Miracle-dz/UniFAR-FTUs huggingface dataset:
Knowledge of Vulvar Anatomy and Self-examination in a Sample of Italian Women.

OBJECTIVE The aim of the study was to investigate the knowledge of vulvar anatomy and vulvar self-examination (VSE) in a sample of Italian women attending a gynecology clinic. METHODS For this original research from May to July 2019, 512 women attending the Lower Genital Tract Clinic at the Department of Surgical Sciences of the University of Torino were invited to participate in a 29-question survey about vulvar anatomy, VSE, and sociodemographic details. Data were analyzed using descriptive statistics. RESULTS Of 512 patients, 500 completed the questionnaire (98% response rate). The mean age of respondents was 41 years (range = 17-77 years). Education level was evenly distributed between elementary, high school, and university graduates. Only 15% of interviewed women were able correctly sketching vulvar anatomy. Seventy-six percent of the women had not heard about VSE, and 61% of the women approach their genitalia with feelings of shame and embarrassment. Only 23% of the women would seek medical advice after identification of possible abnormalities during VSE. A majority (69%) of the women would like to have more information about VSE and vulvar health through educational videos and social media. CONCLUSIONS Education about VSE may lead to earlier diagnosis of vulvar cancers and other pathologies. Further efforts are needed to disperse information about normal external female genital anatomy and VSE to achieve self-confidence among women.
Structure, Activation and Regulation of NLRP3 and AIM2 Inflammasomes

The inflammasome is a three-component (sensor, adaptor, and effector) filamentous signaling platform that shields from multiple pathogenic infections by stimulating the proteolytical maturation of proinflammatory cytokines and pyroptotic cell death. The signaling process initiates with the detection of endogenous and/or external danger signals by specific sensors, followed by the nucleation and polymerization from sensor to downstream adaptor and then to the effector, caspase-1. Aberrant activation of inflammasomes promotes autoinflammatory diseases, cancer, neurodegeneration, and cardiometabolic disorders. Therefore, an equitable level of regulation is required to maintain the equilibrium between inflammasome activation and inhibition. Recent advancement in the structural and mechanistic understanding of inflammasome assembly potentiates the emergence of novel therapeutics against inflammasome-regulated diseases. In this review, we have comprehensively discussed the recent and updated insights into the structure of inflammasome components, their activation, interaction, mechanism of regulation, and finally, the formation of densely packed filamentous inflammasome complex that exists as micron-sized punctum in the cells and mediates the immune responses.
From Cell Culture to Organoids-Model Systems for Investigating Prion Strain Characteristics

Prion diseases are the hallmark protein folding neurodegenerative disease. Their transmissible nature has allowed for the development of many different cellular models of disease where prion propagation and sometimes pathology can be induced. This review examines the range of simple cell cultures to more complex neurospheres, organoid, and organotypic slice cultures that have been used to study prion disease pathogenesis and to test therapeutics. We highlight the advantages and disadvantages of each system, giving special consideration to the importance of strains when choosing a model and when interpreting results, as not all systems propagate all strains, and in some cases, the technique used, or treatment applied, can alter the very strain properties being studied.
Biological Subphenotypes of ARDS Show Prognostic Enrichment in Mechanically Ventilated Patients Without ARDS.

RATIONALE Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment. OBJECTIVES To determine whether these subphenotypes and their prognostic- and potential for predictive enrichment could be extended to other ICU patients, irrespective of fulfilling the definition of ARDS. METHODS This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latent-class analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-, 30-day mortality and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and presence of ARDS. MEASUREMENTS AND MAIN RESULTS We included 2499 mechanically ventilated patients (674 with and 1825 without ARDS). The cluster-derived "reactive" subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, a higher 30-day mortality, and a lower probability of successful extubation while alive compared to the "uninflamed" subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles. CONCLUSION The prognostic- and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill.
IFN-γ and CD38 in Hyperprogressive Cancer Development

Simple Summary Hyperprogressive disease (HPD) is a pattern of paradoxical tumor progression that has been reported in patients treated with immune checkpoint inhibitors (ICIs). Although a large number of studies have investigated HPD and several associated factors have been reported, the mechanisms that drive the acceleration of tumor growth remain unknown. In this review, we discuss the possible role of IFN-γ and CD38 in the development of HPD, and we report the main findings in the scientific literature on the signaling pathways in which these factors take part, and their involvement in response and resistance to ICI therapy. Abstract Immune checkpoint inhibitors (ICIs) improve the survival of patients with multiple types of cancer. However, low response rates and atypical responses limit their success in clinical applications. The paradoxical acceleration of tumor growth after treatment, defined as hyperprogressive disease (HPD), is the most difficult problem facing clinicians and patients alike. The mechanisms that underlie hyperprogression (HP) are still unclear and controversial, although different factors are associated with the phenomenon. In this review, we propose two factors that have not yet been demonstrated to be directly associated with HP, but upon which it is important to focus attention. IFN-γ is a key cytokine in antitumor response and its levels increase during ICI therapy, whereas CD38 is an alternative immune checkpoint that is involved in immunosuppressive responses. As both factors are associated with resistance to ICI therapy, we have discussed their possible involvement in HPD with the conclusion that IFN-γ may contribute to HP onset through the activation of the inflammasome pathway, immunosuppressive enzyme IDO1 and activation-induced cell death (AICD) in effector T cells, while the role of CD38 in HP may be associated with the activation of adenosine receptors, hypoxia pathways and AICD-dependent T-cell depletion.
Prognostic and Predictive Values of Mismatch Repair Deficiency in Non-Metastatic Colorectal Cancer

Simple Summary A subset of colorectal cancers (CRCs) displays deficient DNA mismatch repair (dMMR) that leads to microsatellite instability (MSI). These tumors have distinct clinicopathological features and have been associated with a more favorable prognosis. Knowledge of mismatch repair (MMR) status has important implications for disease diagnosis, surgical intervention, and adjuvant treatment decisions. Abstract Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to identify patients with Lynch Syndrome due to a germline mutation in an MMR gene, but also detects those with sporadic dMMR/MSI-high CRCs. The prognostic utility of MMR/MSI status in non-metastatic colorectal cancer has been studied extensively, yet more limited data are available for its predictive utility. Results have not been entirely consistent due to potential stage-related differences and limited numbers of dMMR/MSI-H patients included in the studies. In this review, we summarize the current evidence for the prognostic and predictive value of dMMR/MSI-H in non-metastatic CRC, and discuss the use of this biomarker for patient management and treatment decisions in clinical practice.
Evaluation of Chemical Composition, Radical Scavenging and Antitumor Activities of Satureja hortensis L. Herb Extracts

Satureja hortensis L. is an annual herbaceous plant of the Lamiaceae Lindl. family. S. hortensis L. , related to thyme and rosemary, is used as spice and traditional medicinal herb in Europe. Mainly due to the polyphenols contained in S. hortensis L. , this plant exhibits multiple biological effects. However, therapeutic effects on cells, including skin tumors, have not yet been studied. Therefore, the aim of this study was to compare the composition and the resulting antioxidant as well as biological properties [on melanocytes and melanoma cells] of summer, savory growing in botanical garden of Vytautas Magnus University in middle Lithuania climatic conditions, collected during various phases of vegetation. It has been shown that the budding phase alcohol extract of this plant contains the largest amounts of polyphenols, including rutin and rosemary acid, which promote the radical scavenging activity and antioxidant properties. In contrast, the extract from the massive flowering phase already at a concentration of 12.5 µg/mL reduces the survival of melanoma cells to 60% with 90% melanocytes survival. In addition, extracts from beginning of flowering and end of flowering at a concentration of 25 µg/mL, containing significantly less rutin and rosmarinic acid, in combination with irradiation of cells with UVB, significantly increased the lipid peroxidation process, particularly in melanoma cells. These data indicate the possibility of using extracts from S. hortensis L. to modulate/differentiate the metabolism of normal and tumor skin cells.
Rational design and testing of abiotic stress‐inducible synthetic promoters from poplar cis‐regulatory elements

Summary Abiotic stress resistance traits may be especially crucial for sustainable production of bioenergy tree crops. Here, we show the performance of a set of rationally designed osmotic‐related and salt stress‐inducible synthetic promoters for use in hybrid poplar. De novo motif‐detecting algorithms yielded 30 water‐deficit (SD) and 34 salt stress (SS) candidate DNA motifs from relevant poplar transcriptomes. We selected three conserved water‐deficit stress motifs (SD18, SD13 and SD9) found in 16 co‐expressed gene promoters, and we discovered a well‐conserved motif for salt response (SS16). We characterized several native poplar stress‐inducible promoters to enable comparisons with our synthetic promoters. Fifteen synthetic promoters were designed using various SD and SS subdomains, in which heptameric repeats of five‐to‐eight subdomain bases were fused to a common core promoter downstream, which, in turn, drove a green fluorescent protein (GFP) gene for reporter assays. These 15 synthetic promoters were screened by transient expression assays in poplar leaf mesophyll protoplasts and agroinfiltrated Nicotiana benthamiana leaves under osmotic stress conditions. Twelve synthetic promoters were induced in transient expression assays with a GFP readout. Of these, five promoters (SD18‐1, SD9‐2, SS16‐1, SS16‐2 and SS16‐3) endowed higher inducibility under osmotic stress conditions than native promoters. These five synthetic promoters were stably transformed into Arabidopsis thaliana to study inducibility in whole plants. Herein, SD18‐1 and SD9‐2 were induced by water‐deficit stress, whereas SS16‐1, SS16‐2 and SS16‐3 were induced by salt stress. The synthetic biology design pipeline resulted in five synthetic promoters that outperformed endogenous promoters in transgenic plants.
Metabolic Exchange and Energetic Coupling between Nutritionally Stressed Bacterial Species: Role of Quorum-Sensing Molecules

Bacteria have usually been studied in single culture in rich media or under specific starvation conditions. However, in nature they coexist with other microorganisms and build an advanced society. ABSTRACT Formation of multispecies communities allows nearly every niche on earth to be colonized, and the exchange of molecular information among neighboring bacteria in such communities is key for bacterial success. To clarify the principles controlling interspecies interactions, we previously developed a coculture model with two anaerobic bacteria, Clostridium acetobutylicum (Gram positive) and Desulfovibrio vulgaris Hildenborough (Gram negative, sulfate reducing). Under conditions of nutritional stress for D. vulgaris, the existence of tight cell-cell interactions between the two bacteria induced emergent properties. Here, we show that the direct exchange of carbon metabolites produced by C. acetobutylicum allows D vulgaris to duplicate its DNA and to be energetically viable even without its substrates. We identify the molecular basis of the physical interactions and how autoinducer-2 (AI-2) molecules control the interactions and metabolite exchanges between C. acetobutylicum and D. vulgaris (or Escherichia coli and D. vulgaris). With nutrients, D. vulgaris produces a small molecule that inhibits in vitro the AI-2 activity and could act as an antagonist in vivo. Sensing of AI-2 by D. vulgaris could induce formation of an intercellular structure that allows directly or indirectly metabolic exchange and energetic coupling between the two bacteria. IMPORTANCE Bacteria have usually been studied in single culture in rich media or under specific starvation conditions. However, in nature they coexist with other microorganisms and build an advanced society. The molecular bases of the interactions controlling this society are poorly understood. Use of a synthetic consortium and reducing complexity allow us to shed light on the bacterial communication at the molecular level. This study presents evidence that quorum-sensing molecule AI-2 allows physical and metabolic interactions in the synthetic consortium and provides new insights into the link between metabolism and bacterial communication.
Development and Implementation of a Hybrid Wireless Sensor Network of Low Power and Long Range for Urban Environments

The urban population, worldwide, is growing exponentially and with it the demand for information on pollution levels, vehicle traffic, or available parking, giving rise to citizens connected to their environment. This article presents an experimental long range (LoRa) and low power consumption network, with a combination of static and mobile wireless sensors (hybrid architecture) to tune and validate concentrator placement, to obtain a large coverage in an urban environment. A mobile node has been used, carrying a gateway and various sensors. The Activation By Personalization (ABP) mode has been used, justified for urban applications requiring multicasting. This allows to compare the coverage of each static gateway, being able to make practical decisions about its location. With this methodology, it has been possible to provide service to the city of Malaga, through a single concentrator node. The information acquired is synchronized in an external database, to monitor the data in real time, being able to geolocate the dataframes through web mapping services. This work presents the development and implementation of a hybrid wireless sensor network of long range and low power, configured and tuned to achieve efficient performance in a mid-size city, and tested in experiments in a real urban environment.
Ruminal Lipopolysaccharides Analysis: Uncharted Waters with Promising Signs

Simple Summary Lipopolysaccharide (LPS) is a component of the outer membranes of Gram-negative bacterial cell wall made of three covalently linked regions: the O-antigen, the core oligosaccharide, and the endotoxin lipid A moiety, which carries the endotoxic activity of LPS. Among Gram-negative bacteria there is significant structural diversity in the lipid A region. Specifically, the number of lipid A acyl chains directly correlates with the ability to induce cytokine production whereas the hexa-acylated forms usually are the most immunostimulant ones, contrary to penta- or tetra- acylated forms that result in weak inflammatory host responses. Ruminal bacteria are predominantly Gram-negative, and their respective LPS presence has been suggested to be associated with ruminal acidosis, a metabolic disorder of cattle with negative effects on health and production. In the rumen, the most predominant phylum is Bacteroidetes which exhibit weak host immunological response compared to widely used Escherichia coli LPS. This review aims to present accumulated knowledge regarding ruminal LPS, pointing out the differences in ruminal LPS compared to widely known LPS, and introduce hypotheses that could contribute to further understanding and planning strategies to tackle ruminal acidosis. Abstract The objective of this review is to present the need for the development of a comprehensive ruminal lipopolysaccharide (LPS) extraction, purification and analysis protocol and state hypotheses that could contribute to planning novel strategies against ruminal acidosis. Lipopolysaccharide is an immunostimulatory molecule of Gram-negative bacterial outer membranes and has been reported to contribute to ruminal acidosis in cattle. Bacterial death and lysis are normal processes, and thus LPS is normally present in ruminal fluid. However, ruminal LPS concentration is much greater during subacute ruminal acidosis (SARA). Contrary to the widely known LPSs, ruminal LPS seems to be composed of a variety of LPS chemotypes that may interact with each other resulting in an LPS “mixture”. Hypotheses regarding the influence of each specific ruminal bacterial specie to innate immunity during SARA, and the representativeness of the exclusive use of the Escherichia coli LPS to rumen epithelial tissue challenges, could expand our knowledge regarding SARA. In addition, possible correlation between the monomeric Toll-like Receptor 4 (TRL4) and the antagonistic penta-acylated lipid A of LPS could contribute to novel strategies to tackle this nutrition disorder.
Insight into the Epidemiology of Leptospirosis: A Review of Leptospira Isolations from “Unconventional” Hosts

Simple Summary The isolation of Leptospira is the most important test to assess infection in animal species. Several animals play a role as maintenance-host for specific serovars and in the last 30 years the incidence of leptospirosis has constantly increased in well-known reservoirs as well as in “unconventional” hosts. The emergence and the identification of Leptospira infection in such “unconventional” hosts could be related to several factors including problematic or inaccurate sampling modes during the Leptospira isolation, newly identified Leptospira strains, underestimated leptospirosis cases and climatic changes causing modifications of ecological niches. The aim of this review was to report the Leptospira isolations of the last 60 years from animals that could be considered “unconventional” hosts. Thus, the identification of “unconventional” hosts is crucial because they almost surely play an important role in the epidemiology of Leptospira infection. Abstract Leptospirosis is a re-emerging worldwide zoonotic disease. Even though the primary serological test for diagnosis and surveying is the microscopic agglutination test (MAT), isolation remains the gold-standard test to detect Leptospira infections. The leptospirosis transmission is linked to maintenance and accidental hosts. In the epidemiology of Leptospira some serovar are strictly related to specific maintenance hosts; however, in recent years, the bacterium was isolated from an even wider spectrum of species. The aim of this review is to report the isolation of Leptospira strains in animals which could be recognized as “unconventional” hosts, analyzing studies from 1960 to 2020 that highlighted the Leptospira isolation. This scientific literature aimed to provide evidence of infection in several animal species including of the Carnivora, Didelphimorphia, Rodentia, Cetacea, Cingulata, Afrosoricida, Chiroptera and Primate orders, as well as in Reptilia and Amphibia classes. In conclusion, the spreading of Leptospira is attention-worthy because the infection could occur in all the animal species ranging in a specific area. Further screening and isolations are needed to collect all necessary data to gain a complete understanding of leptospirosis epidemiology and its modifications.
Dual Carbonic Anhydrase IX/XII Inhibitors and Carbon Monoxide Releasing Molecules Modulate LPS-Mediated Inflammation in Mouse Macrophages

Low concentrations of carbon monoxide (CO) were reported to exhibit anti-inflammatory effects when administered in cells by suitable chemotypes such as CO releasing molecules (CO-RMs). In addition, the pH-modulating abilities of specific carbonic anhydrase isoforms played a crucial role in different models of inflammation and neuropathic pain. Herein, we report a series of chemical hybrids consisting of a Carbonic Anhydrase (CA) inhibitor linked to a CO-RM tail (CAI/CO-RMs). All compounds and their precursors were first tested in vitro for their inhibition activity against the human CA I, II, IX, and XII isoforms as well their CO releasing properties, aiming at corroborating the data by means of molecular modelling techniques. Then, their impact on metabolic activity modulation of RAW 264.7 mouse macrophages for 24 and 48 h was assessed with or without lipopolysaccharide (LPS) stimulation. The compounds were shown to counteract the inflammatory stimulus as also indicated by the reduced tumor necrosis factor alpha (TNF-α) release after treatment. All the biological results were compared to those of N-acetylcysteine (NAC) as a reference antioxidant compound. Within the series, two CAI/CO-RM hybrids (1 and 2), bearing both the well-known scaffold able to inhibit CAs (acesulfame) and the cobalt-based CO releasing portion, induced a higher anti-inflammatory effect up to 48 h at concentrations lower than NAC.