PERK inhibition in zebrafish mimics human Wolcott-Rallison syndrome phenotypes.

Wolcott-Rallison Syndrome (WRS) is the most common cause of permanent neonatal diabetes mellitus among consanguineous families. The diabetes associated with WRS is non-autoimmune, insulin-requiring and associated with skeletal dysplasia and growth retardation. The therapeutic options for WRS patients rely on permanent insulin pumping or on invasive transplants of liver and pancreas. WRS has a well identified genetic cause: loss-of-function mutations in the gene coding for an endoplasmic reticulum kinase named PERK (protein kinase R-like ER kinase). Currently, WRS research is facilitated by cellular and rodent models with PERK ablation. While these models have unique strengths, cellular models incompletely replicate the organ/system-level complexity of WRS, and rodents have limited scalability for efficiently screening potential therapeutics. To address these challenges, we developed a new in vivo model of WRS by pharmacologically inhibiting PERK in zebrafish. This small vertebrate displays high fecundity, rapid development of organ systems and is amenable to highly efficient in vivo drug testing. PERK inhibition in zebrafish produced typical WRS phenotypes such as glucose dysregulation, skeletal defects, and impaired development. PERK inhibition in zebrafish also produced broad-spectrum WRS phenotypes such as impaired neuromuscular function, compromised cardiac function and muscular integrity. These results show that zebrafish holds potential as a versatile model to study WRS mechanisms and contribute to the identification of promising therapeutic options for WRS.

Edaravone counteracts redox and metabolic disruptions in an emerging zebrafish model of sporadic ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which the death of motor neurons leads to loss of muscle function. Additionally, cognitive and circadian disruptions are common in ALS patients, contributing to disease progression and burden. Most ALS cases are sporadic, and environmental exposures contribute to their aetiology. However, animal models of these sporadic ALS cases are scarce. The small vertebrate zebrafish is a leading organism to model neurodegenerative diseases; previous studies have proposed bisphenol A (BPA) or ß-methylamino-l-alanine (BMAA) exposure to model sporadic ALS in zebrafish, damaging motor neurons and altering motor responses. Here we characterise the face and predictive validity of sporadic ALS models, showing their potential for the mechanistic study of ALS drugs. We phenotypically characterise the BPA and BMAA-induced models, going beyond motor activity and motor axon morphology, to include circadian, redox, proteostasis, and metabolomic phenotypes, and assessing their predictive validity for ALS modelling. BPA or BMAA exposure induced concentration-dependent activity impairments. Also, exposure to BPA but not BMAA induced motor axonopathy and circadian alterations in zebrafish larvae. Our further study of the BPA model revealed loss of habituation to repetitive startles, increased oxidative damage, endoplasmic reticulum (ER) stress, and metabolome abnormalities. The BPA-induced model shows predictive validity, since the approved ALS drug edaravone counteracted BPA-induced motor phenotypes, ER stress, and metabolic disruptions. Overall, BPA exposure is a promising model of ALS-related redox and ER imbalances, contributing to fulfil an unmet need for validated sporadic ALS models.

Stress Inoculation in Police Officers Using Virtual Reality: A Controlled Study.

Policing is a highly demanding and stressful profession. Virtual reality (VR) has emerged as a promising tool for enhancing stress management programs, including for police officers. The use of VR in combination with biosensors enables measurement of psychophysiological responses such as peripheral temperature (PT) and skin conductance level (SCL). This study investigated the psychophysiological responses of police officers exposed to a VR scenario simulating a car accident. The study included a total of 63 police officers from the Public Security Police. Participants were divided into three groups based on their police divisions: the Investigation Brigade of Traffic Accidents, the Traffic Surveillance Squad (TSS), and a control group from the Lisbon Metropolitan Command. The results indicated that the VR environment effectively induced psychophysiological arousal, particularly in less experienced officers (TSS), that is, there were significant group differences in mean SCL and PT, showing this group with higher SCL and lower PT during the VR exposure. These results support the potential of VR as a stress inoculation strategy for training police officers and highlight the complex nature of stress responses that are influenced by individual factors and psychopathology.

Effects of the pyriproxyfen and fenthion on the gonadal morphology of Nile tilapia (Oreochromis niloticus: Perciformes, Cichlidae).

Commercially available insecticides present acute toxicity to the health of fish and other aquatic organisms, which may impair the local aquaculture. This study evaluated the gonadal morphology of freshwater fish exposed to pyriproxyfen and fenthion. Forty-five juvenile male Nile tilapias (Oreochromis niloticus) were divided into control, pyriproxyfen-exposed (0.01 g/L), and fenthion-exposed (0.001 g/L) groups. They were evaluated in three moments (30, 60, and 90 days). The variables analyzed were the gonadosomatic index (GSI), weight to length ratio, seminiferous tubules morphometry (diameter and height), tissue damage, and immunohistochemical analysis for caspase-3, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). Pyriproxyfen and fenthion injured the seminiferous tubule tissue, and the damage progressed according to the exposure time. In addition, the GSI gradually reduced over time in all groups compared with the first moment (30 days), while caspase-3, TNF-α, and VEGF values increased only in the fenthion-exposed group. Therefore, pyriproxyfen and fenthion changed the gonadal morphology of male Oreochromis niloticus, which may affect their reproduction in the wild or captivity.

Exploring Rice Consumption Habits and Determinants of Choice, Aiming for the Development and Promotion of Rice Products with a Low Glycaemic Index.

Current consumption drivers, particularly those related to health and wellbeing, have been influencing trends for the lower consumption of cereals, particularly rice, due to their typical high glycaemic index (GIs) and consequent impacts on obesity. To satisfy this consumer concern, more food innovations that promote healthy eating habits are required. Such innovations must be consumer-oriented to succeed, understanding the dynamics of consumer habits and responding to consumer expectations. This study explored these habits, from acquisition to consumption practices, and the expectations of the European market from the perspective of the major European consumer, Portugal, to obtain insights that support the development of low glycaemic index (GI) rice products. A mixed-methods approach was applied. For the first quantitative questionnaire, 256 Portuguese rice consumers aged 18-73 years were recruited. Twenty-four individuals were selected according to their gender and rice consumption profiles for in-depth interviews. The results confirmed that rice was the main side dish for the participants and was mainly consumed at home, cooked from raw milled rice. The drivers of consumption differ according to the provisioning process stage. In the acquisition stage, participants reported benefits from the rice's dynamic market by comparing products on price, brand, and rice types. In the preparation stage, participants reported the adequacy of the recipe and occasion, while in the consumption stage, participants enhanced their sensory preferences, depending on the rice dish. Although the GI concept was unknown to half of the participants, it was perceived as interesting and positive for healthy eating. Consumers showed concern about the taste and naturalness of the product, preferring it to be as close to a homemade dish as possible. The negative perceptions we verified were interpreted to be due to a lack of knowledge about the GI concept. Therefore, awareness actions and informative campaigns are recommended to promote low-GI rice products.

Multiple mask and boundary scoring R-CNN with cGAN data augmentation for bladder tumor segmentation in WLC videos.

Automatic diagnosis systems capable of handling multiple pathologies are essential in clinical practice. This study focuses on enhancing precise lesion localization, classification and delineation in transurethral resection of bladder tumor (TURBT) to reduce cancer recurrence. Despite deep learning models success, medical applications face challenges like small and limited datasets and poor image characterization, including the absence lack of color/texture modeling. To address these issues, three solutions are proposed: (1) an improved texture-constrained version of the pix2pixHD cGAN for data augmentation, addressing the tradeoff of generating high-quality images with enough stochasticity using the Fréchet Inception Distance (FID) measure. (2) Introducing the Multiple Mask and Boundary Scoring R-CNN (MM&BS R-CNN), a new mask sub-net scheme where multiple masks are generated from the different levels of the mask sub-net pipeline, improving segmentation accuracy by including a new scoring module to refine object boundaries. (3) A novel accelerated training strategy based on the SGD optimizer with the second momentum. Experimental results show significant mAP improvements: the data generation scheme improves by more than 12 %; MM&BS R-CNN proposed architecture is responsible for an improvement of about 1.25 %, and the training algorithm based on the second-order momentum increases mAP by 2-3 %. The simultaneous use of all three proposals improved the state-of-the-art mAP by 17.44 %.

Exercise Training Benefits Health-Related Quality of Life and Functional Capacity during Breast Cancer Chemotherapy: An RCT.

PURPOSE: To examine the effectiveness of a supervised exercise training program (SETP) on health-related quality of life (HRQoL) and functional capacity in women with breast cancer (BC) undergoing chemotherapy. METHODS: Ninety-three women with early-stage BC were randomly allocated to a SETP plus usual care (Exercise, n = 47) or usual care alone (UC, n = 46). The SETP included 3 sessions per week, combining aerobic and resistance training, conducted concurrently over the chemotherapy. The EORTC Cancer Quality-of-Life-Questionnaire-Core-30 (QLQ-C30) and the BC-specific module (QLQ-BR23) were used to assess HRQoL. Functional capacity was analyzed by maximum voluntary handgrip strength (MVHS) and by the 30-second chair sit-to-stand test (30-s CST). These endpoints were assessed at baseline (t0); middle (t1; after 8 or 12 weeks of t0); and at the end of chemotherapy (t2; after 20 weeks of t0). Mean changes from baseline were assessed by an intention-to-treat approach. RESULTS: Mixed linear model analyses showed that Exercise group experienced less deterioration in several domains of QLQ-C30 at t2, including in global health status/QoL (Δ = 9.39 units; p = 0.034), QLQ-C30 summary score (Δ = 8.08 units; p < 0.001), physical (Δ = 15.14 units; p < 0.001), role (Δ = 21.81 units; p < 0.001), cognitive (Δ = 9.16 units; p = 0.032) and social functioning (Δ = 11.67 units; p = 0.038), compared to the UC group. Similarly, Exercise group exhibited significant lower levels of fatigue (Δ = -20.19 units; p < 0.001) and appetite loss (Δ = -13.69 units; p = 0.034), compared to the UC group. Significant between-group differences were observed on MVHS of the tumor/surgery upper limb side (Δ = 2.64 kg; p < 0.001) and contralateral limb (Δ = 2.22 kg; p < 0.001), and on the 30-s CST score (Δ = 3.56repetitions; p < 0.001), favoring the Exercise group. No differences were observed on QLQ-BR23 domains. CONCLUSIONS: Exercise training was an effective complementary therapy to prevent the deterioration of HRQoL and functional capacity during chemotherapy in women with early-stage BC.

Female sexual dysfunction in an outpatient andrology clinic—A therapeutic opportunity? / Disfunción sexual femenina en clínica de andrología. ¿Una oportunidad terapéutica?

Introduction: The sexual life of a couple is a dynamic entity, in which the two influence each other mutually, thus the existence of female sexual dysfunction (FSD) can influence the treatment of the man who seeks clinical help. Identify sexual dysfunction in female partners of patients attending an andrology clinic may provide a therapeutic opportunity. The authors aim to assess proportion of FSD in this population by comparison with a control group. Material and methods: A longitudinal study over 12 months timespan. The female partners of patients attending the andrology clinic participating in the study (study group – SG) completed the Female Sexual Function Index (FSFI), as did the women serving as controls (control group – CG). Further data such as age, duration and quality of the relationship and previous relationships was also collected. Results: Of the 30 women included in the SG, 14 (46.6%) considered that their current sex life was worse than in previous relationships. Of the 20 women in the CG, 60% considered that their current sex life was better. In the SG, 22 (73.3%) had FSD, with a mean score in the FSFI of 20.5, whereas only 3 women in the CG (15%) had FSD, with a mean score of 30.7 (p<0.01). Conclusions: Our study demonstrated that the proportion of FSD in female partners of patients attending an andrology clinic is significantly higher than control group. FSD treatment should be considered as a therapeutic opportunity for the couple in this setting. (AU)

Introducción: La vida sexual de una pareja es una entidad dinámica, en la que ambos se influyen mutuamente, por lo que la existencia de disfunción sexual femenina (DSF) puede influir en el tratamiento del hombre que busca ayuda clínica. Identificar la disfunción sexual en las parejas femeninas de los pacientes que asisten a una Clínica de Andrología puede brindar una oportunidad terapéutica. Los autores pretenden evaluar la proporción de DSF en esta población comparándola con un grupo de control. Material y métodos: Estudio longitudinal durante 12 meses. Las parejas femeninas de los pacientes que asistieron a la Clínica de Andrología y que participaron en el estudio (grupo de estudio) completaron el Índice de Función Sexual Femenina, de la misma forma que las mujeres, que sirvieron como control (grupo de control). También se recopilaron datos adicionales como edad, duración, calidad de la relación y las relaciones entre los anteriores. Resultados: De las 30 mujeres incluidas en el grupo de estudio, 14 (46,6%) consideraron que su vida sexual actual era peor que en relaciones anteriores. De las 20 mujeres del grupo control, el 60% consideró que su vida sexual actual era mejor. En el grupo de estudio, 22 (73,3%) tenían DSF, con una puntuación media de Índice de Función Sexual Femenina de 20,5, mientras que solo 3 mujeres en el grupo control (15%) tenían DSF, con una puntuación media de 30,7 (p <0,01). Conclusiones: Nuestro estudio demostró que la proporción de DSF en parejas femeninas de pacientes que acuden a una Clínica de Andrología es significativamente mayor que en el grupo control. El tratamiento de la disfunción sexual femenina debe considerarse como una oportunidad terapéutica para la pareja en este escenario. (AU)

Association between sociodemographic and clinical features, health behaviors, and health literacy of patients with prostate cancer and prostate cancer prognostic stage.

Patient characteristics may influence access and acceptance of Prostate Specific Antigen test, and therefore, the timing of prostate cancer (PCa) diagnosis. A group of 361 patients from a cohort (n = 451) diagnosed with PCa in 2018-2020 at the Portuguese Institute of Oncology of Porto was evaluated before treatment, using a structured interview, the Medical Term Recognition Test, and the EORTC Quality of Life Questionnaire QLQ-PR25. PCa prognostic stages (I, II, III, IV) were attributed according to the American Joint Committee on Cancer eighth edition. Multinomial logistic regression was used to compute the odds ratio and 95% confidence interval (OR [95% CI]), considering PCa stage II, the most frequent, as reference. Older age (OR = 4.21 [2.24-7.93]), living outside the Porto Metropolitan Area while having low income (OR = 6.25 [1.53-25.62]), and erectile dysfunction (OR = 2.22 [0.99-4.99]) were associated with stage III, while urination during the night (OR = 3.02 [1.42-6.41]) was associated with stage IV. Urine leakage was less frequent in stage III (OR = 0.23 [0.08-0.68]), and living with a partner (OR = 0.41 [0.19-0.88]) and family history of cancer (OR = 0.25 [0.07-0.86]) in stage IV. Health literacy was not associated with PCa stage but lower education was less frequent in stage I (OR = 0.27 [0.11-0.69]). Patient sociodemographic and clinical characteristics should be considered as targets to improve PCa early detection and prognosis.

Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses.

INTRODUCTION: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks. Thus, we implemented two alternative and innovative protocols to mimic a particular sub-group of LSDs, the Mucopolysaccharidoses both in vitro and in vivo. METHODS: The first one relies on a non-invasive approach using dental pulp stem cells from deciduous teeth (SHEDs). SHEDs are multipotent neuronal precursors that can easily be collected. The second uses a state-of-the-art gene editing technology (CRISPR/Cas9) to generate zebrafish disease models. RESULTS: Even though this is an ongoing project, we have already established and characterized two MPS II and one MPS VI SHED cell models. These cells self-maintain through several passages and can give rise to a variety of cells including neurons. Furthermore, all MPS-associated sub-cellular phenotypes we have assessed so far are easily observable in these cells. Regarding our zebrafish models, we have successfully knocked down both naglu and hgsnat and the first results we got from the behavioral analysis are promising ones, as we can observe altered activity and sleep patterns in the genetically modified fish. For this particular approach we chose MPS III forms as our target disorders, since their neurological features (hyperactivity, seizures and motor impairment) and lifespan decrease would be easily recognizable in zebrafish. CONCLUSION: Now that these methods are well-established in our lab, their potential is immense. On one hand, the newly developed models will be of ultimate value to understand the mechanisms underlying MPS sub-cellular pathology, which have to be further elucidated. On the other hand, they will constitute an optimal platform for drug testing in house. Also noteworthy, our models will be published as lab resources and made available for the whole LSD community.

How much is a chef's touch worth? Affective, emotional and behavioural responses to food images: A multimodal study.

BACKGROUND: Food aesthetics influences affective dimensions (valence and arousal) and subsequent emotional and behavioural responses in images presented in more traditional form, almost rustic in some cases, to the signature dishes of haute cuisine. However, the visual impact of images of haute cuisine dishes on consumers' affective and emotional responses compared to traditional dishes is still understudied. METHODS: We recorded electrodermal activity, ocular movements and self-report affect of 35 volunteers while they performed a picture viewing paradigm using images of haute cuisine food, traditional food, and non-food. Additionally, the moderating role of age was examined. RESULTS: Our results showed that subjects had higher feelings of pleasure and arousal toward images of food (haute cuisine and traditional dishes) compared to non-food images. However, no difference in self-report affect, physiological and behavioural responses was found between haute cuisine and traditional dishes. Interestingly, a moderating effect of age was revealed, reporting that younger participants had greater feelings of pleasure and shorter eye-to-screen distance towards traditional food than haute cuisine. CONCLUSIONS: As a whole, our findings suggest that food aesthetics could at least partially affect consumers' affective and emotional responses. Interestingly, physiological responses to food pictures seemed to be relatively independent of approach/avoidance motivational states, supporting the assumption that traditional visual restaurant menus with attractive images might be insufficient for eliciting intense positive emotions. This study also contributes to advancing the understanding of the role that age plays in emotional impact when images of haute cuisine dishes are presented to consumers.

Temporal validation of the MMCD score to predict kidney replacement therapy and in-hospital mortality in COVID-19 patients.

BACKGROUND: Acute kidney injury has been described as a common complication in patients hospitalized with COVID-19, which may lead to the need for kidney replacement therapy (KRT) in its most severe forms. Our group developed and validated the MMCD score in Brazilian COVID-19 patients to predict KRT, which showed excellent performance using data from 2020. This study aimed to validate the MMCD score in a large cohort of patients hospitalized with COVID-19 in a different pandemic phase and assess its performance to predict in-hospital mortality. METHODS: This study is part of the "Brazilian COVID-19 Registry", a retrospective observational cohort of consecutive patients hospitalized for laboratory-confirmed COVID-19 in 25 Brazilian hospitals between March 2021 and August 2022. The primary outcome was KRT during hospitalization and the secondary was in-hospital mortality. We also searched literature for other prediction models for KRT, to assess the results in our database. Performance was assessed using area under the receiving operator characteristic curve (AUROC) and the Brier score. RESULTS: A total of 9422 patients were included, 53.8% were men, with a median age of 59 (IQR 48-70) years old. The incidence of KRT was 8.8% and in-hospital mortality was 18.1%. The MMCD score had excellent discrimination and overall performance to predict KRT (AUROC: 0.916 [95% CI 0.909-0.924]; Brier score = 0.057). Despite the excellent discrimination and overall performance (AUROC: 0.922 [95% CI 0.914-0.929]; Brier score = 0.100), the calibration was not satisfactory concerning in-hospital mortality. A random forest model was applied in the database, with inferior performance to predict KRT requirement (AUROC: 0.71 [95% CI 0.69-0.73]). CONCLUSION: The MMCD score is not appropriate for in-hospital mortality but demonstrates an excellent predictive ability to predict KRT in COVID-19 patients. The instrument is low cost, objective, fast and accurate, and can contribute to supporting clinical decisions in the efficient allocation of assistance resources in patients with COVID-19.

Multisystemic RFC1-Related Disorder: Expanding the Phenotype Beyond Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

Background and Objectives: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1-positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1-related patients. Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test. Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems. Discussion: The presence of MN involvement, motor neuropathy, small fiber neuropathy, or extrapyramidal signs should not preclude RFC1 testing in cases of sensory neuronopathy. Indeed, the RFC1 spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical.

Brief Form of the Affective Neuroscience Personality Scales: Preliminary Psychometric Properties in a European Portuguese Community Sample.

Personality theory based on affective neuroscience research suggests the presence of seven affective neurobiological systems. These dimensions have been identified using psychometric instruments such as the Affective Neuroscience Personality Scales (ANPS) and its brief version known as the Brief Affective Neuroscience Personality Scales (BANPS). Despite being a psychometric valid instrument, the BANPS was not adapted to European Portuguese. This study describes a psychometric analysis of the BANPS in a Portuguese population sample. A European Portuguese-speaking sample was recruited (N = 355, Mage = 27.31, DP = 12.75). Confirmatory factor analysis (CFA) was used to confirm the BANPS factorial structure. Pearson correlations were used to explore convergent validity with self-reports for psychological distress and psychopathology. Six factor model was confirmed with adequate goodness-of-fit indices (χ2(449) = 808,9841, TLI = .90, CFI = .92, RMSEA = .048 (.042-.053). Non-agreeable affective systems (anger, fear, distress), correlated positively with psychological distress and symptomology, while play and care systems correlated negatively. Seek and care subscales showed the weakest psychometric properties. The original factor structure was confirmed, suggesting the BANPS may be a valid measure to assess affective behavioral traits in the Portuguese population. Further studies in clinical populations may improve the psychometric data of the BANPS.

Heart murmur detection from phonocardiogram recordings: The George B. Moody PhysioNet Challenge 2022.

Cardiac auscultation is an accessible diagnostic screening tool that can help to identify patients with heart murmurs, who may need follow-up diagnostic screening and treatment for abnormal cardiac function. However, experts are needed to interpret the heart sounds, limiting the accessibility of cardiac auscultation in resource-constrained environments. Therefore, the George B. Moody PhysioNet Challenge 2022 invited teams to develop algorithmic approaches for detecting heart murmurs and abnormal cardiac function from phonocardiogram (PCG) recordings of heart sounds. For the Challenge, we sourced 5272 PCG recordings from 1452 primarily pediatric patients in rural Brazil, and we invited teams to implement diagnostic screening algorithms for detecting heart murmurs and abnormal cardiac function from the recordings. We required the participants to submit the complete training and inference code for their algorithms, improving the transparency, reproducibility, and utility of their work. We also devised an evaluation metric that considered the costs of screening, diagnosis, misdiagnosis, and treatment, allowing us to investigate the benefits of algorithmic diagnostic screening and facilitate the development of more clinically relevant algorithms. We received 779 algorithms from 87 teams during the Challenge, resulting in 53 working codebases for detecting heart murmurs and abnormal cardiac function from PCG recordings. These algorithms represent a diversity of approaches from both academia and industry, including methods that use more traditional machine learning techniques with engineered clinical and statistical features as well as methods that rely primarily on deep learning models to discover informative features. The use of heart sound recordings for identifying heart murmurs and abnormal cardiac function allowed us to explore the potential of algorithmic approaches for providing more accessible diagnostic screening in resource-constrained environments. The submission of working, open-source algorithms and the use of novel evaluation metrics supported the reproducibility, generalizability, and clinical relevance of the research from the Challenge.

Perfil sociodemográfico e citológico de mulheres em investigação de neoplasia cérvico-uterina em um serviço secundário / Sociodemographic and cytological profile of women undergoing investigation for cervical-uterine neoplasia in a secondary service

Objetivo: analisar o perfil sociodemográfico e comparar as diferenças das características de mulheres com alterações citológicas de alto grau em um serviço da atenção secundária. Método: estudo transversal retrospectivo de 2017 a 2021 realizado em 160 prontuários (CAAE 51800621.3.0000.5240). Resultados: predominaram mulheres com média de idade 40,7 anos, escolaridade abaixo do ensino médio, tiveram um a três filhos, não utilizavam preservativos e anticoncepcionais, não tabagistas e com alterações citopatológicas alto grau. As características com maiores percentuais para lesões citopatológicas de alto grau foram mulheres com quatro ou mais gestações, idade do parto menor ou igual a 18 anos, coitarca menor ou igual a 15 anos e tabagistas. Conclusão: serviços da rede de atenção, especialmente da atenção primária à saúde, devem capacitar permanentemente os profissionais visando cumprimento de fluxos assistenciais preconizadas pelas recomendações das diretrizes brasileiras de rastreamento da neoplasia cérvico-uterina atentando ao perfil encontrado de mulheres encaminhadas a atenção secundária.(AU)

Objective: analyzes the sociodemographic profile and compare the differences in the characteristics of women with high-grade cytological alterations in a secondary care service. Method: retrospective cross-sectional study from 2017 to 2021 carried out in 160 medical records (CAAE 51800621.3.0000.5240). Results: women predominated with a mean age of 40.7 years, education below high school, had one to three children, did not use condoms and contraceptives, non-smokers and with high-grade cytopathological alterations. The characteristics with the highest percentages for high-grade cytopathological lesions were women with four or more pregnancies, age at birth less than or equal to 18 years, coitarche less than or equal to 15 years, and smokers. Conclusion: services of the care network, especially primary health care, should permanently train professionals in order to comply with the care flows recommended by the recommendations of the Brazilian guidelines for screening cervical uterine neoplasia, paying attention to the profile found of women referred to secondary care.(AU)

Objetivo: analizar el perfil sociodemográfico y comparar las diferencias en las características de mujeres con alteraciones citológicas de alto grado en un servicio de segundo nivel de atención. Método: estudio transversal retrospectivo de 2017 a 2021 realizado en 160 historias clínicas (CAAE 51800621.3.0000.5240). Resultados: predominaron las mujeres con edad media de 40,7 años, escolaridad inferior a la secundaria, con uno a tres hijos, no usuarias de preservativo y anticonceptivos, no fumadoras y con alteraciones citopatológicas de alto grado. Las características con mayor porcentaje de lesiones citopatológicas de alto grado fueron mujeres con cuatro o más embarazos, edad al nacer menor o igual a 18 años, coitarquia menor o igual a 15 años y fumadoras. Conclusión: servicios de la red de atención, especialmente la atención primaria a la salud, deben capacitar permanentemente a los profesionales para cumplir con los flujos de atención recomendados por las recomendaciones de las directrices brasileñas para el tamizaje de la neoplasia cérvico-uterina, prestando atención al perfil encontrado de las mujeres referidas atención secundaria.(AU)

Stress response mechanisms in protein misfolding diseases: Profiling a cellular model of Huntington's disease.

Stress response pathways like the integrated stress response (ISR), the mitochondrial unfolded protein response (UPRmt) and the heat shock response (HSR) have emerged as part of the pathophysiology of neurodegenerative diseases, including Huntington's disease (HD) - a currently incurable disease caused by the production of mutant huntingtin (mut-Htt). Previous data from HD patients suggest that ISR is activated while UPRmt and HSR are impaired in HD. The study of these stress response pathways as potential therapeutic targets in HD requires cellular models that mimic the activation status found in HD patients of such pathways. PC12 cells with inducible expression of the N-terminal fragment of mut-Htt are among the most used cell lines to model HD, however the activation of stress responses remains unclear in this model. The goal of this study is to characterize the activation of ISR, UPRmt and HSR in this HD cell model and evaluate if it mimics the activation status found in HD patients. We show that PC12 HD cell model presents reduced levels of Hsp90 and mitochondrial chaperones, suggesting an impaired activation or function of HSR and UPRmt. This HD model also presents increased levels of phosphorylated eIF2α, the master regulator of the ISR, but overall similar levels of ATF4 and decreased levels of CHOP - transcription factors downstream to eIF2α - in comparison to control, suggesting an initial activation of ISR. These results show that this model mimics the ISR activation and the impaired UPRmt and HSR found in HD patients. This work suggests that the PC12 N-terminal HD model is suitable for studying the role of stress response pathways in the pathophysiology of HD and for exploratory studies investigating the therapeutic potential of drugs targeting stress responses.