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β-lactoglobulin I (β-Lg I) is one of the most important whey proteins in donkey milk. However to our knowledge, there has been no study focusing on the full nucleotide sequences of this gene (BLG I). Current investigation of donkey BLG I gene is very limited with only two variants (A and B) characterized so far at the protein level. Recently, a new β-Lg I variant, with a significantly higher mass (+1915 Da) than known variants has been detected. In this study, we report the whole nucleotide sequence of the BLG I gene from two donkeys, whose milk samples are characterized by the β-Lg I SDS-PAGE band with a normal electrophoretic mobility (18,514.25 Da, β-Lg I B1 form) the first, and by the presence of a unique β-Lg I band with a higher electrophoretic mobility (20,428.5 Da, β-Lg I D form) the latter. A high genetic variability was found all over the two sequenced BLG I alleles. In particular, 16 polymorphic sites were found in introns, one in the 5’ flanking region, three SNPs in the 5’ untranslated region (UTR) and one SNP in the coding region (g.1871G/A) located at the 40th nucleotide of exon 2 and responsible for the amino acid substitutions p.Asp28>Asn in the mature protein. Two SNPs (g.920-922CAC>TGT and g.1871G/A) were genotyped in 93 donkeys of two Italian breeds (60 Ragusana and 33 Amiatina, respectively) and the overall frequencies of g.920-922CAC and g.1871A were 0.3065 and 0.043, respectively. Only the rare allele g.1871A was observed to be associated with the slower migrating β-Lg I. Considering this genetic diversity and those found in the database, it was possible to deduce at least five different alleles (BLG I A, B, B1, C, D) responsible for four potential β-Lg I translations. Among these alleles, B1 and D are those characterized in the present research, with the D allele of real novel identification. Haplotype data analysis suggests an evolutionary pathway of donkey BLG I gene and a possible phylogenetic map is proposed. Analyses of mRNA secondary structure showed relevant changes in the structures, as consequence of the g.1871G>A polymorphism, that might be responsible for the recognition of an alternative initiation site providing an additional signal peptide. The extension of 19 amino acids sequence to the mature protein, corresponding to the canonical signal peptide with an additional Alanine residue, is sufficient to provide the observed molecular weight of the slower migrating β-Lg I encoded by the BLG I D allele

Background: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. Aim: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the “Delirium Day project”. Methods: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the “Delirium Day project” (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Results: Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17–1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08–2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62–2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10–1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02–1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68–3.36, p value < 0.0001). Conclusion: This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

Robotic rovers equipped with articulated rocker-bogie suspension have aroused great interest after the explorations on Mars; this interest has also shifted to different types of terrestrial applications such as in the agriculture, military, and rescue fields. The suspension can be designed so that, when the rover is on flat and horizontal ground, the weight is evenly distributed among the wheels; in this way, all wheels have the same traction capability and offer the same rolling resistance. As the operating conditions vary due to sloping ground, uneven ground surface, or different payload position, the weight distribution can undergo considerable variations. This type of suspension is statically determined with respect to weight, but it is indeterminate with respect to traction forces; the traction control system aims to avoid the wheels slippage. In this paper, the traction contribution that each wheel can provide, to overcome a step obstacle, is shown. Furthermore, the possibility of regulating the distribution of vertical loads among the wheels adopting a torsion spring, with adjustable preload, arranged between rocker and bogie, is evaluated. A suitable spring preload facilitates the initial phase of the obstacle overcoming if the rover advances with the bogie forward. Numerical simulations show that to increase the possibility of overcoming an obstacle it is sufficient for the spring preload to reduce the vertical load on the front wheel; in any case, a higher load variation would not be advisable as it could involves an excessive load difference among the wheels.

The employment of mobile robots, remotely or autonomously controlled for field operations, is an emerging topic. The development of suitable simulation models can aid the design and testing of such mobile robots. Here a small commercial prototype of a Rocker-Bogie Rover has been employed in experimental tests compared to simulations on a multibody model. In particular, the tests have dealt with the acquisition and processing of accelerometer signals both on experimental prototype and in simulation environment. The paper proposes a real time signal processing approach that could aid the motion planning and rover navigation control.

Background: Celiac disease (CD) is still underestimated. To close this diagnostic gap, the Health Sicilian Authorities have constituted the "Sicilian Network for CD". Aims: A) To verify the quality of the current diagnostic approach using the data sheet of the Network. B) To evaluate the clinical, serologic and histologic data of new diagnoses in the context of the Network METHODS: We retrospectively evaluated the data collection forms of 369 patients with CD from three Centers within the Sicilian Network. All the Centers used a standard data collection form. Results: A non-classical CD presentation was more frequent than the classical one, anemia being the most frequent symptom (50%). An IBS-like presentation was found in one third of the cases. A diagnostic delay of about 9 years following the onset of symptoms was observed. Almost half of the patients had not undergone multiple duodenal biopsies; unrecommended CD serology assays were prescribed in 59.9% of the cases. Conclusions: The regional data sheets allowed an assessment of the diagnostic delay. We recorded a frequent use of unrecommended tests prescribed before referring patients to the regional Centers. Updating the education of physicians regarding CD is necessary to avoid unwarranted health expenditure.

The dog was probably the first domesticated animal. Despite extensive archaeological and genetic investigations, the origin and the evolution of the extant dogs are still being debated. Dog breeds that have over time been selected for hunting share common ancestral traits. This study represents the first comprehensive attempt to survey at the genomic and mitochondrial level eight hound-like dogs breeds indigenous to the Mediterranean Basin to determine if they share common ancient origins. Results from the microsatellite analysis indicate that all the dog populations have a low inbreeding value.The Kelb tal-Fenek has a high divergence from the current Egyptian street population, however there is not enough evidence from this study to exclude completely the potential of an ancient common relationship. Overall, the mitochondrial results indicate high frequencies of haplogroups A and B and a low representation of haplogroup C, while only one Egyptian dog could be assigned to haplogroup D. Results reveal identities and shared clades, suggesting the conservation of ancient European mitotypes in the Mediterranean hound-like breeds, especially in the Egyptian population. Although none of the dog populations/breeds participating in this study indicate to be direct descendants of the Egyptian dogs, they still have a very close morphologically resemblance to those iconic Egyptian dogs often depicted in ancient art forms and share some genetic links with the current Egyptian population. Further research is required with other markers such us complete mitogenomes and SNP panels to confirm the complex history of the Mediterranean dogs involved in this study.

A covid19 gerou uma crise mundial em vários setores, dentre eles podemos destacar o setor da educação. A solução em muitos casos foi o ensino remoto para manter a regularidade do ensino. O Instituto Alberto Luiz Coimbra de Pós-Graduação e Investigação em Engenharia (COPPE) da Universidade Federal do Rio de Janeiro (UFRJ) foi uma das instituições que adotou essa medida. O Instituto acreditava que os estudantes preferiam estar a salvo de epidemias, uma vez que o seu equilíbrio emocional seria preservado enquanto prosseguiam os seus estudos. Analisando este cenário, foi possível avaliar a qualidade do ensino remoto e como essa mudança afetou os estudantes na dimensão intelectual. A Lógica Fuzzy possibilita a análise de modelos dinâmicos aplicados à realidade e desta forma contribuiu para a avaliação da Qualidade de Vida dos estudantes de ensino remoto, por meio da coleta de dados a partir de um questionário aplicado aos estudantes de uma turma do Programa de Engenharia de Produção da COPPE/UFRJ. Por fim, podemos afirmar, a partir dos resultados obtidos, que este modelo pode ser considerado uma boa ferramenta de avaliação.

Adolescentes e jovens encontram diferentes formas de se evadirem da cena do mundo. No contexto contemporâneo, encontramos os suicídios lentos ou ‘não violentos’ a partir do uso de substâncias químicas, da ingestão ou da recusa de alimentos, da exposição a fatores de risco, do suicídio inconscientemente buscado mediante acidentes letais, dentre outros. Neste artigo nos debruçaremos sobre a abordagem psicanalítica do suicídio na adolescência, a partir da localização do tema na obra freudiana e lacaniana, além da discussão de autores contemporâneos.

Jamestown Canyon virus (JCV) is a mosquito-borne arbovirus that circulates in North America. We detected JCV in 4 pools of mosquitoes collected from midcoastal Maine, USA, during 2017-2019. Phylogenetic analysis of a JCV sequence obtained from Aedes cantator mosquitoes clustered within clade A, which also circulates in Connecticut, USA.

Shared decision making (SDM) is recommended for common pediatric conditions; however, there are limited data on measures of SDM in pediatrics. This study adapted the SDM Process scale and examined validity and reliability of the scale for attention-deficit/hyperactivity disorder (ADHD) treatment decisions.Cross-sectional survey of caregivers (n = 498) of children (aged 5-13) diagnosed with ADHD, who had made a decision about ADHD medication in the last 2 years. Surveys included the adapted SDM Process scale (scores range 0-4, higher scores indicate more SDM), decisional conflict, decision regret, and decision involvement. Validity was assessed by testing hypothesized relationships between these constructs. A subset of participants was surveyed a week later to assess retest reliability.Pediatric Caregiver version of the SDM Process scale (M = 2.8, SD = 1.05) showed no evidence of floor or ceiling effects. The scale was found to be acceptable (1% missing data) and reliable (intraclass correlation coefficient = 0.74). Scores demonstrated convergent validity, as they were higher for those without decisional conflict than those with decisional conflict (2.93 vs 2.46, P.001, d = 0.46), and higher for caregivers who stated they made the decision with the provider than those who made the decision themselves (3.0 vs 2.7; P = .003). Higher scores were related to less regret (r = -0.15, P.001), though the magnitude of the relationship was small.The adapted Pediatric Caregiver version of the SDM Process scale demonstrated acceptability, validity and reliability in the context of ADHD medication decisions made by caregivers of children 5-13. Scores indicate pediatricians generally involve caregivers in decision making about ADHD medication.

Supplementary files: Figure S1. The 3D representation of the amino acids 123-137 of αs2-casein is shown in both the normal primary frame (A) and the opposite frame (B), providing the right orientation (Thr-X-Glu) for the casein kinase to perform phosphorylation. Table S1. Amplicons, sequences and annealing temperatures of the primers used for the characterization of CSN1S2 gene in the Old World camels (C. dromedarius and C. bactrianus). Table S2. Inter-species polymorphisms detected by sequencing the CSN1S2 gene in C. bactrianus and C. dromedarius. &nbsp

Marker-less vision techniques represent a promising route in the development of experimental methods to study the kinematic and the dynamic parameters of mechanical systems. The knowledge of a great number of these parameters is a fundamental issue in the system behaviour analysis and represents an even more crucial aspect for underactuated mechanical systems. In this paper, a technique is proposed to identify the kinematics of the phalanges of an underactuated mechanical finger, starting from the acquisition of the finger point cloud data by means of contactless vision system devices. The analytical model identified allows to determine the underactuated finger configuration as function of the shaft rotation of the single motor of the mechanical system.

Calcium-sensitive caseins are the main protein component of milk. In the goat, they are encoded by three genes (CSN1S1, CSN2, and CSN1S2) located on chromosome 6. A high number of alleles has been discovered for these genes in the goat species, responsible for changes in the milk’s qualitative and quantitative characteristics. This study aimed to develop an Allele-Specific PCR (AS-PCR), which allowed us to unequivocally detect goat carriers of the CSN201 allele. Subsequently, the calcium-sensitive casein loci genotype was investigated in three native goat breeds of the Lazio Region (Bianca Monticellana, Capestrina, and Ciociara Grigia). No individuals were carriers of the CSN1S101, CSN1S1E, CSN201, CSN1S2D, and CSN1S20 alleles, while a high frequency of the alleles CSN1S1F and CSN1S1A*,B* was observed. Association analyses between the different genotypes at the CSN1S1 locus and some milk traits, namely the fat and protein yielded and the fat, protein, solids-not-fat, and casein percentages without an effect on the milk yield, were observed.

Background: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. Methods: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. Results: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of −0.62 (95%CI − 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (β = −1.019, 95% CI − 1.827; −0.210, p-value = 0.0135). Conclusions: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy.

Factory acceptance test is the inspection of equipment and components at the supplier’s premises before delivery or final inspection. However, this control can represent a considerable cost for the customer, especially when the manufacturer’s company is geographically far from the customer one and inspections must be frequent. In this paper, the authors present a framework to support the factory acceptance test based on augmented reality (AR) techniques and model-based definition aimed at dimensional checks that does not require the physical presence of the customer at the supplier's premises. The supplier must be previously equipped with an automatic measuring machine. Once the component under inspection is placed inside the machine, this reads the type and the position of the features to be measured along with the related specification limits directly from the annotated 3D model of the component. The results are automatically transmitted to the customer’s site. Through a tablet, the supplier, guided by the customer, reads the results of the measures directly on the measured object through augmented or mixed reality techniques. Any out-of-specification dimension can be remeasured in real time with the customer’s remote assistance using traditional measurement techniques. The proposed architecture, at an advanced stage of experimentation, is discussed with reference to an industrial case study proposed and using an entry level commercial 3D scanner.

Several studies have examined age differences in affective decision-making utilizing the Iowa Gambling Task (IGT). However, findings are mixed, with some studies reporting impairments due to aging and others showing no age-related differences. The few studies that have explored personality correlates of IGT performance suggest that underlying personality characteristics may impact performance on the IGT beyond aging. Therefore, the present study investigated the interplay between chronological age, temporal perspective, and gambling-related cognitions in affective decision-making while controlling for gambling severity. Through snowball sampling, 302 adults aged 18–75 years were recruited. They administered the South Oaks Gambling Screen (SOGS), Consideration of Future Consequences scale (CFC-14), Gambling-Related Cognitions Scale (GRCS), and IGT. Regression analysis showed that future orientation and gambling-related cognitions (namely gambling expectancies, illusion of control, and predictive control) predicted IGT performance. Gender, age, education, and gambling severity were not included in the final model. Path analysis showed that gambling expectancies positively impacted the performance, whereas illusion of control and predictive control were detrimental to decision-making. Being oriented toward the future mitigated the negative effects of the two cognitive biases on IGT performance. The present study shows that aging does not affect negatively IGT performance. The quality of performance appears to depend upon individual characteristics, such as future orientation and gambling-related cognitions, irrespective of gambling severity. These findings suggest that individual characteristics should be considered in the clinical evaluation of IGT performance.

Produced waters (PWs) are oilfield waste streams rich in minerals and hydrocarbons whose production rate is largely increased in last decades following the corresponding increase of energy demand. The high salinity level of PWs inhibits the adoption of cheap biological treatments. Also, desalination techniques based on osmotic membranes would require severe pre-treatments. As an alternative, Reverse ElectroDialysis (RED) and Assisted Reverse ElectroDialysis (ARED) are here proposed for the first time to reduce the salinity level of PWs. RED may also guarantee an operation cost reduction thanks to its energy generation. An ad-hoc model for RED and ARED is here developed in order to deal suitably with PWs. This is done by a calibration and validation with experimental data purposely collected via RED and ARED units fed by real PWs. The model is integrated with economical equations and a techno-economic analysis is carried out in order to identify the best configuration for the desalination purposes. Results suggest that ARED operation mode is the best option guaranteeing a minimum in the controlled dilution cost corresponding to a 1.32 € per m3 of PWs treated, thus leaving room for an affordable future implementation of more sophisticated treatment chains based on bioremediation.

Gearwheels are a common mechanism for distributing torque from mechanical devices to other mechanical devices. The tribological state of gears reduces their performance and lifespan. This paper presents a signal-processing basis for evaluating the vibrational dynamics of a single pair of gears under various tribological situations. This method not only identifies the tribological state of the system, but also leads to different applications in several mechanical systems.

Somatic rearrangements resulting in genomic structural variation drive malignant phenotypes by altering the expression or function of cancer genes. Pan-cancer studies have revealed that structural variants (SVs) are the predominant class of driver mutation in most cancer types, but because they are difficult to discover, they remain understudied when compared with point mutations. This review provides an overview of the current knowledge of somatic SVs, discussing their primary roles, prevalence in different contexts, and mutational mechanisms. SVs arise throughout the life history of cancer, and 55% of driver mutations uncovered by the Pan-Cancer Analysis of Whole Genomes project represent SVs. Leveraging the convergence of cell biology and genomics, we propose a mechanistic classification of somatic SVs, from simple to highly complex DNA rearrangement classes. The actions of DNA repair and DNA replication processes together with mitotic errors result in a rich spectrum of SV formation processes, with cascading effects mediating extensive structural diversity after an initiating DNA lesion has formed. Thanks to new sequencing technologies, including the sequencing of single-cell genomes, open questions about the molecular triggers and the biomolecules involved in SV formation as well as their mutational rates can now be addressed.

Objetivo: O Modo de Falha em Saúde e Análise de Efeitos (HFMEA) ou FMEA na saúde é uma ferramenta prospectiva para análise de riscos na gestão da saúde. A utilização deste método está espalhada na literatura causando um entendimento local sobre o assunto. Sendo assim, este artigo tem como objetivo fornecer uma visão ampliada e sistematizada sobre o método HFMEA apresentando o que é, como elaborar e quais foram os impactos causados por esta ferramenta nas instituições de saúde. Projeto/metodologia/abordagem: Foi efetuada uma revisão bibliográfica na literatura em 56 artigos. A seleção dos documentos foi através de um processo de triagem aplicado aos registros identificados através da busca por artigos com a palavra-chave “HFMEA”. Constatações: Os estudos analisados indicam que 5 dos 8 principais erros e eventos adversos mais comuns na assistência de saúde utilizaram o HFMEA como ferramenta de mitigação dos erros e riscos vigentes. Além disso, foi apresentado uma análise dos impactos da HFMEA, classificando-os quanto as principais áreas de aplicação. Logo, os notáveis efeitos da adoção da HFMEA são aumento da segurança do paciente e melhoria da gestão. Originalidade: Este estudo deseja servir de estímulo para o desenvolvimento de pesquisas futuras em gestão de risco por meio do método HFMEA para eliminação e/ou redução de erros, como a principal lacuna a ser preenchida como também a propagação deste método às organizações de prestação a saúde.

This study aimed to exhaustively explore the characteristics of food advertising on TV in Guatemala and Costa Rica. The International Network for Food and Obesity Non-Communicable Diseases (NCDs) Research, Monitoring and Action Support (INFORMAS) methodology was applied. In 2016, we recorded 1440 h of video among 10 TV channels. We used the Pan American Health Organization (PAHO) Nutrient Profile (NP) Model to identify ‘critical nutrients’, whose excessive consumption is associated with NCDs. We created a nutritional quality score (0 if the product did not exceed any critical nutrient, 1 if the product exceeded one and 2 if it exceeded ≥2). We classified food ads as permitted (score = 0) and not-permitted (score 1 or 2) for marketing. Persuasive marketing techniques were classified as promotional characters (e.g. Batman), premium offers (e.g. toys), brand benefit claims (e.g. tasty) and health-related claims (e.g. nutritious). In Guatemala, foods that exceeded one critical nutrient were more likely to use persuasive marketing techniques, and in Costa Rica were those with an excess of ≥2 critical nutrients, compared with foods without any excess in critical nutrients [Guatemala: promotional characters (odds ratio, OR = 16.6, 95% confidence interval, CI: 5.8, 47.3), premium offers (OR = 3.4, 95% CI: 1.4, 8.2) and health-related claims (OR = 3.5, 95% CI: 2.2, 5.7); Costa Rica: health-related claims (OR = 4.2, 95% CI: 2.0, 8.5)]. In conclusion, Guatemalan and Costa Rican children are exposed to an overabundance of not-permitted food ads on TV. This justifies implementing national policies to reduce exposure to not-permitted food for marketing, including on TV and other media.

Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is applied in patients with refractory hemodynamic failure. Exposure of blood components to high shear stress and the large extracorporeal surfaces in the ECMO circuit trigger a complex inflammatory response syndrome and coagulopathy which are believed to worsen the already poor prognosis of these patients. Mass spectrometry-based proteomics allow a detailed characterization of the serum proteome as it provides the identity and concentration of large numbers of individual proteins at the same time. In this study, we aimed to characterize the serum proteome of patients receiving VA-ECMO. Methods Serum samples were collected on day 1 and day 3 after initiation of VA-ECMO. Samples underwent immunoaffinity based depletion for the 14 most abundant serum proteins, in-solution digestion and PreOmics clean-up. A spectral library was built with multiple measurements of a master-mix sample using variable mass windows. Individual samples were measured in data independent acquisition (DIA) mode. Raw files were analyzed by DIA-neural network. Unique proteins were log transformed and quantile normalized. Differential expression analysis was conducted with the LIMMA—R package. ROAST was applied to generate gene ontology enrichment analyses. Results Fourteen VA-ECMO patients and six healthy controls were recruited. Seven patients survived. Three hundred and fifty-one unique proteins were identified. One hundred and thirty-seven proteins were differentially expressed between VA-ECMO patients and controls. One hundred and forty-five proteins were differentially expressed on day 3 compared to day 1. Many of the differentially expressed proteins were involved in coagulation and the inflammatory response. The serum proteomes of survivors and non-survivors on day 3 differed from each other according to partial least-squares discriminant analysis (PLS-DA) and 48 proteins were differentially expressed. Many of these proteins have also been ascribed to processes in coagulation and inflammation (e.g., Factor IX, Protein-C, Kallikrein, SERPINA10, SEMA4B, Complement C3, Complement Factor D and MASP-1). Conclusion The serum proteome of VA-ECMO patients displays major changes compared to controls and changes from day 1 until day 3. Many changes in the serum proteome are related to inflammation and coagulation. Survivors and non-survivors can be differentiated according to their serum proteomes using PLS-DA analysis on day 3. Our results build the basis for future studies using mass-spectrometry based serum proteomics as a tool to identify novel prognostic biomarkers. Trial registration: DRKS00011106.

Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite Trypanosoma cruzi. Currently there are about 8 million infected people worldwide, most of them at the chronic phase of the disease, which involves cardiac, digestive or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective at the initial phase of the infection, which is generally underdiagnosed. Selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that T. cruzi has a complex life cycle with both intracellular and bloodstream circulating parasite stages in the vertebrate host. Here we report the effectiveness of the vaccination with a T. cruzi-specific protein family (TcTASV), employing both recombinant proteins with aluminum hydroxide and recombinant baculovirus displaying a TcTASV antigen at the capsid. Vaccination stimulated immunological responses with production of lytic antibodies and antigen-specific CD4+ and CD8+ IFNɣ secreting lymphocytes. More than 90% of vaccinated animals survived after lethal challenges with T. cruzi while all control mice died before 30 days post infection. Vaccination also induced a strong decrease of chronic tissue parasitism, and generated immunological memory that allowed vaccinated and infected animals to control both the reactivation of the infection after immunosuppression as well as a second challenge with T. cruzi. Interestingly, inoculation with wild type baculovirus trained the immune system to partially protect mice against T. cruzi. In brief, we demonstrated, for the first time, that the combination of the baculovirus platform and the TcTASV family provides effective protection against Trypanosoma cruzi, being a promising vaccine for Chagas’ disease.

BackgroundSleep disorders are one of the most common problems in children with Autism Spectrum Disorder (ASD). However, they often tend to be underdiagnosed and incorrectly treated in clinical practice. This study aims to identify sleep disorders in preschool children with ASD and to explore their relationship with the core symptoms of autism, the child’s developmental and cognitive level as well as the psychiatric comorbidities.MethodsWe recruited 163 preschool children with a diagnosis of ASD. The Children’s Sleep Habits Questionnaire (CSHQ) assessed sleep conditions. Multiple standardized tests were used to evaluate intellectual abilities, the presence of repetitive behaviors (through the Repetitive Behavior Scale-Revised), as well as the emotional-behavioral problems and the psychiatric comorbidities (through the Child Behavior Checklist -CBCL 11/2-5).ResultsThe results showed that poor disorders had consistently higher scores in all areas assessed by the CSHQ and on the CBCL across all domains. The correlational analysis showed that severe sleep disorders were associated with higher scores in internalizing, externalizing, and total problems at the CBCL syndromic scales, and in all DSM-oriented CBCL subscales. Moreover, we found that the association between sleep disorders and restricted and repetitive behaviors (RRBs) is explained by the anxiety-related symptoms.ConclusionBased on these findings, the study recommends that screening for sleep problems followed by early intervention should constitute a routine part of clinical practice for children with ASD.

Muito se tem falado na utilização de dados no apoio ao processo decisório, este presente artigo tem o intuito de explicar quais são as fases e premissas que uma organização deve observar desde a Inteligência de Negócios clássica baseada em fatos ocorridos no passado ou Business Intelligence (BI) até os recursos mais avançados de Business Analytics (BA) ou Análise de Negócios que possibilite a criação e análise de cenários futuros com o propósito de antecipar acontecimentos, melhorar o processo decisório e por seguinte possibilitar uma gestão mais eficaz. Visa identificar como as empresas podem tirar o máximo dos dados para que os líderes das organizações possam utilizá-los de forma eficaz para a tomada de decisão, evoluindo do BI para o BA com foco no processo decisório. O BA se torna essencial para que o processo de tomada de decisão baseado em dados mitigue o fator “suposição” e impacte diretamente na performance da organização. Quais são os passos e premissas necessárias para evoluir o BI que utiliza análises descritivas e diagnosticas para o BA através de análise preditiva, prescritiva e cognitiva? Pesquisa exploratória, bibliográfica e documental, será baseada em modelos de gestão e governança das organizações empresariais. Demonstrar como as organizações podem evoluir para um patamar que lhes permitam acompanhar, analisar tendências e predições impactando diretamente o processo decisório das organizações. O presente trabalho tem por objetivo oferecer um caminho para evolução do processo de tomada de decisão das organizações baseando-se em dados e mitigando a suposição no processo decisório.

Today digital revolution is having a dramatic impact on the pharmaceutical industry and the entire healthcare system. The implementation of machine learning, extreme-scale computer simulations, and big data analytics in the drug design and development process offers an excellent opportunity to lower the risk of investment and reduce the time to the patient. Within the LIGATE project, we aim to integrate, extend, and co-design best-in-class European components to design Computer-Aided Drug Design (CADD) solutions exploiting today's high-end supercomputers and tomorrow's Exascale resources, fostering European competitiveness in the field. The proposed LIGATE solution is a fully integrated workflow that enables to deliver the result of a virtual screening campaign for drug discovery with the highest speed along with the highest accuracy. The full automation of the solution and the possibility to run it on multiple supercomputing centers at once permit to run an extreme scale in silico drug discovery campaign in few days to respond promptly for example to a worldwide pandemic crisis., Paper Accepted to the 20th ACM International Conference on Computing Frontiers (CF'23)

A new understanding of plankton ecology has been obtained by studying the phenotypic traits of free-living prokaryotes in the Sicily Channel (Central Mediterranean Sea), an area characterised by oligotrophic conditions. During three cruises carried out in July 2012, January 2013 and July 2013, the volume and morphology of prokaryotic cells were assessed microscopically using image analysis in relation to environmental conditions. The study found significant differences in cell morphologies among cruises. The largest cell volumes were observed in the July 2012 cruise (0.170 ± 0.156 µm3), and the smallest in the January 2013 cruise (0.060 ± 0.052 µm3). Cell volume was negatively limited by nutrients and positively by salinity. Seven cellular morphotypes were observed among which cocci, rods and coccobacilli were the most abundant. Cocci, although they prevailed numerically, always showed the smallest volumes. Elongated shapes were positively related to temperature. Relationships between cell morphologies and environmental drivers indicated a bottom-up control of the prokaryotic community. The morphology/morphometry-based approach is a useful tool for studying the prokaryotic community in microbial ecology and should be widely applied to marine microbial populations in nature.

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs.Clinical trial identifierNCT04673240.

Protein expression is a primary area of interest for routine histological diagnostics and tissue-based research projects, but the limitations of its post-mortem applicability remain largely unclear. On the other hand, tissue specimens obtained during autopsies can provide unique insight into advanced disease states, especially in cancer research. Therefore, we aimed to identify the maximum post-mortem interval (PMI) which is still suitable for characterizing protein expression patterns, to explore organ-specific differences in protein degradation, and to investigate whether certain proteins follow specific degradation kinetics. Therefore, the proteome of human tissue samples obtained during routine autopsies of deceased patients with accurate PMI (6, 12, 18, 24, 48, 72, 96 h) and without specific diseases that significantly affect tissue preservation, from lungs, kidneys and livers, was analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). For the kidney and liver, significant protein degradation became apparent at 48 h. For the lung, the proteome composition was rather static for up to 48 h and substantial protein degradation was detected only at 72 h suggesting that degradation kinetics appear to be organ specific. More detailed analyses suggested that proteins with similar post-mortem kinetics are not primarily shared in their biological functions. The overrepresentation of protein families with analogous structural motifs in the kidney indicates that structural features may be a common factor in determining similar postmortem stability. Our study demonstrates that a longer post-mortem period may have a significant impact on proteome composition, but sampling within 24 h may be appropriate, as degradation is within acceptable limits even in organs with faster autolysis.

Virtual screening is an early stage of the drug discovery process that selects the most promising candidates. In the urgent computing scenario it is critical to find a solution in a short time frame. In this paper, we focus on a real-world virtual screening application to evaluate out-of-kernel optimizations, that consider input and architecture features to improve the computation efficiency on GPU. Experiment results on a modern supercomputer node show that we can almost double the performance. Moreover, we implemented the optimization using SYCL and it provides a consistent benefit with the CUDA optimization. A virtual screening campaign can use this gain in performance to increase the number of evaluated candidates, improving the probability of finding a drug.

Volatile fatty acids (VFAs) produced by acidogenic digestion of sewage sludge are very interesting bio-products which can contribute to carbon neutrality of wastewater treatment plants. Studies on the production of VFAs from sewage sludge from fermenters with membrane are limited. In view of above, VFAs from a fermenter pilot plant equipped with a membrane bioreactor and fed with real sewage sludge has been monitored. The effect of headspace volume (HdV) on VFA production was studied for the first time to elucidate the optimal operation conditions. Specifically, three fermenter HdV values (namely, 20, 40 and 60% of the total volume) have been investigated. Results revealed that the HdV of 20% ensured the highest sCOD production (900 mgCOD/L) and VFA/COD ratio (45.4%). High value of HdV (namely, 40 and 60%) strongly decreased the acidogenic fermentation performance in terms of VFA production.

Conversion of wastewater treatment plants into biorefineries is a sustainable alternative for obtaining valuable compounds, thus reducing pollutants and costs and protecting the environment and human health. Under specific operating conditions, microbial fermentative products of sewage sludge are volatile fatty acids (VFA) that can be precursors of polyhydroxyalkanoate thermoplastic polyesters. The role of various operating parameters in VFA production has yet to be elucidated. This study aimed to correlate the levels of VFA yields with prokaryotic microbiota structures of sewage sludge in two sets of batch fermentations with an initial pH of 8 and 10. The sewage sludge used to inoculate the batch fermentations was collected from a Sicilian WWTP located in Marineo (Italy) as a case study. Gas chromatography analysis revealed that initial pH 10 stimulated chemical oxygen demands (sCOD) and VFA yields (2020 mg COD/L) in comparison with initial pH 8. Characterization of the sewage sludge prokaryotic community structures—analyzed by next-generation sequencing of 16S rRNA gene amplicons—demonstrated that the improved yield of VFA paralleled the increased abundance of fermenting bacteria belonging to Proteobacteria, Bacteroidetes, Chloroflexi, and Firmicutes phyla and, conversely, the reduced abundance of VFA-degrading strains, such as archaeal methanogens.

Produced waters (PWs) are wastewaters generated by crude-oil extraction processes. They can present very different characteristics depending on the field location and production process. Dispersed oil, dissolved organics and solid particles are usually the main components. Moreover, PWs can contain a very high quantity of dissolved salts 1, with a total dissolved solid (TDS) concentration up to 300 g/L. Each barrel of extracted oil requires the simultaneous extraction of 3 barrels of produced water2 on average. PWs are often discharged into the sea, or sent in evaporation ponds thus leading to a dramatic environment impact3. Reinjection in the extraction well is currently the most common and safest option. With this respect, the high salt solution concentration of such solutions may be used in salinity gradient power (SGP) technologies in order to valorize them before the reinjection by producing clean energy. Reverse Electrodialysis (RED) is one of the most promising SGP technology, and has attracted the attention of research especially when natural solutions are involved. RED units are composed of several repetitive units, consisting of two channels, an anion exchange membrane (AEM) and a cation exchange membrane (CEM). When fed by two solutions with different salt concentrations, a potential difference is generated by a salinity gradient across each membrane, leading to an ionic flux between the two solutions. At the ends of the stack, two electrodes are inserted, rinsed by a solution containing redox couples, allowing the conversion of the ionic flux into electric current when an external load is connected to the RED unit. In the present work, the possibility to generate power, from real oil-industry brines via RED is investigated. An experimental campaign was performed by testing a 10 cm x 10 cm unit in long-run continuous operations, monitoring its performance for more than 25 days. Several anti-fouling strategies were adopted in order to prevent the system channels from clogging issues. As a result, a positive net power density was obtained for more than 18 days of continuous operations. A maximum power density of about 2.5 W/m2 was observed, demonstrating how the RED technology could be a strategy to harvest energy from produced waters.

Culture media used in industrial bioprocessing and the emerging field of cellular agriculture is difficult to optimize due to the lack of rigorous mathematical models of cell growth and culture conditions, as well as the complexity of the design space. Rapid growth assays are inaccurate yet convenient, while robust measures of cell number can be time-consuming to the point of limiting experimentation. In this study, we optimized a cell culture media with 14 components using a multi-information source Bayesian optimization algorithm that locates optimal media conditions based on an iterative refinement of an uncertainty-weighted desirability function. As a model system, we utilized murine C2C12 cells, using AlamarBlue, LIVE stain, and trypan blue exclusion cell counting assays to determine cell number. Using this experimental optimization algorithm, we were able to design media with 181% more cells than a common commercial variant with a similar economic cost, while doing so in 38% fewer experiments than an efficient design-of-experiments method. The optimal medium generalized well to long-term growth up to four passages of C2C12 cells, indicating the multi-information source assay improved measurement robustness relative to rapid growth assays alone.

Semi- and nonparametric models are popular in the area-based approach (ABA) using airborne laser scanning. It is unclear, however, how many predictors and training plots are needed to provide accurate predictions without overfitting. This work aims to explore these limits for various approaches: ordinary least squares regression (OLS), generalized additive models (GAM), least absolute shrinkage and selection operator (LASSO), random forest (RF), support vector machine (SVM), and Gaussian process regression (GPR). We modeled timber volume (m3·ha–1) for four boreal sites using ABA with 2–39 predictors and 20–500 training plots. OLS, GAM, LASSO, and SVM overfitted as the number of predictors approached the number of training plots. They required ≥15 plots per predictor to provide accurate predictions (RMSE ≤30%). GAM required ≥250 plots regardless of the number of predictors. The number of predictors only mildly affected RF and GPR, but they required ≥200 and ≥250 training plots, respectively. RF did not overfit in any circumstances, whereas GPR overfit even with 500 training plots. Overall, using up to 39 predictors did not generally result in overfit, and for most model types, it resulted in better accuracy for sufficiently large datasets (≥250 plots).

Background Amino acid-based formula (AAF) is a relevant dietary strategy for paediatric patients affected by cow’s milk allergy (CMA). The present study was designed to evaluate the hypoallergenicity of a new AAF in children with immunoglobulin (Ig)E-mediated CMA. Methods According to the criteria provided by the American Academy of Pediatrics Subcommittee on Nutrition and Allergic Diseases, we designed a prospective trial in CMA children (aged 1–36 months) aimed to demonstrate the hypoallergenicity of the new AAF in 90% of subjects with 95% confidence during the double-blind, placebo-controlled challenge (DBPCFC). A skin prick test (SPT) with the new AAF was also performed. Results Twenty-nine children [all Caucasian, 55.2% male, mean age (±SD) 16.9 ± 5.7 months] were enrolled. The SPT and the DBPCFC with the new AAF were negative in all study subjects. Conclusions The study results support the hypoallergenicity of the new AAF. This formula could be considered an additional dietary option for non-breastfed children affected by CMA. Trial registration The trial was registered in the ClinicalTrials.gov Protocol Registration System (ID number: NCT03909113).

A leading challenge in the assembly process of aircraft skin panels is the precise control of part-to-part gaps to avoid excessive pre-tensions of the fastening element which, if exceeded, impair the durability and the response under dynamics loads of the whole skin assembly. The current practice is to measure the gap in specific points of the assembly with parts already at their final location, and then be-spoke shims are machined and inserted between the mating components to fill the gap. This process involves several manual measurement-fit-adjust quality loops, such as loading parts on the assembly frame, measuring gaps, off-loading parts, adding be-spoke shims and re-positioning parts ready for the fastening operation—as a matter of fact, the aircraft is re-assembled at least twice and therefore the current practice has been proved highly cost and time ineffective. Additionally, the gap measurement relies on manual gauges which are inaccurate and unable to follow the actual 3D profile of the gap. Taking advantage of emerging tools such as in-line measurement systems and large-scale physics-based simulations, this paper proposes a novel methodology to predict the part-to-part gap and therefore minimise the need for multiple quality loops. The methodology leverages a physics-driven digital twin model of the skin assembly process, which combines a physical domain (in-line measurements) and a digital domain (physics-based simulation). Central to the methodology is the variation model of the multi-stage assembly process via a physics-based simulation which allows to capture the inherent deformation of the panels and the propagation of variations between consecutive assembly stages. The results were demonstrated during the assembly process of a vertical stabiliser for commercial aircraft, and findings showed a significant time saving of 75% by reducing costly and time-consuming measurement-fit-adjust quality loops.

Wastewaters generated by crude oil extraction processes, called “produced waters” (PWs), are complex solutions that contain organic compounds, mainly hydrocarbons, and often exhibit high salinity. The large amounts of PWs represent a global issue because of their environmental impact. An approach widely used in the oil industry is the reinjection of this wastewater into the extraction wells after a suitable treatment. The high salt concentration of such solutions may be used in salinity gradient technologies to produce green electricity. Among these technologies, reverse electrodialysis (RED) is one of the most promising. In this work, the application of RED for energy generation from two different real oil industry brines was investigated. An experimental campaign was performed by testing 10 × 10 cm2 units in long-run continuous operations, monitoring the performance for more than 25 days. Fouling phenomena, occurring during the continuous operation, decrease the unit performance and several anti-fouling strategies were adopted to tackle this issue. As a result, a positive net power density for up to 18 days of continuous operation was obtained. A maximum power density of about 2.5 W/m2 was observed, demonstrating how the RED technology could be an important strategy to harvest energy from an industrial waste.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are severe inflammatory disorders that often involve focal necrotizing glomerulonephritis (FNGN) and consequent glomerular scarring, interstitial fibrosis, and chronic kidney disease. Robust murine models of scarring in FNGN that may help to further our understanding of deleterious processes are still lacking. Here, we present a murine model of severe FNGN based on combined administration of antibodies against the glomerular basement membrane (GBM) and myeloperoxidase (MPO), and bacterial lipopolysaccharides (LPS), that recapitulates acute injury and was adapted to investigate subsequent glomerular and interstitial scarring. Hematuria without involvement of other organs occurs consistently and rapidly, glomerular necrosis and crescent formation are evident at 12 days, and consequent glomerular and interstitial scarring at 29 days after initial treatment. Using mass-spectrometric proteome analysis, we provide a detailed overview of matrisomal and cellular changes in our model. We observed increased expression of the matrisome including collagens, fibronectin, tenascin-C, in accordance with human AAV as deduced from analysis of gene expression microarrays and tissue staining. Moreover, we observed tissue infiltration by neutrophils, macrophages, T cells and myofibroblasts upon injury. Experimental inhibition of CXCR4 using AMD3100 led to a sustained histological presence of fibrin extravasate, reduced chemokine expression and leukocyte activation, but did not markedly affect ECM composition. Altogether, we demonstrate an adapted FNGN model that enables the study of matrisomal changes both in disease and upon intervention, as exemplified via CXCR4 inhibition.

To elucidate D-methionine's (D-met) dose and time rescue parameters from steady-state or impulse noise-induced permanent threshold shift (PTS) and determine D-met rescue's influence on serum and cochlear antioxidant levels.Five D-met doses at 0, 50, 100, or 200 mg/kg/dose administered starting at 1, 24, or 36 hours post steady-state or impulse noise exposure. Auditory brainstem responses at baseline and 21 days post-noise measured PTS. Serum (superoxide dismutase [SOD], catalase [CAT],, glutathione reductaseand glutathione peroxidase [GPx]) and cochlear (Glutathione [GSH] and glutathione disulphide [GSSG]) antioxidant levels measured physiological impact.D-met significantly reduced PTS for impulse noise (100 mg [2, 6, 14 and 20 kHz]; 200 mg [2, 14 and 20 kHz]) and steady-state noise (all dosing groups, time parameters and tested frequencies). PTS reduction did not significantly vary by rescue time. D-met significantly increased serum SOD (100 and 200 mg for 24 hour rescue) and GPx (50 mg/kg at 24 hour rescue) at 21 days post-noise. Cochlear GSH and GSSG levels were unaffected relative to control.D-met rescues from steady-state and impulse noise-induced PTS even when administered up to 36 hours post-noise and dose-dependently influences serum antioxidant levels even 21 days post-noise. D-met's broad and effective dose/time window renders it a promising antioxidant rescue agent.

Zero death’s society and social legitimacy between thought, technology and future of democracy The interview attempts to articulate some of the key points that emerged over the long pandemic months. First, the relationship with the Death of our society, absorbed hiding and concealing its presence. This does not lead philosophy to think about some issues of our time such as trust in the scientific institution, the crisis of its legitimacy and the political fallout of such conceptions.