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.     

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.     

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.     

An Alternate Double–Single Track Proposal for High‐Speed Peripheral Railway Lines

This article presents alternate double–single track (ADST) lines as an alternative to double‐track lines. The idea consists of using single track where the infrastructure is very expensive (tunnels and viaducts) and double track where it is cheaper (smooth orography) combined with small changes in departure times so that trains may cross in the double‐track segments with no reduction in travel times. The solution is shown to be very efficient for traffic demands between 30 and 40 trains per day and the costs are reduced substantially (close to 40%). A linear programming program is given that (1) decides the optimal sequence of single and double tracks and (2) optimizes the timetables for the optimal or other alternative sequences. The Palencia–Santander line is used to illustrate the proposal and some suggestions are given to use the ADST lines in several countries.     

Wheat gluten-based materials plasticised with glycerol and water by thermoplastic mixing and thermomoulding

BACKGROUND: Gluten has been investigated as a source for biodegradable polymeric materials because it is a renewable, available and low‐cost raw material. The aim of this study was to evaluate the influence of some variables involved in the two stages of protein/plasticiser thermo‐mechanical processing, where a mixture of glycerol and water was used as the plasticiser. RESULTS: Gluten/glycerol/water blends mixed under different thermal conditions (adiabatic starting at 25 °C and isothermal at 60 and 90 °C) exhibited shear thinning capillary flow behaviour, where a marked increase in flow properties was obtained at the highest temperature. Two thermal events, glass transitions related to the plasticiser blend and gluten, were detected by Modulated Differential Scanning Calorimetry (MDSC) and Dynamic Mechanical Analysis (DMA) tests. Moderate moulding temperature led to less resistant materials showing higher ductility, whereas higher mixing and moulding temperatures led to bioplastics with higher mechanical properties. CONCLUSION: A moulding temperature of 130 °C (close to the denaturation temperature) was found to be suitable for the thermomoulding process. In addition, the use of moderate mixing temperature seems to be convenient for those applications that required materials exhibiting high water absorption behaviour and suitable mechanical properties. Protein extractability results reflect the benefits of combining high shear and high temperature during processing to improve cross‐linking reactions. Copyright © 2010 Society of Chemical Industry     

Microbiological and physicochemical quality of fresh-cut apple enriched with the probiotic strain Lactobacillus rhamnosus GG

The effectiveness as protective culture of the probiotic Lactobacillus rhamonosus GG (L. rham. GG) against Salmonella and Listeria monocytogenes on minimally-processed apples throughout storage as well as its effect on apple quality and natural microflora was evaluated. Survival to subsequent exposure to gastric stress was also reported. Apples were cut into wedges and dipped in a solution containing Salmonella and L. monocytogenes (10⁵ cfu mL⁻¹) and/or L. rham. GG (10⁸ cfu mL⁻¹). Apple wedges were packed and stored at 5 and 10 °C. Periodically, microbial population, bacterial survival to gastric stress and quality of apple wedges were evaluated. Although Salmonella was not affected by co-inoculation with L. rham. GG, L. monocytogenes population was 1-log units lower in the presence of L. rham. GG. L. rham. GG population maintained over recommended levels for probiotic action (10⁶ cfu g⁻¹) along storage, however, viable cells after gastric stress were only above this level during the first 14 days. Pathogen survival after gastric stress was <1% after 7 days at 5 °C. Moreover, apple wedges quality was not affected by L. rham. GG addition. Thus, L. rham. GG could be a suitable probiotic for minimally-processed apples capable to reduce L. monocytogenes growth; nevertheless shelf life should not be higher to 14 days to guarantee the probiotic effect.     

Biogenic amine content during the manufacture of dry-cured lacón, a Spanish traditional meat product: Effect of some additives

The content of nine biogenic amines (agmatine, tryptamine, 2-phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine and spermine) was determined throughout the manufacture of dry-cured lacón, a traditional dry-salted and ripened meat product made in the north-west of Spain from the fore leg of the pig following a similar process to that of dry-cured ham. The effect of the use of additives (glucose, sodium nitrite, sodium nitrate, sodium ascorbate and sodium citrate) on the biogenic amine content during manufacture was also studied. Tryptamine and spermine were the main biogenic amines in fresh meat, while tryptamine and cadaverine were the most abundant at the end of the manufacturing process. During ripening the total amine content increased significantly (P<0.05) in the batches made both without and with additives. The use of additives significantly (P<0.05) increased the total amine content and the content of tryptamine, tyramine and histamine. The total biogenic amine content at the end of the manufacturing process was low as expected for a product in which there is little active microbial metabolism during manufacture.     

Influence of type,concentration and flow behaviour of hydrocolloid solutions on aroma perception

The effects of the addition of two hydrocolloids—locust bean (LBG) and xanthan gums—at two concentrations (0.2 and 0.5%, w/v) on the intensity of the aroma of limonene and of isopentyl acetate solutions was studied using the pairwise ranking test. Previously, the rheological behaviour of the studied gums was analysed, finding that while LBG solutions were slightly pseudoplastic at the lower concentration and more so at the higher one, the xanthan solutions were clearly pseudoplastic at both concentrations. Addition of 0.2% LBG did not alter the limonene aroma intensity perceived, but on adding 0.5% LBG, above the coil overlap concentration (c*), the decrease in aroma intensity was significant. Addition of xanthan gum at any concentration did not modify the limonene aroma intensity perceived by judges, which can be attributed to the low value of c* for solutions of this gum. No difference in isopentyl acetate aroma was found among samples.