Pathogenesis of Penile Squamous Cell Carcinoma: Molecular Update and Systematic Review

Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve TP53, CDKN2A, FAT1, NOTCH-1 and PIK3CA. Numerical alterations involve gains in MYC and EGFR, as well as amplifications in HPV integration loci. A few genes including TP53, CDKN2A, PIK3CA and CCND1 harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.     

The Endometrial Microbiome and Its Impact on Human Conception

Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.     

Anthocyanin fingerprint of grapes: environmental and genetic variations

The anthocyanin content and fingerprint of four different Vitis vinifera L. varieties (Cabernet Sauvignon, Merlot, Syrah and Monastrell), the last grown in two different locations, were studied during three growing seasons to determine how seasonal conditions and location affect the content of berry anthocyanins and their relative percentages. Important differences in the content of anthocyanins were detected among varieties—Monastrell grapes from one of the locations presenting the highest anthocyanin content—when expressed as µg g^?1 of skin. However, due to the large berry size of Monastrell grapes, when the results were expressed as mg kg^?1 of berry, Cabernet Sauvignon and Syrah grapes presented the highest concentration. Significant differences were found as regards growing season, the concentration of anthocyanins being lowest in 2003, the warmest year. As regards the relative percentage of the different anthocyanins, substantial differences were found between varieties, but again, the results were also influenced by the year under study. When the percentages of anthocyanins were used as variables in a discriminant analysis, a 100% correct classification of the four different varieties was obtained. Moreover, to check the suitability of this tool for classifying varieties, data referring to the anthocyanin percentages of the four varieties grown in very different agroecological conditions and at different ripening stages were tested with the model we have built, 89% of correct classification being achieved. Copyright © 2006 Society of Chemical Industry     

Modification of the adsorption properties of high surface area graphites by oxygen functional groups

The role of the concentration of oxygen functional groups on the surface of commercial high surface area graphite has been studied in this work. For this purpose, two samples of the parent HSAG have been both oxidized with aqueous HNO₃ solution and pyrolysed at 900 °C under an He flow, in order to remove surface oxygen groups. TPD results, in agreement with XPS experiments, reveal the existence of oxygen groups on the surface of the parent HSAG, whose concentration increases substantially after the oxidative treatment, whereas they disappear after the thermal treatment. The adsorption of different alkanes, aromatics and chlorohydrocarbons on the three samples were compared. Adsorption capacities were derived from the adsorption isotherms, whereas thermodynamic properties have been determined from chromatographic retention data. Both the capacity and the strength of adsorption decrease after the oxidative treatment of the graphites. For n-alkanes and cyclic compounds, it was demonstrated that the presence of oxygen surface groups affects their interaction in lower extension. In the adsorption of aromatics and double-bonded compounds, the influence of surface functionalization is more pronounced, since the removal of electrons from the π-electron system of the basal planes, weaken these forces.     

Sunflower protein hydrolysates for dietary treatment of patients with liver failure

A method is described to obtain hydrolysates with defined characteristics and a high Fischer ratio for patients with liver failure, using sunflower proteins (globulin fraction-II) as starting material. Protein with a branched chain amino acid (BCAA) concentration of 29.7±1.7% is treated in a first step with immobilized chymotrypsin (raw hydrolysate-1). Subsequent ultrafiltration (cut-off 3 kDa) of the hydrolysate gives sunflower protein hydrolysate-I (SFPH-I). In a second step, SFPH-I is treated with immobilized carboxypeptidase-A at alkaline pH for quasi-selective removal of aromatic amino acids (AAA). This sequential two-step process, followed by size exclusion chromatography on a Sephadex G-15 column, yields a product (SFPH-II) with a BCAA concentration of 37.4±2.2% and an AAA concentration of 0.5±0.1%, which gives a very high Fischer ratio (≈75). The product, comprising mainly peptides with molecular weights in the range of 3500 to 750 Da and free amino acids, is hypoallergenic and shows no or only a trace of bitterness. Any bitterness can be completely removed by treatment with Flavozyme^®, giving a hydrolysate that is composed mainly by tri- and dipeptides and free amino acids, and is termed highly hydrolyzed protein hydrolysate (HHPH). Both SFPH-II and HHPH can be used in enteral, parenteral, and oral nutrition for the treatment of patients with liver failure. This product presents all the conditions required for use in the treatment of patients with liver failure: high content in BCAA and low content in AAA, below 2%, and consequently, a very high Fischer ratio, ≈75.     

Ethanol Enhances Hyperthermia-Induced Cell Death in Human Leukemia Cells

Ethanol has been shown to exhibit therapeutic properties as an ablative agent alone and in combination with thermal ablation. Ethanol may also increase sensitivity of cancer cells to certain physical and chemical antitumoral agents. The aim of our study was to assess the potential influence of nontoxic concentrations of ethanol on hyperthermia therapy, an antitumoral modality that is continuously growing and that can be combined with classical chemotherapy and radiotherapy to improve their efficiency. Human leukemia cells were included as a model in the study. The results indicated that ethanol augments the cytotoxicity of hyperthermia against U937 and HL60 cells. The therapeutic benefit of the hyperthermia/ethanol combination was associated with an increase in the percentage of apoptotic cells and activation of caspases-3, -8 and -9. Apoptosis triggered either by hyperthermia or hyperthermia/ethanol was almost completely abolished by a caspase-8 specific inhibitor, indicating that this caspase plays a main role in both conditions. The role of caspase-9 in hyperthermia treated cells acquired significance whether ethanol was present during hyperthermia since the alcohol enhanced Bid cleavage, translocation of Bax from cytosol to mitochondria, release of mitochondrial apoptogenic factors, and decreased of the levels of the anti-apoptotic factor myeloid cell leukemia-1 (Mcl-1). The enhancement effect of ethanol on hyperthermia-activated cell death was associated with a reduction in the expression of HSP70, a protein known to interfere in the activation of apoptosis at different stages. Collectively, our findings suggest that ethanol could be useful as an adjuvant in hyperthermia therapy for cancer.     

Comprehensive review and future perspectives on the photocatalytic hydrogen production

Hydrogen represents a renewable energy alternative that may positively contribute to get over the global energy crisis while at the same time reducing its environmental burden. Overcoming the challenge of reaching this potential could be helped by careful choice of hydrogen (H₂) sources. Photocatalytic generation of H₂, although a minor alternative, appears to be a very good option at the time that liquid wastes are being degraded; therefore, this approach has given rise to an increasing number of interesting studies. Here, we aim to provide an integrated overview of the different photocatalytic, heterogeneous, homogeneous and hybrid systems. First, we categorize the units and mechanisms that take part in the photocatalytic process, and secondly we analyze their role and draw comparative conclusions. Thus, we analyze the role of (i) the electron source to carry out proton reduction, (ii) the proton source, which can be free protons in the medium or a proton donor compound, (iii) the catalyst nature and concentration, and (iv) the photosensitizer nature and concentration. We also provide an analysis of the influence of the solvent, especially in homogenous systems as well as the influence of pH. We provide a comparison of the photocatalytic performance, highlighting the advantages and disadvantages, of different systems. Thus, this review is, on the one hand, an update on the state of the art of photocatalytic generation of H₂ from a full perspective that integrates homogeneous, heterogeneous and hybrid systems, and, on the other, a source of useful information for future research. © 2019 Society of Chemical Industry     

A shape grammar interpreter for rectilinear forms

Shape grammars play an important role in a new generation of tools for the analysis and design of products. Up until now there has been numerous attempts to create a general shape grammar interpreter, but most of the existing tools are either very specific in their purpose, have only limited functionality or were programmed for one operating system. In this work, we present a tool named Shape Grammar Interpreter (SGI) for the automatic generation of designs. The developed shape grammar framework allows designers to automatically synthetize designs and to actively participate in the generation process. Great effort has been devoted to provide an interactive way of defining shapes and later using them in shape grammar rules and designs’ generation process. The tool implements two different types of algorithms for the generation of designs. First, Tree-search algorithms which store the state of the generation process in a tree structure and uses traditional tree-search algorithms to find the next rule to apply. Second, and most importantly, an optimized subshape detection algorithm. Hence, subshapes of the existing shapes can be detected and used in the generation process obtaining not only a wider set of designs but potentially more appealing ones. In this paper, we also describe the architecture of the framework and provide a performance evaluation of proposed algorithms, showing a significant gain in performance. Potential applications of our research can be found in the educational field (i.e. architecture and arts) and in the automatic generation of architectural, mechanical and product designs.     

A knowledge-based architecture for the management of patient-focused care pathways

There is need for software systems in order to coordinate the activities of healthcare professionals involved in the treatment of a patient, aligning the care delivery around already existing Clinical Practice Guidelines (CPGs). This is being carried out in care organizations by implementing integrated Care Pathways (CPs). Nonetheless, the generation of these care pathways is not trivial, and multiple barriers exist for their development and enactment. In this paper, a knowledge-based architecture is presented that, by means of Knowledge Engineering methods and Artificial Intelligence Planning and Scheduling (AI P&S) techniques, is able to automatically generate these care pathways from a computer-interpretable representation of CPGs, tackling some of these barriers. Firstly, these techniques consider the patient profile, the care organization details as well as the temporal and resource constraints, implicit in a care process, in order to generate a patient-focused care pathway. Moreover, they also allow the enactment of personalized care plans in a web-based format, powered by a workflow runtime engine, thus providing an ubiquitous and interactive execution to healthcare professionals. Finally, the architecture also includes monitoring and replanning techniques in order to check the current health status of patients and adapt care plans when they do not progress as expected. For the experimental evaluation of the architecture, several tests have been carried out in order to simulate a clinical environment where different care plans were automatically executed, monitored and adapted regarding the health conditions of patients as well as the recommendations specified in a real, CPG of the paediatric oncology area. As conclusion, the proposed architecture seems to be an adequate infrastructure for supporting the automated generation as well as the interactive execution and monitoring of patient-focused care pathways.