Cell- and Pathway-Specific Disruptions in the Accumbens of Fragile X Mouse.

Fragile X syndrome (FXS) is a genetic cause of intellectual disability and autism spectrum disorder. The mesocorticolimbic system, which includes the prefrontal cortex (PFC), basolateral amygdala (BLA), and nucleus accumbens core (NAcC), is essential for regulating socioemotional behaviors. We employed optogenetics to compare the functional properties of the BLA→NAcC, PFC→NAcC, and reciprocal PFC↔BLA pathways in Fmr1-/y::Drd1a-tdTomato male mice. In FXS mice, the PFC↔BLA reciprocal pathway was unaffected, while significant synaptic modifications occurred in the BLA/PFC→NAcC pathways. We observed distinct changes in D1 striatal projection neurons (SPNs) and separate modifications in D2 SPNs. In FXS mice, the BLA/PFC→NAcC-D2 SPN pathways demonstrated heightened synaptic strength. Focusing on the BLA→NAcC pathway, linked to autistic symptoms, we found increased AMPAR and NMDAR currents and elevated spine density in D2 SPNs. Conversely, the amplified firing probability of BLA→NAcC-D1 SPNs was not accompanied by increased synaptic strength, AMPAR and NMDAR currents, or spine density. These pathway-specific alterations resulted in an overall enhancement of excitatory-to-spike coupling, a physiologically relevant index of how efficiently excitatory inputs drive neuronal firing, in both BLA→NAcC-D1 and BLA→NAcC-D2 pathways. Finally, the absence of fragile X messenger ribonucleoprotein 1 (FMRP) led to impaired long-term depression specifically in BLA→D1 SPNs. These distinct alterations in synaptic transmission and plasticity within circuits targeting the NAcC highlight the potential role of postsynaptic mechanisms in selected SPNs in the observed circuit-level changes. This research underscores the heightened vulnerability of the NAcC in the context of FMRP deficiency, emphasizing its pivotal role in the pathophysiology of FXS.

Multinational evaluation of genetic diversity indicators for the Kunming-Montreal Global Biodiversity Framework.

Under the recently adopted Kunming-Montreal Global Biodiversity Framework, 196 Parties committed to reporting the status of genetic diversity for all species. To facilitate reporting, three genetic diversity indicators were developed, two of which focus on processes contributing to genetic diversity conservation: maintaining genetically distinct populations and ensuring populations are large enough to maintain genetic diversity. The major advantage of these indicators is that they can be estimated with or without DNA-based data. However, demonstrating their feasibility requires addressing the methodological challenges of using data gathered from diverse sources, across diverse taxonomic groups, and for countries of varying socio-economic status and biodiversity levels. Here, we assess the genetic indicators for 919 taxa, representing 5271 populations across nine countries, including megadiverse countries and developing economies. Eighty-three percent of the taxa assessed had data available to calculate at least one indicator. Our results show that although the majority of species maintain most populations, 58% of species have populations too small to maintain genetic diversity. Moreover, genetic indicator values suggest that IUCN Red List status and other initiatives fail to assess genetic status, highlighting the critical importance of genetic indicators.

Spread and persistence of antimicrobial resistance genes in wastewater from human and animal sources in São Paulo, Brazil.

The spread of antimicrobial resistance (AMR) through multiple reservoirs is a global concern. Wastewater is a critical AMR dissemination source, so this study aimed to assess the persistence of resistance genetic markers in wastewater using a culture-independent approach. Raw and treated wastewater samples (n = 121) from a wastewater treatment plant (WWTP), a human hospital, a veterinary hospital, and a pig farm were monthly collected and concentrated by filtration. DNA was extracted directly from filter membranes, and PCR was used in the qualitative search of 32 antimicrobial resistance genes (ARGs). Selected genes (blaCTX-M, blaKPC, qnrB, and mcr-1) were enumerated by quantitative real-time PCR (qPCR). Twenty-six ARGs were detected in the qualitative ARGs search, while quantitative data showed a low variation of the ARG's relative abundance (RA) throughout the months, especially at the human hospital and the WWTP. At the WWTP, despite significantly reducing the absolute number of gene copies/L after each treatment stage (p < 0.05), slight increases (p > 0.05) in the RAs of genes blaCTX-M, qnrB, and mcr-1 were observed in reused water (tertiary treatment) when compared with secondary effluent. Although the increase is not statistically significant, it is worth noting that there was some level of ARGs concentration after the disinfection process. No significant absolute or relative after-treatment quantification reductions were observed for any ARGs at the veterinary hospital or the pig farm. The spread of ARGs through sewage needs to be continuously addressed, because their release into natural environments may pose potential risks of exposure to resistant bacteria and impact local ecosystems.

Ablative margin quantification using deformable versus rigid image registration in colorectal liver metastasis thermal ablation: a retrospective single-center study.

PURPOSE: To investigate the correlation of minimal ablative margin (MAM) quantification using biomechanical deformable (DIR) versus intensity-based rigid image registration (RIR) with local outcomes following colorectal liver metastasis (CLM) thermal ablation. METHODS: This retrospective single-institution study included consecutive patients undergoing thermal ablation between May 2016 and October 2021. Patients who did not have intraprocedural pre- and post-ablation contrast-enhanced CT images for MAM quantification or follow-up period less than 1 year without residual tumor or local tumor progression (LTP) were excluded. DIR and RIR methods were used to quantify the MAM. The registration accuracy was compared using Dice similarity coefficient (DSC). Area under the receiver operating characteristic curve (AUC) was used to test MAM in predicting local tumor outcomes. RESULTS: A total of 72 patients (mean age 57; 44 men) with 139 tumors (mean diameter 1.5 cm ± 0.8 (SD)) were included. During a median follow-up of 29.4 months, there was one residual unablated tumor and the LTP rate was 17% (24/138). The ranges of DSC were 0.96-0.98 and 0.67-0.98 for DIR and RIR, respectively (p < 0.001). When using DIR, 27 (19%) tumors were partially or totally registered outside the liver, compared to 46 (33%) with RIR. Using DIR versus RIR, the corresponding median MAM was 4.7 mm versus 4.0 mm, respectively (p = 0.5). The AUC in predicting residual tumor and 1-year LTP for DIR versus RIR was 0.89 versus 0.72, respectively (p < 0.001). CONCLUSION: Ablative margin quantified on intra-procedural CT imaging using DIR method outperformed RIR for predicting local outcomes of CLM thermal ablation. CLINICAL RELEVANCE STATEMENT: The study supports the role of biomechanical deformable image registration as the preferred image registration method over rigid image registration for quantifying minimal ablative margins using intraprocedural contrast-enhanced CT images. KEY POINTS: • Accurate and reproducible image registration is a prerequisite for clinical application of image-based ablation confirmation methods. • When compared to intensity-based rigid image registration, biomechanical deformable image registration for minimal ablative margin quantification was more accurate for liver registration using intraprocedural contrast-enhanced CT images. • Biomechanical deformable image registration outperformed intensity-based rigid image registration for predicting local tumor outcomes following colorectal liver metastasis thermal ablation.

Association between COVID-19 and the incidence of type 1 diabetes in Portugal - a registry study.

BACKGROUND: Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D. METHODS: Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers. RESULTS: In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25-75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356-568), 11.8% (10.1-13.4) and 0.50 µg/L (0.30-0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period. CONCLUSION: The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.

Reliability and validity of the London Chest Activity of Daily Living scale for adults with asthma.

INTRODUCTION: Dyspnea during activities of daily living (ADL) is frequently reported by adults with asthma. However, instruments that specifically assess that in people with asthma have not yet been validated. OBJECTIVES: To investigate the validity and reliability, including standard error of measurement (SEM) and Minimum Detectable Change (MDC), of the London Chest Activity of Daily Living (LCADL) scale for adults with asthma. METHODS: Adults with asthma answered the LCADL scale which was performed twice by the same rater. Spirometry, 6-min walk test (6MWT), St George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea scale, Asthma Quality of Life questionnaire (AQLQ), Asthma Control Test (ACT), and Glittre-ADL test were assessed. For statistical analyses, Spearman correlation, Wilcoxon test, Intraclass Correlation Coefficient (ICC), Cronbach's alpha coefficient, SEM, MDC were performed. RESULTS: Seventy participants were included (30% men, 44 ± 15 years old, BMI 27[23-31]kg/m2, FEV1 80 ± 17%predicted). For convergent validity, the LCADL scale was moderately correlated with SGRQ, AQLQ, and Glittre-ADL (r = 0.57, -0.46, and 0.41 respectively; p < 0.0001). The LCADL scale correlated weakly with the mMRC scale, ACT, and spirometry measures (-0.23

Londrina Activities of Daily Living Protocol: validity, reliability, minimal detectable change, and standard error of measurement in adults with asthma.

INTRODUCTION: Asthma symptoms are dyspnea, chronic cough, wheezing, chest tightness, or chest discomfort, which can directly limit the activities of daily living (ADL), which is frequently reported by adults with asthma. Evaluating ADL with a reliable protocol at the usual speed is necessary. OBJECTIVES: To investigate the validity, reliability, minimal detectable change (MDC), and standard error of measurement (SEM) of the Londrina ADL Protocol (LAP) for adults with asthma. METHODS: Adults with asthma were evaluated with the LAP test. Spearman's correlation coefficient was used to verify validity with the 6-min walk test (6MWT), Glittre-ADL test, and London Chest Activity of Daily Living (LCADL). To test the reliability, the test was reapplied in at least 30 min; the Wilcoxon test and Intraclass Correlation Coefficient (ICC), SEM, MDC, and learning effect were performed. RESULTS: Fifty-three individuals were included (26% men, 43 ± 15 years, BMI 28 ± 8 kg/m2, FEV1 70 ± 24%predicted). For convergent validity, the LAP test was correlated with the 6MWT, Glittre-ADL, and LCADL scale (r = -0.49, 0.71, and 0.30, respectively; p < 0.03). There was a difference in test-retest (p < 0.0001) and reliability analysis shows ICC3 of 0.94, SEM of 14.88 s (22%), and MDC of 41.23 s (15%). Furthermore, the individuals performed the second test with -23 ± 19 (7.9%) s. CONCLUSION: The LAP test is valid and reliable for assessing limitations during ADL in adults with asthma. Considerable learning effect was observed, therefore, the best of two measures may avoid underestimation.

Efficacy, safety of and adherence to adjustable compression wraps in the control phase of breast cancer-related lymphedema: A randomized controlled trial.

OBJECTIVE: To evaluate efficacy, safety, and adherence to using adjustable compression wraps (ACWs) for upper limb volume control in women with breast cancer-related lymphedema. DESIGN AND SETTING: Randomized controlled trial at a reference hospital for breast cancer treatment in Brazil. PARTICIPANTS: Women in control phase of the breast cancer-related lymphedema. INTERVENTIONS: Compared use of ACWs versus compressive mesh. MAIN MEASURES: Evaluated before treatment, at 30 days, and 6 months after initiating therapy. The primary outcome was the change in excess limb volume. Secondary outcomes included adherence, incidence of adverse events, functionality, quality of life, and hand grip. Statistical analysis involved calculating the effect size (ES) with a 95% confidence interval. RESULTS: Were included 71 women with mean excess limb volume of 321.79 mL (±194.98). In the 30-day analysis (Time 1), a reduction of 37.6 mL in volume was observed only in the ACW group (p = .041, ES 0.20), with improved functionality (p = .013, ES 0.22). In the six months analysis (Time 2), the compressive mesh group increased by 2.48% in volume (p = .023, ES 0.26) and demonstrated improvement functionality (p = .036, ES 0.27). Mild adverse events and satisfactory adherence were observed. However, in the intergroup comparison, no statistically significant difference was observed for any evaluated outcome-excess volume, incidence of adverse events, adherence, hand grip, quality of life, and functionality between the groups (p > .05) at both times. CONCLUSIONS: Both compression therapies achieved satisfactory adherence, were safe, effective and equivalent for controlling limb volume in breast cancer-related lymphedema.

Exploring SoySNP50K and USDA Germplasm Collection Data to Find New QTLs Associated with Protein and Oil Content in Brazilian Genotypes.

Genetic diversity within a germplasm collection plays a vital role in the success of breeding programs. However, comprehending this diversity and identifying accessions with desirable traits pose significant challenges. This study utilized publicly available data to investigate SNP markers associated with protein and oil content in Brazilian soybeans. Through this research, twenty-two new QTLs (Quantitative Trait Loci) were identified, and we highlighted the substantial influence of Roanoke, Lee and Bragg ancestor on the genetic makeup of Brazilian soybean varieties. Our findings demonstrate that certain markers are being lost in modern cultivars, while others maintain or even increase their frequency. These observations indicate genomic regions that have undergone selection during soybean introduction in Brazil and could be valuable in breeding programs aimed at enhancing protein or oil content.

Development of collagenous scaffolds for wound healing: characterization and in vivo analysis.

The development of wound dressings from biomaterials has been the subject of research due to their unique structural and functional characteristics. Proteins from animal origin, such as collagen and chitosan, act as promising materials for applications in injuries and chronic wounds, functioning as a repairing agent. This study aims to evaluate in vitro effects of scaffolds with different formulations containing bioactive compounds such as collagen, chitosan, N-acetylcysteine (NAC) and ε-poly-lysine (ε-PL). We manufactured a scaffold made of a collagen hydrogel bioconjugated with chitosan by crosslinking and addition of NAC and ε-PL. Cell viability was verified by resazurin and live/dead assays and the ultrastructure of biomaterials was evaluated by SEM. Antimicrobial sensitivity was assessed by antibiogram. The healing potential of the biomaterial was evaluated in vivo, in a model of healing of excisional wounds in mice. On the 7th day after the injury, the wounds and surrounding skin were processed for evaluation of biochemical and histological parameters associated with the inflammatory process. The results showed great cell viability and increase in porosity after crosslinking while antimicrobial action was observed in scaffolds containing NAC and ε-PL. Chitosan scaffolds bioconjugated with NAC/ε-PL showed improvement in tissue healing, with reduced lesion size and reduced inflammation. It is concluded that scaffolds crosslinked with chitosan-NAC-ε-PL have the desirable characteristics for tissue repair at low cost and could be considered promising biomaterials in the practice of regenerative medicine.

A three-dimensional cell culture approach to investigate cytotoxic effects and production of inflammatory mediators by epoxy resin-based and calcium silicate-based endodontic sealer.

OBJECTIVES: The aim of the present study was to assess the cytocompatibility of epoxy resin-based AH Plus Jet (Dentsply De Trey, Konstanz, Germany), Sealer Plus (MK Life, Porto Alegre, Brazil), calcium silicate-based Bio-C Sealer (Angelus, Londrina, PR, Brazil), Sealer Plus BC (MK Life) and AH Plus BC (Dentsply) through a tridimensional (3D) culture model of human osteoblast-like cells. METHODS: Spheroids of MG-63 cells were produced and exposed to fresh root canal sealers extracts by 24 h, and the cytotoxicity was assessed by the Lactate Dehydrogenase assay (LDH). The distribution of dead cells within the microtissue was assessed by fluorescence microscopy, and morphological effects were investigated by histological analysis. The secreted inflammatory mediators were detected in cell supernatants through flow luminometry (XMap Luminex). RESULTS: Cells incubated with AH Plus Jet, AH Plus BC, Sealer Plus BC and Bio-C Sealer extracts showed high rates of cell viability, while the Sealer Plus induced a significant reduction of cell viability, causing reduction on the spheroid structure. Sealer Plus and Seaker Plus BC caused alterations on 3D microtissue morphology. The AH Plus BC extract was associated with the downregulation of secretion of pro-inflammatory cytokines IL-5, IL-7, IP-10 and RANTES. CONCLUSIONS: The new AH Plus BC calcium silicate-based endodontic sealer did not reduce cell viability in vitro, while led to the downregulation of pro-inflammatory cytokines. CLINICAL SIGNIFICANCE: Choosing the appropriate endodontic sealer is a crucial step. AH Plus BC demonstrated high cell viability and downregulation of pro-inflammatory cytokines, appearing reliable for clinical use, while Sealer Plus presented lower cytocompatibility.

Spatialized PM2.5 during COVID-19 pandemic in Brazil's most populous southern city: implications for post-pandemic era.

Brazil has experienced one of the highest COVID-19 fatality rates globally. While numerous studies have explored the potential connection between air pollution, specifically fine particulate matter (PM2.5), and the exacerbation of SARS-CoV-2 infection, the majority of this research has been conducted in foreign regions-Europe, the United States, and China-correlating generalized pollution levels with health-related scopes. In this study, our objective is to investigate the localized connection between exposure to air pollution exposure and its health implications within a specific Brazilian municipality, focusing on COVID-19 susceptibility. Our investigation involves assessing pollution levels through spatial interpolation of in situ PM2.5 measurements. A network of affordable sensors collected data across 9 regions in Curitiba, as well as its metropolitan counterpart, Araucaria. Our findings distinctly reveal a significant positive correlation (with r-values reaching up to 0.36, p-value < 0.01) between regions characterized by higher levels of pollution, particularly during the winter months (with r-values peaking at 0.40, p-value < 0.05), with both COVID-19 mortality and incidence rates. This correlation gains added significance due to the intricate interplay between urban atmospheric pollution and regional human development indices. Notably, heightened pollution aligns with industrial hubs and intensified vehicular activity. The spatial analysis performed in this study assumes a pivotal role by identifying priority regions that require targeted action post-COVID. By comprehending the localized dynamics between air pollution and its health repercussions, tailored strategies can be implemented to alleviate these effects and ensure the well-being of the public.

Challenges on the development of a dengue vaccine: a comprehensive review of the state of the art.

Dengue virus (DENV) is the mosquito-borne virus of greatest human health concern. There are four serotypes of DENV (1-4) that co-circulate in endemic areas. Each serotype of DENV is individually capable of causing the full spectrum of disease, ranging from self-resolving dengue fever to the more severe dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Based on data published by the CDC, one in four people who become infected with dengue will become ill. Of those that do develop symptomology, the symptoms can range from mild to severe. Symptoms can vary from rash, ocular aches and pains to more intense symptoms in the manifestation of severe dengue. Roughly, 1 in 20 people who become ill will develop severe dengue, which can result in shock, internal bleeding and death. There is currently no specific treatment for dengue and only one licensed vaccine (Dengvaxia) for children 9 through 16 years of age in just a few countries. Despite its licensure for clinical use, Dengvaxia has performed with low efficacy in children and dengue naïve individuals and critically has resulted in increased risk of developing severe dengue in young, vaccinated recipients. Currently, there are various novel strategies for the development of a dengue vaccine. In this review we have conducted a detailed overview of the DENV vaccine landscape, focusing on nine vaccines in the pipeline to provide a comprehensive overview of the most state-of-the-art developments in strategies for vaccines against DENV.

Progress and Challenges of Understanding Cardiorenal Syndrome Type 3.

The pathologies of the kidney and heart have instigated a large number of researchers around the world to try to better understand what the exact connectors responsible for the emergence and establishment of these diseases are. The classification of these pathologies into different types of cardiorenal syndromes (CRSs) over the last 15 years has greatly contributed to understanding pathophysiological and diagnostic aspects, as well as treatment strategies. However, with the advent of new technologies classified as "Omics", a new range of knowledge and new possibilities have opened up in order to effectively understand the intermediaries between the kidney-heart axis. The universe of micro-RNAs (miRNAs), epigenetic factors, and components present in extracellular vesicles (EVs) have been protagonists in studying different types of CRSs. Thus, the new challenge that is imposed is to select and link the large amount of information generated from the use of large-scale analysis techniques. The present review seeks to present some of the future perspectives related to understanding CRSs, with an emphasis on CRS type 3.

Anticonvulsant Role of Adenosine is Blunted During Alcohol Withdrawal Syndrome in an Adult Zebrafish Model.

Alcohol (ethanol) dependence and related disorders are life-threatening conditions and source of suffering for the user, family members and society. Alcohol withdrawal syndrome (AWS) is a little-known dynamic process associated with a high frequency of relapses. A state of hyperglutamatergic neurotransmission and imbalanced GABAergic function is related to an increased susceptibility to seizures during alcohol withdrawal. Adenosine signaling display an important role in endogenous response to decrease seizure and related damages. Here, an intermittent alcohol exposure regimen (1 h daily of 0.5% ethanol solution) for 16 days or 8 days of the same ethanol exposure regimen followed by 1 or 8 days of ethanol withdrawal was used to assess adenosine signaling in the context of seizure susceptibility using adult zebrafish. In both abstainer groups, a sub-convulsant dose of pentylenetetrazol (2.5 mM) was able to increase the frequency of animals reaching a clonic seizure-like state, while continuous-treated animals had no seizure, as did control animals. The total brain mRNA expression of A1 adenosine receptor was decreased in animals with 1 day of ethanol withdrawal. The agonism of A1 adenosine receptor induced an anticonvulsant effect in animals with 1 day of ethanol withdrawal after the injection of the specific agonist (N6-cyclopentyladenosine, 10 mg.Kg- 1; i.p.). These findings reinforce A1 adenosine receptor as a key target in acute alcohol withdrawal syndrome and zebrafish as an excellent platform to study biological mechanism of AWS.

Healing profiles in patients with a chronic diabetic foot ulcer: An exploratory study with machine learning.

Diabetic foot ulcers (DFU) are one of the most frequent and debilitating complications of diabetes. DFU wound healing is a highly complex process, resulting in significant medical, economic and social challenges. Therefore, early identification of patients with a high-risk profile would be important to adequate treatment and more successful health outcomes. This study explores risk assessment profiles for DFU healing and healing prognosis, using machine learning predictive approaches and decision tree algorithms. Patients were evaluated at baseline (T0; N = 158) and 2 months later (T1; N = 108) on sociodemographic, clinical, biochemical and psychological variables. The performance evaluation of the models comprised F1-score, accuracy, precision and recall. Only profiles with F1-score >0.7 were selected for analysis. According to the two profiles generated for DFU healing, the most important predictive factors were illness representations on T1 IPQ-B (IPQ-B ≤ 9.5 and < 10.5) and the DFU duration (≤ 13 weeks). The two predictive models for DFU healing prognosis suggest that biochemical factors are the best predictors of a favorable healing prognosis, namely IL-6, microRNA-146a-5p and PECAM-1 at T0 and angiopoietin-2 at T1. Illness perception at T0 (IPQ-B ≤ 39.5) also emerged as a relevant predictor for healing prognosis. The results emphasize the importance of DFU duration, illness perception and biochemical markers as predictors of  healing in chronic DFUs. Future research is needed to confirm and test the obtained predictive models.

Bayesian parametric models for survival prediction in medical applications.

BACKGROUND: Evidence-based treatment decisions in medicine are made founded on population-level evidence obtained during randomized clinical trials. In an era of personalized medicine, these decisions should be based on the predicted benefit of a treatment on a patient-level. Survival prediction models play a central role as they incorporate the time-to-event and censoring. In medical applications uncertainty is critical especially when treatments differ in their side effect profiles or costs. Additionally, models must be adapted to local populations without diminishing performance and often without the original training data available due to privacy concern. Both points are supported by Bayesian models-yet they are rarely used. The aim of this work is to evaluate Bayesian parametric survival models on public datasets including cardiology, infectious diseases, and oncology. MATERIALS AND METHODS: Bayesian parametric survival models based on the Exponential and Weibull distribution were implemented as a Python package. A linear combination and a neural network were used for predicting the parameters of the distributions. A superiority design was used to assess whether Bayesian models are better than commonly used models such as Cox Proportional Hazards, Random Survival Forest, and Neural Network-based Cox Proportional Hazards. In a secondary analysis, overfitting was compared between these models. An equivalence design was used to assess whether the prediction performance of Bayesian models after model updating using Bayes rule is equivalent to retraining on the full dataset. RESULTS: In this study, we found that Bayesian parametric survival models perform as good as state-of-the art models while requiring less hyperparameters to be tuned and providing a measure of the uncertainty of the predictions. In addition, these models were less prone to overfitting. Furthermore, we show that updating these models using Bayes rule yields equivalent performance compared to models trained on combined original and new datasets. CONCLUSIONS: Bayesian parametric survival models are non-inferior to conventional survival models while requiring less hyperparameter tuning, being less prone to overfitting, and allowing model updating using Bayes rule. Further, the Bayesian models provide a measure of the uncertainty on the statistical inference, and, in particular, on the prediction.

Genomic and proteomic characterization of vB_SauM-UFV_DC4, a novel Staphylococcus jumbo phage.

Staphylococcus aureus is one of the most relevant mastitis pathogens in dairy cattle, and the acquisition of antimicrobial resistance genes presents a significant health issue in both veterinary and human fields. Among the different strategies to tackle S. aureus infection in livestock, bacteriophages have been thoroughly investigated in the last decades; however, few specimens of the so-called jumbo phages capable of infecting S. aureus have been described. Herein, we report the biological, genomic, and structural proteomic features of the jumbo phage vB_SauM-UFV_DC4 (DC4). DC4 exhibited a remarkable killing activity against S. aureus isolated from the veterinary environment and stability at alkaline conditions (pH 4 to 12). The complete genome of DC4 is 263,185 bp (GC content: 25%), encodes 263 predicted CDSs (80% without an assigned function), 1 tRNA (Phe-tRNA), multisubunit RNA polymerase, and an RNA-dependent DNA polymerase. Moreover, comparative analysis revealed that DC4 can be considered a new viral species belonging to a new genus DC4 and showed a similar set of lytic proteins and depolymerase activity with closely related jumbo phages. The characterization of a new S. aureus jumbo phage increases our understanding of the diversity of this group and provides insights into the biotechnological potential of these viruses. KEY POINTS: • vB_SauM-UFV_DC4 is a new viral species belonging to a new genus within the class Caudoviricetes. • vB_SauM-UFV_DC4 carries a set of RNA polymerase subunits and an RNA-directed DNA polymerase. • vB_SauM-UFV_DC4 and closely related jumbo phages showed a similar set of lytic proteins.

Biolixiviation of Metals from Computer Printed Circuit Boards by Acidithiobacillus ferrooxidans and Bioremoval of Metals by Mixed Culture Subjected to a Magnetic Field.

Crushed and ground printed circuit board (PCB) samples were characterized to evaluate copper, lead, and aluminum using X-ray fluorescence spectroscopy (XRF) and the morphology was done by scanning electron microscopy (SEM). The XRF characterizations showed 0.12% lead, 3.72% copper, and 12.73% aluminum in the PCBs. The metal solubilization experiments using Acidithiobacillus ferrooxidans indicated higher values of total metal solubilization when the initial pH of the inoculum was adjusted. However, these experiments did not show higher metal solubilization by bioleaching. The sequential bioremoval experiments using mixed culture after bioleaching assays with A. ferrooxidans with initial adjustment of inoculum pH and without applying a magnetic field removed 100% of Al, 27.34% of Cu, and 96.43% of Pb from the lixiviate medium; with magnetic field application, 100% of Al, 83.82% of Cu, and 98.27% of Pb were removed. A similar bioleaching experiment without inoculum pH adjustment and without field application achieved 99.74% removal for Cu and 91.92% for Pb. When the magnetic field was applied, 100% of Cu and 95.76% of Pb were removed. Bioreactors with a magnetic field do not show significantly better removal of any of the metals analyzed.

Genetic diversity goals and targets have improved, but remain insufficient for clear implementation of the post-2020 global biodiversity framework.

Genetic diversity among and within populations of all species is necessary for people and nature to survive and thrive in a changing world. Over the past three years, commitments for conserving genetic diversity have become more ambitious and specific under the Convention on Biological Diversity's (CBD) draft post-2020 global biodiversity framework (GBF). This Perspective article comments on how goals and targets of the GBF have evolved, the improvements that are still needed, lessons learned from this process, and connections between goals and targets and the actions and reporting that will be needed to maintain, protect, manage and monitor genetic diversity. It is possible and necessary that the GBF strives to maintain genetic diversity within and among populations of all species, to restore genetic connectivity, and to develop national genetic conservation strategies, and to report on these using proposed, feasible indicators.