Machine learning methods for generating high dimensional discrete datasets

The development of platforms and techniques for emerging Big Data and Machine Learning applications requires the availability of real-life datasets. A possible solution is to synthesize datasets that reflect patterns of real ones using a two-step approach: first, a real dataset X is analyzed to derive relevant patterns Z and, then, to use such patterns for reconstructing a new dataset X ' that preserves the main characteristics of X. This survey explores two possible approaches: (1) Constraint-based generation and (2) probabilistic generative modeling. The former is devised using inverse mining (IFM) techniques, and consists of generating a dataset satisfying given support constraints on the itemsets of an input set, that are typically the frequent ones. By contrast, for the latter approach, recent developments in probabilistic generative modeling (PGM) are explored that model the generation as a sampling process from a parametric distribution, typically encoded as neural network. The two approaches are compared by providing an overview of their instantiations for the case of discrete data and discussing their pros and cons. This article is categorized under: Fundamental Concepts of Data and Knowledge > Big Data Mining Technologies > Machine Learning Algorithmic Development > Structure Discover

Verrucous Carcinoma of the Uterine Cervix Arising in a Giant Condyloma Acuminatum, Associated with Ichthyosis of the Endometrial Cavity

We describe a unique presentation of a cervical verrucous carcinoma (VC) associated with ichthyosis of the uterine cavity in an 80-year old woman. Areas of transition from a giant condyloma (GC) were present in the VC. This paper also includes a review of the relevant literature. VC of the cervix is an uncommon malignancy, and transition of a GC to VC is an interesting finding, confuting the theory that they represent distinct entities, with different risk factors. Differently from GC, VC is considered to be causally related to HPV in a minority of instances. Our results of p16 immunohistochemistry, the surrogate marker of high-risk human papillomavirus (HPV) infection, appear to speak against the causal role of HPV in the pathogenesis of VC. Ichthyosis uteri may occasionally be associated with a cervical or endometrial malignancy; however, we are not aware of any patient showing VC, GC and ichthyosis uteri at the same time

Long wavelength optical control of glutamate receptor ion channels using a tetra-ortho-substituted azobenzene derivative

A tetra-ortho-chloro substituted azobenzene unit was incorporated into a photoswitchable tethered ligand for ionotropic glutamate receptors. This compound confers the modified protein with the unusual optical responses of the substituted azo scaffold permitting channel opening with yellow and red light and channel closing with blue light

Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by 1H NMR spectroscopy

Hyperpolarization enhances the intensity of the NMR signals of a molecule, whose in vivo metabolic fate can be monitored by MRI with higher sensitivity. SABRE is a hyperpolarization technique that could potentially be used to image nitric oxide (NO) production in vivo. This would be very important, because NO dysregulation is involved in several pathologies, including cardiovascular ones. The nitric oxide synthase (NOS) pathway leads to NO production via conversion of l-arginine into l-citrulline. NO is a free radical gas with a short half-life in vivo (≈5s), therefore direct NO quantification is challenging. An indirect method - based on quantifying conversion of an l-Arg- to l-Cit-derivative by 1H NMR spectroscopy - is herein proposed. A small library of pyridyl containing l-Arg derivatives was designed and synthesised. In vitro tests showed that compounds 4a-j and 11a-c were better or equivalent substrates for the eNOS enzyme (NO2 - production=19-46μM) than native l-Arg (NO2 - production=25μM). Enzymatic conversion of l-Arg to l-Cit derivatives could be monitored by 1H NMR. The maximum hyperpolarization achieved by SABRE reached 870-fold NMR signal enhancement, which opens up exciting future perspectives of using these molecules as hyperpolarized MRI tracers in vivo

Early histologic findings of pulmonary SARS-CoV-2 infection detected in a surgical specimen

Despite the current pandemic season, reports on pathologic features of coronavirus disease 19 (Covid-19) are exceedingly rare at the present time. Here we describe the pathologic features of early lung involvement by Covid-19 in a surgical sample resected for carcinoma from a patient who developed SARS-CoV-2 infection soon after surgery. The main histologic findings observed were pneumocyte damage, alveolar hemorrhages with clustering of macrophages, prominent and diffuse neutrophilic margination within septal vessels, and interstitial inflammatory infiltrates, mainly represented by CD8+ T lymphocytes. These features are similar to those previously described in SARS-CoV-2 infection. Subtle histologic changes suggestive pulmonary involvement by Covid-19 may be accidentally encountered in routine pathology practice, especially when extensive sampling is performed for histology. These findings should be carefully interpreted in light of the clinical context of the patient and could prompt a pharyngeal swab PCR test to rule out the possibility of SARS-CoV-2 infection in asymptomatic patients

Unburned Tobacco Smoke Affects Neuroinflammation-Related Pathways in the Rat Mesolimbic System.

first_page settings Order Article Reprints Open AccessArticle Unburned Tobacco Smoke Affects Neuroinflammation-Related Pathways in the Rat Mesolimbic System by Camilla Morosini 1,† [ORCID] , Fabio Vivarelli 1,† [ORCID] , Laura Rullo 1,* [ORCID] , Emilia Volino 1,2, Loredana Maria Losapio 1 [ORCID] , Moreno Paolini 1, Patrizia Romualdi 1,* [ORCID] , Donatella Canistro 1,‡ [ORCID] and Sanzio Candeletti 1,‡ [ORCID] 1 Department of Pharmacy and Biotechnology, Alma Mater Studiorum–University of Bologna, 40126 Bologna, Italy 2 Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum–University of Bologna, 40126 Bologna, Italy * Authors to whom correspondence should be addressed. † These authors contributed equally to this work. ‡ These authors contributed equally to this work. Int. J. Mol. Sci. 2024, 25(10), 5259; https://doi.org/10.3390/ijms25105259 Submission received: 10 April 2024 / Revised: 3 May 2024 / Accepted: 9 May 2024 / Published: 11 May 2024 (This article belongs to the Collection Feature Papers in Molecular Neurobiology) Download keyboard_arrow_down Browse Figures Versions Notes Abstract Tobacco use disorder represents a significant public health challenge due to its association with various diseases. Despite awareness efforts, smoking rates remain high, partly due to ineffective cessation methods and the spread of new electronic devices. This study investigated the impact of prolonged nicotine exposure via a heat-not-burn (HnB) device on selected genes and signaling proteins involved in inflammatory processes in the rat ventral tegmental area (VTA) and nucleus accumbens (NAc), two brain regions associated with addiction to different drugs, including nicotine. The results showed a reduction in mRNA levels for PPARα and PPARγ, two nuclear receptors and anti-inflammatory transcription factors, along with the dysregulation of gene expression of the epigenetic modulator KDM6s, in both investigated brain areas. Moreover, decreased PTEN mRNA levels and higher AKT phosphorylation were detected in the VTA of HnB-exposed rats with respect to their control counterparts. Finally, significant alterations in ERK 1/2 phosphorylation were observed in both mesolimbic areas, with VTA decrease and NAc increase, respectively. Overall, the results suggest that HnB aerosol exposure disrupts intracellular pathways potentially involved in the development and maintenance of the neuroinflammatory state. Moreover, these data highlight that, similar to conventional cigarettes, HnB devices use affects specific signaling pathways shaping neuroinflammatory process in the VTA and NAc, thus triggering mechanisms that are currently considered as potentially relevant for the development of addictive behavior

Black and pink. Single lesion or double diagnosis?

Fibroepithelioma of Pinkus (FeP) is an uncommon skin lesion considered to be a rare variant of basal cell carcinoma (BCC), even though some researchers have argued for its classifica- tion as a trichoblastoma. FeP appears frequently as a solitary, flesh-colored, well-demarcated plaque, typically localized on the lumbosacral area of patients aged 40 to 60 years. It often develops in patients with a history of BCC, most commonly in wome

Liver infection and COVID-19: the electron microscopy proof and revision of the literature

OBJECTIVE: COVID-19, the newly emerging infectious disease, has been associated with acute liver injury, often related to progression to severe pneumonia. The association between moderate-severe liver injury and more severe clinical course of COVID-19 has suggested that liver injury is prevalent in severe than in mild cases of COVID-19, while no difference in liver involvement has been reported between survivors and non-survivors. The spectrum of liver involvement during COVID-19 ranges from an asymptomatic elevation of liver enzymes to severe hepatitis. Only rarely, cases with acute hepatitis have been reported in the absence of respiratory symptoms. Both epithelial and biliary cells possess the angiotensin-converting enzyme-2 receptors that SARS-CoV-2 uses to be internalized. However, to our knowledge, no ultrastructural identification of the virus in liver cells has been reported to date. Here we provide evidence of SARS-CoV-2 in the liver of two patients, a 34-year-old woman and a 60-year-old man with COVID-19.PATIENTS AND METHODS: We investigated two patients with COVID-19 showing several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids. In both patients, we performed histological and ultrastructural examinations by liver biopsy. After two months, both patients were free of symptoms, and the SARS-CoV-2 infection had resolved.RESULTS: Liver biopsy histological and ultrastructural examination showed liver injury and several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids.CONCLUSIONS: Although most studies in COVID-19 have been focused on the lungs, recently, cholestatic liver pathology has been introduced in the spectrum of pathological changes related to COVID-19. To the best of our knowledge, those presented in this paper are the first images of hepatic SARS-CoV-2 infected liver cells. Our findings suggest a role for cholangiocytes and biliary structures in the COVID-19