Search

Abstract Background Archaea and Bacteria are distinct domains of life that are adapted to a variety of ecological niches. Several genome-based methods have been developed for their accurate classification, yet many aspects of the specific genomic features that determine these differences are not fully understood. In this study, we used publicly available whole-genome sequences from bacteria ( $$N=2546$$ N = 2546 ) and archaea ( $$N=109$$ N = 109 ). From these, a set of genomic features (nucleotide frequencies and proportions, coding sequences (CDS), non-coding, ribosomal and transfer RNA genes (ncRNA, rRNA, tRNA), Chargaff’s, topological entropy and Shannon’s entropy scores) was extracted and used as input data to develop machine learning models for the classification of archaea and bacteria. Results The classification accuracy ranged from 0.993 (Random Forest) to 0.998 (Neural Networks). Over the four models, only 11 examples were misclassified, especially those belonging to the minority class (Archaea). From variable importance, tRNA topological and Shannon’s entropy, nucleotide frequencies in tRNA, rRNA and ncRNA, CDS, tRNA and rRNA Chargaff’s scores have emerged as the top discriminating factors. In particular, tRNA entropy (both topological and Shannon’s) was the most important genomic feature for classification, pointing at the complex interactions between the genetic code, tRNAs and the translational machinery. Conclusions tRNA, rRNA and ncRNA genes emerged as the key genomic elements that underpin the classification of archaea and bacteria. In particular, higher nucleotide diversity was found in tRNA from bacteria compared to archaea. The analysis of the few classification errors reflects the complex phylogenetic relationships between bacteria, archaea and eukaryotes.

Abstract Background In the context of the RABOLA project, which aimed to identify operational practices that lead to the reduction of antibiotic use in dairy cattle farming, lyophilised Aloe arborescens was administered orally to cows during the dry-off and peripartum periods. In this specific paper we wanted to examine whether oral administration of Aloe arborescens, in combination with the topical application of a teat sealant could exert an effect on the microbial populations of three cow microbiomes (rumen, milk, rectum), between dry-off and peripartum. Dry-off and peripartum are critical physiological phases of the cow’s life, where both the mammary gland and the gastrointestinal tract undergo dramatic modifications, hence the relevance of evaluating the effects of dietary treatments. Methods Thirty multiparous dairy cows were randomly allocated to three groups: Control (antibiotic treatment and internal teat sealant), Sealant (only internal teat sealant) and Aloe (internal teat sealant and Aloe arborescens homogenate administered orally). For 16S rRNA gene sequencing, rumen, rectum and milk samples were collected, not synchronously, at the most critical timepoints around dry-off and calving, considering the physiological activity of each biological site. Results The rumen microbiome was predominantly characterized by Bacteroidetes and Firmicutes followed by Proteobacteria, while the rectum exhibited a prevalence of Firmicutes and Bacteroidetes. The milk microbiome mainly comprised Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes. Alistipes spp., Ruminococcaceae UCG-10 group, Prevotellaceae UCG-001 group, and Bacteroides spp., involved in cellulose and hemicellulose degradation, enhancement of energy metabolism, and peptide breakdown, showed increment in the rectum microbiome with Aloe supplementation. The rectum microbiome in the Aloe group exhibited a significant increase in the Firmicutes to Bacteroidetes ratio and alpha-diversity at seven days after dry-off period. Beta-diversity showed a significant separation between treatments for the rectum and milk microbiomes. Aloe supplementation seemed to enrich milk microbial composition, whereas the Sealant group showed greater diversity compared to the Control group, albeit this included an increase in microorganisms frequently associated with mastitis. Conclusions Aloe arborescens administration during the dry-off period did not demonstrate any observable impact on the microbial composition of the rumen, a finding further supported by volatilome analysis. Instead, the oral Aloe supplementation at dry-off appears to significantly influence the composition of the dairy cow rectum and milk microbiomes in the following lactation.

Abstract Background Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting. Patients and methods Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated. Results Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0–7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RRadjusted 1.59 (95%CI:1.09–2.31), 1.46 (95%CI:1.03–2.07) and 1.73 (95%CI:1.27–2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44–0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39–0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css. Conclusions We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs. Key points Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.

Abstract Genome interpretation (GI) encompasses the computational attempts to model the relationship between genotype and phenotype with the goal of understanding how the first leads to the second. While traditional approaches have focused on sub-problems such as predicting the effect of single nucleotide variants or finding genetic associations, recent advances in neural networks (NNs) have made it possible to develop end-to-end GI models that take genomic data as input and predict phenotypes as output. However, technical and modeling issues still need to be fixed for these models to be effective, including the widespread underdetermination of genomic datasets, making them unsuitable for training large, overfitting-prone, NNs. Here we propose novel GI models to address this issue, exploring the use of two types of transfer learning approaches and proposing a novel Biologically Meaningful Sparse NN layer specifically designed for end-to-end GI. Our models predict the leaf and seed ionome in A.thaliana, obtaining comparable results to our previous over-parameterized model while reducing the number of parameters by 8.8 folds. We also investigate how the effect of population stratification influences the evaluation of the performances, highlighting how it leads to (1) an instance of the Simpson’s Paradox, and (2) model generalization limitations.

Underutilized sheep and goat breeds can adapt to challenging environments due to their genetics. Integrating publicly available genomic datasets with new data will facilitate genetic diversity analyses; however, this process is complicated by data discrepancies, such as outdated assembly versions or different data formats. Here, we present the SMARTER-database, a collection of tools and scripts to standardize genomic data and metadata, mainly from SNP chip arrays on global small ruminant populations, with a focus on reproducibility. SMARTER-database harmonizes genotypes for about 12,000 sheep and 6,000 goats to a uniform coding and assembly version. Users can access the genotype data via File Transfer Protocol and interact with the metadata through a web interface or using their custom scripts, enabling efficient filtering and selection of samples. These tools will empower researchers to focus on the crucial aspects of adaptation and contribute to livestock sustainability, leveraging the rich dataset provided by the SMARTER-database. Availability and implementation The code is available as open-source software under the MIT license at https://github.com/cnr-ibba/SMARTER-database.

Background: Whether solid organ transplant (SOT) can be safely performed in recipients with ongoing SARS-CoV-2 infection is still a debated question. Methods: A systematic review of the literature on recipients with ongoing SARS-CoV-2 infection at the time of surgery and the associated outcomes. Results: From 29 studies, we identified 54 recipients; their median age was 47.5 years, and over half (23/54, 54.85%) were affected by fewer than two comorbidities. Kidney was the most common transplanted organ (24/54, 44.4%). SOT was performed without knowing the ongoing infection in 11.1% (6/54) of patients. On average, 16.1 (SD 23.2) days elapsed between SARS-CoV-2 infection and SOT, with a mean Ct value at diagnosis and transplantation of 29 and 31.9, respectively. Most patients (25/39,64.1%) had received previous COVID-19 vaccinations. Twenty-four patients (45.3%) received an anti-SARS-CoV-2 therapy. Ten patients (18.5%) required oxygen support, while seven (13.7%) were admitted to the intensive care unit. There were two reported cases (3.7%) of all-cause death, while there were no cases of COVID-19-related death. Conclusions: Deliberate SOT of recipients with ongoing SARS-CoV-2 is performed worldwide in candidates of nonlung transplant who are fit, immunized against the virus, and displaying a nonsevere disease course. No COVID-19-related deaths were recorded.

Different yeast strains benefit postweaning piglets by promoting intestinal health. The objective of this study was to investigate the effect of a yeast mixture containing Kluyveromyces marxianus fragilis, Pichia guilliermondii, and Saccharomyces cerevisiae (Vetoquinol italia s.r.l., Italy) on gut health parameters and growth performance traits of weaned piglets. Forty-eight postweaning castrated male piglets (27 ± 1.7 days, 7.19 ± 0.54 kg) were randomly allocated to two homogeneous experimental groups and involved in a 28-day trial. Both the groups received a basal diet with (yeast mixture, YM) or without (control, CTR) the inclusion of 0.8% yeast mixture during weeks 1 and 2, and 0.6% during weeks 3 and 4. Individual BW and box feed intake were determined on days 0, 14, and 28, and average daily gain and Gain:Feed ratio were subsequently calculated for each administration period (0–14, 14–28). Individual faecal samples were collected for microbiota analysis on days 4, 14, 21, and 28, and faecal score was evaluated on the same days. At the end of the trial, 12 piglets for each group were sacrificed, and ileal tissue was sampled for morphological analysis and the evaluation of mucins profile, using Alcian-Blue/Periodic Acid-Shiff (PAS) staining. On ileum samples, dividing and differentiated epithelial cells were also identified using proliferating cell nuclear antigen and alkaline phosphatase expression, respectively. Differences in the means between the experimental groups were determined by ANOVA, while the metataxonomics analyses were performed by sequencing for V3 and V4 hypervariable regions of the 16S rRNA gene. Growth performance traits were not different among the two experimental groups when considering the whole trial period, while treated animals showed increased faecal consistency on weeks 1 and 4 (P = 0.036 and 0.021, respectively). Yeast mixture administration increased the abundance of Bifidobacterium (P = 0.006) and Coprococcus 2 (P = 0.015), and decreased Clostridium Sensu Stricto 1 (P = 0.019) at all the considered timepoints. Ileum villous height, villous width, and crypt depth were significantly increased by yeast mixture supplementation (P = 0.019; P = 0.013; P = 0.036, respectively), while no differences were observed for the villous:crypt ratio among the groups. The mucin profile showed no differences among experimental groups for acid and neutral glycoconjugates. However, a higher presence of PAS-positive mucins was highlighted in the villi of YM piglets (P

Abstract Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized by symptoms such as excessive daytime sleepiness, sudden sleep episodes, disrupted nocturnal sleep, cataplexy, sleep paralysis, and hypnagogic hallucinations, which significantly impact the overall well-being and quality of life of individuals. While psychological factors have gained attention, there is limited research on the coping strategies employed by patients with NT1 and their association with quality of life. This study aimed to compare coping strategies in patients with NT1 and controls, as well as assess the relationship between coping strategies and quality of life in patients with NT1. A total of 122 individuals diagnosed with NT1 and 138 controls were enrolled in this cross-sectional study. Participants completed questionnaires assessing coping strategies and health-related quality of life. A Mann–Whitney U test was conducted to compare the use of different coping strategies by patients with NT1 and controls. Spearman's rho correlation was performed to examine the association between coping strategies and quality of life in the NT1 group. Results showed that patients with NT1 exhibited differences in the use of coping strategies compared to controls. They reported lower use of active coping, planning, instrumental, and emotional social support, and higher use of behavioral and mental disengagement. Denial and behavioral disengagement were significantly and negatively associated with quality of life. Identifying coping strategies and their association with quality of life may aid in the development of tailored interventions aimed at improving the adoption of effective coping strategies and reducing the use of maladaptive coping strategies.

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

The 6th assessment report by IPCC underscores the necessity to switch from immediate to timely actions to foster (urban) climate change adaptation and mitigation. Green areas such as tactical urban parks could represent a strategic asset towards healthier and more sustainable cities and societies. Specifically studied greenery may indeed improve local microclimate and air quality conditions, supporting the socio-ecological resilience of cities while enhancing social interactions.Using a multidisciplinary approach, this study aims to evaluate the environmental quality and local community needs of a neighbourhood located near the historic centre of Perugia (Italy) to provide guidelines for its requalification, especially for outdoor spaces. To achieve this goal, the study conducted dedicated environmental monitoring, demonstrating the massive thermal behavior differences (by about 5K in summer) within the same urban area all over the year, and carried out surveys campaigns focusing on outdoor perceptions and needs reported by the local community. The results confirm that local residents mainly use the area as a thoroughfare to access established activities by car (63% of respondants), leading to high vehicular traffic and pollutants emissions during peak hours, with PM10 concentration peaks reaching 55 μg/m3 and 180 μg/m3 close to the parking lot in winter and spring, respectively. An effective intervention was recognized in the introduction of furniture in the area, creating attractive places to spend the lunch break, enabling people to enjoy the outdoors and maximize thermal comfort benefits. Moreover, reducing vehicular traffic and fostering slow mobility also demonstrated to be attractive measures to improve comfort, health and well-being and reduce negative consequences on air quality.

Bedding materials are aimed at providing a safe and comfortable resting environment for cows. Control of pathogen proliferation in these substrates is crucial to prevent intramammary infections in dairy cows, as these can significantly impact milk quality, cow health, and farm productivity. This is particularly relevant in the case of organic bedding substrates, including manure-derived materials. This study aimed to evaluate the in vitro effect of a lime-based conditioner (LBC), composed of CaCO3MgCO3 and Ca(OH)2*Mg(OH)2, at increasing concentrations on the physical-chemical characteristics and bacterial counts of untreated anaerobically digested manure solids (ADMS) and separated raw manure solids (SRMS). Unused ADMS and SRMS were evaluated at four LBC weight-based concentrations: 0 (as untreated control), 10, 15, and 20% of LBC inclusion. The bedding materials were assessed immediately after LBC addition (0 h) and after 24, 72, and 168 h of storage at 28°C. The dry matter content (DM), and pH were measured for all the time points. Standard microbiological methods were used to assess total bacterial counts (TBC), other Gram-negative bacteria, coliforms, Escherichia coli, and streptococci and streptococci-like organism (SSLO). It was observed a linear increase in both DM and pH with increasing concentrations of LBC. Specifically, for each percentage unit increase of LBC, the DM of ADMS and SRMS increased by 0.73 and 0.71%, respectively. Similarly, for each percentage unit of LBC, the pH of ADMS and SRMS increased by 0.15 and 0.19, respectively. Conversely, a linear decrease in TBC, Gram-negative bacteria, coliforms, E. coli, and SSLO was observed with increasing concentrations of the LBC. Manure-derived materials without the inclusion of the LBC had bacterial counts that tended to remain high or increase over time. Otherwise, bedding materials with LBC application had reduced bacterial counts. Based on the results of the present study, it was observed that the higher the concentration of LBC, the more significant the reduction of bacterial counts. Specifically, bacterial recovery was lower when higher concentrations of LBC were applied. Our findings underscore the potential of LBC in effectively controlling environmental bacteria and improving the physical-chemical characteristics of manure-derived bedding materials to improve cow health and welfare.

IntroductionMindful movement is a comprehensive approach that integrates various bodily, emotional and cognitive aspects into physical activity, promoting overall well-being. This study assessed the impact of a mindful movement program, known as Movimento Biologico (MB), on participants psychological well-being (PWB), positive mental health (PMH), sense of coherence (SOC), and interoceptive awareness.MethodsMB program was conducted for students attending the bachelor’s degree in Kinesiology and Sport Sciences of University of Perugia over 8 weeks (from October 16 to November 27, 2022). Participants were requested to fill in four questionnaires before and after the MB program: (1) 18-item PWB scale; (2) 9-item PMH scale; (3) 13-item SOC scale; (4) 32-item scale for Multidimensional Assessment of Interoceptive Awareness (MAIA). Wilcoxon signed-rank tests were used to assess changes, with significance set at p

Abstract The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value

Abstract Heterozygosity-rich regions (HRR) are genomic regions of high heterozygosity, which may harbor loci related to key functional traits such as immune response, survival rate, fertility, and other fitness traits. This study considered 30 Italian and 19 worldwide goat breeds genotyped with the Illumina GoatSNP50k BeadChip. The aim of the work was to study inter-breed relationships and HRR patterns using Sliding Window (SW) and Consecutive Runs (CR) detection methods. Genetic relationships highlighted a clear separation between non-European and European breeds, as well as the north–south geographic cline within the latter. The Pearson correlation coefficients between the descriptive HRR parameters obtained with the SW and CR methods were higher than 0.9. A total of 166 HRR islands were detected. CHI1, CHI11, CHI12 and CHI18 were the chromosomes harboring the highest number of HRR islands. The genes annotated in the islands were linked to various factors such as productive, reproductive, immune, and environmental adaptation mechanisms. Notably, the Montecristo feral goat showed the highest number of HRR islands despite the high level of inbreeding, underlining potential balancing selection events characterizing its evolutionary history. Identifying a species-specific HRR pattern could provide a clearer view of the mechanisms regulating the genome modelling following anthropogenic selection combined with environmental interaction.

Homemade diets integrated with functional ingredients may help to ensure that companion animals have a good life quality given the rise in their average lifespan. This study investigates the effects of a complete and well-balanced homemade diet supplemented with hulled hemp seeds. Twelve adult dogs divided into two groups: CTRL, fed the basal diet and HEMP, fed the diet integrated hulled Cannabis sativa L. seeds (4 g/100g of ration) were enrolled in the trial. The following samples were collected: (a) individual faecal samples to assess the diet digestibility through an indirect method of acid-insoluble ash; b) blood samples to evaluate the oxidative state through an OXI adsorbent test; and c) rectal swabs for intestinal microbiota analysis (alpha- and beta-diversity and taxonomy). The results reveal that with respect to the commercial diet used in this study, our homemade diet increased the total and protein digestibility (total: 53.97 ± 2.54% and 58.20 ± 2.58%; p

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.

Narcolepsy is a chronic central disorder of hypersomnolence most frequently arising during childhood/adolescence. This review article examined the literature concerning the etiology, prevalence, clinical course, and treatment of children with type 1 narcolepsy (NT1). Core symptoms of pediatric NT1 include excessive daytime sleepiness (EDS) and cataplexy, together with disrupted night sleep, sleep paralysis, and hypnagogic and hypnopompic hallucinations that can also occur. This disease frequently presents several comorbidities, such as obesity and precocious puberty, conditions ranging from psychological distress to psychiatric disorders, and cognitive aspects that further worsen the clinical picture. NT1 impairs the quality of life of children, thus calling for an early diagnosis and adequate treatment. To date, pharmacological treatments have been registered for childhood NT1 and can improve symptoms. Non-pharmacological approaches are also essential to improve patients’ well-being, ranging from behavioral treatments (e.g., planned napping) to psychosocial interventions (e.g., school programs). Multidisciplinary treatment management and early diagnosis are key factors in order to allow for adequate quality of life and development in children with NT1.

Abstract The next generation of brain–machine interfaces are envisioned to couple signal transduction, filtering, and sorting on board with minimum power consumption and maximum bio‐integrability. These functional needs shall be mandatorily met in order to design efficient closed‐loop brain–machine interfaces aimed at treating and monitoring various disorders of the central and peripheral nervous system. Here, the pivotal role is highlighted that organic bioelectronics may have in the contextual development of all these three desiderata, by demonstrating a modular organic‐electronics circuit toward real‐time signal filtering. The inherent filtering capabilities of electrolyte‐gated organic transistor are tuned via adjustment of operational conditions and benchmarked in an electromyography experiment. Additionally, a whole‐organic signal processing circuitry is presented, coupling such transistors with ad hoc designed organic passive components. This provides the possibility to sort complex signals into their constitutive frequency components in real time, thereby delineating innovative strategies to devise organic‐based functional building‐blocks for brain–machine interfaces.

ABSTRACT: From an initial data set involving 84,189 lactations, this research evaluated the relationship between dry period length (DPL) and milk production, culling risk, and fertility. The data set included a total of 48,297 multiparous cow lactation records, with a calving event occurring in 2019 and 2020, belonging to 62 Italian herds with at least 150 cows. The DPL was classified into 5 categories (70 d) and these categories were used to establish the association between DPL and the outcome variables. All data obtained were assessed with simple and multiple linear regressions and Cox proportional hazard models. Cumulative milk production at 60 d in milk (DIM) was the highest in DPL categories of 61 to 70 d (2,480.29 kg/cow) and 50 to 60 d (2,474.39 kg/cow), and the lowest in 70 d had slightly, but significant, lower milk production both as cumulative 60 DIM and predicted 305-d milk production. Culling risk had a curvilinear behavior, with DPL 70 d showing significantly higher odds for culling during the first 60 DIM compared with DPL of 50 to 60 d [relative risk (RR): 1.53; RR: 1.46]. Within the same comparison, DPL of 61 to 70 d also had a slightly higher risk for culling (RR: 1.13). The DPL was associated also with fertility, with DPL of 40 to 49 d and 50 to 60 d having the greatest odds for pregnancy within the first 200 DIM. The DPL of 70 d were negatively associated with fertility and showed pregnancy risks of 0.87, 0.95, and 0.94, respectively. This paper reinforces the importance of DPL as we demonstrated its association with milk production, culling, and fertility. Despite being attractive for high production dairy cows, very short dry periods are at the same time also associated with higher culling risk, lower milk production and fertility. Long DPL is detrimental, especially regarding culling and fertility. In summary, reducing variability in DPL and avoiding extremes by improving reproductive performance, maximizing late lactation milk production and making wise decisions on dry-off timing, may lead to better performances and lower early culling under Italian dairy conditions.

Abstract Background Availability of single nucleotide polymorphism (SNP) genotyping arrays and progress in statistical analyses have allowed the identification of genomic regions and genes under selection in chicken. In this study, SNP data from the 600 K Affymetrix chicken array were used to detect signatures of selection in 23 local Italian chicken populations. The populations were categorized into four groups for comparative analysis based on live weight (heavy vs light) and geographical area (Northern vs Southern Italy). Putative signatures of selection were investigated by combining three extended haplotype homozygosity (EHH) statistical approaches to quantify excess of haplotype homozygosity within (iHS) and between (Rsb and XP-EHH) groups. Presence of runs of homozygosity (ROH) islands was also analysed for each group. Results After editing, 541 animals and 313,508 SNPs were available for statistical analyses. In total, 15 candidate genomic regions that are potentially under selection were detected among the four groups: eight within a group by iHS and seven by combining the results of Rsb and XP-EHH, which revealed divergent selection between the groups. The largest overlap between genomic regions identified to be under selection by the three approaches was on chicken chromosome 8. Twenty-one genomic regions were identified with the ROH approach but none of these overlapped with regions identified with the three EHH-derived statistics. Some of the identified regions under selection contained candidate genes with biological functions related to environmental stress, immune responses, and disease resistance, which indicate local adaptation of these chicken populations. Conclusions Compared to commercial lines, local populations are predominantly reared as backyard chickens, and thus, may have developed stronger resistance to environmental challenges. Our results indicate that selection can play an important role in shaping signatures of selection in local chicken populations and can be a starting point to identify gene mutations that could have a useful role with respect to climate change.

Abstract To compare the diagnostic accuracy of the immunofluorescence (IF) technique and aSyn-seed amplification assay (aSyn-SAA) of skin and cerebrospinal fluid (CSF) in disclosing pathological α-syn in idiopathic idiopathic REM sleep behavior disorder (iRBD) as early phase of a synucleinopathy. We prospectively recruited 41 patients with iRBD and 40 matched clinical controls including RBD associated with type 1 Narcolepsy (RBD-NT1, 21 patients), iatrogenic causes (2 pt) or OSAS (6 pt) and 11 patients with peripheral neuropathies. IF from samples taken by skin biopsy and aSyn-SAA from skin and CSF samples were analysed blinded to the clinical diagnosis. IF showed a good diagnostic accuracy (89%) that was lower in the case of skin and CSF-based aSyn-SAA (70% and 69%, respectively) because of a lower sensitivity and specificity. However, IF showed a significant agreement with CSF aSyn-SAA. In conclusion, our data may favor the use of skin biopsy and aSyn-SAA as diagnostic tools for a synucleinopathy in iRBD.

Abstract An in vitro trial was carried out to investigate the effects of natural Thymbra capitata essential oil (NEO) and its main compounds [including carvacrol, p-cymene, γ-terpinene given alone or in a synthetic combination (SEO)] on ruminal fermentation and the bacterial community using batch cultures inoculated with ruminal digesta and incubating two different basal diets [high-forage (F) and high-concentrate (C) diet]. After 24 h of incubation, primary fermentation end-products [gas, methane, volatile fatty acids (VFAs) and ammonia] and rumen microbial diversity were determined. NEO reduced the total VFA concentration (P 0.05) by any of the experimental treatments or diets evaluated. Microbial diversity analysis showed only a moderate effect of carvacrol and SEO on 13 genera, including, mainly, Atopobium and Blautia (involved in subacute ruminal acidosis) or Candidatus Saccharimonas (related to laminitis). In conclusion, T. capitata EO has a limited potential to attain nutritional or environmental benefits, but further research should be carried out to clarify its effects on animal health and microbial food safety.

Abstract A growth mode of pentacene thin films deposited by high vacuum sublimation where the morphology versus thickness h “rings” back and forth between rough 3D films with pyramid islands and smooth 2D films with ziqqurat islands is discovered. The roughness σ versus h exhibits seamless coherent oscillations whose amplitude and wavelength increase as integer multiples of 1.5 ML thickness. The quantized oscillations are reconducted to dynamic wetting/dewetting transitions involving the upper layers of pentacene film. Importantly, the transconductance of organic field effect transistors, either in solid state or electrolyte‐gated, exhibits antiphase oscillations with one‐decade swing. Charge mobilities in the wetting regime reach 0.1 cm2 V−1 s−1, in line with high‐end values reported for thin‐film pentacene transistors. Controlling this growth mode enables the limitations of charge transport imposed by the roughening transition to be overcome, a universal feature of high vacuum growth to date.

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p

REM-sleep behavior disorder often precedes Parkinson’s disease or dementia. Here, the authors perform a genome-wide association study for REM-sleep behavior disorder, and discover how it potentially affects gene expression in the brain.

Abstract Deep learning is impacting many fields of data science with often spectacular results. However, its application to whole-genome predictions in plant and animal science or in human biology has been rather limited, with mostly underwhelming results. While most works focus on exploring alternative network architectures, in this study we propose an innovative representation of marker genotype data and tested it against the GBLUP (Genomic BLUP) benchmark with linear and nonlinear phenotypes. From publicly available cattle SNP genotype data, different types of genomic kinship matrices are stacked together in a 3D pile from where 2D grayscale slices are extracted and fed to a deep convolutional neural network (DNN). We simulated nine phenotype scenarios with combinations of additivity, dominance and epistasis, and compared the DNN to GBLUP-A (computed using only the additive kinship matrix) and GBLUP-optim (additive, dominance, and epistasis kinship matrices, as needed). Results varied depending on the accuracy metric employed, with DNN performing better in terms of root mean squared error (1–12% lower than GBLUP-A; 1–9% lower than GBLUP-optim) but worse in terms of Pearson’s correlation (0.505 for DNN compared to 0.672 and 0.669 of GBLUP-A and GBLUP-optim for fully additive case; 0.274 for DNN, 0.279 for GBLUP-A, and 0.477 for GBLUP-optim for fully dominant case). The proposed approach offers a basis to explore further the application of DNN to tabular data in whole-genome predictions.

(1) Background: Most daily activities and sport gestures involve asymmetric movement patterns of the upper and lower extremities, transferring asymmetric mechanical loadings to the spine. Therefore, asymmetric lumbar stabilization exercises are frequently prescribed in athletic programs and preventive/rehabilitation interventions. This study analyzed the bilateral activity of the thoracic erector spinae (ES), lumbar multifidus (MF), external oblique (EO), and internal oblique (IO) during asymmetric lumbar stabilization exercises executed in prone, quadruped, and standing-prone positions, rising an upper and/or lower limb in all possible combinations. A limited subset of these data has been previously published in earlier studies. (2) Methods: Surface EMG signals were bilaterally recorded from the selected muscles using wireless EMG sensors. (3) Results: ES, MF, and oblique muscles’ activity was significantly higher in prone, standing-prone, and quadruped positions, respectively, and was maximized by specific limb rise combinations (up to 69%, 64%, 34%, and 24% maximum-voluntary-isometric-contraction for ES, MF, EO, and IO). The bilateral difference in muscle activation was significantly higher in the quadruped position and revealed different strategies used to stabilize the body in response to the different exercise conditions. (4) Conclusions: The study results can provide deeper insights into the stabilizing function of the lumbar and oblique muscles and aid in designing optimal progressions for lumbar stabilization exercises.

A novel organic neuromorphic device performing pattern classification is presented and demonstrated. It features an artificial soma capable of dendritic integration from three pre-synaptic neurons. The time-response of the interface between electrolytic solutions and organic mixed ionic-electronic conductors is proposed as the sole computational feature for pattern recognition, and it is easily tuned in the organic dendritic integrator by simply controlling electrolyte ionic strength. The classifier is benchmarked in speech-recognition experiments, with a sample of 14 words, encoded either from audio tracks or from kinematic data, showing excellent discrimination performances in a planar, miniaturizable, fully passive device, designed to be promptly integrated in more complex architectures where on-board pattern classification is required.

ABSTRACT: Natural whey cultures (NWC) are undefined multiple-strain bacterial starter communities that can be affected by even small changes along the entire dairy chain. We applied a multidisciplinary approach to investigate how the addition of 2 mycotoxin-detoxifying agents [sodium smectite and lignocellulose-based material (B1); leonardite and betaine (B2)] to cow diets modified the microbiota of the NWC in manufacture of a Grana-like cheese. Microbiological and flow cytometry analyses showed that the content and viability of lactic acid bacteria (LAB) and the total whey microbiota were not affected by the detoxifying agents, and Streptococcus thermophilus, Lactobacillus helveticus, and Limosilactobacillus fermentum were the dominant taxa. Random amplified polymorphic DNA-PCR fingerprinting and metagenomic analysis highlighted differences in the bacterial community of the NWC and in the relative abundance of Bacteroidetes that increased when B1 and B2 were included in the diet. Two of 6 St. thermophilus biotypes were detected only in control samples; conversely, none of the Lb. helveticus biotypes found in control samples were isolated from B1 and B2. In vitro tests showed that the 2 binders did not significantly affect the development of St. thermophilus, but they stimulated the growth of Lb. helveticus strains recovered only from B1 and B2 NWC. The addition of binders in cow feed can affect the LAB biotypes present in NWC.

Abstract Background The oral ecosystem conditions dental health, and is known to be positively modified by oral hygiene which cannot always be performed between meals, especially outside home. It is therefore important to identify the practices to be adopted to influence the oral environment in an anticariogenic direction. Milk and cheese are considered functional foods and have a role on oral health. There are several mechanisms by which cheese exerts its beneficial effects on teeth. The aim of the present study was to examine whether short term consumption of hard cheese would affect the oral pH and microbial flora of healthy adults modifying ecological oral environment. The Next Generation Sequencing (NGS) approach was applied to study the effect of Italian Grana Padano (GP), as a prototype of typical hard cheese, on the oral microbiota composition. Finally, we explored Streptococcus mutans/sanguinis ratio as a marker of protective biofilm composition. Methods Nine oral-healthy adults were instructed to eat 25 gr of GP cheese for 5 consecutive days. Three time points were chosen for supragingival samples collection and pH measurement. 16S rRNA-gene sequences were obtained both from oral samples and GP cheese using the MiSeq platform and analyzed against the expanded Human Oral Microbiome Database (eHOMD). ProgPerm was used to perform statistical analyses to investigate strain differential representation after cheese consumption. Results Taxonomic analyses of the oral microbiota revealed that Firmicutes was the most abundant phylum, followed by Proteobacteria and Actinobacteria. GP cheese significantly modifies oral pH, causing a shift toward basic conditions which are kept for a few hours. The Streptococcus mutans/Streptococcus sanguinis ratio lowers in the last observed timepoint. Conclusion Our results reveal that a portion of GP cheese eaten after dinner provides important micronutrients (i.e. calcium, vitamins and some aminoacids such as arginine) and changes oral pH toward basic conditions, resulting in a light modification of the oral microbiome towards the reduction of the overall amount of acidophilic bacteria. Furthermore, the S. mutans/S. sanguinis ratio is reduced, contributing to obtain a more protecting environment towards caries establishment and evolution.

ABSTRACT: Direct measurements of methane (CH4) from individual animals are difficult and expensive. Predictions based on proxies for CH4 are a viable alternative. Most prediction models are based on multiple linear regressions (MLR) and predictor variables that are not routinely available in commercial farms, such as dry matter intake (DMI) and diet composition. The use of machine learning (ML) algorithms to predict CH4 emissions from across-country heterogeneous data sets has not been reported. The objectives were to compare performances of ML ensemble algorithm random forest (RF) and MLR models in predicting CH4 emissions from proxies in dairy cows, and assess effects of imputing missing data points on prediction accuracy. Data on CH4 emissions and proxies for CH4 from 20 herds were provided by 10 countries. The integrated data set contained 43,519 records from 3,483 cows, with 18.7% missing data points imputed using k-nearest neighbor imputation. Three data sets were created, 3k (no missing records), 21k (missing DMI imputed from milk, fat, protein, body weight), and 41k (missing DMI, milk fat, and protein records imputed). These data sets were used to test scenarios (with or without DMI, imputed vs. nonimputed DMI, milk fat, and protein), and prediction models (RF vs. MLR). Model predictive ability was evaluated within and between herds through 10-fold cross-validation. Prediction accuracy was measured as correlation between observed and predicted CH4, root mean squared error (RMSE) and mean normalized discounted cumulative gain (NDCG). Inclusion of DMI in the model improved within and between-herd prediction accuracy to 0.77 (RMSE = 23.3%) and 0.58 (RMSE = 31.9%) in RF and to 0.50 (RMSE = 0.327) and 0.13 (RMSE = 42.71) in MLR, respectively than when DMI was not included in the predictive model. When missing DMI records were imputed, within and between-herd accuracy increased to 0.84 (RMSE = 18.5%) and 0.63 (RMSE = 29.9%), respectively. In all scenarios, RF models out-performed MLR models. Results suggest routinely measured variables from dairy farms can be used in developing globally robust prediction models for CH4 if coupled with state-of-the-art techniques for imputation and advanced ML algorithms for predictive modeling.

Summary: Here, we describe a conserved motor neuron-specific long non-coding RNA, Lhx1os, whose knockout in mice produces motor impairment and postnatal reduction of mature motor neurons (MNs). The ER stress-response pathway result specifically altered with the downregulation of factors involved in the unfolded protein response (UPR). Lhx1os was found to bind the ER-associated PDIA3 disulfide isomerase and to affect the expression of the same set of genes controlled by this protein, indicating that the two factors act in conjunction to modulate the UPR. Altogether, the observed phenotype and function of Lhx1os indicate its important role in the control of MN homeostasis and function.

Organic Electrochemical Transistors (OECTs) are suitable for developing ultra-sensitive bioelectronic sensors. In the organic electrochemical transistors architecture, the source-drain channel is made of a conductive polymer film either cast from a formulated dispersion or electrodeposited from a monomer solution. The commercial poly(3,4-ethylenedioxidethiophene)/poly(styrene sulfonate) (PEDOT:PSS) water dispersion is the workhorse of organic bioelectronics for its high conductance, low impact and ease of processability. In this study, a hybrid organic electrochemical transistors channel fabrication strategy is presented, where electrochemical deposition of a PEDOT/X (with X indicating the counterion) is performed on a dispersion-cast PEDOT:PSS film. Six different counterions where used: X = PSS, Nafion, Hyaluronate, Dextran sulfate, Dexamethasone phosphate and tauroursodeoxycholic acid, each potentially endowing organic electrochemical transistors with additional functions such as ion exchange and pharmacological activity upon release of X. The PEDOT/X-PEDOT:PSS bilayers were characterized by means of electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and focused ion beam tomography combined with scanning electron microscopy (FIB-SEM). In addition, their respective organic electrochemical transistorss were characterized and compared to PEDOT:PSS organic electrochemical transistors. Our results show that the hybrid bilayer strategy is viable to fabricate multifunctional organic electrochemical transistorss with biologically-relevant function, thereby retaining the outstanding figures of merit of commercial PEDOT:PSS.

Abstract Background Human milk is a vehicle for bioactive compounds and beneficial bacteria which promote the establishment of a healthy gut microbiome of newborns, especially of preterm infants. Pasteurized donor human milk (PDHM) is the second-best option when preterm mother’s own milk is unavailable. Since pasteurization affect the microbiological quality of donor milk, PDHM was inoculated with different preterm milk samples and then incubated, in order to evaluate the effect in terms of bacterial growth, human milk microbiome and proteolytic phenomena. Methods In an in-vitro study PDHM was inoculated at 10% v/v using ten preterm milk samples. Microbiological, metataxonomic and peptidomic analyses, on preterm milk samples at the baseline (T0), on PDHM and on inoculated milk (IM) samples at T0, after 2 h (T1) and 4 h (T2) of incubation at 37 °C, were conducted. Results IM samples at T2 showed a Total Bacterial Count not significantly different (p > 0.01) compared to preterm milk samples. At T2 lactic acid bacteria level was restored in all IM. After inoculation, metataxonomic analysis in IM samples showed that Proteobacteria remained the predominant phylum while Firmicutes moved from 3% at T1 to 9.4% at T2. Peptidomic profile of IM resembled that of PDHM, incubated for the same time, in terms of number and type of peptides. Conclusion The study demonstrated that inoculation of PDHM with mother’s own milk could restore bacterial growth and personalize human milk microbiome in PDHM. This effect could be beneficial because of the presence of maternal probiotic bacteria which make PDHM more similar to mother’s own milk.

Recently, the use of antimicrobials on dairy farms has been significantly limited from both the legislative and consumer points of view. This study aims to check the efficacy of selective dry cow therapy (SDCT) versus blanket dry cow therapy (BDCT) on bovine udder in healthy animals. SDTC is when an antibiotic is administered only to infected cows, compared with BDCT, where all cows receive an antimicrobial, regardless of their infection status. The milk samples were collected from enrolled Holstein Friesian cows 7 days before dry-off (T0) and 10 days after calving (T1) to assess somatic cell count (SCC), intramammary infections (IMIs), and milk microbiota variation. After pre-drying sampling, cows are randomly assigned to the following treatments: internal teat sealant alone (ITS; 24 cows), which is a treatment in a cow that does not receive antibiotics in SDTC, or in combination with intramammary antibiotic treatment (A+ITS; 22 cows). Non-statistically significant results are found between the two treatment groups at T1 for SCC, milk yield, and alpha diversity in milk microbiota. A statistically (p < 0.033) T1 IMI decrease is reported in the A+ITS group, and a significant beta diversity analysis is shown between the two timepoints (p = 0.009). This study confirms the possibility of selective drying without new IMI risk or increased SCC at calving, considering healthy cows without contagious infections and SCC values >200,000 cells/mL in the previous lactation.

(1) Background: The “bird dog” exercise is considered one of the most effective therapeutic exercises for lumbopelvic rehabilitation and the prevention and treatment of low back pain. The “standing bird dog” (SBD) exercise, executed in a single-leg stance, constitutes a natural and challenging variation in the “bird dog”; nevertheless, this exercise has not yet been investigated. This study provides a stabilometric and electromyographic analysis of the SBD performed in static and dynamic conditions and in ipsilateral and contralateral variations; (2) Methods: A time-synchronized motion capture system, wireless electromyography sensors, and triaxial force platform were used to analyze the selected SBD exercises; (3) Results: In dynamic conditions, the gluteus maximum, multifidus, lumbar erector spinae, and gluteus medius reached a mean activation level higher than in the static condition, with peak activation levels of 80%, 60%, 55%, and a 45% maximum voluntary isometric contraction, respectively. In the static condition, balance control was more challenging in the mediolateral compared to the anteroposterior direction. In the dynamic condition, the balance challenge was higher in the anteroposterior direction and higher than the static condition in both directions; (4) Conclusions: The SBD was proved to be effective for strengthening the hip and lumbar extensor muscles and provided a powerful challenge to single-leg balance control in both mediolateral and anteroposterior directions.

Poly (3,4-ethylendioxythiophene) polystyrene sulphonate (PEDOT:PSS) is the workhorse of organic bioelectronics and is steadily gaining interest also in tissue engineering due to the opportunity to endow traditional biomaterials for scaffolds with conductive properties. Biomaterials capable of promoting neural stem cell differentiation by application of suitable electrical stimulation protocols are highly desirable in neural tissue engineering. In this study, we evaluated the adhesion, proliferation, maintenance of neural crest stemness markers and neurogenic commitment of neural crest-derived human dental pulp stem cells (hDPSCs) cultured on PEDOT:PSS nanostructured thin films deposited either by spin coating (SC-PEDOT) or by electropolymerization (ED-PEDOT). In addition, we evaluated the immunomodulatory properties of hDPSCs on PEDOT:PSS by investigating the expression and maintenance of the Fas ligand (FasL). We found that both SC-PEDOT and ED-PEDOT thin films supported hDPSCs adhesion and proliferation; however, the number of cells on the ED-PEDOT after 1 week of culture was significantly higher than that on SC-PEDOT. To be noted, both PEDOT:PSS films did not affect the stemness phenotype of hDPSCs, as indicated by the maintenance of the neural crest markers Nestin and SOX10. Interestingly, neurogenic induction was clearly promoted on ED-PEDOT, as indicated by the strong expression of MAP-2 and β—Tubulin-III as well as evident cytoskeletal reorganisation and appreciable morphology shift towards a neuronal-like shape. In addition, strong FasL expression was detected on both undifferentiated or undergoing neurogenic commitment hDPSCs, suggesting that ED-PEDOT supports the expression and maintenance of FasL under both expansion and differentiation conditions.

Ground-based microwave radiometer (MWR) observations of downwelling brightness temperature (TB) are commonly used to estimate atmospheric attenuation at relative transparent channels for radio propagation and telecommunication purposes. The atmospheric attenuation is derived from TB by inverting the radiative transfer equation with a priori knowledge of the mean radiating temperature (TMR). TMR is usually estimated by either time-variant site climatology (e.g., monthly average computed from atmospheric thermodynamical profiles) or condition-variant estimation from surface meteorological sensors. However, information on TMR may also be extracted directly from MWR measurements at channels other than those used to estimate atmospheric attenuation. This paper proposes a novel approach to estimate TMR in clear and cloudy sky from independent MWR profiler measurements. A linear regression algorithm is trained with a simulated dataset obtained by processing 1 year of radiosonde observations of atmospheric thermodynamic profiles. The algorithm is trained to estimate TMR at K- and V–W-band frequencies (22–31 and 72–82 GHz, respectively) from independent MWR observations at the V band (54–58 GHz). The retrieval coefficients are then applied to a 1-year dataset of real V-band observations, and the estimated TMR at the K and V–W band is compared with estimates from nearly colocated and simultaneous radiosondes. The proposed method provides TMR estimates in better agreement with radiosondes than a traditional method, with 32 %–38 % improvement depending on frequency. This maps into an expected improvement in atmospheric attenuation of 10 %–20 % for K-band channels and ∼30 % for V–W-band channels.

Objectives: The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods: A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results: Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p

Objectives: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. Methods: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalisation and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson’s chi-square or Fisher’s exact test for categorical variables, whereas the Wilcoxon rank–sum test was employed for continuous ones. Kaplan–Meier curves were produced to compare the time to nasopharyngeal swab negativity. Results: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups regarding clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p = 0.088) emerged. Conclusions: Early treatment of SARS-CoV-2 infection with TIX/CIL showed favourable outcomes in a small group of immunocompromised patients, reporting no significant difference compared to similar patients treated with other mAbs.

Abstract Background Graves’ disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves’ orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks). Results In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors’ microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO. Conclusions These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract

Abstract An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. 426 adult patients [median age 68 (IQR 56 to 77 years)] were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Among these 46 patients, updated as of 30 May, 2020, 5 (10.9%) had died, 8 (17.4%) were still in ICU, 12 (26.1%) were transferred to lower intensity care units and 21 (45.7%) were discharged. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4th were independent risk factors associated with in-hospital mortality. Older age, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19.

Abstract Neurofilaments are structural scaffolding proteins of the neuronal cytoskeleton. Upon axonal injury, the neurofilament light chain (NF‐L) is released into the interstitial fluid and eventually reaches the cerebrospinal fluid and blood. Therefore, NF‐L is emerging as a biomarker of neurological disorders, including neurodegenerative dementia, Parkinson's disease, and multiple sclerosis. It is challenging to quantify NF‐L in bodily fluids due to its low levels. This work reports the detection of NF‐L in aqueous solutions with an organic electronic device. The biosensor is based on the electrolyte‐gated organic field‐effect transistor (EGOFET) architecture and can quantify NF‐L down to sub‐pM levels; thanks to modification of the device gate with anti‐NF‐L antibodies imparted with potentially controlled orientation. The response is fitted to the Guggenheim–Anderson–De Boer adsorption model to describe NF‐L adsorption at the gate/electrolyte interface, to consider the formation of a strongly adsorbed protein layer bound to the antibody and the formation of weakly bound NF‐L multilayers, an interpretation which is also backed up by morphological characterization via atomic force microscopy. The label‐free, selective, and rapid response makes this EGOFET biosensor a promising tool for the diagnosis and monitoring of neuronal damages through the detection of NF‐L in physio‐pathological ranges.

Abstract Successful translation of organic transistors as sensors and transducers to clinical settings is hampered by safety and stability issues. The operation of such devices demands driving voltages across the biotic/abiotic interface, which may result in undesired electrochemical reactions that may harm both the patient and the device. In this study, a novel operational mode is presented for electrolyte‐gated organic transistors that avoid these drawbacks: the common‐drain/grounded‐source configuration. This approach reverts the standard common‐source/common‐ground configuration and achieves maximum signal amplification while applying null net bias across the electrolyte, with no parasitic currents. The viability of the proposed configuration is demonstrated by recording in vivo the somatosensory evoked activity from the barrel cortex of rats. The main inherent advantage of transistors with respect to passive electrodes is preserved in the proposed scheme: a superior signal‐to‐noise ratio is achieved which enables the detection of evoked activity at the single‐trial level. Then, common‐drain/grounded‐source organic transistors are proposed as ideal candidate devices for a harmless translational recording platform.

Abstract Next‐generation neural interfaces for bidirectional communication with the central nervous system aim to achieve the intimate integration with the neural tissue with minimal neuroinflammatory response, high spatio‐temporal resolution, very high sensitivity, and readout stability. The design and manufacturing of devices for low power/low noise neural recording and safe and energy‐efficient stimulation that are, at the same time, conformable to the brain, with matched mechanical properties and biocompatibility, is a convergence area of research where neuroscientists, materials scientists, and nanotechnologists operate synergically. The biotic–abiotic neural interface, however, remains a formidable challenge that prompts for new materials platforms and innovation in device layouts. Conductive polymers (CP) are attractive materials to be interfaced with the neural tissue and to be used as sensing/stimulating electrodes because of their mixed ionic‐electronic conductivity, their low contact impedance, high charge storage capacitance, chemical versatility, and biocompatibility. This manuscript reviews the state‐of‐the‐art of poly(3,4‐ethylenedioxythiophene)‐based neural interfaces for extracellular recording and stimulation, focusing on those technological approaches that are successfully demonstrated in vivo. The aim is to highlight the most reliable and ready‐for‐clinical‐use solutions, in terms of materials technology and recording performance, other than spot major limitations and identify future trends in this field.

BackgroundThe use of electromagnetic (EM) technologies for military applications is gaining increasing interest to satisfy different operational needs, such as improving battlefield communications or jamming counterpart's signals. This is achieved by the use of high-power EM waves in several frequency bands (e.g., HF, VHF, and UHF). When considering military vehicles, several antennas are present in close proximity to the crew personnel, which are thus potentially exposed to high EM fields.MethodsA typical exposure scenario was reproduced numerically to evaluate the EM exposure of the human body in the presence of an HF vehicular antenna (2–30 MHz). The antenna was modeled as a monopole connected to a 3D polygonal structure representing the vehicle. Both the EM field levels in the absence and in the presence of the human body and also the specific absorption rate (SAR) values were calculated. The presence of the operator, partially standing outside the vehicle, was simulated with the virtual human body model Duke (Virtual Population, V.3). Several exposure scenarios were considered. The presence of a protective helmet was modeled as well.ResultsIn the area usually occupied by the personnel, E-field intensity radiated by the antenna can reach values above the limits settled by international safety guidelines. Nevertheless, local SAR values induced inside the human body reached a maximum value of 14 mW/kg, leading to whole-body averaged and 10-g averaged SAR values well below the corresponding limits.ConclusionA complex and realistic near-field exposure scenario of the crew of a military vehicle was simulated. The obtained E-field values radiated in the free space by a HF vehicular antenna may reach values above the safety guidelines reference levels. Such values are not necessarily meaningful for the exposed subject. Indeed, SAR and E-field values induced inside the body remain well below safety limits.

Early feed restriction of lambs may program animals to achieve reduced feed efficiency traits as a consequence of permanent mitochondrial dysfunction. The hypothesis at the background of the present study is that dietary administration of L-Carnitine (a compound that promotes the activation and transportation of fatty acids into the mitochondria) during the fattening period of early feed restricted lambs can: (a) improve the biochemical profile of early feed restricted lambs, (b) improve feed efficiency, (c) modulate the ruminal and intestinal microbiota, and (d) induce changes in the gastrointestinal mucosa, including the immune status. Twenty-two newborn male Merino lambs were raised under natural conditions but separated from the dams for 9 h daily to allow feed restriction during the suckling period. At weaning, lambs were assigned to a control group being fed ad libitum a complete pelleted diet during the fattening phase (CTRL, n = 11), whereas the second group (CARN, n = 11) received the same diet supplemented with 3 g of L-Carnitine/kg diet. The results revealed that even though L-Carnitine was absorbed, feed efficiency was not modified by dietary L-Carnitine during the fattening period (residual feed intake, p > 0.05), whereas ruminal fermentation was improved [total short-chain fatty acids (SCFAs), 113 vs. 154 mmol/l; p = 0.036]. Moreover, a trend toward increased concentration of butyrate in the ileal content (0.568 vs. 1.194 mmol/100 ml SCFA; p = 0.074) was observed. Other effects, such as reduced heart weight, lower levels of markers related to muscle metabolism or damage, improved renal function, and increased ureagenesis, were detected in the CARN group. Limited changes in the microbiota were also detected. These findings suggest that L-Carnitine may improve ruminal fermentation parameters and maintain both the balance of gut microbiota and the health of the animals. However, the improved ruminal fermentation and the consequent greater accumulation of intramuscular fat might have hidden the effects caused by the ability of dietary L-Carnitine to increase fatty acid oxidation at the mitochondrial level. This would explain the lack of effects of L-Carnitine supplementation on feed efficiency and points toward the need of testing lower doses, probably in the context of animals being fed in excess non-protein nitrogen.

Mastitis is a most common disease of dairy cows and causes tremendous economic loss to the dairy industry worldwide. Somatic cell counts (SCC) reflect the inflammatory response to infections and is a metric used as key indicator in mastitis screening programs, typically within the framework of national milk recording schemes. Besides the determination of total SCC, the differentiation of cell types has been described to be beneficial for a more definite description of the actual udder health status of dairy cows. Differential somatic cell count (DSCC) represents the combined proportion of polymorphonuclear leukocytes (PMN) and lymphocytes expressed as a percentage of the total. The aim of this study was to investigate the relationship between SCC and differential somatic cell count (DSCC) in individual quarter milk samples collected at different time points: at dry-off, after calving and at the lactation peak. We used individual quarter data from farms representing the specialized production system of Parmigiano Reggiano cheese in Northern Italy. Average DSCC values ranged between 44.9% and 56.3%, with higher values (60.4%-72.1%) in milk samples with ≥ 1 million SCC/ml (where the proportion of samples with DSCC > 70% can be as high as 0.73). Moderate overall correlations between DSCC and log(SCC) were estimated (Pearson = 0.42, Spearman = 0.38), with a clear increasing trend with parity and around the lactation peak (e.g. Pearson = 0.59 at 60 DIM in parity 4). Taking SCC values as indicators of subclinical mastitis, DSCC would diagnose mastitis with 0.75 accuracy. Data editing criteria do have an impact on results, with stricter filtering leading to lower correlations between log(SCC) and DSCC. In conclusion DSCC and SCC provide different descriptions of the udder health status of dairy cows which, at least to some extent, are independent. DSCC alone doesn't provide more accurate information than SCC at quarter level but, used in combination with SCC, can be of potential interest within the framework of milk recording programs, especially in the context of selective dry-cow therapy (SDCT). However, this needs further investigation and updated threshold values need to be selected and validated.