Molecular Epidemiology of Mayaro Virus among Febrile Patients, Roraima State, Brazil, 2018-2021.

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

Validation of an mHealth System for Monitoring Fundamental Physiological Parameters in the Clinical Setting.

The aim of this work was to validate the measurements of three physiological parameters, namely, body temperature, heart rate, and peripheral oxygen saturation, captured with an out-of-the-lab device using measurements taken with clinically proven devices. The out-of-the-lab specialized device was integrated into a customized mHealth application, e-CoVig, developed within the AIM Health project. To perform the analysis, single consecutive measurements of the three vital parameters obtained with e-CoVig and with the standard devices from patients in an intensive care unit were collected, preprocessed, and then analyzed through classical agreement analysis, where we used Lin's concordance coefficient to assess the agreement correlation and Bland-Altman plots with exact confidence intervals for the limits of agreement to analyze the paired data readings. The existence of possible systematic errors was also addressed, where we found the presence of additive errors, which were corrected, and weak proportional biases. We obtained the mean overall agreement between the measurements taken with the novel e-CoVig device and the reference devices for the measured quantities. Although some limitations in this study were encountered, we present more advanced methods for their further assessment.

Decreased adiponectin/leptin ratio relates to insulin resistance in adults with obesity.

Adipose tissue dysfunction is a key mechanism that leads to adiposity-based chronic disease. This study aimed to investigate the reliability of the adiponectin/leptin ratio (AdipoQ/Lep) as an adipose tissue and metabolic function biomarker in adults with obesity, without diabetes. Data were collected from a clinical trial conducted in 28 adults with obesity (mean body mass index: 35.4 ± 3.7 kg/m2) (NCT02169778). With the use of a forward stepwise multiple linear regression model to explore the relationship between AdipoQ/Lep and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), it was observed that 48.6% of HOMA-IR variance was explained by triacylglycerols, AdipoQ/Lep, and waist-to-hip ratio (P < 0.001), AdipoQ/Lep being the strongest independent predictor (Beta = -0.449, P < 0.001). A lower AdipoQ/Lep was correlated with higher body mass index (Rs = -0.490, P < 0.001), body fat mass (Rs = -0.486, P < 0.001), waist-to-height ratio (Rs = -0.290, P = 0.037), and plasma resistin (Rs = -0.365, P = 0.009). These data highlight the central role of adipocyte dysfunction in the pathogenesis of insulin resistance and emphasize that AdipoQ/Lep may be a promising early marker of insulin resistance development in adults with obesity.NEW & NOTEWORTHY Adiponectin/leptin ratio, triacylglycerols, and waist-to-hip ratio explained almost half of HOMA-IR variance in the context of obesity. This study provides evidence to support adipose tissue dysfunction as a central feature of the pathophysiology of obesity and insulin resistance. Early identification of individuals at higher risk of developing metabolic complications through adipose tissue dysfunction assessment and the staging of obesity and its transient phenotypes can contribute to improve therapeutic decision-making.

Association of B Cells with Idiopathic Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis.

Recurrent pregnancy loss (RPL) affects 1-2% of women and is defined as having experienced two or more failed pregnancies. In almost 50% of cases, the causes are idiopathic (IRPL), but increasing evidence has suggested an immunological cause. B cells are known to provide crucial support for a successful pregnancy outcome. However, their involvement in the mechanisms underlying IRPL is still unclear. This systematic review and meta-analysis aimed to comprehensively summarise the existing evidence regarding the levels and profiles of B cells in IRPL. An extensive computerized search in PubMed/Medline, Embase, Scopus, and Web of Science databases was performed with no imposed limits. Two reviewers independently screened all retrieved studies, extracted all the data, and assessed the methodological quality. Disagreements were resolved by a third reviewer. From a total of 1125 retrieved studies, 19 studies were included in the systematic review, and 8 studies were quantitatively analysed. We highlight a potential association between women with IRPL and increased levels of endometrial B cells. In addition, the flow cytometry technique seems to be preferred over immunohistochemistry for identifying those differences, while further studies are necessary to clarify the role of B cells as an immunological risk factor for RPL.

Natural Killer Cell Receptors and Endometriosis: A Systematic Review.

Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies correlate the immune system with endometriosis, particularly NK receptors (NKR), which have been suggested to play an essential role in the pathogenesis of the disease. This systematic review aims to enlighten the role of NKR in endometriosis. A literature search was performed independently by two reviewers, to identify studies assessing the role of NKR in endometriosis. In total, 18 studies were included. Endometriosis pathogenesis seems to be marked by the overexpression of NK inhibitor receptors (KIRS), namely, CD158a+, KIR2DL1, CD94/NKG2A, PD-1, NKB1, and EB6, and inhibiting ligands such as PD-L1, HLA-E, HLA-G, and HLA-I. Concurrently, there is a decrease in NK-activating receptors and natural cytotoxicity receptors (NCRs), such as NKp46, NKp30, and NKG2D. The immune shift from NK surveillance to NK suppression is also apparent in the greater relative number of ITIM domains compared with ITAM domains in NKRs. In conclusion, NK receptor activity seems to dictate the immunocompetency of women to clear endometriotic cells from the peritoneal cavity. Future research could explore NKRs as therapeutic targets, such as that which is now well established in cancer therapy through immunotherapy.

A New Mouse Model for Complete Congenital Stationary Night Blindness Due to Gpr179 Deficiency.

Mutations in GPR179 lead to autosomal recessive complete congenital stationary night blindness (cCSNB). This condition represents a signal transmission defect from the photoreceptors to the ON-bipolar cells. To confirm the phenotype, better understand the pathogenic mechanism in vivo, and provide a model for therapeutic approaches, a Gpr179 knock-out mouse model was genetically and functionally characterized. We confirmed that the insertion of a neo/lac Z cassette in intron 1 of Gpr179 disrupts the same gene. Spectral domain optical coherence tomography reveals no obvious retinal structure abnormalities. Gpr179 knock-out mice exhibit a so-called no-b-wave (nob) phenotype with severely reduced b-wave amplitudes in the electroretinogram. Optomotor tests reveal decreased optomotor responses under scotopic conditions. Consistent with the genetic disruption of Gpr179, GPR179 is absent at the dendritic tips of ON-bipolar cells. While proteins of the same signal transmission cascade (GRM6, LRIT3, and TRPM1) are correctly localized, other proteins (RGS7, RGS11, and GNB5) known to regulate GRM6 are absent at the dendritic tips of ON-bipolar cells. These results add a new model of cCSNB, which is important to better understand the role of GPR179, its implication in patients with cCSNB, and its use for the development of therapies.

Role of Honey in Advanced Wound Care.

Honey is a natural product rich in several phenolic compounds, enzymes, and sugars with antioxidant, anticarcinogenic, anti-inflammatory, and antimicrobial potential. Indeed, the development of honey-based adhesives for wound care and other biomedical applications are topics being widely investigated over the years. Some of the advantages of the use of honey for wound-healing solutions are the acceleration of dermal repair and epithelialization, angiogenesis promotion, immune response promotion and the reduction in healing-related infections with pathogenic microorganisms. This paper reviews the main role of honey on the development of wound-healing-based applications, the main compounds responsible for the healing capacity, how the honey origin can influence the healing properties, also highlighting promising results in in vitro and in vivo trials. The challenges in the use of honey for wound healing are also covered and discussed. The delivery methodology (direct application, incorporated in fibrous membranes and hydrogels) is also presented and discussed.

Regulatory T cells and IL-17A levels in noninfectious uveitis.

PURPOSE: Regulatory T cells (Tregs) have been intensively studied in a myriad of autoimmune diseases. As for noninfectious uveitis (NIU), results have been contradictory, and studies have failed to demonstrate a consistent reduction in Treg cell frequency in patients with active disease. The present study aims to characterize T lymphocyte subsets, including naïve and memory Tregs as well as their respective CD39 expression, in the peripheral blood of NIU patients. Inflammatory as well as suppressive cytokine profiles were also evaluated. METHODS: T cell subpopulations were evaluated by multiparametric flow cytometry using anti-CD3, anti-CD4, anti-CD45, anti-CD45RA, anti-CD197, anti-CD25, anti-CD127, and anti-CD39. Treg cells were defined as CD3 + CD4+CD25hiCD127low. A multiplex bead-based immunoassay was used to determine TNF-α, IFN-É£, IL-17A, IL-10, and TGF-ß levels. RESULTS: Twenty-nine patients with active NIU were included as well as 15 sex- and age-matched controls. There were no significant differences in T lymphocyte subsets, including Tregs, between patients and controls. However, patients with a lower grade of anterior chamber or vitreous inflammatory cellular reaction showed higher memory Treg counts than controls, with no respective increase in CD39+ expression, and a tendency for higher IL-17A levels (p = 0.06). This IL-17A elevation was present in the total NIU group (p = 0.08) as well as a positive correlation between IL-17A levels and the absolute counts of memory Tregs (p = 0.013; R = 0.465). Patients with higher IL-17A levels also showed higher serum concentrations of memory (p = 0.001) and naïve (p = 0.003) Tregs as well as elevated TNF-α (p < 0.0001) and IFN-É£ (p = 0.016) levels. Negative correlations were observed between IL-10 and TGF-ß levels and the percentages of memory (p = 0.030; R = - 0.411) and total CD39+ Tregs (p = 0.051; R = - 0.373) in the peripheral blood of NIU patients. CONCLUSION: Our results showed that total Treg levels were not reduced in patients with NIU. Further characterization of Treg subsets, including memory Tregs and respective CD39 expression, may provide additional insight on the role of Treg cells in NIU. Consistent high levels of circulating IL-17A in NIU patients are in accordance with previous studies and reinforce this cytokine's vital role in uveitis pathogenesis and its possible use as a therapeutic target.

Physiological Arousal Quantifying Perception of Safe and Unsafe Virtual Environments by Older and Younger Adults.

Physiological arousal has been increasingly applied to monitor exploration (or navigation) of a virtual environment (VE), especially when the VE is designed to evoke an anxiety-related response. The present work aims to evaluate human physiological reactions to safe and unsafe VEs. We compared the effect of the presence of handrails in the VE in two different samples, young and older adults, through self-reports and physiological data: Electrodermal activation (EDA) and electrocardiogram (ECG) sensors. After navigation, self-report questionnaires were administered. We found that the VEs evoked a clearly differentiated perception of safety and unsafety demonstrated through self-reports, with older adults being more discriminative in their responses and reporting a higher sense of presence. In terms of physiological data, the effect of handrails did not provoke significant differences in arousal. Safety was better operationalized by discriminating neutral/non-neutral spaces, where the reaction of older adults was more pronounced than young adults. Results serve as a basis for orienting future experiments in the line of VE and applied physiology usage in the architectural spaces design process. This specific work also provided a basis for the development of applications that integrate virtual reality and applied biofeedback, tapping into mobility and ageing.

Novel splice-site mutation in TTLL5 causes cone dystrophy in a consanguineous family.

PURPOSE: To report the clinical and genetic findings of one family with autosomal recessive cone dystrophy (CD) and to identify the causative mutation. METHODS: An institutional study of three family members from two generations. The clinical examination included best-corrected Snellen visual acuity measurement, fundoscopy, the Farnsworth D-15 color vision test, a full-field electroretinogram (ERG) that incorporated the International Society for Clinical Electrophysiology of Vision standards and methodology, fundus autofluorescence (FAF) and infrared (IR), and spectral-domain optical coherence tomography (SD-OCT). Genetic findings were achieved with DNA analysis using whole exome sequencing (WES) and Sanger sequencing. RESULTS: The proband, a 9-year-old boy, presented with a condition that appeared to be congenital and stationary. The clinical presentation initially reflected incomplete congenital stationary night blindness (icCSNB) because of myopia, a decrease in visual acuity, abnormal oscillatory potentials, and reduced amplitudes on the 30 Hz flicker ERG but was atypical because there were no clear electronegative responses. However, no disease-causing mutations in the genes underlying icCSNB were identified. Following WES analysis of family members, a homozygous splice-site mutation in intron 3 of TTLL5 (c.182-3_182-1delinsAA) was found cosegregating within the phenotype in the family. CONCLUSIONS: The distinction between icCSNB and CD phenotypes is not always straightforward in young patients. The patient was quite young, which most likely explains why the progression of the CD was not obvious. WES analysis provided prompt diagnosis for this family; thus, the use of this technique to refine the diagnosis is highlighted in this study.

New COL6A6 variant detected by whole-exome sequencing is linked to break points in intron 4 and 3'-UTR, deleting exon 5 of RHO, and causing adRP.

PURPOSE: This study aimed to test a newly devised cost-effective multiplex PCR assay for the molecular diagnosis of autosomal dominant retinitis pigmentosa (adRP), as well as the use of whole-exome sequencing (WES) to detect disease-causing mutations in adRP. METHODS: Genomic DNA was extracted from peripheral blood lymphocytes of index patients with adRP and their affected and unaffected family members. We used a newly devised multiplex PCR assay capable of amplifying the genetic loci of RHO, PRPH2, RP1, PRPF3, PRPF8, PRPF31, IMPDH1, NRL, CRX, KLHL7, and NR2E3 to molecularly diagnose 18 index patients with adRP. We also performed WES in affected and unaffected members of four families with adRP in whom a disease-causing mutation was previously not found. RESULTS: We identified five previously reported mutations (p.Arg677X in the RP1 gene, p.Asp133Val and p.Arg195Leu in the PRPH2 gene, and p.Pro171Leu and p.Pro215Leu in the RHO gene) and one novel mutation (p.Val345Gly in the RHO gene) representing 33% detection of causative mutations in our adRP cohort. Comparative WES analysis showed a new variant (p.Gly103Arg in the COL6A6 gene) that segregated with the disease in one family with adRP. As this variant was linked with the RHO locus, we sequenced the complete RHO gene, which revealed a deletion in intron 4 that encompassed all of exon 5 and 28 bp of the 3'-untranslated region (UTR). CONCLUSIONS: The novel multiplex PCR assay with next-generation sequencing (NGS) proved effective for detecting most of the adRP-causing mutations. A WES approach led to identification of a deletion in RHO through detection of a new linked variant in COL6A6. No pathogenic variants were identified in the remaining three families. Moreover, NGS and WES were inefficient for detecting the complete deletion of exon 5 in the RHO gene in one family with adRP. Carriers of this deletion showed variable clinical status, and two of these carriers had not previously been diagnosed with RP.

Fermented Grapevine Leaves: Potential Preserving Agent in Yogurt.

In this study, we monitored the fermentative process of Vitis vinifera L. leaves (grapevine), spontaneously or promoted by Saccharomyces cerevisiae, in both solid and liquid media. We also aimed to evaluate the effect on the bioactivity and shelf life of yogurt incorporating fermented and non-fermented grapevine leaves compared to yogurt produced with the preservative potassium sorbate. The results revealed that fermented grapevine leaf extracts increased their bioactive compounds and antioxidant activity, particularly in fermentations in a solid medium. In yogurt samples with incorporation extract from solid spontaneous fermentation and extract from solid yeast fermentation, even in small quantities, they exhibited higher levels of total phenols (1.94 and 2.16 mg GAE/g of yogurt, respectively) and antioxidant activity (5.30 and 5.77 mg TroloxE/g of yogurt; and 1.33 and 1.34 mg Fe(II)E/g of yogurt, respectively) compared to control yogurt (1.44 mg GAE/g of yogurt, 4.00 mg TroloxE/g of yogurt, and 1.01 mg Fe(II)E/g of yogurt). Additionally, yogurts supplemented with fermented grapevine leaves demonstrated the potential to inhibit microbial growth without impairing the multiplication of lactic acid bacteria.

TIM-3 Expression in Endometriosis.

PROBLEM: Endometriosis is a prevalent chronic gynecological disease linked to immune dysfunction. The protein T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) plays a crucial role in immune system balance. Malfunction of TIM-3 may result in excessive immune activation and inflammatory tissue damage. Given TIM-3's established role in the development of cancer and autoimmune diseases, we decided to study its role in women suffering from endometriosis. STUDY METHOD: We included a total of 62 female patients, all of whom had undergone laparoscopic surgery. Of these, 47 had endometriosis and 15 did not. During surgery, we collected peritoneal fluid (PF) and peripheral blood (PB) samples from every patient for analysis using flow cytometry. To mark the samples, we used a panel of monoclonal antibodies and examined TIM-3 expression in their immune cells. RESULTS: Endometriosis patients in PB demonstrated a significantly lower percentage of CD56+ T cells with TIM-3 expression. As endometriosis progressed through its stages, this expression lessened. This decrease was particularly notable in women with stage III/IV endometriosis. Additionally, both women diagnosed with intestinal endometriosis and those with recent endometriosis diagnoses showed a significantly reduced percentage of CD56+ T cells expressing TIM-3. CONCLUSIONS: Patients with endometriosis exhibit diminished TIM-3 expression within circulating T cells. This warrants further investigation to discern whether it contributes to the progression of endometriosis, potentially through the amplification of autoreactive T cells and inflammation.

Safety of Fibrinogen Concentrate in Non-Trauma and Non-Obstetric Adult Patients during Perioperative Care: Systematic Review and Meta-Analysis.

Background: Low fibrinogen levels are associated with an increased risk of perioperative bleeding. However, there is an ongoing debate over the ideal treatment threshold, the benefits of prophylactic supplementation with fibrinogen concentrate, and the best source of fibrinogen. While fibrinogen concentrate supplementation is being widely used to treat bleeding related to acquired haemostatic deficiencies, there is a lack of evidence regarding its dosage, effectiveness, and safety. This systematic review provides an up-to-date summary of the relationship between fibrinogen concentrate supplementation and safety measures in the perioperative care of non-trauma, non-obstetric adult patients. Methods: A comprehensive online search was conducted on PubMed/Medline, EMBASE, Scopus, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Results: This systematic review and meta-analysis encompasses ten studies involving 1391 patients. There was a decreased risk of total thromboembolic events in patients treated with fibrinogen compared to the control (OR 0.65, 95% CI 0.43 to 0.98, I2 = 0%). In addition, when fibrinogen was used prophylactically, it resulted in shorter ICU stays (MD -1.50, 95% CI -2.64 to -0.36), when set against its therapeutic use. A sensitivity analysis on cardiovascular surgery studies did not reveal any statistically significant difference. Conclusions: The use of fibrinogen concentrate in the perioperative care of non-trauma and non-obstetric adult patients may lead to potential benefits.

Cytokine Dynamics in Acute Pancreatitis: The Quest for Biomarkers from Acute Disease to Disease Resolution.

Background: Acute pancreatitis (AP) is an inflammatory disease of the pancreas with incompletely known pathogenic mechanisms. This study aimed to explore the temporal changes in serum cytokines in patients with AP and to assess the association of these changes with disease severity. Methods: Fifty patients hospitalized with AP were enrolled, and their serum cytokine levels were analyzed at four different time points. A healthy control (HC) group of 30 outpatients was included. Results: AP patients showed increased levels of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, and monocyte chemoattractant protein (MCP)-1 at admission when compared with HC. IL-6, VEGF, and EGF remained elevated 1 month after hospitalization and 6 months after discharge. Conclusions the Bedside Index of Severity in Acute Pancreatitis (BISAP) and severity classification of the revised Atlanta classification system, IL-6 and VEGF, determined 48 h after hospitalization, were the two cytokines consistently elevated in the most severe patients. Increased levels of IL-4, IL-6, IL-10, and TNF-alpha at admission and MCP-1 48 h after admission are also related to the length of hospital stay. Conclusions: Our study highlights the role cytokines play in the pathogenesis of AP and can be useful in the development of future drug trials for AP.

B Cells and Double-Negative B Cells (CD27-IgD-) Are Related to Acute Pancreatitis Severity.

Acute pancreatitis (AP) is an increasingly frequent disease in which inflammation plays a crucial role. Fifty patients hospitalized with AP were included and peripheral blood samples were analyzed for B and T cell subpopulations at the time of hospitalization and 48 h after diagnosis. The Bedside Index of Severity in Acute Pancreatitis (BISAP) and length of hospital stay were also recorded. A healthy control (HC) group of 15 outpatients was included. AP patients showed higher neutrophil/lymphocyte (N/L) ratios and higher percentages of B cells than the HC group. The total B cell percentages were higher in patients with moderate/severe AP than in patients with mild AP. The percentages of B cells as well as the percentages of the CD27-IgD- B cell subset decreased from admission to 48 h after admission. The patients with higher BISAP scores showed lower percentages of peripheral lymphocytes but higher percentages of CD27-IgD- B cells. Higher BISAP scores, N/L ratios, and peripheral blood B cell levels emerged as predictors of hospital stay length in AP patients. Our findings underscore the importance of early markers for disease severity. Additionally, the N/L ratio along with the BISAP score and circulating B cell levels form a robust predictive model for hospital stay duration of AP patients.

Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population.

PURPOSE: To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). METHODS: Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. RESULTS: We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two). CONCLUSIONS: The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1.

Detection of novel mutations that cause autosomal dominant retinitis pigmentosa in candidate genes by long-range PCR amplification and next-generation sequencing.

PURPOSE: To devise an effective method for detecting mutations in 12 genes (CA4, CRX, IMPDH1, NR2E3, RP9, PRPF3, PRPF8, PRPF31, PRPH2, RHO, RP1, and TOPORS) commonly associated with autosomal dominant retinitis pigmentosa (adRP) that account for more than 95% of known mutations. METHODS: We used long-range PCR (LR-PCR) amplification and next-generation sequencing (NGS) performed in a GS Junior 454 benchtop sequencing platform. Twenty LR-PCR fragments, between 3,000 and 10,000 bp, containing all coding exons and flanking regions of the 12 genes, were obtained from DNA samples of patients with adRP. Sequencing libraries were prepared with an enzymatic (Fragmentase technology) method. RESULTS: Complete coverage of the coding and flanking sequences of the 12 genes assayed was obtained with NGS, with an average sequence depth of 380× (ranging from 128× to 1,077×). Five previous known mutations in the adRP genes were detected with a sequence variation percentage between 35% and 65%. We also performed a parallel sequence analysis of four samples, three of them new patients with index adRP, in which two novel mutations were detected in RHO (p.Asn73del) and PRPF31 (p.Ile109del). CONCLUSIONS: The results demonstrate that genomic LR-PCR amplification together with NGS is an effective method for analyzing individual patient samples for mutations in a monogenic heterogeneous disease such as adRP. This approach proved effective for the parallel analysis of adRP and has been introduced as routine. Additionally, this approach could be extended to other heterogeneous genetic diseases.

The impact of sound in people's behaviour in outdoor settings: A study using virtual reality and eye-tracking.

This paper presents an analysis of space perception and how visual cues, such as landmarks and sound, are perceived and impact people's behaviour while exploring a given outdoor space. The primary goal of the research is to investigate how auditory sensations and visual stimuli influence people's behaviour in outdoor built environments. Our technique compares people's perception of the built environment in different conditions: the real world and a replicated virtual world. As a case study, a university campus was used, and four experimental conditions were designed. The study followed a between-subjects design, and the data collection included gaze data acquired from an eye-tracking device as well as self-reports. The study concludes that sound influences human behaviour in such settings. More specifically conclusions are that: i) human behaviour in virtual replications of the real space, including both visual and sound stimuli, is tendentially more similar to human behaviour in the real world than in simulations omitting sound; and ii) there is a difference in human behaviour when people explore the same virtually replicated outdoor space, by varying the presence of sound. This study is particularly useful for researchers working on the comparison between human behaviour in virtual and real environments, related to visual and sound stimuli.

AI-Driven Decision Support for Early Detection of Cardiac Events: Unveiling Patterns and Predicting Myocardial Ischemia.

Cardiovascular diseases (CVDs) account for a significant portion of global mortality, emphasizing the need for effective strategies. This study focuses on myocardial infarction, pulmonary thromboembolism, and aortic stenosis, aiming to empower medical practitioners with tools for informed decision making and timely interventions. Drawing from data at Hospital Santa Maria, our approach combines exploratory data analysis (EDA) and predictive machine learning (ML) models, guided by the Cross-Industry Standard Process for Data Mining (CRISP-DM) methodology. EDA reveals intricate patterns and relationships specific to cardiovascular diseases. ML models achieve accuracies above 80%, providing a 13 min window to predict myocardial ischemia incidents and intervene proactively. This paper presents a Proof of Concept for real-time data and predictive capabilities in enhancing medical strategies.