0 to 10). Results: Overall satisfaction during the hospital stay was higher in the group operated on in the autonomous major surgery unit (3.54 ± 0.57 vs 3.28 ± 0.64, P = .004). Whether parents respond as being very satisfied with the hospital stay is influenced by several factors, among which are: being treated at major ambulatory surgery units (odds ratio [OR] = 2.16), good or very good information received prior to surgery (OR = 2.03), and good or very good information received at discharge (OR = 2.48). Conclusions: Parents of children who received surgery on an outpatient basis were more satisfied if the procedure was performed in an autonomous major ambulatory surgery unit compared with hospitalization, even if it was not overnight. The information received during the care process influenced the parents' satisfaction. These findings suggest that efforts should be devoted to the creation of autonomous units for ambulatory surgery and to the improvement of perioperative information.
Absorption and excretion of chromium from orally administered chromium chloride, chromium acetate and chromium oxide in rats

There is a growing interest in the absorption of different forms of trivalent chromium. In the current study, we evaluated the absorption and excretion of chromium after single-dose administration of 3 chromium compounds (chromium chloride hexahydrate, chromium oxide and chromium acetate hydroxide), compared to a control, in male Sprague Dawley rats. These rats were dosed at 1000 mg/kg per compound. 24-hour urine collection and tissue samples were analyzed for chromium content. Animals were observed twice daily for mortality and clinical signs of toxicity. Gross observations were recorded at necropsy. Postmortem findings were observed only in rats administered chromium chloride. These findings included stomachs distended with fluid and gas, and ulceration of the mucosal lining of the stomachs. Trace levels of chromium were detected in urine samples from rats administered chromium oxide (group mean < 0.2 mg/l) while urinary chromium levels for the rats given chromium chloride and chromium acetate were 174 mg/l and 93 mg/l, respectively. Elevated levels of chromium were observed in liver, kidney, heart and pancreas samples collected from the rats administered chromium chloride and chromium acetate, compared to chromium levels detected in the chromium oxide and control groups. Evaluation of chromium levels in urine and tissues show that chromium oxide was poorly absorbed compared to chromium chloride hexahydrate and chromium acetate hydroxide. Additionally, while chromium chloride hexahydrate was readily absorbed, toxic effects were observed.
Diagnostic Value of MicroRNA 21 in Endometrial Cancer and Benign Lesions and its Differential Expression in Relation to Clinicopathological Parameters.

BACKGROUND Endometrial cancer is one of the most common malignancies among women worldwide. Although this cancer is often diagnosed at early stages, the need for biomarkers of diagnosis remains a necessity to overcome conventional invasive procedures of diagnosis. OBJECTIVE In our study, we aim to investigate the diagnostic value of microRNA-21 in endometrial cancer and its relation to clinicopathological features. METHODS We used RT-qPCR to measure the expression of microRNA-21 in 71 tumor tissues, 53 adjacent tissues, and 54 benign lesions. RESULTS Our results show that microRNA-21 is a potential biomarker for endometrial cancer with an area under the receiver operating characteristic curve of 0.925 (95% CI = 0.863 - 0.964, P<0.0001). The sensitivity was 84.51% (95% CI = 74.0 - 92.0) and specificity was 86.79% (95% CI = 74.7 - 94.5). For discrimination between benign lesions and controls the AUC was 0,881 with a sensitivity of 100% (95% CI = 93.4 - 100.0) and specificity of 66.04 % (95% CI = 51.7 - 78.5), and for discriminating benign lesions from tumors the AUC was 0,750 with a sensitivity of 54.93% (95% CI = 42.7 - 66.8) and specificity of 90.74% (95% CI = 79.7 - 96.9). We also found that tumors with elevated microRNA-21 expression are of advanced FIGO stage, high histological grades, and have cervical invasion, myometrial invasion and distant metastasis. CONCLUSION Our findings support the important role of miR-21 as a biomarker for the diagnosis of endometrial cancer. Further studies on minimally invasive/noninvasive samples such as serum, blood, and urine are necessary to provide a better alternative to current diagnosis methods.
MoNuSAC2020: A Multi-Organ Nuclei Segmentation and Classification Challenge

Detecting various types of cells in and around the tumor matrix holds a special significance in characterizing the tumor micro-environment for cancer prognostication and research. Automating the tasks of detecting, segmenting, and classifying nuclei can free up the pathologists’ time for higher value tasks and reduce errors due to fatigue and subjectivity. To encourage the computer vision research community to develop and test algorithms for these tasks, we prepared a large and diverse dataset of nucleus boundary annotations and class labels. The dataset has over 46,000 nuclei from 37 hospitals, 71 patients, four organs, and four nucleus types. We also organized a challenge around this dataset as a satellite event at the International Symposium on Biomedical Imaging (ISBI) in April 2020. The challenge saw a wide participation from across the world, and the top methods were able to match inter-human concordance for the challenge metric. In this paper, we summarize the dataset and the key findings of the challenge, including the commonalities and differences between the methods developed by various participants. We have released the MoNuSAC2020 dataset to the public.
Implications of FDA Approval of a First Disease-Modifying Therapy for a Neurodegenerative Disease on the Design of Subsequent Clinical Trials

The goal of clinical research is to improve clinical practice. In progressive neurodegenerative conditions without any disease-slowing therapies, this will result in eventual approval of a first disease-modifying treatment. Clinical trials will still be needed to discover treatments that are more effective, safer, or more convenient. This will generate controversies over how to design these trials; specifically, controversies about the use of a placebo control. We consider ethical guidance for these studies with attention to 3 designs: placebo-controlled trials in the absence of the new drug, placebo-controlled trials with the approved drug as background therapy, and trials with the new drug as an active control. To understand the practical implications of these designs, we examine experiences in drug development in multiple sclerosis. We conclude by contemplating the future of clinical trials in Alzheimer disease.
Exploring the Food and Drug Administration’s review and approval of Entresto (sacubitril/valsartan)

Federal regulatory agencies such as the United States Food and Drug Administration review pharmacological evidence to ensure the safety and efficacy of new and repurposed pharmaceuticals prior to market approval. The discussions, disagreements and procedural decisions contained within such reviews offer unique insight into a pharmaceutical's strengths, weaknesses and opportunities, yet are often overlooked as a significant source of pharmacological information for research and development. To highlight the value of such resources, we present a case study on Entresto, a first‐in‐class angiotensin receptor‐neprilysin inhibitor for the treatment of heart failure with reduced ejection fraction, and explore the regulatory rationale underlying its market approval. Using information extracted from Entresto's online approval package at Drugs@FDA, we explore some of the procedural complexities underlying market approval of new pharmaceuticals, discuss the broad pharmacological implications contained within regulatory agency grey literature, and highlight opportunities for future therapeutic development.
Intraocular Pressure Elevation Following Intravitreal Anti-VEGF Injections: Short- and Long-term Considerations

Published studies agree that transient intraocular pressure (IOP) spikes are common after intravitreal injections of anti–vascular endothelial growth factor agents. Currently, there is no standard of care guiding if and when to prevent these IOP spikes. Furthermore, there are challenges in determining the impact of postinjection IOP elevation on the health of the retinal ganglion cells, particularly given the often-existing comorbidities of retinal and glaucoma pathology. This review highlights the current literature regarding both acute and chronic postinjection IOP elevations and discusses management of postinjection IOP elevation, especially in patients at high risk for glaucomatous damage.
A panel of 8-lncRNA predicts prognosis of breast cancer patients and migration of breast cancer cells

Background Breast cancer (BCa) is the most commonly diagnosed cancer and the leading cause of cancer death among females around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) can serve as an independent biomarker for diagnosis and prognosis in many types of cancer, including pancreatic adenocarcinoma, gastric cancer, liver cancer, and lung cancer. Previous studies have shown that many lncRNAs are associated with the occurrence and development of BCa. However, few studies have combined multiple lncRNAs to predict the prognosis of early-stage BCa patients. Methods Systematic and comprehensive analysis of data from The Cancer Genome Atlas (TCGA) was conducted to identify lncRNA signatures with prognostic value in BCa. Additionally, the relative expression levels of the 8 lncRNA of several BCa cell lines were detected by quantitative real-time PCR (qPCR) and the results were substituted into a risk score formula. Finally, migration assays were used to verify the result from prognostic analysis according to the risk scores among cell lines with different risk scores. Results Our study included 808 BCa patients with complete clinical data. A panel of 8 lncRNAs was identified using Wilcox tests as different between normal and tumor tissue of the BCa patients. This panel was used to analyze the survival of BCa patients. Patients with low risk scores had greater overall survival (OS) than those with high risk scores. Multivariate Cox regression analyses demonstrated that the lncRNA signature was an independent prognostic factor. Gene Set Enrichment Analysis (GSEA) suggested that the lncRNAs might be involved in several molecular signaling pathways implicated in BCa such as the DNA replication pathway, the cell cycle pathway, and the pentose phosphate pathway. Validation experiments in breast cancer cells to test cell migration by using wound-healing assays supported the results of the model. Conclusion Our study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa.
Enterprise Digital Divide: Website e-Commerce Functionalities among European Union Enterprises

Abstract Background: Information and communication technologies (ICTs) gained prevalent organizational and structural value in the modern economy. E-commerce is one of the sectors directly influenced by technological change. However, not all countries have the same opportunities to develop e-commerce growth; there are significant discrepancies in ICT utilization worldwide, known as the digital divide. Objectives: The purpose of this paper is to explore the level of difference among European countries regarding the e-commerce functionalities in their enterprises using a cluster analysis. Methods/Approach: To accomplish the paper goal, the k-means cluster analysis was conducted on the Eurostat data from 2019. Enterprises from 28 European countries were taken into consideration. The Kruskal-Wallis test is used to explore if the differences among clusters regarding the digital development, measured by the Digital Economy and Society Index are significant. Results: The investigation confirmed that there are significant differences among European countries regarding the development of e-commerce. However, a similar level of e-commerce is not related to economic and digital development. Conclusions: Since the relationship between economic development and e-commerce development in European countries is not linear, country-level policies are likely to be significant factors driving e-commerce development, which leads to the need for further investigation of this issue.
Cultural Tourism and Community Engagement: Insight from Montenegro

Abstract Background: Cultural tourism in Montenegro is growing, mostly due to the integral growth and development of tourism products. However, an in-depth insight into the relationship between cultural tourism and community engagement is missing. Objectives: The paper aims to examine the relationship between cultural tourism development and community engagement in Montenegro. Methods/Approach: Using the extensive literature, available secondary data, and an analysis of relevant policies, the paper explores new possibilities for diversifying tourism offer at heritage sites, by engaging volunteers, enhancing understanding of the socio-historical background, promoting the usage of digital tools, partnering with relevant stakeholders, introducing innovative funding tools and schemes. Results: Several management issues associated with heritage tourism and community participation are acknowledged. Conclusions: Key findings indicate the need for a systemic, dynamic, and innovative framework for sustainable and highly impactful heritage tourism in Montenegro, which policymakers, heritage ventures, and other stakeholders might use to strengthen community engagement and development at the heritage sites.
International Trade and Investment Behaviour of Firms

54 BOOK REVIEW Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons AttributionNonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-Commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https:// us.sagepub.com/en-us/nam/open-access-at-sage). B O O K R E V I E W International Trade and Investment
I Know What You Bought At Chipotle for $9.81 by Solving A Linear Inverse Problem

We consider the question of identifying which set of products are purchased and at what prices in a given transaction by observing only the total amount spent in the transaction, and nothing more. The ability to solve such an inverse problem can lead to refined information about consumer spending by simply observing anonymized credit card transactions data. Indeed, when considered in isolation, it is impossible to identify the products purchased and their prices from a given transaction based on just the transaction total. However, given a large number of transactions, there may be a hope. As the main contribution of this work, we provide a robust estimation algorithm for decomposing transaction totals into the underlying, individual product(s) purchased by utilizing a large corpus of transactions. Our method recovers a (product prices) vector $p ∈ RN>0 of unknown dimension (number of products) N as well as matrix $A ∈ ZM x N≥0 simply from M observations (transaction totals) y ∈ RM>0 such that y = A p + η with η ∈ RM representing noise (taxes, discounts, etc.). We formally establish that our algorithm identifies N, A precisely and p approximately, as long as each product is purchased individually at least once, i.e. M ≥ N and A has rank N. Computationally, the algorithm runs in polynomial time (with respect to problem parameters), and thus we provide a computationally efficient and statistically robust method for solving such inverse problems. We apply the algorithm to a large corpus of anonymized consumer credit card transactions in the period 2016-2019, with data obtained from a commercial data vendor. The transactions are associated with spending at Apple, Chipotle, Netflix, and Spotify. From just transactions data, our algorithm identifies (i) key price points (without access to the listed prices), (ii) products purchased within a transaction, (iii) product launches, and (iv) evidence of a new 'secret' product from Netflix - rumored to be in limited release.
Algorithm Trading with Google Trends Data

Nowadays, with the development of social media search system When people want to make financial decisions, they tend to use online search engine like Google to find information. According to Herbert Simon [1], people search only for events related to themselves, so an increase in search volume can reflect the fact that the event has an impact on more and more people. I find that I can learn about the orientation of the public and their views on the same thing through Google trend, thus I can infer the impact on the stock market in advance. In this paper, I investigate to see how google trends can help the financial practitioner predict the changes in stock market.
Refining Mean-field Approximations by Dynamic State Truncation

Mean-field models are an established method to analyze large stochastic systems with N interacting objects by means of simple deterministic equations that are asymptotically correct when N tends to infinity. For finite N, mean-field equations provide an approximation whose accuracy is model- and parameter-dependent. Recent research has focused on refining the approximation by computing suitable quantities associated with expansions of order $1/N$ and $1/N^2$ to the mean-field equation. In this paper we present a new method for refining mean-field approximations. It couples the master equation governing the evolution of the probability distribution of a truncation of the original state space with a mean-field approximation of a time-inhomogeneous population process that dynamically shifts the truncation across the whole state space. We provide a result of asymptotic correctness in the limit when the truncation covers the state space; for finite truncations, the equations give a correction of the mean-field approximation. We apply our method to examples from the literature to show that, even with modest truncations, it is effective in models that cannot be refined using existing techniques due to non-differentiable drifts, and that it can outperform the state of the art in challenging models that cause instability due orbit cycles in their mean-field equations.
Chasm in Hegemony

In networks with a minority and a majority community, it is well-studied that minorities are under-represented at the top of the social hierarchy. However, researchers are less clear about the representation of minorities from the lower levels of the hierarchy, where other disadvantages or vulnerabilities may exist. We offer a more complete picture of social disparities at each social level with empirical evidence that the minority representation exhibits two opposite phases: at the higher rungs of the social ladder, the representation of the minority community decreases; but, lower in the ladder, which is more populous, as you ascend, the representation of the minority community improves. We refer to this opposing phenomenon between the upper-level and lower-level as the chasm effect. Previous models of network growth with homophily fail to detect and explain the presence of this chasm effect. We analyze the interactions among a few well-observed network-growing mechanisms with a simple model to reveal the sufficient and necessary conditions for both phases in the chasm effect to occur. By generalizing the simple model naturally, we present a complete bi-affiliation bipartite network-growth model that could successfully capture disparities at all social levels and reproduce real social networks. Finally, we illustrate that addressing the chasm effect can create fairer systems with two applications in advertisement and fact-checks, thereby demonstrating the potential impact of the chasm effect on the future research of minority-majority disparities and fair algorithms.