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A bactéria Mycoplasma pneumoniae (M. pneumoniae) é uma causa comum de pneumonia adquirida na comunidade em idade escolar, podendo manifestar-se sob variadas formas. Os autores reportam dois casos de infeção por M. pneumoniae. Rapariga 10 anos, clinicamente com febre, cefaleia e tosse seca com quatro dias de evolução. Audíveis crepitações e sibilos inspiratórios no campo pulmonar direito. Imagiologicamente verificou-se hipotransparência na base direita associada a derrame pleural ipsilateral. O painel PCR (Polymerase Chain Reaction) respiratório foi positivo para M. Pneumoniae. Adolescente 13 anos, asmática, clinicamente com tosse seca e dispneia com uma semana de evolução. Apresentava sinais de dificuldade respiratória, hipoxemia e, sibilos e crepitações bilaterais. Imagiologicamente verificou-se infiltrado bibasal com derrame pleural de pequeno volume. O painel PCR respiratório identificou o M. Pneumoniae. Os dois relatos de caso corroboram diversidade de sintomas e gravidade clínica que a infeção porM. pneumoniae pode manifestar: desde sintomas respiratórios superiores a inferiores ou mesmo sintomas extra-respiratórios como, manifestações mucocutâneas, anemia hemolítica ou alterações neurológicas. Para o diagnóstico estão disponíveis as serologias e a pesquisa por PCR da bactéria nas secreções respiratórias; no entanto, estes exames apresentam baixa sensibilidade e especificidade, respetivamente. Assim, o diagnóstico deve assentar essencialmente na clínica. A terapêutica de primeira linha são os macrólidos. Globalmente, tem-se verificado um aumento das infeções por M. Pneumoniae com crescentes resistências aos macrólidos e formas de apresentação mais graves. Torna-se, portanto, fundamental uma elevada suspeita diagnóstica por forma a realizar o diagnóstico precocemente e instituir atempadamente a terapêutica adequada.

A massagem infantil é uma terapia complementar que tem suscitado um interesse crescente na comunidade científica pelos seus potenciais benefícios no alívio sintomático de condições pediátricas frequentes. O seu mecanismo fisiopatológico ainda não está completamente estabelecido, porém é uma prática que favorece a comunicação e o vínculo com os cuidadores, promovendo uma sensação de conforto e bem-estar do lactente. Segundo a literatura mais recente, a massagem infantil parece ser promissora no alívio da dor, na diminuição da icterícia, no tratamento adjuvante da obstipação funcional, na melhoria da qualidade do sono e no crescimento e desenvolvimento infantis. Assim, como terapêutica não farmacológica, parece ter benefícios, sendo praticamente desprovida de efeitos adversos. Contudo, atualmente, ainda existem poucos estudos randomizados acerca desta temática, pelo que a qualidade da evidência é baixa, constituindo uma limitação para a sua recomendação universal na prática clínica.

Age-related loss of gene expression coordination has been reported for distinct cell types and may lead to impaired cellular function. Here we propose a method for quantifying age-related changes in transcriptional regulatory relationships between genes, based on a model learned from external data. We used this method to uncover age-related trends in gene-gene relationships across eight human tissues, which demonstrates that reduced co-expression may also result from coordinated transcriptional responses. Our analyses reveal similar numbers of strengthening and weakening gene-gene relationships with age, impacting both tissue-specific (for example, coagulation in blood) and ubiquitous biological functions. Regulatory relationships becoming weaker with age were established mostly between genes operating in distinct cellular processes. As opposed to that, regulatory relationships becoming stronger with age were established both within and between different cellular functions. Our work reveals that, although most transcriptional regulatory gene-gene relationships are maintained during aging, those with declining regulatory coupling result mostly from a loss of coordination between distinct cellular processes., (© 2024. The Author(s).)

Background: In Portugal, trained physicians undertake the clinical coding process, which serves as the basis for hospital reimbursement systems. In 2017, the classification version used for coding of diagnoses and procedures for hospital morbidity changed from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS)., Objective: To assess the perceptions of medical coders on the transition of the clinical coding process from ICD-9-CM to ICD-10-CM/PCS in terms of its impact on data quality, as well as the major differences, advantages, and problems they faced., Method: We conducted an observational study using a web-based survey submitted to medical coders in Portugal. Survey questions were based on a literature review and from previous focus group studies., Results: A total of 103 responses were obtained from medical coders with experience in the two versions of the classification system (i.e. ICD-9-CM and ICD-10-CM/PCS). Of these, 82 (79.6%) medical coders preferred the latest version and 76 (73.8%) considered that ICD-10-CM/PCS guaranteed higher quality of the coded data. However, more than half of the respondents ( N  = 61; 59.2%) believed that more time for the coding process for each episode was needed., Conclusion: Quality of clinical coded data is one of the major priorities that must be ensured. According to the medical coders, the use of ICD-10-CM/PCS appeared to achieve higher quality coded data, but also increased the effort., Implications: According to medical coders, the change off classification systems should improve the quality of coded data. Nevertheless, the extra time invested in this process might also pose a problem in the future., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We report a case of Taenia solium taeniasis in a 10-year-old child in Timor-Leste, confirmed by molecular analysis, suggesting T. solium transmission to humans is occurring in Timor-Leste. Proactive measures are needed to improve public understanding of prevalence, geographic spread, and health implications of human taeniasis and cysticercosis in Timor-Leste.

Neuroinflammation is a process involved in a variety of central nervous system (CNS) diseases and is being increasingly recognized as a key mediator of cognitive impairments. Neuroinflammatory responses including glial activation, increased production of proinflammatory cytokines, and aberrant neuronal signaling, contribute to cognitive dysfunctions. Histamine is a key peripheral inflammatory mediator, but plays an important role in neuroinflammatory processes as well. The unique localization of histamine H3 receptor (H3R) in the CNS along with the modulation of the release of other neurotransmitters via its action on heteroreceptors on non-histaminergic neurons have led to the development of several H3R ligands for various brain diseases. H3R antagonists/ inverse agonists have revealed potential to treat diverse neuroinflammatory CNS disorders, including neurodegenerative diseases, attention-deficit hyperactivity syndrome and schizophrenia. In this mini review, we provide a brief overview on the crucial involvement of the histaminergic transmission in the neuroinflammatory processes underlying these cognitive disorders, with a special focus on H3R involvement. The anti-neuroinflammatory potential of single-targeted and multi-targeted H3R antagonists/inverse agonists for the treatment of these conditions is discussed here., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

All patient refined-diagnosis related groups (APR-DRGs) includes severity of illness (SOI) and risk of mortality (ROM) subclasses. For predictions, both subscales are used together or interchangeably. We aimed to compare SOI and ROM by evaluating the reliability and agreement between both. We performed a retrospective observational study using mainland Portuguese public hospitalisations of adult patients from 2011 to 2016. Reliability (quadratic weighted kappa) and agreement (proportion of agreement) between SOI and ROM were analysed overall and by APR-DRG. While overall reliability and agreement between SOI and ROM were high (weighted kappa: 0.717, 95% CI 0.717-0.718; proportion of agreement: 69.0%, 95% CI 69.0-69.0) there was high heterogeneity across APR-DRGs, ranging from 0.016 to 0.846 on reliability and from 23.1% to 94.8% on agreement. Most of APR-DRGs (263 out of 284) showed a higher proportion of episodes with ROM level above the SOI level than the opposite. In conclusion, SOI and Risk of Mortality measures must be clearly distinguished and are 'two scales of different concepts' rather than 'two sides of the same coin'. However, this is more evident for some APR-DRGs than for others., (© 2024 John Wiley & Sons Ltd.)

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases in which abdominal pain, bloody diarrhea, weight loss, and fatigue collectively result in diminished quality of patient life. The disappearance of intestinal helminth infections in Western societies is associated with an increased prevalence of IBD and other immune-mediated inflammatory diseases. Evidence indicates that helminths induce tolerogenic dendritic cells (tolDCs), which promote intestinal tolerance and attenuate intestinal inflammation characteristic of IBD, but the exact mechanism is unclear. Helminth-derived excretory-secretory (HES) products including macromolecules, proteins, and polysaccharides have been shown to modulate the antigen presenting function of DCs with down-stream effects on effector CD4 + T cells. Previous studies indicate that DCs in helminth-infected animals induce tolerance to unrelated antigens and DCs exposed to HES display phenotypic and functional features of tolDCs. Here, we identify that nonpolar metabolites (HnpM) produced by a helminth, the murine gastrointestinal nematode Heligmosomoides polygyrus bakeri (Hpb), induce tolDCs as evidenced by decreased LPS-induced TNF and increased IL-10 secretion and reduced expression of MHC-II, CD86, and CD40. Furthermore, these DCs inhibited OVA-specific CD4 + T cell proliferation and induced CD4 + Foxp3 + regulatory T cells. Adoptive transfer of HnpM-induced tolDCs attenuated DSS-induced intestinal inflammation characteristic of IBD. Mechanistically, HnpM induced metabolic and transcriptional signatures in BMDCs consistent with tolDCs. Collectively, our findings provide groundwork for further investigation into novel mechanisms regulating DC tolerance and the role of helminth secreted metabolites in attenuating intestinal inflammation associated with IBD. Summary Sentence: Metabolites produced by Heligmosomoides polygyrus induce metabolic and transcriptional changes in DCs consistent with tolDCs, and adoptive transfer of these DCs attenuated DSS-induced intestinal inflammation.

Objective: Seizure prediction is a promising solution to improve the quality of life for drug-resistant patients, which concerns nearly 30% of patients with epilepsy. The present study aimed to ascertain the impact of incorporating sleep-wake information in seizure prediction., Methods: We developed five patient-specific prediction approaches that use vigilance state information differently: i) using it as an input feature, ii) building a pool of two classifiers, each with different weights to sleep/wake training samples, iii) building a pool of two classifiers, each with only sleep/wake samples, iv) changing the alarm-threshold concerning each sleep/wake state, and v) adjusting the alarm-threshold after a sleep-wake transition. We compared these approaches with a control method that did not integrate sleep-wake information. Our models were tested with data (43 seizures and 482 hours) acquired during presurgical monitoring of 17 patients from the EPILEPSIAE database. As EPILEPSIAE does not contain vigilance state annotations, we developed a sleep-wake classifier using 33 patients diagnosed with nocturnal frontal lobe epilepsy from the CAP Sleep database., Results: Although different patients may require different strategies, our best approach, the pool of weighted predictors, obtained 65% of patients performing above chance level with a surrogate analysis (against 41% in the control method)., Conclusion: The inclusion of vigilance state information improves seizure prediction. Higher results and testing with long-term recordings from daily-life conditions are necessary to ensure clinical acceptance., Significance: As automated sleep-wake detection is possible, it would be feasible to incorporate these algorithms into future devices for seizure prediction.

Macrophages sense pathogens and orchestrate specific immune responses. Stimulus specificity is thought to be achieved through combinatorial and dynamical coding by signaling pathways. While NFκB dynamics are known to encode stimulus information, dynamical coding in other signaling pathways and their combinatorial coordination remain unclear. Here, we established live-cell microscopy to investigate how NFκB and p38 dynamics interface in stimulated macrophages. Information theory and machine learning revealed that p38 dynamics distinguish cytokine TNF from pathogen-associated molecular patterns and high doses from low, but contributed little to information-rich NFκB dynamics when both pathways are considered. This suggests that immune response genes benefit from decoding immune signaling dynamics or combinatorics, but not both. We found that the heterogeneity of the two pathways is surprisingly uncorrelated. Mathematical modeling revealed potential sources of uncorrelated heterogeneity in the branched pathway network topology and predicted it to drive gene expression variability. Indeed, genes dependent on both p38 and NFκB showed high scRNAseq variability and bimodality. These results identify combinatorial signaling as a mechanism to restrict NFκB-AND-p38-responsive inflammatory cytokine expression to few cells., (© 2024. The Author(s).)

Infertility affects millions worldwide, with significant medical, financial, and emotional challenges, particularly in low- and middle-income countries (LMICs). Cultural, religious, financial, and gender-related barriers hinder access to treatment, exacerbating social and economic consequences, especially for women. Despite its prevalence, infertility often remains overlooked due to competing health priorities. However, global initiatives recognise infertility as a reproductive health concern, advocating for universal access to high-quality fertility care. In LMICs, limited resources and infrastructure impede access to treatment, prompting people to turn to alternative, often ineffective, non-biomedical solutions. Addressing these challenges requires implementing affordable fertility care services tailored to local contexts, supported by political commitment and community engagement. Emerging technologies offer promising solutions, but comprehensive education and training programs are essential for their effective implementation. By integrating fertility care into broader health policies and fostering partnerships, we can ensure equitable access to infertility treatment and support reproductive health worldwide.

Summary: We present RokaiXplorer, an intuitive web tool designed to address the scarcity of user-friendly solutions for proteomics and phospho-proteomics data analysis and visualization. RokaiXplorer streamlines data processing, analysis, and visualization through an interactive online interface, making it accessible to researchers without specialized training in proteomics or data science. With its comprehensive suite of modules, RokaiXplorer facilitates phospho-proteomic analysis at the level of phosphosites, proteins, kinases, biological processes, and pathways. The tool offers functionalities such as data normalization, statistical testing, activity inference, pathway enrichment, subgroup analysis, automated report generation, and multiple visualizations, including volcano plots, bar plots, heat maps, and network views. As a unique feature, RokaiXplorer allows researchers to effortlessly deploy their own data browsers, enabling interactive sharing of research data and findings. Overall, RokaiXplorer fills an important gap in phospho-proteomic data analysis by providing the ability to comprehensively analyze data at multiple levels within a single application., Availability and Implementation: Access RokaiXplorer at: http://explorer.rokai.io., Competing Interests: No competing interest is declared., (Published by Oxford University Press 2024.)

According to the literature, seizure prediction models should be developed following a patient-specific approach. However, seizures are usually very rare events, meaning the number of events that may be used to optimise seizure prediction approaches is limited. To overcome such constraint, we analysed the possibility of using data from patients from an external database to improve patient-specific seizure prediction models. We present seizure prediction models trained using a transfer learning procedure. We trained a deep convolutional autoencoder using electroencephalogram data from 41 patients collected from the EPILEPSIAE database. Then, a bidirectional long short-term memory and a classifier layers were added on the top of the encoder part and were optimised for 24 patients from the Universitätsklinikum Freiburg individually. The encoder was used as a feature extraction module. Therefore, its weights were not changed during the patient-specific training. Experimental results showed that seizure prediction models optimised using pretrained weights present about four times fewer false alarms while maintaining the same ability to predict seizures and achieved more 13% validated patients. Therefore, results evidenced that the optimisation using transfer learning was more stable and faster, saving computational resources. In summary, adopting transfer learning for seizure prediction models represents a significant advancement. It addresses the data limitation seen in the seizure prediction field and offers more efficient and stable training, conserving computational resources. Additionally, despite the compact size, transfer learning allows to easily share data knowledge due to fewer ethical restrictions and lower storage requirements. The convolutional autoencoder developed in this study will be shared with the scientific community, promoting further research., (© 2024. The Author(s).)

Importance: Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study., Objective: To examine the extent of stigma, dependence on disease visibility and severity, and association with mental health and quality of life (QOL) in chronic pediatric skin disease., Design, Setting, and Participants: A cross-sectional, single-visit study was conducted at 32 pediatric dermatology centers in the US and Canada from November 14, 2018, to November 17, 2021. Participants included patients aged 8 to 17 years with chronic skin disease and 1 parent., Main Outcomes and Measures: Using the Patient-Reported Outcomes Measurement Instrumentation System (PROMIS) Stigma-Skin, the extent of stigma with child-, caregiver-, and physician-assessed disease visibility (primary outcome) and severity was compared, as well as reduced QOL (assessed by Skindex-Teen), depression, anxiety, and poor peer relationships (PROMIS child and proxy tools) (secondary outcomes)., Results: The study included 1671 children (57.9% female; mean [SD] age, 13.7 [2.7] years). A total of 56.4% participants had self-reported high disease visibility and 50.5% had moderate disease severity. Stigma scores significantly differed by level of physician-assessed and child/proxy-assessed disease visibility and severity. Among children with chronic skin disorders, predominantly acne, atopic dermatitis, alopecia areata, and vitiligo, only 27.0% had T scores less than 40 (minimal or no stigma) and 43.8% had at least moderate stigma (T score ≥45) compared with children with a range of chronic diseases. Stigma scores correlated strongly with reduced QOL (Spearman ρ = 0.73), depression (ρ = 0.61), anxiety (ρ = 0.54), and poor peer relationships (ρ = -0.49). Overall, 29.4% of parents were aware of bullying of their child, which was strongly associated with stigma (Cohen d = -0.79, with children who were not bullied experiencing lower levels of stigma). Girls reported more stigma than boys (Cohen d = 0.26). Children with hyperhidrosis and hidradenitis suppurativa were most likely to have increased depression and anxiety., Conclusions and Relevance: The findings of this study suggest that physician assessment of disease severity and visibility is insufficient to evaluate the disease impact in the patient/caregiver. Identifying stigmatization, including bullying, and tracking improvement through medical and psychosocial interventions may be a key role for practitioners.

The decline of children's opportunities to play outdoors raises a new concern about the quality of outdoor play environments, and their developmental and well-being benefits for children. This systematic review aims to synthesize the associations between outdoor play features and children's behavior and health. PRISMA guidelines were followed (2021). The inclusion criteria were studies with children aged between 5 and 12 (Population); that addressed presence, absence or disposition of equipment, natural elements, loose parts, resources availability, type of terrain and space modifications (Intervention or Exposure); in pre-post intervention or between groups (Comparison); related to health and behavior in different domains (Outcomes); with an experimental, observational, descriptive or longitudinal design (Study design). Indoor context, adult-led activities and structured activities were excluded. A literature search of five databases (PubMed, Web of Science, ERIC, Scopus, and PsycINFO) was concluded in March 2022. After identifying 28,772 records, duplicates and irrelevant titles were removed, and abstracts and full-text articles were screened in duplicate. The remaining 51 eligible articles (45 primary studies) were assessed for risk of bias with QualSyst. A narrative synthesis of the results was conducted. The most frequent behavioral or health outcome addressed was physical activity. Included studies focused on the following space features: fixed structures, space naturalness, floor markings, loose parts/equipment, area available, and the combination of factors. Although some positive effects were found, the heterogeneity between studies did not allow to draw firm conclusions on the effects of each environmental feature on primary children's health and behavior. Systematic review registration: PROSPERO CRD42020179501., Competing Interests: Declaration of competing interest Authors declare they have no known conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The objectives of this study are to clarify the scientific definition of comfort food, identify which methodologies are being used in research on this topic and which factors are associated with the consumption of comfort food., Introduction: The consumption of comfort foods is subjective and influenced by individual experiences, as they are known and appreciated by the person. However, divergences about the definition of comfort food in the scientific literature reflect the heterogeneity of the methods used in the research, and consequently identification of possible factors associated with the consumption of this type of food, which can influence the knowledge about the consumption of these foods and their potential effects on the health of those who consume them., Inclusion Criteria: Works with a qualitative and quantitative approach published in full in indexed sources or in gray literature, available online in the databases consulted, without restriction on language or year of publication will be included., Methods: The protocol was built based on the methodological recommendations of the Joanna Briggs Institute (JBI) for scoping reviews and the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The Participants, Concept and Context (PCC) mnemonic strategy was built: general population, comfort food concept and world context. Based on this, search strategies were developed for different databases. Instruments were also developed for recording documents, extracting data, justifying the exclusion of documents and not obtaining access to content. A Pilot Study was conducted to test the developed methodology and instruments. The protocol has been registered with the Open Science Framework (OSF) (https://osf.io/gnza4/). The results will be presented in the review resulting from this protocol in three ways: accounting of the documents will be recorded in a PRISMA Flow Diagram, the main information of the studies and their frequencies will be presented in a table, and the union of these outcomes will be presented visually in a Graphical Abstract., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pereira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Seizure prediction remains a challenge, with approximately 30% of patients unresponsive to conventional treatments. Addressing this issue is crucial for improving patients' quality of life, as timely intervention can mitigate the impact of seizures. In this research field, it is critical to identify the preictal interval, the transition from regular brain activity to a seizure. While previous studies have explored various Electroencephalogram (EEG) based methodologies for prediction, few have been clinically applicable. Recent studies have underlined the dynamic nature of EEG data, characterised by data changes with time, known as concept drifts, highlighting the need for automated methods to detect and adapt to these changes. In this study, we investigate the effectiveness of automatic concept drift adaptation methods in seizure prediction. Three patient-specific seizure prediction approaches with a 10-minute prediction horizon are compared: a seizure prediction algorithm incorporating a window adjustment method by optimising performance with Support Vector Machines (Backwards-Landmark Window), a seizure prediction algorithm incorporating a data-batch (seizures) selection method using a logistic regression (Seizure-batch Regression), and a seizure prediction algorithm with a dynamic integration of classifiers (Dynamic Weighted Ensemble). These methods incorporate a retraining process after each seizure and use a combination of univariate linear features and SVM classifiers. The Firing Power was used as a post-processing technique to generate alarms before seizures. These methodologies were compared with a control approach based on the typical machine learning pipeline, considering a group of 37 patients with Temporal Lobe Epilepsy from the EPILEPSIAE database. The best-performing approach (Backwards-Landmark Window) achieved results of 0.75 ± 0.33 for sensitivity and 1.03 ± 1.00 for false positive rate per hour. This new strategy performed above chance for 89% of patients with the surrogate predictor, whereas the control approach only validated 46%., (© 2024. The Author(s).)

Biofilm-based cultivation systems are emerging as a promising technology for microalgae production. However, efficient and non-invasive monitoring routines are still lacking. Here, a protocol to monitor microalgae biofilms based on reflectance indices (RIs) is proposed. This framework was developed using a rotating biofilm system for astaxanthin production by cultivating Haematococcus pluvialis on cotton carriers. Biofilm traits such as biomass, astaxanthin, and chlorophyll were characterized under different light and nutrient regimes. Reflectance spectra were collected to identify the spectral bands and the RIs that correlated the most with those biofilm traits. Robust linear models built on more than 170 spectra were selected and validated on an independent dataset. Astaxanthin content could be precisely predicted over a dynamic range from 0 to 4% of dry weight, regardless of the cultivation conditions. This study demonstrates the strength of reflectance spectroscopy as a non-invasive tool to improve the operational efficiency of microalgae biofilm-based technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: to evaluate the main factors associated with mortality and determine the life expectancy of SLE patients between 2000 and 2019 years in Brazil., Methods: death data related to SLE available in the Brazilian Unified Health System (SUS) (DATASUS) were evaluated in all Brazilian states. Three groups of death causes potentially associated from SLE were evaluated: cardiovascular and kidney diseases and infections., Results: The main causes of death associated with SLE were infection and kidney disease. Most SLE patients died between 19 and 50 years of age. Deaths associated with kidney disease were proportionally higher than in the general population with progressive decrease during the period. Instead, there have been an increase in the proportion of deaths due to infections both in SLE and in the general population., Conclusions: SLE patients presented higher mortality compared to the general population matched for sex and age and the main causes associated with death were infection and kidney disease. Public health policies that promote early diagnosis, treatment and prevention of damage are necessary to reduce morbidity and mortality in SLE patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that the research was carried out in the absence of any commercial or financial relationship that could be interpreted as a potential conflict of interest. Edgard Torres dos Reis-Neto received speaker fees and/or consultancies from GSK, AstraZeneca, Novartis. Odirlei Andre Monticielo received speaker fees and/or consultancies from ABBVIE, AstraZeneca, CELLTRION, GSK and JANSSEN-CILAG. Evandro Mendes Klumb received speaker fees and/or consultancies from AstraZeneca and GSK.

Background: Liquid biopsy (LB) is a non-invasive tool to evaluate the heterogeneity of tumors. Since RAS mutations (RAS-mut) play a major role in resistance to antiepidermal growth factor receptor inhibitors (EGFR) monoclonal antibodies (Mabs), serial monitoring of RAS-mut with LB may be useful to guide treatment. The main aim of this study was to evaluate the prognostic value of the loss of RAS-mut (NeoRAS-wt) in LB, during the treatment of metastatic colorectal cancer (mCRC)., Methods: A retrospective study was conducted on patients with mCRC between January 2018 and December 2021. RAS-mut were examined in tissue biopsy, at mCRC diagnosis, and with LB, during treatment., Results: Thirty-nine patients with RAS-mut mCRC were studied. LB was performed after a median of 3 lines (0-7) of systemic treatment including anti-vascular endothelial growth factor (anti-VEGF) Mabs. NeoRAS-wt was detected in 13 patients (33.3%); 9 (69.2%) of them received further treatment with anti-EGFR Mabs with a disease control rate of 44.4%. Median overall survival (OS), from the date of LB testing, was 20 months in the NeoRAS-wt group and 9 months in the persistent RAS-mut group (log-rank 2.985; P = .08), with a 12-month OS of 84.6% and 57.7%, respectively. NeoRAS-wt was identified as a predictor of survival (HR = 0.29; P = .007), with an 11-month improvement in median OS and a 71% decrease in risk of death, in heavily pretreated patients., Conclusions: In conclusion, monitoring clonal evolution in mCRC by LB may provide an additional treatment line for patients with NeoRAS-wt in advanced disease., (© The Author(s) 2023. Published by Oxford University Press.)

Microalgae biofilm emerged as a solid alternative to conventional suspended cultures which present high operative costs and complex harvesting processes. Among several designs, rotating biofilm-based systems stand out for their scalability, although their primary applications have been in wastewater treatment and aquaculture. In this work, a rotating system was utilized to produce a high-value compound (astaxanthin) using Haematococcus pluvialis biofilms. The effect of nitrogen regime, light intensity, and light history on biofilm traits was assessed to better understand how to efficiently operate the system. Our results show that H. pluvialis biofilms follow the classical growth stages described for bacterial biofilms (from adhesion to maturation) and that a two-stage (green and red stages) allowed to reach astaxanthin productivities of 204 mg m -2  d -1 . The higher light intensity applied during the red stage (400 and 800 µmol m -2  s -1 ) combined with nitrogen depletion stimulated similar astaxanthin productivities. However, by training the biofilms during the green stage, using mild-light intensity (200 µmol m -2  s -1 ), a process known as priming, the final astaxanthin productivity was enhanced by 40% with respect to biofilms pre-exposed to 50 µmol m -2  s -1 . Overall, this study shows the possibility of utilizing rotating microalgae biofilms to produce high-value compounds laying the foundation for further biotechnological applications of these emerging systems., (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Background: Hikikomori refers to the extreme isolation of individuals in their own homes, lasting at least six months. In recent years social isolation has become an important clinical, social, and public health problem, with increased awareness of hikikomori around the globe. Portuguese is one of the six most spoken languages in the world, but no studies have analysed the content regarding this phenomenon expressed in Portuguese., Objective: To explore the hikikomori phenomenon on Twitter in Portuguese, utilising a mixed-methods approach encompassing content analysis, emotional analysis, and correlation analysis., Methods: A mixed methods analysis of all publicly available tweets in the Portuguese language using a specific keyword (hikikomori) between 1st January 2008 and 19th October 2022. The content analysis involved categorising tweets based on tone, content, and user types, while correlation analysis was used to investigate user engagement and geographical distribution. Statistical analysis and artificial intelligence were employed to classify and interpret the tweet data., Results: Among the total of 13,915 tweets generated, in terms of tone 10,731 were classified as "negative", and 3184 as "positive". Regarding content, "curiosities" was the most posted, as well as the most retweeted and liked topic. Worldwide, most of the hikikomori related tweets in Portuguese were posted in Europe, while "individuals with hikikomori" were the users most active posting. Regarding emotion analysis, the majority of tweets were "neutral"., Conclusions: These findings show the global prevalence of the discourse on hikikomori phenomenon among Portuguese speakers. It also indicates an increase in the number of tweets on this topic in certain continents over the years. These findings can contribute to developing specific interventions, support networks, and awareness-raising campaigns for affected individuals., (© 2024. The Author(s).)

Tuberculosis (TB) disease, caused by Mycobacterium tuberculosis (Mtb) is the leading cause of death among people with human immunodeficiency virus (HIV) infection. No dual-target drug is currently being used to simultaneously treat both infections. This work aimed to obtain new multitarget HIV-TB agents, with the goal of optimizing treatments and preventing this coinfection. These compounds incorporate the structural features of azaaurones as anti-Mtb and zidovudine (AZT) as the antiretroviral moiety. The azaaurone scaffold displayed submicromolar activities against Mtb, and AZT is a potent antiretroviral drug. Six derivatives were synthetically generated, and five were evaluated against both infective agents. Evaluations of anti-HIV activity were carried out in HIV-1-infected MT-4 cells and on endogenous HIV-1 reverse transcriptase (RT) activity. The H37Rv strain was used for anti-Mtb assessments. Most compounds displayed potent antitubercular and moderate anti-HIV activity. (E)-12 exhibited a promising multitarget profile with an MIC 90 of 2.82 µM and an IC 50 of 1.98 µM in HIV-1-infected T lymphocyte cells, with an 84% inhibition of RT activity. Therefore, (E)-12 could be the first promising compound from a family of multitarget agents used to treat HIV-TB coinfection. In addition, the compound could offer a prototype for the development of new strategies in scientific research to treat this global health issue., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

In the food industry, successful bacterial pathogen colonization and persistence begin with their adhesion to a surface, followed by the spatial development of mature biofilm of public health concerns. Compromising bacterial settlement with natural inhibitors is a promising alternative to conventional anti-fouling treatments typically based on chemical biocides that contribute to the growing burden of antimicrobial resistance. In this study, three extracellular polymeric substance (EPS) fractions extracted from microalgae biofilms of Cylindrotheca closterium (fraction C) and Tetraselmis suecica (fraction Ta rich in insoluble scale structure and fraction Tb rich in soluble EPS) were screened for their anti-adhesive properties, against eight human food-borne pathogens belonging to Escherichia coli, Staphylococcus aureus, Salmonella enterica subsp. enterica, and Listeria monocytogenes species. The results showed that the fraction Ta was the most effective inducing statistically significant reduction for three strains of E. coli, S. aureus, and L. monocytogenes. Overall, EPSs coating on polystyrene surfaces of the different fractions increased the hydrophilic character of the support. Differences in bacterial adhesion on the different coated surfaces could be explained by several dissimilarities in the structural and physicochemical EPS compositions, according to HPLC and ATR-FTIR analysis. Interestingly, while fractions Ta and Tb were extracted from the same microalgal culture, distinct adhesion patterns were observed, highlighting the importance of the extraction process. Overall, the findings showed that EPS extracted from microalgal photosynthetic biofilms can exhibit anti-adhesive effects against food-borne pathogens and could help develop sustainable and non-toxic anti-adhesive surfaces for the food industry. KEY POINTS: •EPSs from a biofilm-based culture of C. closterium/T. suecica were characterized. •Microalgal EPS extracted from T. suecica biofilms showed bacterial anti-adhesive effects. •The anti-adhesive effect is strain-specific and affects both Gram - and Gram + bacteria., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The interest by biofilm-based microalgae technologies has increased lately due to productivity improvement, energy consumption reduction and easy harvesting. However, the effect of light, one key factor for system's operation, received less attention than for planktonic cultures. This work assessed the impact of Photon Flux Density (PFD) on Chlorella vulgaris biofilm dynamics (structure, physiology, activity). Microalgae biofilms were cultivated in a flow-cell system with PFD from 100 to 500 [Formula: see text]. In the first stage of biofilm development, uniform cell distribution was observed on the substratum exposed to 100 [Formula: see text] while cell clusters were formed under 500 [Formula: see text]. Though similar specific growth rate in exponential phase (ca. 0.3 [Formula: see text]) was obtained under all light intensities, biofilm cells at 500 [Formula: see text] seem to be ultimately photoinhibited (lower final cell density). Data confirm that Chlorella vulgaris showed a remarkable capability to cope with high light. This was marked for sessile cells at 300 [Formula: see text], which reduce very rapidly (in 2 days) their chlorophyll-a content, most probably to reduce photodamage, while maintaining a high final cell density. Besides cellular physiological adjustments, our data demonstrate that cellular spatial organization is light-dependent., (© 2024. The Author(s).)

The influence of environmental factors on Salmonella sensitivity to nisin in vitro and in refrigerated orange juice were investigated. Nisin activity was observed in the different conditions, but the highest efficiency was achieved at lower pH (4.0) and with higher bacteriocin concentration (174 µM). Moreover, the bactericidal action was directly proportional to the incubation period. When tested in orange juice, nisin caused a reduction of up to 4.05 logarithm cycles in the Salmonella population. So, environmental factors such as low pH and low temperature favored the sensitization of Salmonella cells to the bactericidal action of nisin. Therefore, this may represent an alternative to control Salmonella in refrigerated foods., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Almost one-third of epileptic patients fail to achieve seizure control through anti-epileptic drug administration. In the scarcity of completely controlling a patient's epilepsy, seizure prediction plays a significant role in clinical management and providing new therapeutic options such as warning or intervention devices. Seizure prediction algorithms aim to identify the preictal period that Electroencephalogram (EEG) signals can capture. However, this period is associated with substantial heterogeneity, varying among patients or even between seizures from the same patient. The present work proposes a patient-specific seizure prediction algorithm using post-processing techniques to explore the existence of a set of chronological events of brain activity that precedes epileptic seizures. The study was conducted with 37 patients with Temporal Lobe Epilepsy (TLE) from the EPILEPSIAE database. The designed methodology combines univariate linear features with a classifier based on Support Vector Machines (SVM) and two post-processing techniques to handle pre-seizure temporality in an easily explainable way, employing knowledge from network theory. In the Chronological Firing Power approach, we considered the preictal as a sequence of three brain activity events separated in time. In the Cumulative Firing Power approach, we assumed the preictal period as a sequence of three overlapping events. These methodologies were compared with a control approach based on the typical machine learning pipeline. We considered a Seizure Prediction horizon (SPH) of 5 mins and analyzed several values for the Seizure Occurrence Period (SOP) duration, between 10 and 55 mins. Our results showed that the Cumulative Firing Power approach may improve the seizure prediction performance. This new strategy performed above chance for 62% of patients, whereas the control approach only validated 49% of its models., (© 2024. The Author(s).)

This study evaluated the effects of supplementation of rumen-protected methionine (RPM) on body thermoregulation and conception rate of Nelore cows exposed to high temperature-humidity index (THI). On -31 days before the artificial insemination protocol, 562 lactating, multiparous cows were assigned to receive (MG) or not (CG) RPM supplementation (3 g/cow mixed into 100 g of mineral supplement). Both groups remained in tropical pastures and received supplementation for 77 days. A subset of cows (n = 142) remained with an intravaginal thermometer collecting intravaginal temperature (IT). The respective minimum, average, and maximum environmental THI were 72.8, 78.0, and 83.3. Effects of treatment × hour of the day were detected (P < 0.0001) for IT. From 1330 to 1730 h and 1830 to 1900 h, IT was higher (P < 0.05) for CG versus MG cows when exposed to moderate and high THI. The supplementation with RPM did not affect conception rate (CG = 64.4% vs. MG = 58.2%; P > 0.05). In conclusion, 3 g of RPM supplementation lowered internal body temperature and possibly altered critical THI threshold in Nelore cows with no impact on reproduction., (© 2024 Japanese Society of Animal Science.)