Miracle-dz/UniFAR-FTUs huggingface dataset:
The enigmatic role of matrix metalloproteinases in epithelial‐to‐mesenchymal transition of oral squamous cell carcinoma: Implications and nutraceutical aspects

The most prevalent malignancy in the oral cavity is represented by oral squamous cell carcinoma, an aggressive disease mostly detected in low‐income communities. This neoplasia is mostly diffused in older men particularly exposed to risk factors such as tobacco, alcohol, and a diet rich in fatty foods and poor in vegetables. In oral squamous cell carcinoma, a wide range of matrix‐cleaving proteinases are involved in extracellular matrix remodeling of cancer microenvironment. In particular, matrix metalloproteinases (MMPs) represent the major and most investigated protagonists. Owing to their strong involvement in malignant pathologies, MMPs are considered the most promising new biomarkers in cancer diagnosis and prognosis. The interest in studying MMPs in oral cancer biology is also owing to their prominent role in epithelial‐to‐mesenchymal transition (EMT). EMT is an intricate process involving different complex pathways. EMT‐related proteins are attractive diagnostic biomarkers that characterize the activation of biological events that promote cancer's aggressive expansion. Different antioncogenic natural compounds have been investigated to counteract oral carcinogenesis, with the scope of obtaining better clinical results and lower morbidity. In particular, we describe the role of different nutraceuticals used for the regulation of MMP‐related invasion and proliferation of oral cancer cells.
Quantification of DNA damage in patients undergoing non-contrast and contrast enhanced whole body PET/CT investigations using comet assay and micronucleus assay

Abstract Objective: To quantify DNA damage in patients undergoing non-contrast and contrast-enhanced 18F-FDG PET/CT whole body positron emission tomography/computed tomography (WB PET/CT) investigations using comet assay technique and micronucleus assay, and to study the effect of other baseline parameters of patients on DNA damage. Methodology: Eighty-four patients referred for 18F-FDG PET/CT investigation were included in the study of which 44 patients underwent contrast-enhanced WB PET/CT and 40 patients underwent non-contrast WB PET/CT investigations. The investigations were performed on Discovery 690 PET/CT. For contrast-enhanced investigation, Omnipaque300 was injected intravenously based on the patient body weight. Absorbed dose resulting from the intravenous administration of 18F-FDG was estimated using the ICRP 106 dose coefficients. Radiation dose from the acquisition of CT scans was estimated using CT dose index and dose-length product. Blood samples were collected from the patients for DNA damage analysis. Comet assay and MN assay was used to assess the DNA damage. The Differences in the comet TM (Tail Moment) and MNBC % in both groups were calculated. Result: The radiation dose received by the study population during 18F-FDG WB PET/CT examination was 27.03 ± 2.33 mSv. Comet TM and percentage frequency of MNBC % was 65.22 ± 35.42 and 18.55 ± 10.14, respectively in the patients injected with contrast and 42.49 ± 28.52 and 13.76 ± 7.52 for non-contrast group. Significant increase in DNA damage was observed in the contrast group as compared to non-contrast group. Significant association was observed between patient weight, contrast volume and TM and MNBC%. Baseline parameters of the patients did not show significant correlation with TM and MNBC%. Conclusion: The patients undergoing contrast-enhanced WB PET/CT investigations have demonstrated higher DNA damage. The DNA damage was also observed to be more in heavier patients. The other baseline parameters of patients like age, sex, CBG, serum creatinine did not show any correlation with DNA damage.
Patellar and quadriceps tendons acute repair with suture anchors

Background and aim of the work: Quadriceps and patellar tendon rupture are relatively uncommon but can result in a disabling condition if untreated. We retrospectively review all our cases treated with suture anchors from 2014 to 2018, to evaluate midterm outcome of this technique. Methods: Traumatic and atraumatic quadriceps and patellar tendon preinsertional lesions were acutely treated with Healix Ti and FaStin RC 5mm suture anchors and an aggressive rehabilitation protocol was prescribed to patients. Results: Good to excellent results according to the Modified Cincinnati Rating System Questionnaire was obtained at a mean 12 months followup, without major complications. Conclusions: Suture anchors are a promising alternative to transosseus suture for acute repair of quadriceps and patellar tendon lesions, but longer followups are needed for detect long-term complications. (www.actabiomedica.it)
Nanostructured cochleates: a multi-layered platform for cellular transportation of therapeutics

Abstract Among lipid-based nanocarriers, multi-layered cochleates emerge as a novel delivery system because of prevention of oxidation of hydrophobic and hydrophilic drugs, enhancement in permeability, and reduction in dose of drugs. It also improves oral bioavailability and increases the safety of a drug by targeting at a specific site with less side effects. Nanostructured cochleates are used as a carrier for the delivery of water-insoluble or hydrophobic drugs of anticancer, antiviral and anti-inflammatory action. This review article focuses on different methods for preparation of cochleates, mechanism of formation of cochleates, mechanism of action like cochleate undergoes macrophagic endocytosis and release the drug into the systemic circulation by acting on membrane proteins, phospholipids, and receptors. Advanced methods such as calcium-substituted and β-cyclodextrin-based cochleates, novel techniques include microfluidic and modified trapping method. Cochleates showed enhancement in oral bioavailability of amphotericin B, delivery of factor VII, oral mucosal vaccine adjuvant-delivery system, and delivery of volatile oil. In near future, cochleate will be one of the interesting delivery systems to overcome the stability and encapsulation efficiency issues associated with liposomes. The current limiting factors for commercial preparation of cochleates involve high cost of manufacturing, lack of standardization, and specialized equipments.
Activity monitoring: noticing interesting changes in behavior

We introduce a problem class which we term activity monitoring. Such problems involve monitoring the behavior of a large population of entities for interesting events requiring action. We present a framework within which each of the individual problems has a natural expression, as well as a methodology for evaluating performance of activity monitoring techniques. We show that two superficially different tasks, news story monitoring and intrusion detection, can be expressed naturally within the framework, and show that key differences in solution methods can be compared.
Mitogenomes Uncover Extinct Penguin Taxa and Reveal Island Formation as a Key Driver of Speciation.

The emergence of islands has been linked to spectacular radiations of diverse organisms. Although penguins spend much of their lives at sea, they rely on land for nesting, and a high proportion of extant species are endemic to geologically young islands. Islands may thus have been crucial to the evolutionary diversification of penguins. We test this hypothesis using a fossil-calibrated phylogeny of mitochondrial genomes (mitogenomes) from all extant and recently extinct penguin taxa. Our temporal analysis demonstrates that numerous recent island-endemic penguin taxa diverged following the formation of their islands during the Plio-Pleistocene, including the Galápagos (Galápagos Islands), northern rockhopper (Gough Island), erect-crested (Antipodes Islands), Snares crested (Snares) and royal (Macquarie Island) penguins. Our analysis also reveals two new recently extinct island-endemic penguin taxa from New Zealand's Chatham Islands: Eudyptes warhami sp. nov. and a dwarf subspecies of the yellow-eyed penguin, Megadyptes antipodes richdalei ssp. nov. Eudyptes warhami diverged from the Antipodes Islands erect-crested penguin between 1.1 and 2.5 Ma, shortly after the emergence of the Chatham Islands (∼3 Ma). This new finding of recently evolved taxa on this young archipelago provides further evidence that the radiation of penguins over the last 5 Ma has been linked to island emergence. Mitogenomic analyses of all penguin species, and the discovery of two new extinct penguin taxa, highlight the importance of island formation in the diversification of penguins, as well as the extent to which anthropogenic extinctions have affected island-endemic taxa across the Southern Hemisphere's isolated archipelagos.
Surgical Enlargement of the Aortic Root Does Not Increase the Operative Risk of Aortic Valve Replacement

Background: Surgical aortic root enlargement (ARE) during aortic valve replacement (AVR) allows for larger prosthesis implantation and may be an important adjunct to surgical AVR in the transcatheter valve-in-valve era. The incremental operative risk of adding ARE to AVR has not been established. We aimed to evaluate the early outcomes of patients undergoing AVR with or without ARE. Methods: From January 1990 to August 2014, 7039 patients underwent AVR (AVR+ARE, n=1854; AVR, n=5185) at a single institution. Patients with aortic dissection and active endocarditis were excluded. Mean age was 65±14 years and 63% were male. Logistic regression and propensity score matching were used to adjust for unbalanced variables in group comparisons. Results: Patients undergoing AVR+ARE were more likely to be female (46% versus 34%, P<0.001) and had higher rates of previous cardiac surgery (18% versus 12%, P<0.001), chronic obstructive pulmonary disease (5% versus 3%, P=0.004), urgent/emergent status (6% versus 4%, P=0.01), and worse New York Heart Association status (P<0.001). Most patients received bioprosthetic valves (AVR+ARE: 73.4% versus AVR: 73.3%, P=0.98) and also underwent concomitant cardiac procedures (AVR+ARE: 68% versus AVR: 67%, P=0.31). Mean prosthesis size implanted was slightly smaller in patients requiring AVR+ARE versus AVR (23.4±2.1 versus 24.1±2.3, P<0.001). In-hospital mortality was higher after AVR+ARE (4.3% versus 3.0%, P=0.008), although when the cohort was restricted to patients undergoing isolated aortic valve replacement with or without root enlargement, mortality was not statistically different (AVR+ARE: 1.7% versus AVR: 1.1%, P=0.29). After adjustment for baseline characteristics, AVR+ARE was not associated with an increased risk of in-hospital mortality when compared with AVR (odds ratio, 1.03; 95% confidence interval, 0.75–1.41; P=0.85). Furthermore, AVR+ARE was not associated with an increased risk of postoperative adverse events. Results were similar if propensity matching was used instead of multivariable adjustments for baseline characteristics. Conclusions: In the largest analysis to date, ARE was not associated with increased risk of mortality or adverse events. Surgical ARE is a safe adjunct to AVR in the modern era.
Imaging-Genomic Study of Head and Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes and Genomic Mechanisms via Integration of The Cancer Genome Atlas and The Cancer Imaging Archive.

PURPOSE Recent data suggest that imaging radiomic features of a tumor could be indicative of important genomic biomarkers. Understanding the relationship between radiomic and genomic features is important for basic cancer research and future patient care. We performed a comprehensive study to discover the imaginggenomic associations in head and neck squamous cell carcinoma (HNSCC) and explore the potential of predicting tumor genomic alternations using radiomic features. METHODS Our retrospective study integrated whole-genome multiomics data from The Cancer Genome Atlas with matched computed tomography imaging data from The Cancer Imaging Archive for the same set of 126 patients with HNSCC. Linear regression and gene set enrichment analysis were used to identify statistically significant associations between radiomic imaging and genomic features. Random forest classifier was used to predict the status of two key HNSCC molecular biomarkers, human papillomavirus and disruptive TP53 mutation, on the basis of radiomic features. RESULTS Widespread and statistically significant associations were discovered between genomic features (including microRNA expression, somatic mutations, and transcriptional activity, copy number variations, and promoter region DNA methylation changes of pathways) and radiomic features characterizing the size, shape, and texture of tumor. Prediction of human papillomavirus and TP53 mutation status using radiomic features achieved areas under the receiver operating characteristic curve of 0.71 and 0.641, respectively. CONCLUSION Our exploratory study suggests that radiomic features are associated with genomic characteristics at multiple molecular layers in HNSCC and provides justification for continued development of radiomics as biomarkers for relevant genomic alterations in HNSCC.
Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting

Abstract The transcription factor p53 plays pivotal roles in numerous biological processes, including the suppression of tumours. The rich availability of biophysical data aimed at understanding its structure–function relationships since the 1990s has enabled the application of a variety of computational modelling techniques towards the establishment of mechanistic models. Together they have provided deep insights into the structure, mechanics, energetics, and dynamics of p53. In parallel, the observation that mutations in p53 or changes in its associated pathways characterize several human cancers has resulted in a race to develop therapeutic modulators of p53, some of which have entered clinical trials. This review describes how computational modelling has played key roles in understanding structural-dynamic aspects of p53, formulating hypotheses about domains that are beyond current experimental investigations, and the development of therapeutic molecules that target the p53 pathway.
Baseline Depressive Symptoms Are Not Associated With Clinically Important Levels of Incident Hypertension During Two Years of Follow-Up: The Multi-Ethnic Study of Atherosclerosis

Previous longitudinal cohort studies have suggested an association between baseline depressive symptoms and incident hypertension. We assessed this possible association using data from the Multi-ethnic Study of Atherosclerosis, a population-based prospective cohort study of 6814 US adults from 4 different racial/ethnic groups. Baseline users of antihypertensive medications and participants lost to follow-up were excluded leaving 3914 participants. Patients with baseline depressive symptoms (n=622) were defined using a high score on the Center for Epidemiological Studies Depression Scale (≥16) or the use of an antidepressant medication. Hypertension was defined as systolic blood pressure of ≥140 mm Hg, diastolic blood pressure of ≥90 mm Hg or new use of antihypertensive medications plus physician diagnosis. Estimates were adjusted for known risk factors, including age, sex, baseline blood pressure, diabetes, and body mass index. Untreated blood pressure was estimated using an imputation approach. A total of 477 participants developed hypertension. Using relative risk regression, patients with baseline depressive symptoms did not have an increased risk of incident hypertension (relative risk: 1.02; 95% confidence interval [CI]: 0.99 to 1.05), although an association between tricyclic antidepressants and hypertension (relative risk: 1.20; 95% CI: 1.05 to 1.37) was observed in subgroup analysis. Depression, even after adjustment for covariates, was associated with small changes in systolic (+2.4 mm Hg; 95% CI: 0.2 to 4.7) and diastolic (+0.8 mm Hg; 95% CI: −0.6 to 2.3) blood pressures. Depressive symptoms may be associated with slight increases in blood pressure in this multiethnic cohort, but it is premature to conclude much without longer studies in other populations.
Diverse Components of Resistance to Fusarium verticillioides Infection and Fumonisin Contamination in Four Maize Recombinant Inbred Families

The fungus Fusarium verticillioides can infect maize ears, causing Fusarium ear rot (FER) and contaminating the grain with fumonisins (FUM), which are harmful to humans and animals. Breeding for resistance to FER and FUM and post-harvest sorting of grain are two strategies for reducing FUM in the food system. Kernel and cob tissues have been previously associated with differential FER and FUM. Four recombinant inbred line families from the maize nested associated mapping population were grown and inoculated with F. verticillioides across four environments, and we evaluated the kernels for external and internal infection severity as well as FUM contamination. We also employed publicly available phenotypes on innate ear morphology to explore genetic relationships between ear architecture and resistance to FER and FUM. The four families revealed wide variation in external symptomatology at the phenotypic level. Kernel bulk density under inoculation was an accurate indicator of FUM levels. Genotypes with lower kernel density—under both inoculated and uninoculated conditions—and larger cobs were more susceptible to infection and FUM contamination. Quantitative trait locus (QTL) intervals could be classified as putatively resistance-specific and putatively shared for ear and resistance traits. Both types of QTL mapped in this study had substantial overlap with previously reported loci for resistance to FER and FUM. Ear morphology may be a component of resistance to F. verticillioides infection and FUM accumulation.
Learning Cancer-Related Drug Efficacy Exploiting Consensus in Coordinated Motility Within Cell Clusters

Objective: The ability of cells to collectively move is essential in various biological contexts including cancer metastasis. In this paper, we propose an automatic video analysis tool to correlate the cell movement inhibition with replication block induced by dose-dependent chemotherapy administration. Methods: The novel approach combines individual and collective cell kinematic analysis performed over time-lapse microscopy video frames. Cells are first localized and tracked, and then kinematic descriptors are extracted for each track. Selective track identification is performed assuming diversified cell roles within the same cluster (spontaneously forming groups of cells), and finally individual results are grouped exploiting consensus of coordinated motility within cell clusters. Results: Recognition performance of three different experimental conditions (no drug, 0.5–5 μM merged in the same condition, and 50 μM) reached an average accuracy value of 88% over 958 different tracks collected in 36 clusters of diverse dimensions in eight independent experiments. Conclusion: An extensive application of this methodology could give a different point of view of the cancer mechanisms.
Examining Training Motivations Among Public Health Workers

Context: As public health needs and priorities evolve, maintaining a trained public health workforce is critical to the success of public health efforts. Researchers have examined training needs in various contexts and subpopulations, but a nationally representative study of what motivates public health workers to seek out training has yet to be conducted. By understanding these motivations, public health agencies and policy makers can appeal to worker motivations in both training programs and organizational incentives. Objective: The purpose of this article was to describe overall training motivations and identify patterns of training motivations among public health workers. This study also explored whether or not training needs differ across prevalent motivational patterns. Design and Participants: Using data from the 2017 Public Health Workforce Interests and Needs Survey (PH WINS), the study used latent class analysis (LCA) to identify motivational patterns and logistic regression to analyze associations with training needs. Results: The most prominent motivation to seek training was personal growth (82.7% of respondents). LCA identified 4 motivational classes of public health workers: those motivated by organizational pressure and requirements (31.8%), those motivated indiscriminately by all factors (28.4%), those motivated primarily by personal growth (21.7%), and those motivated by organizational accommodations and supports (18.2%). Motivational class was not associated with indicating training needs in any of 8 training domains, nor was it associated with indicating any training need in any domain. Conclusions: Public health agencies should consider the different motivational classes present in the public health workforce. In particular, motivational classes that represent organizational choices suggest that public health agencies should both motivate workers with organizational requirements and pressure from managers and offer institutional support via paid travel and covered time for training.
Influence of activation mode and preheating on intracanal irrigant temperature.

This ex vivo study assessed the effectiveness of two activation modes to increase the intracanal temperature of 5.25% NaOCl solution and the time for a preheated-irrigant to return to its initial temperature. Ten single-rooted extracted human teeth were used. Thermocouples were adapted to the root surface and the temperature was registered following two activation modes: ultrasound (US) and thermal. Furthermore, a preheated-solution (45°C/60°C) was flushed into root canal to test the time needed to return to its initial temperature. Data were analysed using two-way ANOVA and Tukey's post-hoc tests (P = 0.05). Statistical analysis showed differences between the activation modes. US and thermal activation increased from 37 to 40.4°C and to 62.8°C respectively in 60 s. Time for preheated-irrigant to return to its initial temperature was longer for 60°C. Preheating irrigant at 60°C and using thermal activation to keep it warm may represent a further step of the irrigation protocol.
Metformin prevents nephrolithiasis formation by inhibiting the expression of OPN and MCP-1 in vitro and in vivo

Treatment targeting osteopontin (OPN) and monocyte chemoattractant protein 1 (MCP-1) has been recognized as a novel approach in renal crystal formation. The present study was designed to investigate the suppressive effects of metformin on nephrolithiasis formation and its potential mechanism. The cytotoxicity of metformin on MDCK and HK-2 cells was determined using a Cell Counting Kit-8 assay in vitro. Subsequently, the mRNA transcription and protein expression levels of MCP-1 and OPN were detected by reverse transcription-quantitative-polymerase chain reaction analysis, western blot analysis and ELISA. Male Sprague-Dawley rats were divided into a control group, ethylene glycol (EG) group and EG + metformin group. The expression levels of MCP-1 and OPN and crystal formations were evaluated in renal tissues following an 8-week treatment period. In vitro, metformin significantly inhibited the production of MCP-1 and OPN induced by oxalate at the mRNA and protein expression levels. In vivo, increased expression levels of MCP-1 and OPN were detected in the EG group compared with the controls, and this upregulation was reversed in the EG + metformin group. Renal crystal deposition in the EG + metformin group was markedly decreased compared with that in the EG group. Therefore, the results of the study suggest that metformin suppressed urinary crystal deposit formation, possibly by mediating the expression of inflammatory mediators OPN and MCP-1.