One-class modelling applied to ATR-FTIR spectroscopy for determining document forgeries related to paper aging.

One of the great challenges of document analysis is determining document forgeries. The present work proposes a non-destructive approach to discriminate natural and artificially aged papers using infrared spectroscopy and soft independent modeling by class analogy (SIMCA) algorithms. This is of particular interest in cases of document falsifications made by artificial aging, for this study, SIMCA, and Data-Driven SIMCA (DD-SIMCA) classification models were built using naturally aged paper samples, taken from three time periods: 1st period from 1998 to 2003; 2nd period from 2004 to 2009; and 3rd period from 2010 to 2015. Artificially aged samples (exposed to high temperature or UV radiation) were used as test sets. Promising results in detecting document falsifications related to aging were obtained. Samples artificially aged at high temperature were correctly discriminated from the authentic samples (naturally aged) with 100% accuracy. In contrast, the samples under the photodegradation process showed a lower classification performance, with results above 90%.

State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus.

Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts' confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.

Gut Microbiota-Related Biomarkers in Immuno-Oncology.

Carcinogenesis is associated with the emergence of protracted intestinal dysbiosis and metabolic changes. Increasing evidence shows that gut microbiota-related biomarkers and microbiota-centered interventions are promising strategies to overcome resistance to immunotherapy. However, current standard methods for evaluating gut microbiota composition are cost- and time-consuming. The development of routine diagnostic tools for intestinal barrier alterations and dysbiosis constitutes a critical unmet medical need that can guide routine treatment and microbiota-centered intervention decisions in patients with cancer. In this review, we explore the influence of gut microbiota on cancer immunotherapy and highlight gut-associated biomarkers that have the potential to be transformed into simple diagnostic tools, thus guiding standard treatment decisions in the field of immuno-oncology. Mechanistic insights toward leveraging the complex relationship between cancer immunosurveillance, gut microbiota, and metabolism open exciting opportunities for developing novel biomarkers in immuno-oncology.

From the mechanism of action to clinical management: A review of cardiovascular toxicity in adult treated with CAR-T therapy.

Chimeric antigen receptor T-cell therapy represents an innovative approach to immunotherapy and currently stands out, particularly for oncohematological patients refractory to traditional treatments. Ongoing trials are further expanding its clinical use for new oncological and non-oncological indications, potentially leading to newer treatment options soon. This new approach, however, also presents challenges, including cardiovascular toxicity. Little is reported in pivotal studies, and some recent retrospective observations suggest a non-negligible incidence of side effects with presentation ranging from mild adverse cardiovascular events to fatal complications in which, in most cases, there is a direct or indirect association with cytokine release syndrome. In this literature review, the hypotheses of an important interface between cytokine release syndrome and cardiotoxicity by chimeric antigen receptor T-cell therapy will be addressed, as will current knowledge about risk factors for cardiotoxicity and recommendations for pre-therapy evaluation, post-infusion monitoring and clinical management of these complications.

Is use of flowable resin composite an option for occluso-proximal restorations in primary teeth? A fracture strength analysis.

BACKGROUND: Use of flowable resin composites for ocluso-proximal restorations in primary molars could improve cervical adaptation, and reduce the failure risk. AIM: To investigate the fracture strength of occluso-proximal restorations in primary teeth using different flowable resin composites (as an intermediate layer or entire cavity) and a conventional resin composite (incremental technique). DESIGN: Two standardized occluso-proximal cavities were prepared on mesial and distal surfaces of 50 sound primary molars. The teeth were randomly assigned into five groups (n = 10): 2 mm Filtek Bulk Fill Flow + Z350 XT; 4 mm Filtek Bulk Fill Flow; 2 mm Z350 XT Flow + Z350 XT; 4 mm Z350 XT Flow; and Z350 XT inserted by incremental technique. All restored teeth were subjected to cariogenic challenge and then submitted to fracture strength test. The failure pattern of each specimen was categorized as reparable or irreparable/need for replacement based on the World Dental Federation (FDI) criteria. Fracture strength means were submitted to one-way ANOVA and Tukey's post hoc tests. Failure pattern was analyzed descriptively. RESULTS: There was no statistically significant difference on fracture strength among groups (p = .48). A similar distribution of reparable (35%-40%) and irreparable (60%-65%) failures was observed among groups. CONCLUSION: Based on a laboratorial setting, the use of different flowable resin composites (as an intermediate layer or entire cavity) may be an option to restore occluso-proximal cavities in primary molars.

ß-enaminoester derivatives exhibit promising in vitro and in silico antiviral potential against Mayaro virus.

Mayaro virus (MAYV) is the causative agent of Mayaro fever, which is characterized mainly by acute fever and long-term severe arthralgia, common manifestations of other arbovirus infections, making the correct diagnosis a challenge. Besides, MAYV infections have been reported in South America, especially in Brazil. However, the lack of vaccines or specific antiviral drugs to control these infections makes the search for new antivirals an urgent need. Herein, we evaluated the antiviral potential of synthetic ß-enaminoesters derivatives against MAYV replication and their pharmacokinetic and toxicological (ADMET) properties using in vitro and in silico strategies. For this purpose, Vero cells were infected with MAYV at an MOI of 0.1, treated with compounds (50 µM) for 24 h, and virus titers were quantified by plaque reduction assays. Compounds 2b (83.33%) and 2d (77.53%) exhibited the highest activity with inhibition rates of 83.33% and 77.53%, respectively. The most active compounds 2b (EC50 = 18.92 µM; SI > 52.85), and 2d (EC50 = 14.52 µM; SI > 68.87) exhibited higher potency and selectivity than the control drug suramin (EC50 = 38.97 µM; SI > 25.66). Then, we investigated the mechanism of action of the most active compounds. None of the compounds showed virucidal activity, neither inhibited virus adsorption, but compound 2b inhibited virus entry (62.64%). Also, compounds 2b and 2d inhibited some processes involved with the release of new virus particles. Finally, in silico results indicated good ADMET parameters of the most active compounds and reinforced their promising profile as drug candidates against MAYV.

Acyl-CoA binding protein for the experimental treatment of anorexia.

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

Efficacy and threshold dose of intensive training targeting mobility for children with cerebral palsy: A systematic review and meta-analysis.

AIM: To systematically review the evidence for intensive mobility training in cerebral palsy (CP) and to determine the minimum effective dose to improve mobility. METHOD: Randomized controlled trials (RCTs) or quasi-RCTs that included participants with CP, and which used intensive task-oriented training (TOT) mobility interventions and reported mobility outcomes, were included. Five databases were searched; two independent reviewers selected studies and extracted data. The Grading of Recommendations Assessment, Development, and Evaluation system and the Cochrane Risk of Bias 2 tool were used to rate the certainty of evidence at the outcomes level and to determine the risk of bias respectively. Meta-analyses were conducted with clinically homogeneous studies. Threshold dose was analysed through meta-regression. RESULTS: Forty-six RCTs with 1449 participants (mean age range 1 year 2 months to 16 years 4 months) were included. TOT had statistically and clinically significant effects on walking speed (p = 0.001), cadence (p = 0.02), gross motor function (p = 0.03), and functional mobility (p = 0.009) compared with control interventions. The threshold dose was undeterminable owing to the high heterogeneity of studies. INTERPRETATION: TOT may improve walking speed, walking endurance, and balance. Studies with homogeneous samples and outcomes are needed to support clinical recommendations for intensive mobility interventions.

Checklist of marine macroalgae in two contiguous Marine Protected Areas in the south-western Atlantic.

Background: The Costa das Algas Environmental Protection Area (EPA) and the Santa Cruz Wildlife Refuge (WR), located in the Espírito Santo Continental Shelf, Brazil, are outstanding marine protected areas due to their high biodiversity, particularly of macroalgae. Together, these two relatively small protected areas (1,150 and 177 km2, respectively) harbour about a quarter of all macroalgal species recorded in Brazil.The checklist presented herein updates the algal flora of these two protected areas with data obtained until 2019. Two hundred and sixty-five macroalgal taxa were recorded, most of which with vouchers. Checklists based on the collections of each protected area were published on: "Catálogo de Plantas das Unidades de Conservação do Brasil" (https://catalogo-ucs-brasil.jbrj.gov.br/). New information: Besides specimens collected between 2018 and 2019, the algal flora presented herein includes previous records from different Brazilian herbaria (e.g., SP, SPF, ALCB). Herbaria records may include species that do not occur in intertidal reefs (e.g., Laminaria). Overall, 249 macroalgal taxa and one marine angiosperm were recorded in the Costa das Algas EPA (87 new records) and 136 macroalgal taxa and one marine angiosperm in the Santa Cruz WR (46 new records). All taxa are native to Brazil and nine are endemic to Brazil. Our results provide a taxonomic foundation to support management, long-term monitoring and conservation in these protected areas.

Applicability of terahertz spectroscopy in dentistry: a scoping review.

OBJECTIVE: This study aimed to analyze the scope, nature, and extent of the applicability of terahertz (THz) spectroscopy in dentistry. STUDY DESIGN: A scoping review was conducted following the 5-step methodology of Arksey and O'Malley, the PRISMA-ScR checklist, and the Evidence Synthesis Manual of the Joanna Briggs Institute. Electronic literature searches were performed in the PubMed/MEDLINE, Scopus, and Cochrane Library databases, including full-text articles with no specific publication period. The following research question was formulated: "What are the applications of THz spectroscopy in the field of dentistry?" RESULTS: Seventeen laboratory studies were identified, detailing oral and dental applications of THz. In restorative dentistry, 8 investigations sought to identify the properties of human and animal dental tissues and differentiate between healthy and decayed tissue. In oral pathology, 5 articles analyzed the identification of cancer cells in comparison to the identification of these cells in histological or cytological analysis. In biomaterials, 4 papers studied the changes in properties of restorative materials and effects on polymerization. CONCLUSION: While the potential for early diagnosis using THz spectroscopy in dentistry is evident, our findings underscore its limitations. The studies were exclusively conducted in vitro, emphasizing the need for innovative clinical research using intraoral devices. Bridging this gap is essential to unlock the full potential of this noninvasive technology for early diagnosis and informed clinical decision-making.

Intraoperative 3D fluoroscopy accurately predicts final electrode position in deep brain stimulation surgery.

PURPOSE: In the absence of an intraoperative CT or MRI setup, post-implantation confirmation of electrode position in deep brain stimulation (DBS) requires patient transportation to the radiology unit, prolonging surgery time. This project aims to validate intraoperative 3D fluoroscopy (3DF), a widely available tool in Neurosurgical units, as a method to determine final electrode position. METHODS: We performed a retrospective study including 64 patients (124 electrodes) who underwent DBS at our institution. Intraoperative 3DF after electrode implantation and postoperative volumetric CT were acquired. The Euclidean coordinates of the electrode tip displayed in both imaging modalities were determined and inter-method deviations were assessed. Pneumocephalus was quantified and its potential impact in determining the electrode position analyzed. Finally, 3DF and CT-imposed exposure to radiation was compared. RESULTS: The difference between the electrode tip estimated by 3DF and CT was 0.85 ± 0.03 mm, and not significantly different (p = 0.11 for the distance to MCP assessed by both methods), but was, instead, highly correlated (p = 0.91; p < 0.0001). Even though pneumocephalus was larger in 3DF (6.89 ± 1.76 vs 5.18 ± 1.37 mm3 in the CT group, p < 0.001), it was not correlated with the difference in electrode position measured by both techniques (p = 0.17; p = 0.06). Radiation exposure from 3DF is significantly lower than CT (0.36 ± 0.03 vs 2.08 ± 0.05 mSv; p < 0.0001). CONCLUSIONS: Intraoperative 3DF is comparable to CT in determining the final DBS electrode position. Being a method with fewer radiation exposure, less expensive, faster and that avoids patient transportation outside the operation room, it is a valid tool to replace postoperative CT.

Restoration-repair potential of resin-modified glass ionomer cement.

This in vitro study aimed to evaluate the repair bond strength of resin-modified glass ionomer cement using either the same material or a universal adhesive in the etch-and-rinse and self-etch modes plus resin composite. Twenty-four resin-modified glass ionomer cement blocks were stored in distilled water for 14 d and thermocycled. Sandpaper ground specimens were randomly assigned to three experimental groups according to the repair protocol: resin-modified glass ionomer cement (Riva Light Cure, SDI) and universal adhesive (Scotchbond Universal Adhesive, 3M Oral Care) in etch-and-rinse or self-etch modes and nanohybrid resin composite (Z350 XT, 3M Oral Care). After 24 h of water storage, the blocks were sectioned, and bonded sticks were subjected to the microtensile bond strength (µTBS) test. One-way ANOVA and Tukey's test were used to analyze the data. The failure mode was descriptively analyzed. The highest µTBS values were obtained when the resin-modified glass ionomer cement was repaired using the same material (p < 0.01). In addition, the mode of application of the universal adhesive system did not influence the repair bond strength of the resin-modified glass ionomer cement. Adhesive/mixed failures prevailed in all groups. Repair of resin-modified glass ionomers with the same material appears to be the preferred option to improve bond strength.

Oenothein B from Eugenia uniflora leaves exerts pro-angiogenic effects by increasing VEGF and TNF-α levels.

Oenothein B (OeB), a dimeric ellagitannin with a macrocyclic structure, is reported to have beneficial effects, including antioxidant, antitumor, antiviral, and antimutagenic effects, on human health. Despite the remarkable properties of OeB, its role in neovascularization process has not yet been evaluated. Thus, this study aimed to evaluate the angiogenic activity of OeB using a chorioallantoic membrane (CAM) assay at different concentrations (6.25, 12.5, and 25 µg/µL), employing digital imaging and histological analysis. Furthermore, to elucidate the mechanisms by which OeB influences angiogenesis, we assessed the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM using immunohistochemical analysis. All concentrations of OeB significantly increased (p < 0.05) the percentage of vascularization as well as the levels of all the angiogenesis-associated parameters evaluated, indicating the pronounced pro-angiogenic activity of OeB. Our results showed that inflammation was one of the most relevant phenomena observed in CAM histology along with angiogenesis. In addition, a significant increase in VEGF and TNF-α levels was observed in all the CAMs compared to the negative control (p < 0.05). We suggest that OeB may induce the presence of inflammatory cells in CAM, leading to increased VEGF and TNF-α levels that result in the induction of angiogenesis. Therefore, OeB presents a favorable profile that could be further explored for the development of drugs for pro-angiogenic and tissue repair therapies.

Linezolid and vancomycin for nosocomial infections in pediatric patients: a systematic review

Abstract Objective: To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old. Data sources: This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO. Summary of findings: The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria. Conclusion: Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence.

Suboptimal bioinformatic predictions of antimicrobial resistance from whole-genome sequences in multidrug-resistant Corynebacterium isolates.

Herein, we combined different bioinformatics tools and databases (BV-BRC, ResFinder, RAST, and KmerResistance) to perform a prediction of antimicrobial resistance (AMR) in the genomic sequences of 107 Corynebacterium striatum isolates for which trustable antimicrobial susceptibility (AST) phenotypes could be retrieved. Then, the reliabilities of the AMR predictions were evaluated by different metrics: area under the ROC curve (AUC); Major Error Rates (MERs) and Very Major Error Rates (VMERs); Matthews Correlation Coefficient (MCC); F1-Score; and Accuracy. Out of 15 genes that were reliably detected in the C. striatum isolates, only tetW yielded predictive values for tetracycline resistance that were acceptable considering Food and Drug Administration (FDA)'s criteria for quality (MER < 3.0% and VMER with a 95% C.I. ≤1.5-≤7.5); this was accompanied by a MCC score higher than 0.9 for this gene. Noteworthy, our results indicate that other commonly used metrics (AUC, F1-score, and Accuracy) may render overoptimistic evaluations of AMR-prediction reliabilities on imbalanced datasets. Accordingly, out of 10 genes tested by PCR on additional multidrug-resistant Corynebacterium spp. isolates (n = 18), the tetW gene rendered the best agreement values with AST profiles (94.11%). Overall, our results indicate that genome-based AMR prediction can still be challenging for MDR clinical isolates of emerging Corynebacterium spp.

Innate and adaptive immune responses that control lymph-borne viruses in the draining lymph node.

The interstitial fluids in tissues are constantly drained into the lymph nodes (LNs) as lymph through afferent lymphatic vessels and from LNs into the blood through efferent lymphatics. LNs are strategically positioned and have the appropriate cellular composition to serve as sites of adaptive immune initiation against invading pathogens. However, for lymph-borne viruses, which disseminate from the entry site to other tissues through the lymphatic system, immune cells in the draining LN (dLN) also play critical roles in curbing systemic viral dissemination during primary and secondary infections. Lymph-borne viruses in tissues can be transported to dLNs as free virions in the lymph or within infected cells. Regardless of the entry mechanism, infected myeloid antigen-presenting cells, including various subtypes of dendritic cells, inflammatory monocytes, and macrophages, play a critical role in initiating the innate immune response within the dLN. This innate immune response involves cellular crosstalk between infected and bystander innate immune cells that ultimately produce type I interferons (IFN-Is) and other cytokines and recruit inflammatory monocytes and natural killer (NK) cells. IFN-I and NK cell cytotoxicity can restrict systemic viral spread during primary infections and prevent serious disease. Additionally, the memory CD8+ T-cells that reside or rapidly migrate to the dLN can contribute to disease prevention during secondary viral infections. This review explores the intricate innate immune responses orchestrated within dLNs that contain primary viral infections and the role of memory CD8+ T-cells following secondary infection or CD8+ T-cell vaccination.

Metagenomic analysis of the bacterial microbiome, resistome and virulome distinguishes Portuguese Serra da Estrela PDO cheeses from similar non-PDO cheeses: An exploratory approach.

This study aimed to evaluate the microbiome, resistome and virulome of two types of Portuguese cheese using high throughput sequencing (HTS). Culture-dependent chromogenic methods were also used for certain groups/microorganisms. Eight samples of raw ewe's milk cheese were obtained from four producers: two producers with cheeses with a PDO (Protected Designation of Origin) label and the other two producers with cheeses without a PDO label. Agar-based culture methods were used to quantify total mesophiles, Enterobacteriaceae, Escherichia coli, Staphylococcus, Enterococcus and lactic acid bacteria. The presence of Listeria monocytogenes and Salmonella was also investigated. The selected isolates were identified by 16S rRNA gene sequencing and evaluated to determine antibiotic resistance and the presence of virulence genes. The eight cheese samples analyzed broadly complied with EC regulations in terms of the microbiological safety criteria. The HTS results demonstrated that Leuconostoc mesenteroides, Lactococcus lactis, Lactobacillus plantarum, Lacticaseibacillus rhamnosus, Enterococcus durans and Lactobacillus coryniformis were the most prevalent bacterial species in cheeses. The composition of the bacterial community varied, not only between PDO and non-PDO cheeses, but also between producers, particularly between the two non-PDO cheeses. Alpha-diversity analyses showed that PDO cheeses had greater bacterial diversity than non-PDO cheeses, demonstrating that the diversity of spontaneously fermented foods is significantly higher in cheeses produced without the addition of food preservatives and dairy ferments. Despite complying with microbiological regulations, both PDO and non-PDO cheeses harbored potential virulence genes as well as antibiotic resistance genes. However, PDO cheeses exhibited fewer of these virulence and antibiotic resistance genes compared to non-PDO cheeses. Therefore, the combination of conventional microbiological methods and the metagenomic approach could contribute to improving the attribution of the PDO label to this type of cheese.