Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactive teaching and repeat exposure maximize medical student satisfaction but do not promote long-term retention of dermatologic knowledge.

BACKGROUND Instructional methods for teaching medical students to recognize common skin lesions vary widely. There is little published data comparing various teaching methods and their impact on medical student retention of dermatologic knowledge. METHODS Our prospective cohort study analyzed how teaching methods (interactive teaching versus. traditional didactic teaching versus. self-guided review alone) impacted second year medical students' ability to recognize common skin lesions one year after initial exposure to the material. Our study also looked at student satisfaction with different teaching methods. RESULTS There was no significant difference in long-term retention of knowledge between different teaching methods. However, students preferred the interactive format over the traditional didactic format. Spaced review is important for long-term retention, but an in-class review session two months after content was initially taught provided no added benefit over spaced self-review alone. CONCLUSIONS Medical students are able to maintain long-term retention of dermatologic knowledge irrespective of in-class teaching method. Repeat exposure to material is important but self-review of dermatology alone is sufficient for long-term retention. Dermatology course directors should incorporate interactive teaching into medical school curricula to increase learner satisfaction.
Analisi costo-efficacia di darbepoetina dopo switch da epoietina-beta nei pazienti in emodialisi: studio retrospettivo monocentrico italiano

Darbepoetin (DARB), a human erythropoietin with improved pharmacological parameters (longer half life and a dose-response relationship independent from the route of administration) is a new treatment option for chronic nephropathy-induced anemia that in many Italian dialysis centers is substituting older erythropoietins, mainly due to greater ease of use. At current prices and at the theoretical and recommended 200:1 dose conversion factor, DARB pharmaceutical cost ranges from –9% to +17% of EPO cost. In this monocentric study, real drug consumption and related actual costs of a pre-switch semester with EPO were analysed and compared to the first two post-switch semesters with DARB therapy. Furthermore, erythropoetic response was recorded and related to drug exposition levels, in order to establish a real life EPO:DARB dose conversion factor. In this experience, the conversion factor was estimated in at least 250-280:1, depending on the method adopted for the estimation. The initial dose, chosen on the basis of the recommended conversion factor, induced an excessive erythropoietic response, which was generally followed by a dose reduction and successive titration to target desired Hb levels, generating the spiraliform dose-response curve associated with delayed feed-back mechanisms. The pharmacoeconomical analysis, conducted in the perspective of the public health service, indicated that the choice of substituting DARB for EPO in the treatment of chronic kidney failure-associated anemia is univocally convenient, the former being less costly and more effective.
Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer

Background The aim of the study was to assess the expression of the MMP-9 gene and –1562 C/T polymorphism in MMP-9 gene promoter in relation to clinicopathological parameters in predicting the clinical outcome of prostate cancer patients. Methods A total of 82 patients with histopathologically diagnosed prostate cancer were enrolled in the study. MMP-9 gene expression was assessed by reverse transcription-PCR method. MMP-9 (-1562 C/T) polymorphism variants were determined by the polymerase chain reaction-based restriction fragment length polymorphism method. Results MMP-9 expression and MMP-9 –1562 polymorphism variants in relation to disease pathological stage (P = 0.006; P <0.0001, respectively), as well as to prognostic group (P = 0.019; P <0.0001, respectively), were statistically significant. Only MMP-9 –1562 polymorphism variants in relation to tumor differentiation grade (P = 0.044) were found to be statistically significant. Positive MMP-9 gene expression was associated with 5-year survival rate of prostate cancer patients with pathological stage III (P = 0.036) and for the patients in prognostic group III (P = 0.012). Patients with tumor differentiation grade G2 and with the identified CC variant had a significantly longer survival time than patients with the identified TT variant (P = 0.007). Conclusions MMP-9 gene expression and MMP-9 –1562 polymorphism variants were associated with prostate cancer pathological stage and prognostic group. MMP-9 –1562 polymorphism CC variant was associated with prostate cancer tumor differentiation grade. Five-year survival analysis showed the relationship between MMP-9 gene expression and pathological stage III, as well as prognostic group III, whereas MMP-9 –1562 polymorphism variants, with tumor differentiation grade G2.
DNA damage responses in ageing

Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular functionality, and an organism's ability to respond to stress has been linked to functional maintenance and longevity. Stress response pathways might indeed become therapeutic targets of therapies aimed at extending the healthy lifespan. Various progeroid syndromes have been linked to genome instability, indicating an important causal role of DNA damage accumulation in the ageing process and the development of age-related pathologies. Recently, non-cell-autonomous mechanisms including the systemic consequences of cellular senescence have been implicated in regulating organismal ageing. We discuss here the role of cellular and systemic mechanisms of ageing and their role in ageing-associated diseases.
Giving clinics man appeal.

Family planning clinics must recognize that they cannot market family planning to men in the same way as to women. When it comes to reaching men clinics must adopt a marketing approach as there are many rival outlets for their family planning needs. Mens motives for participation in family planning need to be a primary consideration. Successful marketing depends most heavily on identifying and meeting the need of the client and not just that of the seller. Clinics should consider providing other male-oriented products and services: pre-employment physicals literacy or job-skill training treatment of sexually transmitted diseases and information on enchancing sexual enjoyment. Recongizing that retail stores and other nonclinic distribution channels also supply men with condoms clinics can learn some lessons through observation. Whenever possible condoms should be made available in various designs and promoted as easy and fun to use. Many advantages would be realized if male contraception could be treated as a nonmedical issue. Family planning workers should stop denigrating coitus interruptus. Consistent withdrawal is moderately effective in preventing pregnancy and it also can serve as a convenient "emergency" method. The couple who use coitus interruptus are demonstrating that they accept the principle of fertility control. They may be encouraged to supplement or replace coitus interruptus with even more effective methods but they deserve support for having shown initiative in using the most natural form of contraception. A man may not be interested in personal counseling but he may want more information about other available contraceptive methods. To deal with any apprehension women staff members may have about extending services to men training sessions can help staff express their fears and practice effective ways to deal with male clients. Male services should be integrated into the family planning clinics functions in ways which make it clear that success of the mens program contributes to a successful womens program.
Changing environments and genetic variation: natural variation in inbreeding does not compromise short-term physiological responses

Selfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce their long-term evolutionary potential. However, appropriate short-term plastic responses to new environmental conditions might not require high levels of standing genetic variation. In this study, we tested whether mating system variation among populations, and associated changes in genetic variability, affected short-term responses to environmental challenges. We compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a perennial plant, Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range. We found no effect of inbreeding on survival, flowering phenology or short-term physiological responses. Specifically, naturally occurring inbreeding had no significant effects on the plasticity of metabolome profiles, using either multivariate approaches or analysis of variation in individual metabolites, with inbreeding populations showing similar physiological responses to outbreeding populations over time in both growing environments. We conclude that low genetic diversity in naturally inbred populations may not always compromise fitness or short-term physiological capacity to respond to environmental change, which could help to explain the global success of selfing mating strategies.
Modified Vaccinia Ankara–Vectored Vaccine Expressing Nucleoprotein and Matrix Protein 1 (M1) Activates Mucosal M1-Specific T-Cell Immunity and Tissue-Resident Memory T Cells in Human Nasopharynx-Associated Lymphoid Tissue

Abstract Background Increasing evidence supports a critical role of CD8+ T-cell immunity against influenza. Activation of mucosal CD8+ T cells, particularly tissue-resident memory T (TRM) cells recognizing conserved epitopes would mediate rapid and broad protection. Matrix protein 1 (M1) is a well-conserved internal protein. Methods We studied the capacity of modified vaccinia Ankara (MVA)–vectored vaccine expressing nucleoprotein (NP) and M1 (MVA-NP+M1) to activate M1-specific CD8+ T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue from children and adults. Results After MVA-NP+M1 stimulation, M1 was abundantly expressed in adenotonsillar epithelial cells and B cells. MVA-NP+M1 activated a marked interferon γ–secreting T-cell response to M1 peptides. Using tetramer staining, we showed the vaccine activated a marked increase in M158–66 peptide-specific CD8+ T cells in tonsillar mononuclear cells of HLA-matched individuals. We also demonstrated MVA-NP+M1 activated a substantial increase in TRM cells exhibiting effector memory T-cell phenotype. On recall antigen recognition, M1-specific T cells rapidly undergo cytotoxic degranulation, release granzyme B and proinflammatory cytokines, leading to target cell killing. Conclusions MVA-NP+M1 elicits a substantial M1-specific T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue, demonstrating its strong capacity to expand memory T-cell pool exhibiting effector memory T-cell phenotype, therefore offering great potential for rapid and broad protection against influenza reinfection.
Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain

Irisin, a newly discovered muscle‐derived hormone, acts in different organs and tissues, improving energy homeostasis. In this study, we assessed, for the first time, the effects of intraperitoneal irisin injections on circulating levels of leptin and ghrelin, mRNA expression of the major hypothalamic appetite regulators and brain neurotrophic factors, as well as feeding behaviour in healthy mice.
Parechovirus A Pathogenesis and the Enigma of Genotype A-3

Parechovirus A is a species in the Parechovirus genus within the Picornaviridae family that can cause severe disease in children. Relatively little is known on Parechovirus A epidemiology and pathogenesis. This review aims to explore the Parechovirus A literature and highlight the differences between Parechovirus A genotypes from a pathogenesis standpoint. In particular, the curious case of Parechovirus-A3 and the genotype-specific disease association will be discussed. Finally, a brief outlook on Parechovirus A research is provided.
Advances in the discovery of microRNA-based anticancer therapeutics: latest tools and developments

ABSTRACT Introduction: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that repress the expression of their target genes by reducing mRNA stability and/or inhibiting translation. miRNAs are known to be aberrantly regulated in cancers. Modulators of miRNA (mimics and antagonists) have emerged as novel therapeutic tools for cancer treatment. Areas covered: This review summarizes the various strategies that have been applied to correct the dysregulated miRNA in cancer cells. The authors also discuss the recent advances in the technical development and preclinical/clinical evaluation of miRNA-based therapeutic agents. Expert opinion: Application of miRNA-based therapeutics for cancer treatment is appealing because they are able to modulate multiple dysregulated genes and/or signaling pathways in cancer cells. Major obstacles hindering their clinical development include drug delivery, off-target effects, efficacious dose determination, and safety. Tumor site-specific delivery of novel miRNA therapeutics may help to minimize off-target effects and toxicity. Combination of miRNA therapeutics with other anticancer treatment modalities could provide a synergistic effect, thus allowing the use of lower dose, minimizing off-target effects, and improving the overall safety profile in cancer patients. It is critical to identify individual miRNAs with cancer type-specific and context-specific regulation of oncogenes and tumor-suppressor genes in order to facilitate the precise use of miRNA anticancer therapeutics.
Energy fluctuation in glycosylated end product formation: a new explanation on pathogenesis for complication in poorly controlled diabetic patient -

Diabetes mellitus (DM) is accepted as the most common endocrine disorder in medicine. Millions of world populations are affected by this disorder. The serious concern for diabetic patients is the development of diabetic complication. It is accepted that the diabetic complication is strongly related to the diabetic control. In poor diabetic control, the complication can be seen earlier. It is accepted that the abnormal glucose level in the blood stream is the big problem that can lead to the vascular pathology. Here, the author focuses the discussion on energy fluctuation in glycosylated end product formation as a new explanation on pathogenesis for complication in poorly controlled diabetic patient. Based on the principle of thermodynamics, the expelled energy from the reaction can be the important factor leading to the vascular pathology. Also, some important publications in this topic is quoted as references.
Constancy (the New Media “C”) and Future Generations

In the past, researchers would consider media’s impact on youth in terms of three “Cs”: consumption, content, and context. This article introduces a new construct—constancy—which supplants the previous terms. Constancy refers to the ubiquitous and continuous state of connected screens in the lives of children and adolescents. Constancy characterizes media content and use, which can be proactive, incidental, or contextual, exerting positive or negative effects on different users. Constancy can influence child development, as persistent access to smartphones and reception of messages will affect future generations’ cognition and education, social interactions, emotions, and health. It will be important to address the developmental needs of the child or adolescent and not the smartphone in his or her pocket. Constancy requires pragmatic and innovative methodologies to understand the new circumstances around children, adolescents, and media. The landscape has changed and so must our approach to research and investigation of media effects.
Population Pharmacokinetics of Total and Free Erdafitinib in Adult Healthy Volunteers and Cancer Patients: Analysis of Phase 1 and Phase 2 Studies

A population pharmacokinetic (PK) model was developed using data pooled from 6 clinical studies (3 in healthy volunteers and 3 in cancer patients) to characterize total and free plasma concentrations of erdafitinib following single‐ and multiple‐dose administration, to understand clinically relevant covariates, and to quantify the inter‐ and intraindividual variability in erdafitinib PK. An open, linear, 3‐compartment disposition model with first‐order absorption and a lag time was used to describe the PK profile of total and free erdafitinib plasma concentrations. The PK of erdafitinib were linear and time independent. After oral administration, erdafitinib was rapidly absorbed, with a time to maximum concentration between 2 and 4 hours. In patients, erdafitinib total apparent oral clearance was 0.200 L/h (median free fraction = 0.24%), and the effective terminal half‐life of total drug was 76.4 hours. Interindividual variability in PK parameters was moderate for oral clearance and central volume of distribution, and large for absorption rate and peripheral volume of distribution. Sex and renal function were significant covariates on free oral clearance, while weight, sex, and α1‐acid‐glycoprotein were significant on oral central volume of distribution. Age, race, and mild hepatic impairment were not significant covariates of erdafitinib exposure. Given that the magnitude of the covariate effects were within 25% of reference values and that the recommended dosing regimen of erdafitinib comprises individual dose up‐titrations and reductions based on presence or absence of toxicities, the clinical relevance of the investigated covariates is expected to be limited, and no dose adjustments are warranted.
EnhancerAtlas 2.0: an updated resource with enhancer annotation in 586 tissue/cell types across nine species

Abstract Enhancers are distal cis-regulatory elements that activate the transcription of their target genes. They regulate a wide range of important biological functions and processes, including embryogenesis, development, and homeostasis. As more and more large-scale technologies were developed for enhancer identification, a comprehensive database is highly desirable for enhancer annotation based on various genome-wide profiling datasets across different species. Here, we present an updated database EnhancerAtlas 2.0 (http://www.enhanceratlas.org/indexv2.php), covering 586 tissue/cell types that include a large number of normal tissues, cancer cell lines, and cells at different development stages across nine species. Overall, the database contains 13 494 603 enhancers, which were obtained from 16 055 datasets using 12 high-throughput experiment methods (e.g. H3K4me1/H3K27ac, DNase-seq/ATAC-seq, P300, POLR2A, CAGE, ChIA-PET, GRO-seq, STARR-seq and MPRA). The updated version is a huge expansion of the first version, which only contains the enhancers in human cells. In addition, we predicted enhancer–target gene relationships in human, mouse and fly. Finally, the users can search enhancers and enhancer–target gene relationships through five user-friendly, interactive modules. We believe the new annotation of enhancers in EnhancerAtlas 2.0 will facilitate users to perform useful functional analysis of enhancers in various genomes.
The fenestrae-associated protein Plvap regulates the rate of blood-borne protein passage into the hypophysis

ABSTRACT To maintain body homeostasis, endocrine systems must detect and integrate blood-borne peripheral signals. This is mediated by fenestrae, specialized permeable pores in the endothelial membrane. Plasmalemma vesicle-associated protein (Plvap) is located in the fenestral diaphragm and is thought to play a role in the passage of proteins through the fenestrae. However, this suggested function has yet to be demonstrated directly. We studied the development of fenestrated capillaries in the hypophysis, a major neuroendocrine interface between the blood and brain. Using a transgenic biosensor to visualize the vascular excretion of the genetically tagged plasma protein DBP-EGFP, we show that the developmental acquisition of vascular permeability coincides with differential expression of zebrafish plvap orthologs in the hypophysis versus brain. Ultrastructural analysis revealed that plvapb mutants display deficiencies in fenestral diaphragms and increased density of hypophyseal fenestrae. Measurements of DBP-EGFP extravasation in plvapb mutants provided direct proof that Plvap limits the rate of blood-borne protein passage through fenestrated endothelia. We present the regulatory role of Plvap in the development of blood-borne protein detection machinery at a neuroendocrine interface through which hormones are released to the general circulation. Summary: Fenestrae play a principal role in regulation of homeostasis. The fenestral protein Plvap regulates the rate of plasma protein entry from the general circulation into the brain parenchyma.
Ethical and responsible tourism: a tool for promoting values and social justice. Two case studies of Sicily, Italy

In recent decades, an ethical and responsible tourism has become increasingly important in the context of a general orientation to promote sustainable development models in the world. The recognition of the negative impacts of mass tourism has led to a profound reflection on tourism and its contribution to the development of a territory. The debate has highlighted the importance of promoting a sustainable and responsible tourism development that brings economic, social and environmental benefits to the local community and its members. The importance of promoting an ethic of tourism for the progress of society has been equally emphasized. Values must not be forgotten in leisure time as they contribute to the civil growth of territories and people. Today, even the tourists are more informed and aware, often interested in traveling responsibly and having significant experiences that satisfy social needs. Studies have also highlighted a widespread need for authenticity and a greater sensitivity of consumers to the ethical aspects of a travel. Organizing ethical and responsible tourism activities means to embrace these principles and to consider these tourists’ expectations. This paper emphasizes and explores the role of tourism in promoting values that favor the development of territories and visitors (such as those of legality, justice and honesty), as well as its aptitude to foster an economic and social redemption of the local community. To this end, we present two case studies concerning innovative forms of ethical and responsible tourism recently established in Southern Italy in a more favorable institutional and cultural context. These are initiatives characterized by a strong ethical profile, being related to the fight against organized crime in Sicily. The analysis shows how the emergence of ethical tourist practices that exploit opportunities and the potential of a disadvantaged area generate various positive effects (economic, social, cultural and symbolic) on the territory, on the local community and tourists, also thanks to a full enhancement of the educational function of the travelling. The cases highlight that: i) human values have a central role both in the development of the entrepreneurial idea and in the contribution to the personal growth of visitors; ii) tourism can be a tool for promoting social and economic justice in a local community with specific problems.