Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of cis-regulatory elements in the design of gene therapy vectors for inherited blindness

Background: Hereditary retinal disease is currently known to involve nearly 200 different genetic loci. There has been remarkable recent progress in the treatment of retinal disease via gene therapy in animal models using virus-based vectors. The majority of retinal diseases affect one of several cell types. In order to target expression of a rescue transgene specifically to the cells in need of therapy, it is necessary to employ a cis-regulatory element (CRE) to drive expression of the transgene specifically in those cells. Objective/methods: This review discusses the repertoire of CREs currently available for use in gene therapy vectors for treatment of retinal disease and outlines the issues that must be taken into consideration in the development of novel CREs for the purpose of gene therapy in the retina. Conclusion: There have been a number of important recent advances in the identification and characterization of retinal CREs and their utilization in gene therapy vectors. Nevertheless, future efforts to rationally manipulate existing CREs and design novel synthetic CREs for therapeutic purposes will require a better understanding of the cis-regulatory rules that govern CRE activity in vivo.
Ultrathin Electrolyte Membranes with PFSA-Vinylon Intermediate Layers for PEM Fuel Cells

We prepared ultrathin PFSA/PFSA-vinylon/PFSA laminated electrolyte membranes (thickness = 10 μm) for fuel cells without using a reinforcing material. Nafion and Aquivion solutions were used as PFSA polymers. Vinylon was synthesized by formalizing polyvinyl alcohol. From the current-voltage measurements using ultrathin PFSA/PFSA-vinylon/PFSA membranes; the cell resistances are significantly lower than that using a 50 μm Nafion membrane. A high current density was obtained under both low- and high-humidity conditions. Ultrathin PFSA/PFSA-vinylon/PFSA laminated membranes will help to further improve the performance of PEMFCs.
Stable phylogenetic patterns in scutigeromorph centipedes (Myriapoda : Chilopoda : Scutigeromorpha): dating the diversification of an ancient lineage of terrestrial arthropods

Abstract. Although stable and well-supported relationships are in place for the three main clades (families) of Scutigeromorpha, the interrelationships of particular taxa within the most diverse family, Scutigeridae, are less clearly resolved. Novel molecular data for taxa from Mesoamerica, the Caribbean, southern Africa, New Guinea and previously unsampled parts of the Pacific are incorporated into phylogenetic analyses. Relationships across the tree are stable under variable analytical conditions, whether these are homology-based (multiple sequence alignment versus implied alignment; untrimmed versus trimmed datasets) or method-based (parsimony versus maximum likelihood). Hypervariable regions, contrary to common belief, add phylogenetic structure to the data, as measured by the increased support for many nodes when compared with the same alignments trimmed with Gblocks. Our analyses show that a Yule-3-rate model best explained the diversification of Scutigeromorpha during their 400 million years of history. More complete molecular data for the New Guinea genus Ballonema stabilise its position as sister group to Thereuoneminae. To reconcile scutigeromorph systematics with the phylogeny, the monotypic genus Madagassophora Verhoeff, 1936, is placed in synonymy with Scutigerina Silvestri, 1901 (n. syn.), its type species M. hova becoming Scutigerina hova (de Saussure & Zehntner, 1902) new comb. (from Scutigera), and Lassophora Verhoeff, 1905, is re-established for an Afro-Malagasy clade containing Lassophora nossibei (de Saussure & Zehntner, 1902) new comb. (from Scutigera) and a newly sequenced species from Mozambique that diverged at the base of the lineage to Thereuoneminae. The dated phylogeny of Scutigeromorpha is more consistent with ancient vicariant splits between Madagascar–southern Africa and Australia–New Caledonia than with younger dispersal scenarios, though some geologically young Pacific islands that harbour lineages dating to the Cretaceous demonstrate the potential for trans-oceanic dispersal.
Management of Hypertension in the Digital Era

Out-of-office blood pressure measurement is an essential part of diagnosing and managing hypertension. In the era of advanced digital health information technology, the approach to achieving this is shifting from traditional methods (ambulatory and home blood pressure monitoring) to wearable devices and technology. Wearable blood pressure monitors allow frequent blood pressure measurements (ideally continuous beat-by-beat monitoring of blood pressure) with minimal stress on the patient. It is expected that wearable devices will dramatically change the quality of detection and management of hypertension by increasing the number of measurements in different situations, allowing accurate detection of phenotypes that have a negative impact on cardiovascular prognosis, such as masked hypertension and abnormal blood pressure variability. Frequent blood pressure measurements and the addition of new features such as monitoring of environmental conditions allows interpretation of blood pressure data in the context of daily stressors and different situations. This new digital approach to hypertension contributes to anticipation medicine, which refers to strategies designed to identify increasing risk and predict the onset of cardiovascular events based on a series of data collected over time, allowing proactive interventions to reduce risk. To achieve this, further research and validation is required to develop wearable blood pressure monitoring devices that provide the same accuracy as current approaches and can effectively contribute to personalized medicine.
3D co-culture spheroid drug screening platform for pancreatic cancer invasion

5 List of publications . 6 Table of abbreviations. 11 List of Figures . 16 List of tables . 19 Introduction . 20 1.1. Pancreatic ductal adenocarcinoma . 20 Epidemiology . 23 Risk factors . 25 Molecular genetics in PDAC progression . 25 Signalling pathways and therapeutic targets in PDAC . 29 Pancreatic cancer subtypes. 32 Current therapies . 34 1.2. The role of the tumour microenvironment in PDAC . 37 Pancreatic stellate cells . 40 1.3. Cancer metastasis . 43 Regulation of cellular morphology during migration and invasion . 43 Epithelial-mesenchymal transition . 44 Collective cell migration . 45 1.4. Aims . 47 Methods and materials . 48 2.1. Cell culture . 48
Cadmium-induced subcellular accumulation of O2·− and H2O2 in pea leaves

Cadmium is a toxic metal that produces disturbances in plant antioxidant defences giving rise to oxidative stress. The effect of this metal on H2O2 and O2·− production was studied in leaves from pea plants growth for 2 weeks with 50 µm Cd, by histochemistry with diaminobenzidine (DAB) and nitroblue tetrazolium (NBT), respectively. The subcellular localization of these reactive oxygen species (ROS) was studied by cytochemistry with CeCl3 and Mn/DAB staining for H2O2 and O2·−, respectively, followed by electron microscopy observation. In leaves from pea plants grown with 50 µm CdCl2 a rise of six times in the H2O2 content took place in comparison with control plants, and the accumulation of H2O2 was observed mainly in the plasma membrane of transfer, mesophyll and epidermal cells, as well as in the tonoplast of bundle sheath cells. In mesophyll cells a small accumulation of H2O2 was observed in mitochondria and peroxisomes. Experiments with inhibitors suggested that the main source of H2O2 could be a NADPH oxidase. The subcellular localization of O2·− production was demonstrated in the tonoplast of bundle sheath cells, and plasma membrane from mesophyll cells. The Cd-induced production of the ROS, H2O2 and O2·−, could be attributed to the phytotoxic effect of Cd, but lower levels of ROS could function as signal molecules in the induction of defence genes against Cd toxicity. Treatment of leaves from Cd-grown plants with different effectors and inhibitors showed that ROS production was regulated by different processes involving protein phosphatases, Ca2+ channels, and cGMP.
Enzymatic Antioxidant Signatures in Hyperthermophilic Archaea

To fight reactive oxygen species (ROS) produced by both the metabolism and strongly oxidative habitats, hyperthermophilic archaea are equipped with an array of antioxidant enzymes whose role is to protect the biological macromolecules from oxidative damage. The most common ROS, such as superoxide radical (O2•−) and hydrogen peroxide (H2O2), are scavenged by superoxide dismutase, peroxiredoxins, and catalase. These enzymes, together with thioredoxin, protein disulfide oxidoreductase, and thioredoxin reductase, which are involved in redox homeostasis, represent the core of the antioxidant system. In this review, we offer a panorama of progression of knowledge on the antioxidative system in aerobic or microaerobic (hyper)thermophilic archaea and possible industrial applications of these enzymes.
Gut Microbiota and Liver Interaction through Immune System Cross-Talk: A Comprehensive Review at the Time of the SARS-CoV-2 Pandemic

Background and aims: The gut microbiota is a complex ecosystem containing bacteria, viruses, fungi, yeasts and other single-celled organisms. It is involved in the development and maintenance of both innate and systemic immunity of the body. Emerging evidence has shown its role in liver diseases through the immune system cross-talk. We review herein literature data regarding the triangular interaction between gut microbiota, immune system and liver in health and disease. Methods: We conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: gut microbiota, microbiome, gut virome, immunity, gastrointestinal-associated lymphoid tissue (GALT), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steato-hepatitis (NASH), alcoholic liver disease, liver cirrhosis, hepatocellular carcinoma. Results: The gut microbiota consists of microorganisms that educate our systemic immunity through GALT and non-GALT interactions. The latter maintain health but are also involved in the pathophysiology and in the outcome of several liver diseases, particularly those with metabolic, toxic or immune-mediated etiology. In this context, gut virome has an emerging role in liver diseases and needs to be further investigated, especially due to the link reported between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and hepatic dysfunctions. Conclusions: Changes in gut microbiota composition and alterations in the immune system response are involved in the pathogenesis of metabolic and immune-mediated liver diseases.
Affective and Sexual Needs of Residents in Psychiatric Facilities: A Qualitative Approach

Background: The affective and sexual needs of psychiatric patients are often under-considered, although they contribute significantly to their general well-being. Such topics are critical for Residential Psychiatric Facilities Users (RPFUs), whose daily life is paced by therapeutic settings. The aim of this paper is to better understand how sexuality and affectivity are expressed by the RPFUs at the Mental Health Department of Modena, within psychiatric residential settings. Methods: Adult RPFUs took part into two audio recorded focus groups. Digital transcripts were analyzed using MAXQDA software in order to perform qualitative narrative analysis, so as to develop a hierarchical code system a posteriori (derived from the data). Results: Eleven participants (eight RPFUs and three investigators) attended the first focus group, and eight participants (5 RPFUs and 3 investigators) attended the second focus group. 175 interventions were analyzed and coded under seven thematic areas: (a) contraception and sexually transmitted disease prevention (N = 17); (b) affective needs (N = 11); (c) personal experiences (N = 61); (d) regulation of sexual relations (N = 18); (e) Mental Health Professionals’ (MHPs) openness towards the topic (N = 17); (f) MHPs’ responses to RPFUs’ sexual behaviors (N = 33); and (g) RPFUs proposals (N = 18). The highlighted topics suggest that affective and sexual relations commonly occur within residential psychiatric facilities, even if mental health services often fail to recognize and address RPFUs’ affective and sexual needs as well as to provide effective solutions to manage them. Conclusions: RPFUs expressed a request for support to fulfill their affective and sexual needs and dedicated spaces for sexual activities to relieve their discomfort, while MHPs highlighted a need for awareness, training, and shared problem-solving strategies.
Phytochemical and pharmacological appraisal of the aerial parts of Lotus corniculatus L. growing in Egypt

Abstract Lotus corniculatus L. (Fabaceae) is widely grown in Egypt. It has a great history of folkloric medicinal uses. All fractions of aerial parts of L. corniculatus L. showed significant antioxidant and immunostimulant activities and could strongly induce lymphoproliferation. However, the light petrol fraction had antifungal activity against C. neoformans with IC50 value (<8 µg/mL) and exhibited strongest in-vitro antiprotozoal activity against protozoan parasites belonging to the genera Trypanosoma with IC50 value (0.98 µg/mL) and Plasmodium (with 100% inhibition using a sample concentration of 15866.7 ng/mL). This is the first study of the immunostimulant and antiprotozoal activities of genus Lotus. By this approach, it was possible to isolate eight compounds (-)-7,2'-dihydroxy-4'-methoxyisoflavan (vestitol) (1), kaempferol (2), kaempferol 3-O-α-L-rhamnoside (afzelin) (3), kaempferol 3, 7-O-α-L-dirhamnoside (kaempferitin) (4), kaempferol-3-O-[β-D-xylopyranosyl (1″′→2″)-β-D-galactopyranoside] (5), 3-O-[β-D-glucuronopyranosyl] soyasapogenol B (6), kaempferol-3-O-[β-D-xylopyranosyl (1″′→2″)-β-D-galactopyranoside]-7-O-α-L-rhamnopyranoside (7) and 3-O-[α-L-rhamnopyranosyl (1″′→2″)-β-D-galactopyranosyl-(1″→2′)-β-D-glucuronopyranosyl] soyasapogenol B (soyasaponin І) (8).
Hypoxic Treatment Decreases the Physiological Action of the Herbicide Imazamox on Pisum sativum Roots

The inhibition of acetolactate synthase (ALS; EC 2.2.1.6), an enzyme located in the biosynthetic pathway of branched-chain amino acids, is the target site of the herbicide imazamox. One of the physiological effects triggered after ALS inhibition is the induction of aerobic ethanol fermentation. The objective of this study was to unravel if fermentation induction is related to the toxicity of the herbicide or if it is a plant defense mechanism. Pea plants were exposed to two different times of hypoxia before herbicide application in order to induce the ethanol fermentation pathway, and the physiological response after herbicide application was evaluated at the level of carbohydrates and amino acid profile. The effects of the herbicide on total soluble sugars and starch accumulation, and changes in specific amino acids (branched-chain, amide, and acidic) were attenuated if plants were subjected to hypoxia before herbicide application. These results suggest that fermentation is a plant defense mechanism that decreases the herbicidal effect.
Body size and conformation in sheep from birth to maturity as affected by breed, crossbreeding, maternal and other factors

Body weight was studied from birth to 5½ years of age and six linear measures of body size from birth to 4¼ years for sheep of five breeds, Scottish Blackface, Cheviot, Welsh Mountain, Lincoln Longwool and Southdown, and of crosses of these breeds with each other and with the Tasmanian Merino, but not in all possible combinations. The sheep were run as a single flock. Numbers ranged from 753 at birth to 150 at the end of the experimental period. There were marked differences among the breeds and crosses in all aspects of body size and some differences in rate of maturity. They also differed in conformation independently of body weight. Crosses of the hill breeds with the Lincoln and probably with the Southdown were heavier than the average of the parental breeds and larger in some linear body measurements from about weaning onwards. The weights of crosses of Blackface and Cheviot with Lincoln eventually exceeded those of the heavier parent of the cross. For the crosses among the three hill breeds only the Blackface Cheviot cross showed significant deviations from mid-parent values for weight and size. Maternal effects were important for all traits studied from birth to weaning and for weight up to a year old. In relation to mature size, Welsh dams produced the biggest and Lincoln the smallest lambs. The data did not permit Southdown maternal effects to be estimated. The effects of birth type and rearing were apparent for late maturing body parts up to a year old and for weight up to 3 years. Males, measured only from birth to weaning, were heavier and generally larger than females. Residual correlations between the various measures of size varied from 0·1 to 0·7.
INTRODUCED SPECIES: A SIGNIFICANT COMPONENT OF HUMAN-CAUSED GLOBAL CHANGE

Humans move species beyond their native ranges both deliberately and inadvertently, and many of these species become established and spread in their new habitat. The list of established introduced species grows annually, as does the number of them that cause significant economic and ecological effects. One recent and notorious example in North America is the Eurasian zebra mussel which like many other aquatic organisms entered in the ballast water of ships, and like many others spread rapidly once it arrived. The invasion of zebra mussels is unusual in the magnitude of its economic consequences; the mussels grow and reproduce rapidly, covering river and lake bottoms and municipal and industrial water inlets. The cost of clearing blocked intake pipes has been calculated to be approximately US$2 billion (Office of Technology Assessment, 1993). Zebra mussels also alter populations of algae and the concentrations of nutrients in whole ecosystems (Caraco et al., 1997), and they are continuing to spread in rivers, lakes, and canals throughout North America. We suggest that biological invasions by notorious species like the zebra mussel, and its many less-famous counterparts, have become so widespread as to represent a significant component of global environmental change. This point has been made before (eg Elton, 1958), but is not widely appreciated, even by the global change research community or by those who study and/or work to control biological invasions. In part, this lack of appreciation reflects the fact that our perception is limited spatially it is possible to document the presence and importance of biological invasions almost anywhere, but more difficult to perceive that invasions are almost everywhere. In part, it may also reflect a narrow view of global environmental change, one that emphasizes climate change (global warming) at the expense of other, equally significant components of human-caused global change. In this paper, we place biological invasions in context with other human-caused global environmental changes; briefly describe the global extent of biological invasion; illustrate the consequences of particular invasions as they affect human health and wealth, and/or the functioning and biological diversity of natural ecosystems; discuss interactions between biological invasions and other components of global change; and describe ways that society can prevent, manage, and/or cope with invasions.
Web Application for the Automated Extraction of Diagnosis and Site From Pathology Reports for Keratinocyte Cancers

PURPOSE Keratinocyte cancers are exceedingly common in high-risk populations, but accurate measures of incidence are seldom derived because the burden of manually reviewing pathology reports to extract relevant diagnostic information is excessive. Thus, we sought to develop supervised learning algorithms for classifying basal and squamous cell carcinomas and other diagnoses, as well as disease site, and incorporate these into a Web application capable of processing large numbers of pathology reports. METHODS Participants in the QSkin study were recruited in 2011 and comprised men and women age 40-69 years at baseline (N = 43,794) who were randomly selected from a population register in Queensland, Australia. Histologic data were manually extracted from free-text pathology reports for participants with histologically confirmed keratinocyte cancers for whom a pathology report was available (n = 25,786 reports). This provided a training data set for the development of algorithms capable of deriving diagnosis and site from free-text pathology reports. We calculated agreement statistics between algorithm-derived classifications and 3 independent validation data sets of manually abstracted pathology reports. RESULTS The agreement for classifications of basal cell carcinoma (κ = 0.97 and κ = 0.96) and squamous cell carcinoma (κ = 0.93 for both) was almost perfect in 2 validation data sets but was slightly lower for a third (κ = 0.82 and κ = 0.90, respectively). Agreement for total counts of specific diagnoses was also high (κ > 0.8). Similar levels of agreement between algorithm-derived and manually extracted data were observed for classifications of keratoacanthoma and intraepidermal carcinoma. CONCLUSION Supervised learning methods were used to develop a Web application capable of accurately and rapidly classifying large numbers of pathology reports for keratinocyte cancers and related diagnoses. Such tools may provide the means to accurately measure subtype-specific skin cancer incidence.
THE β-KETOADIPATE PATHWAY AND THE BIOLOGY OF SELF-IDENTITY

The beta-ketoadipate pathway is a chromosomally encoded convergent pathway for aromatic compound degradation that is widely distributed in soil bacteria and fungi. One branch converts protocatechuate, derived from phenolic compounds including p-cresol, 4-hydroxybenzoate and numerous lignin monomers, to beta-ketoadipate. The other branch converts catechol, generated from various aromatic hydrocarbons, amino aromatics, and lignin monomers, also to beta-ketoadipate. Two additional steps accomplish the conversion of beta-ketoadipate to tricarboxylic acid cycle intermediates. Enzyme studies and amino acid sequence data indicate that the pathway is highly conserved in diverse bacteria, including Pseudomonas putida, Acinetobacter calcoaceticus, Agrobacterium tumefaciens, Rhodococcus erythropolis, and many others. The catechol branch of the beta-ketoadipate pathway appears to be the evolutionary precursor for portions of the plasmid-borne ortho-pathways for chlorocatechol degradation. However, accumulating evidence points to an independent and convergent evolutionary origin for the eukaryotic beta-ketoadipate pathway. In the face of enzyme conservation, the beta-ketoadipate pathway exhibits many permutations in different bacterial groups with respect to enzyme distribution (isozymes, points of branch convergence), regulation (inducing metabolites, regulatory proteins), and gene organization. Diversity is also evident in the behavioral responses of different bacteria to beta-ketoadipate pathway-associated aromatic compounds. The presence and versatility of transport systems encoded by beta-ketoadipate pathway regulons is just beginning to be explored in various microbial groups. It appears that in the course of evolution, natural selection has caused the beta-ketoadipate pathway to assume a characteristic set of features or identity in different bacteria. Presumably such identities have been shaped to optimally serve the diverse lifestyles of bacteria.