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Crowd rating is a continuous and public process of data gathering that allows the display of general quantitative opinions on a topic from online anonymous networks as they are crowds. Online platforms leveraged these technologies to improve predictive tasks in marketing. However, we argue for a different employment of crowd rating as a tool of public utility to support social contexts suffering to adverse selection, like tourism. This aim needs to deal with issues in both method of measurement and analysis of data, and with common biases associated to public disclosure of rating information. We propose an evaluative method to investigate fairness of common measures of rating procedures with the peculiar perspective of assessing linearity of the ranked outcomes. This is tested on a longitudinal observational case of 7 years of customer satisfaction ratings, for a total amount of 26.888 reviews. According to the results obtained from the sampled dataset, analysed with the proposed evaluative method, there is a trade-off between loss of (potentially) biased information on ratings and fairness of the resulting rankings. However, computing an ad hoc unbiased ranking case, the ranking outcome through the time-weighted measure is not significantly different from the ad hoc unbiased case. [ABSTRACT FROM AUTHOR]

Multiverse analysis involves systematically sampling a vast set of model specifications, known as a multiverse, to estimate the uncertainty surrounding the validity of a scientific claim. By fitting these specifications to a sample of observations, statistics are obtained as analytical results. Examining the variability of these statistics across different groups of model specifications helps to assess the robustness of the claim and gives insights into its underlying assumptions. However, the theoretical premises of multiverse analysis are often implicit and not universally agreed upon. To address this, a new formal categorisation of the analytical choices involved in modelling the set of specifications is proposed. This method of indexing the specification highlights that the sampling structure of the multiversal sample does not conform to a model of independent and identically distributed draws of specifications and that it can be modelled as an information network instead. Hamming's distance is proposed as a measure of network distance, and, with an application to a panel dataset, it is shown how this approach enhances transparency in procedures and inferred claims and that it facilitates the check of implicit parametric assumptions. In the conclusions, the proposed theory of multiversal sampling is linked to the ongoing debate on how to weigh a multiverse, including the debate on the epistemic value of crowdsourced multiverses. [ABSTRACT FROM AUTHOR]

Tracheobronchial foreign body (TFB) aspiration is an uncommon but potentially life-threatening event. This case report discusses the successful extraction of a metallic screw aspirated by a 48-year-old woman with intellectual disability, using flexible bronchoscopy through the i-gel® laryngeal mask under general anesthesia. The i-gel® device proved effective in maintaining airway access and facilitating bronchoscopy, emphasizing its utility in challenging cases. The report underscores the significance of careful assessment, skillful intervention, and multidisciplinary teamwork in managing TFB aspirations, especially in uncooperative patients with comorbidities. [ABSTRACT FROM AUTHOR]

To summarize the current knowledge of the clinical impact of Stenotrophomonas maltophilia (SM) in cystic fibrosis (CF) patients. A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline recommendations, was performed through searches in PubMed and EMBASE databases, and CF National and International Registries websites from 2000 to 2022. Overall, 184 articles were initially retrieved, out of which 15 were selected and included in the review. Data form 6 Registries and 9 pertinent articles from the references of the studies selected were also considered, resulting in 30 studies in total. The prevalence of SM in patients with CF is increasing in Europe while it is declining in North America. The role of chronic colonization of SM on lung function and clinical status in CF patients is still under debate. The most recent studies suggested a pathogenic role of SM chronic infections in CF patients with an acceleration in lung function decline, an increase in hospitalization rates and an association with co-infection. Reflecting the uncertainty about the role of SM in CF, little is available about antibiotic therapeutic strategies for both acute exacerbations and chronic infections. Antimicrobial therapy should be performed in the acute exacerbations, while it may be reasonable to attempt eradication when the first colonization is identified. Nevertheless, it is not established which antibiotic regimen should be preferred, and overtreatment could contribute to the selection of antimicrobial-resistant strains. Further studies are warranted in this regard. [ABSTRACT FROM AUTHOR]

Assessing wildlife health in remote regions requires a multi-faceted approach, which commonly involves convenient samplings and the need of identifying and targeting relevant and informative indicators. We applied a novel wildlife health framework and critically assessed the value of different indicators for understanding the health status and trends of an endangered tundra caribou population. Samples and data from the Dolphin and Union caribou herd were obtained between 2015 and 2021, from community-based surveillance programs and from captured animals. We documented and categorized indicators into health determinants (infectious diseases and trace elements), processes (cortisol, pathology), and health outcomes (pregnancy and body condition). During a recent period of steep population decline, our results indicated a relatively good body condition and pregnancy rates, and decreasing levels of stress, along with a low adult cow survival. We detected multiple factors as potential contributors to the reduced survival, including Brucella suis biovar 4, Erysipelothrix rhusiopathiae and lower hair trace minerals. These results remark the need of targeted studies to improve detection and investigations on caribou mortalities. We also identified differences in health indicators between captured and hunter sampled caribou, highlighting the importance of accounting for sampling biases. This integrative approach that drew on multiple data sources has provided unprecedented knowledge on the health in this herd and highlights the value of documenting individual animal health to understand causes of wildlife declines. [ABSTRACT FROM AUTHOR]

The 92/43/EEC Habitats Directive is the main European Union legal tool concerning nature conservation. The habitat types listed in Annex I to the Directive are phytosociology-based. It is widely acknowledged that phytosociological analysis is a crucial approach for habitats characterization and for monitoring their conservation status. Based on bibliographic investigations and new field survey campaigns, a list of habitat types neglected by the Habitats Directive is here presented and described for southern Italy. In this paper, 8 new habitat types and 13 subtypes are proposed. For each of these proposed new habitat types, a wide range of information, including ecology, chorology, species composition, syntaxonomy, threats, and conservation status, is here provided. To supply more detailed phytogeographical and coenological information about the proposed new habitat types, distribution maps based on 10 × 10 km reference grids and phytosociological tables including unpublished relevés were carried out. [ABSTRACT FROM AUTHOR]

Peatland ecosystems are a highly effective long-term carbon sink. However, the CO2 fluxes could be substantially altered by climate changes and the fate of carbon stored in these ecosystems is still uncertain. Currently, most studies concerning the carbon fluxes in peatlands were performed at high latitude sites, where these ecosystems are more widely distributed compared to temperate regions, where peatlands are less frequent and, in addition to climate pressure, increasingly threatened by human activities. However, the information we have on these peatlands is very scarce. To fill this knowledge gap, we studied CO2 fluxes in an alpine peatland, through light and dark incubations. Using the natural variation in ecological conditions, we identified the main drivers of CO2 fluxes, considering in particular their interactions and covariation. Ecosystem respiration and gross primary production were primarily stimulated by the lowering of the water table and the amount of photosynthetic radiation, respectively, whereas net ecosystem CO2 exchange showed greater variation along the growing season. The influence on CO2 fluxes of the interactions between the drivers investigated, including soil temperature and moisture as well as vegetation type and plant functional diversity, was found to be of pivotal importance. Finally, a substantial part of the variation in CO2 emission and uptake processes was regulated by the joint variation of atmospheric and edaphic factors. To understand and predict the CO2 dynamics of alpine peatlands, it is necessary to consider the interplays among ecological factors, especially in relation to the expected changes in climate and vegetation. [ABSTRACT FROM AUTHOR]

Zone Umide della Capitanata, located in the northeastern part of the Apulia Region, is one of the most extensive coastal wetlands of the Italian peninsula and one of the largest components of the Mediterranean wetland system. Despite its high ecological importance, this site has been undergoing a variety of pressures intensified in recent decades. This study analyzes and evaluates the changes occurred in this area between 2010 and 2020. Land cover and habitat maps were performed by photointerpretation and on-site surveys, and classified according to the FAO-LCCS and EUNIS taxonomies, respectively. To focus on local dynamics, four subset areas were analyzed separately. A set of landscape metrics was computed to analyze the landscape structure. The anthropogenic pressures affecting the study area were described through the Driving Forces-Pressures-State-Impact-Response (DPSIR) conceptual framework. Numerous changes were identified, deriving from both finest thematic redefinition and anthropogenic pressures. Both class conversions and class modifications were identified and quantified by means of transition matrices. Most of the observed conversions were borne by classes belonging to saltmarshes and to coastal dune systems. In particular, landscape configuration of coastal dune classes was well highlighted by a set of specific landscape metrics. Agriculture practices and changes in water flow pattern turned out to be the main driving forces exerting pressures on these natural systems. Significant differences were found between the four subsets under analysis, thus indicating that different management strategies lead to different levels of conservation. [ABSTRACT FROM AUTHOR]

The article titled "Comparison of Histological Skin Changes After Massive Weight Loss in Post-Bariatric and Non-Bariatric Patients" by Hany et al. compares the histomorphological differences between patients who underwent bariatric metabolic surgery and those who underwent dietary intervention. Previous studies have found anomalies in dermal elastic and collagen fibers after biliopancreatic diversion and gastric bypass surgery. Plastic surgeons performing bariatric procedures often face a high wound complication rate, and the origin of these complications is believed to be multifactorial. The study suggests that different surgical techniques may have different effects on skin structure and wound healing. However, the specific type of weight loss surgical procedure was not considered in the analysis. Further research is needed to investigate this aspect and determine the best approach to prevent wound dehiscence after bariatric surgery. [Extracted from the article]

Previous research yielded conflicting results on the association between cigarette smoking and risk of SARS-CoV-2 infection. Since the prevalence of smoking is high globally, the study of its impact on COVID-19 pandemic may have considerable implications for public health. This study is the first to investigate the association between the SARS-CoV-2 antibody sero-positivity and biochemically verified smoking status, to refine current estimates on this association. SARS-CoV-2-specific IgG and serum cotinine levels (a well-known marker of tobacco exposure) were assessed in a large sero-epidemiological survey conducted in the town of Troina (Sicily, Italy). A propensity score matching was carried out to reduce the effect of possible factors on SARS-CoV-2 infection risk among study participants. Of the 1785 subjects included in our study, one-third was classified as current smokers, based on serum cotinine levels. The overall proportion of subjects with positive serology for SARS-CoV-2 IgG was 5.4%. The prevalence of SARS-CoV-2 antibody positivity and previous COVID-19 diagnosis were reduced in smokers. This reduced prevalence persisted after adjusting for possible confounders (such as sex, age, previous infection, chronic conditions, and risk group) at regression analyses, and the point estimates based on the PS-matched models resulted consistent with those for the unmatched population. This study found a lower proportion of positive SARS-CoV-2 serology among current smokers, using direct laboratory measures of tobacco exposure and thus avoiding possible bias associated with self-reported smoking status. Results may also serve as a reference for future clinical research on potential pharmaceutical role of nicotine or nicotinic-cholinergic agonists against COVID-19. [ABSTRACT FROM AUTHOR]

It may present with a variable combination of ataxia, dementia, psychosis, and movement disorders including chorea, dystonia, and parkinsonism [[1]]. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant spinocerebellar ataxia (SCA) caused by CAG/CAA expansion in exon 3 of the TBP gene (TATA-box-binding protein gene), located in chromosome 6. [Extracted from the article]

Better models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor. The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation. [ABSTRACT FROM AUTHOR]

Climate-induced relocation is expected to become an adaptive response for one sector of the society that is otherwise already in a vulnerable situation and often living in remote areas, that is, Indigenous Peoples. Several Latin American countries have referred to planned relocation or managed retreat as one of their adaptation strategies within their Nationally Determined Contributions to the United Nations Framework Convention on Climate Change. However, a gap in academic analysis exists regarding not only the potential impacts but also the consequences of climate-induced planned relocations both in the broader context of Latin America and in the specific case of Indigenous Peoples living in that region. In addition, academia has so far underexplored the adverse impacts of managed retreat on Indigenous Peoples, such as the loss of a sense of community, culture, and traditional knowledge. Against this background, this article offers an overview on two key cases of climate-induced (planned) relocation of Indigenous Peoples in Latin America and the Caribbean (the Gunayala people in the San Blás archipelago in Panama and the case of the densely Indigenous-inhabited Mexican state of Chiapas), explores whether managed retreat has been or may become a tool or a threat, and provides a list of specific policy recommendations to be taken into consideration in similar cases. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) patients often express significant behavioral symptoms: for this reason, accessible related biomarkers could be very useful. Neuroinflammation is a key pathogenic process in both AD and delirium (DEL), a clinical condition with behavioral symptoms resembling those of AD. Methods: A total of n = 30 AD patients were recruited together with n = 30 DEL patients and n = 15 healthy controls (CTRL). Serum diazepam binding inhibitor (DBI), IL-17, IL-6, and TNF-α were assessed by ELISA. Results: DBI serum levels were increased in AD patients with respect to CTRL (+ 81%), while DEL values were 70% higher than AD. IL-17 was increased in DEL with respect to CTRL (+ 146%), while AD showed dispersed values and failed to reach significant differences. On the other hand, IL-6 showed a more robust increase in DEL with respect to the other two groups (+ 185% and + 205% vs. CTRL and AD, respectively), and TNF-α failed to show any change. Conclusions: DBI may be a very promising candidate for AD, perhaps marking psychomotor DEL-like symptoms, in view of developing future helping tool for practicing physicians. Furthermore, DBI rise in DEL offers novel cues for a better comprehension of the pathogenesis of this potentially fatal condition. [ABSTRACT FROM AUTHOR]

In the analysis of the difference in the distribution and profiles of the equitable and sustainable well-being, the territorial dimension is a fundamental reading-key for local policies since it allows the areas of advantage or relative deprivation to emerge more accurately. Specifically, in Italy the provincial level coincides with the administrative area of metropolitan cities, which are the subject of growing attention from European and national policies. The BES 2018 report by Italian National Institute of Statistics (ISTAT) has confirmed that from 2015 an improvement in many areas of well-being has been marked, even if territorial differences remain stable both in levels and dynamics. These differences appear in some cases as real structural differences between the North and South of Italy. Then, the measures of equitable and sustainable well-being in the territories allow, in various degrees, to deepen and specify this situation employing synthetic measures of well-being. In this work, we propose a statistical methodology focused on the simultaneous partial least squares structural equation modeling and simultaneous K-means clustering to obtain a composite indicator of Italian well-being and at the same time a classification of Italian territorial micro-areas by means of the just updated provincial data about BES 2018. In this way, the territorial differences of well-being can be more reliably and more exactly defined on the basis of the relationships among all elementary indicators and domains proposed in the analysis of well-being by ISTAT. [ABSTRACT FROM AUTHOR]

In recent years we have witnessed a growing concern in scientific research to understand and improve actionable analytics-driven decision processes, mostly focused on online data. Many researchers have focused their attention on computational and Information and Communications Technology issues in this matter. Only a small share of literature is concerned with how indicators can be improved by Big Data analytics. In this paper, we propose an innovative methodological approach to building indicators by combining Big Data analytics with the analysis of network patterns. Our study aims to define relational structures in a Big Data set, implementing measurements and clustering methods by Network Analysis in order to build decision-making indicators. We describe an audience model both to collect a large amount of online data from large online newspapers and to structure those in a relational form. By analysing readers' comments, we can derive proxies of reliable indicators about specific topics discussed on an online newspaper blog. We show the effectiveness of such an approach in detecting and building indicators to support policy-makers in complex decision-making processes. [ABSTRACT FROM AUTHOR]

Background: Because of the increasing demand for drugs addressing life-threatening and rare diseases, regulatory agencies have developed a variety of accelerated regulatory pathways. These programs are aimed at prioritizing the most promising drug candidates for diseases lacking satisfactory treatments. The most prominent accelerated programs introduced have been Breakthrough-Therapy Designation (BTD) in the United States, Priority Medicine (PRIME) in the European Union and Sakigake in Japan. This article reviews these designations and looks at differences in how they are granted across the 3 jurisdictions focusing on neuroscience and oncology. Methods: Our objective was to analyze BTD, PRIME, and Sakigake approvals between 2012 and 2019 with a focus on numerical disparities of designations granted between the 2 therapeutic areas. A search of public sources pertaining to topics of BTD, PRIME, and Sakigake was undertaken. Results: This analysis revealed that 48% of BTD were granted in oncology, while neuroscience received 8% of these designations, for PRIME designations were 27% received by oncology and 15% by neuroscience and in Japan, 50% of Sakigake were granted to oncology and 22% to neuroscience products. Conclusion: Given the global nature of drug development and relative similarity of these regulatory mechanisms, there is an apparent disparity between the US granting special status at 6:1 (oncology: neuroscience) and both the EU and Japan granting at 2:1. This disproportionate ratio is likely impacted by multifactorial issues; however, this difference is worth further investigation. [ABSTRACT FROM AUTHOR]

High-elevation habitats host a large number of plant species and are characterized by high biodiversity. The vegetation dynamics in these cold adapted ecosystems are difficult to predict, being affected by global warming, especially in the last decades. With the aim to promote a better understanding of climate-driven changes of alpine vegetation, we investigated the variation in species richness, α-diversity, β-diversity, and total cover of plant functional types over a time lapse of 15 years, relying on multiple re-surveys of mountain summit vegetation in 2001, 2008 and 2015. The study area, included in the long term global observation network GLORIA, was at the boundary between temperate and Mediterranean mountains of S-Europe (northern Apennines, Italy). We identified a trend of loss in biodiversity and signals of biotic homogenization using multiple diversity metrics, despite the overall species richness increment observed in the study area. Cold-adapted and rare species declined while dominant species like graminoids and shrubs increased. Our results highlight that long-term vegetation monitoring activities paired with multiple measures of diversity are required to properly assess biodiversity and to obtain useful indications for future conservation activities in alpine environments. The methods here presented could be applied in all GLORIA sites to quantify biodiversity changes over time, obtaining comparable results for biodiversity monitoring in high-elevation habitats from all over the world. [ABSTRACT FROM AUTHOR]

Brucella serostatus was evaluated in 3189 muskoxen sampled between 1989 and 2016 from various locations of the Canadian Arctic archipelago and mainland, near the communities of Sachs Harbour and Ulukhaktok, Northwest Territories, and Cambridge Bay and Kugluktuk, Nunavut. Brucella antibodies were found only in muskoxen sampled around Cambridge Bay, both on southern Victoria Island and on the adjacent mainland (Kent Peninsula). Consistent with participatory epidemiology data documented from local harvesters describing increased Brucella-like syndromes (swollen joints and lameness) and a decreased proportion of juveniles, the apparent Brucella seroprevalence in the sampled muskoxen of the Cambridge Bay area increased from 0.9% (95% CI 0.3–2.1) in the period of 1989–2001 to 5.6% (95% CI 3.3–8.9) in 2010–2016. The zoonotic bacteria Brucella suis biovar 4 was also cultured from tissues of muskoxen sampled on Victoria Island near Ulukhaktok in 1996 (n = 1) and Cambridge Bay in 1998, 2014, and 2016 (n = 3). Overall, our data demonstrate that B. suis biovar 4 is found in muskoxen that are harvested for food and by guided hunts on Victoria Island and Kent Peninsula, adding an important public health dimension to this study. Robust participatory epidemiology data on muskox health and diseases greatly enhanced the interpretation of our Cambridge Bay data and, combined with the serological and microbiological data, provide compelling evidence that the prevalence of B. suis biovar 4 has increased in this area since the late 1990s. This study enhances the available knowledge on Brucella exposure and infection in muskoxen and provides an example of how scientific knowledge and local knowledge can work together to better understand disease status in wildlife. [ABSTRACT FROM AUTHOR]

Video stabilization is a technique used to compensate user hand shaking. It avoids grabbing the unintentional motion in a video sequence, which causes unpleasant effects for the final user. In this paper we present a very simple but effective low power consumption solution, suitable for cheap and small video cameras, running at 31 fps for a VGA sequence with a simple ARM926EJ-S. The proposed solution is robust to common difficult conditions, like noise perturbations, illumination changes, motion blurring and rolling shutter distortions. [ABSTRACT FROM AUTHOR]

Soluble Aβ oligomers are widely recognized as the toxic forms responsible for triggering AD, and Aβ receptors are hypothesized to represent the first step in a neuronal cascade leading to dementia. Cellular prion protein (PrP) has been reported as a high-affinity binder of Aβ oligomers. The interactions of PrP with both Aβ42 and the highly toxic N-truncated pyroglutamylated species (AβpE3-42) are here investigated, at a molecular level, by means of ThT fluorescence, NMR and TEM. We demonstrate that soluble PrP binds both Aβ42 and AβpE3-42, preferentially interacting with oligomeric species and delaying fibril formation. Residue level analysis of Aβ42 oligomerization process reveals, for the first time, that PrP is able to differently interact with the forming oligomers, depending on the aggregation state of the starting Aβ42 sample. A distinct behavior is observed for Aβ42 1-30 region and C-terminal residues, suggesting that PrP protects Aβ42 N-tail from entangling on the mature NMR-invisible fibril, consistent with the hypothesis that Aβ42 N-tail is the locus of interaction with PrP. PrP/AβpE3-42 interactions are here reported for the first time. All interaction data are validated and complemented by cellular tests performed on Wt and PrP-silenced neuronal cell lines, clearly showing PrP dependent Aβ oligomer cell internalization and toxicity. The ability of soluble PrP to compete with membrane-anchored PrP for binding to Aβ oligomers bears relevance for studies of druggable pathways. [ABSTRACT FROM AUTHOR]

Out of hours (OOH) doctors can have an important gate-keeping role over the access to the emergency department (ED), but the outcome and the quality of their ED referrals have been poorly studied. We aimed to investigate the outcome of patients referred to ED from OOH service and the determinants of admission or short-stay dispositions. We collected retrospectively data about referrals to ED from a local OOH service in the north-east of Italy using the OOH paper register and the ED electronic database, over the period of 01/10/2012 to 31/03/2013. Out of 5217 patients accessing the OOH service, 408 referrals were included in our analysis. 45.3% (185) of the referrals were admitted to hospital or the short-stay unit, 26 patients (=6.4%) were discharged as non-urgent outgoing codes after no specialist consultation or test, suggesting inappropriate referrals, and, of the remaining 197 (=48%), only 10 did not undergo any investigation or consultation. Significant determinants of admission were: age ≥65 years (OR = 2.619; 95% CI 1.528-4.491, p < 0.0001), domiciliary examination (OR = 2.168; 95% CI 1.353-3.476, p = 0.001), nursing home/palliative care setting (OR = 2.563; 95% CI 1.228-5.351, p = 0.012) and OOH triage code, ranging from an OR of 7.47 (95% CI 3.028-18.433) for minor urgencies to an OR of 26.835 (95% CI 6.761-106.508, p < 0.0001) for emergencies, in comparison to no urgent codes. OOH service seems to play an effective gate-keeping role limiting ED access. Determinants of admission to hospital suggest some simple interventions that could improve the adequacy of ED referral from OOH service. [ABSTRACT FROM AUTHOR]

Abstract: Chemical inhibition of chromatin-mediated signaling involved proteins is an established strategy to drive expression networks and alter disease progression. Protein methyltransferases are among the most studied proteins in epigenetics and, in particular, disruptor of telomeric silencing 1-like (DOT1L) lysine methyltransferase plays a key role in MLL-rearranged acute leukemia Selective inhibition of DOT1L is an established attractive strategy to breakdown aberrant H3K79 methylation and thus overexpression of leukemia genes, and leukemogenesis. Although numerous DOT1L inhibitors have been several structural data published no pronounced computational efforts have been yet reported. In these studies a first tentative of multi-stage and LB/SB combined approach is reported in order to maximize the use of available data. Using co-crystallized ligand/DOT1L complexes, predictive 3-D QSAR and COMBINE models were built through a python implementation of previously reported methodologies. The models, validated by either modeled or experimental external test sets, proved to have good predictive abilities. The application of these models to an internal library led to the selection of two unreported compounds that were found able to inhibit DOT1L at micromolar level. To the best of our knowledge this is the first report of quantitative LB and SB DOT1L inhibitors models and their application to disclose new potential epigenetic modulators.Graphical Abstract: [ABSTRACT FROM AUTHOR]

The most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity. [ABSTRACT FROM AUTHOR]

Purpose: The functional role of the FSHR promoter −29G/A polymorphism (rs1394205) in men is not clear. Some studies failed to find a relationship between the FSHR −29G/A and follicle-stimulating hormone (FSH) levels and did not associate the SNP with male infertility. Only one study showed that the FSHR −29 SNP modulates serum FSH levels in Baltic young male cohort. Because the SNP −29G/A has to be shown to have a strong effect on in vitro transcription activity of the FSHR promoter and the activation of FSHR is necessary for a normal FSH function, this study was undertaken to assess whether the FSHR -29G/A SNP modulates the gonadal endocrine function in men. Methods: A total of 200 men with alteration of conventional sperm parameters or normozoospermia (according to the parameters WHO 2010), were genotyped by TaqMan Assay. Hormone levels were measured by immunoassay, and sperm analysis was performed according to the World Health Organization criteria. Results: A significant gradient of increasing FSH levels across the FSHR −29G/A genotypes was observed ( p < 0.01). Among normozoospermic men ( n = 110), those with FSHR −29A-allele carriers (GA + AA and AA) had higher serum FSH ( p < 0.01) and LH levels ( p < 0.05) and higher body mass index (BMI) ( p < 0.01) compared to men with the GG genotype. The carrier status of rs1394205 genotypes did not affect the other endocrine parameters neither in men with altered sperm parameters nor in normozoospermic men. Conclusions: The FSHR −29G/A polymorphism modulates FSH and, for the first time, LH serum levels and BMI in normozoospermic men. These findings underline the importance to pay close attention to the studies of genetic variations associated with clinical-endocrine parameters. [ABSTRACT FROM AUTHOR]

This is a note about early attempts of Salicornia patula Duval-Jouve cultivation in the northern part of Apulia region (southern Italy). This species, which occupies the driest parts along the edges of coastal lagoons on mudflats or sands that are inundated in winter, has a long history of gathering from the wild as a source of food. At our knowledge, no information has been reported about the domestication of S. patula in Italy. In the Gargano area of Apulia region, this species was domesticated forty years ago as a minor cultivation limited to private gardens. The growing market demand of this vegetable for both fresh consumption and for processing packinghouses is very recently encouraging some farmers to cultivate it for marketing. S. patula might become an attractive new cash crop for marsh marginal lands, but prerequisites to its success are the selection of superior genotypes and the set-up of its right agro-technique. [ABSTRACT FROM AUTHOR]

Purpose: The FSHB gene -211G/T polymorphism has been reported to modulate gene expression and to cause inter-individual differences in FSH serum levels in men. This study was undertaken to assess the functional relevance of this polymorphism on gonadotropin and total testosterone serum levels and sperm parameters in men from Eastern Sicily (Italy). Methods: To accomplish this, 200 men with abnormal conventional sperm parameters or normozoospermia (according to the parameters of WHO 2010) were genotyped by TaqMan Assay. Results: The frequency of FSHB -211 T allele was significantly higher ( p < 0.005) in patients with altered conventional sperm parameters (18.9% of chromosomes) compared to that observed in men with normozoospermia (10.9% of chromosomes). Decreasing serum levels of FSH and LH were observed across the three FSHB -211 genotype subgroups ( p < 0.001 and p < 0.05, respectively). In addition, the FSHB -211G/T polymorphism showed a total testosterone downward trend that became more evident in men with the TT genotype compared to subjects with the GG genotype ( p = 0.05). Furthermore, we found a trend towards decreased sperm concentration, total sperm count, sperm forward motility and testicular volume in men with GT and TT genotypes. Conclusions: These findings showed that the FSHB -211 G/T polymorphism modulates male gonadal function with a clear influence on hormonal levels and sperm parameters. Capsule: The present study was undertaken to evaluate the distribution of the FSHB -211 G/T in men with normal or abnormal sperm parameters from Southern Italy to assess its functional relevance on the serum levels of reproductive hormones and on sperm parameters in men. [ABSTRACT FROM AUTHOR]

Alpine snowbed communities are among the habitats most threatened by climate change. The warmer temperature predicted, coupled with advanced snowmelt time, will influence flowering phenology, which is a key process in species adaptation to changing environmental conditions and plant population dynamics. However, we know little about the effects of changing micro-climate on flowering time in snowbeds and the mechanisms underlying such phenological responses. The flowering phenology of species inhabiting alpine snowbeds was assessed with weekly observations over five growing seasons. We analysed flowering time in relation to micro-climatic variation in snowmelt date, soil and air temperature, and experimental warming during the snow-free period. This approach allowed us to test hypotheses concerning the processes driving flowering phenology. The plants were finely tuned with inter-annual and intra-seasonal variations of their micro-climate, but species did not track the same micro-climatic feature to flower. At the growing-season time-scale, the air surrounding the plants was the most common trigger of the blooming period. However, at the annual time-scale, the snowmelt date was the main controlling factor for flowering time, even in warmer climate. Moreover, spatial patterns of the snowmelt influenced the developmental rate of the species because in later snowmelt sites the plants needed a lower level of heat accumulation to enter anthesis. Phenological responses to experimental warming differed among species, were proportional to the pre-flowering time-span of plants, and did not show consistent trends of change over time. Finally, warmer temperature produced an overall increase of flowering synchrony both within and among plant species. [ABSTRACT FROM AUTHOR]

The coastal dunes of the Mediterranean area are among the most vulnerable and seriously threatened ecosystems due to human activities. Habitat fragmentation is generally considered as one of the most influential factors in biodiversity loss. In this paper, we investigated the temporal and spatial changes in the floristic composition and abundance in sand dunes along a coastal strip of Sicily (Italy). Six transects perpendicular to the coastal line were selected in southern Sicily. For each transect, the floristic composition and cover of the species were determined using standard relevé methods. A total of 186 plots were collected. The plots data was analyzed using classification (UPGMA, Chord coefficient) and ordination methods (Detrended Correspondence Analysis). A total of 14 plant communities with specific floristic composition were established, belonging mainly to six habitats. To evaluate the reduction of the habitats of the complex dune system in the last 70 years, aerial photos from 1938 to 2007 have been used and elaborated with ArcGis 10.3. The cartographic analysis shows a radical transformation of the Macconi dune system with a reduction of the dune habitats. In particular, the results show a strong reduction/loss of habitats (2250, 2210 and 2120 EU code) as well as a strong alteration of the ecological succession of the psammophilous vegetation. Moreover, floristic richness and diversity index showed an increased trend from the coastal line towards inner dunal zone. [ABSTRACT FROM AUTHOR]

During the last decades, a significant warming was observed in the Alps, cascading into a decrease in snowfall and snow-cover duration. Within the alpine landscape, snowbed communities are regarded as especially vulnerable to the predicted warmer temperatures and earlier snowmelt time. Albeit snowbeds represent a prominent component of the tundra biome, the current vegetation dynamics of these habitats are not yet well understood. In this study, the changes of vascular species richness, co-occurrence, composition, and abundance were evaluated within a late snowbed in the south-eastern Alps. The study was based on a re-survey of 11 permanent plots after a 6-year period. Species richness and abundance significantly increased and species co-occurrence shifted toward higher species segregation. Moreover, the changes in species richness at different spatial scales were related to different environmental factors, and a change in the proportion between snowbed and non-snowbed plants was found. The results suggest an increasing importance of competitive interaction among species in determining the future structure and composition of this community. In conclusion, there is strong evidence that this snowbed community is not in equilibrium with the current climate, and that changes in floristic composition and functional processes of this habitat are underway. [ABSTRACT FROM AUTHOR]