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Background: The deployment of Artificial Intelligence (AI) in healthcare has the potential to transform patient care through improved diagnostics, personalized treatment plans, and more efficient resource management. However, the effectiveness and fairness of AI are critically dependent on the data it learns from. Biased datasets can lead to AI outputs that perpetuate disparities, particularly affecting social minorities and marginalized groups. Objective: This paper introduces the "Data Artifacts Glossary", a dynamic, open-source framework designed to systematically document and update potential biases in healthcare datasets. The aim is to provide a comprehensive tool that enhances the transparency and accuracy of AI applications in healthcare and contributes to understanding and addressing health inequities. Methods: Utilizing a methodology inspired by the Delphi method, a diverse team of experts conducted iterative rounds of discussions and literature reviews. The team synthesized insights to develop a comprehensive list of bias categories and designed the glossary's structure. The Data Artifacts Glossary was piloted using the MIMIC-IV dataset to validate its utility and structure. Results: The Data Artifacts Glossary adopts a collaborative approach modeled on successful open-source projects like Linux and Python. Hosted on GitHub, it utilizes robust version control and collaborative features, allowing stakeholders from diverse backgrounds to contribute. Through a rigorous peer review process managed by community members, the glossary ensures the continual refinement and accuracy of its contents. The implementation of the Data Artifacts Glossary with the MIMIC-IV dataset illustrates its utility. It categorizes biases, and facilitates their identification and understanding. Conclusion: The Data Artifacts Glossary serves as a vital resource for enhancing the integrity of AI applications in healthcare by providing a mechanism to recognize and mitigate dataset biases before they impact AI outputs. It not only aids in avoiding bias in model development but also contributes to understanding and addressing the root causes of health disparities. [ABSTRACT FROM AUTHOR]

Background: The cattle tick is a parasite that adversely affects livestock performance in tropical areas. Although countries such as Australia and Brazil have developed genetic evaluations for tick resistance, these evaluations have not considered genotype by environment (G*E) interactions. Genetic gains could be adversely affected, since breedstock comparisons are environmentally dependent on the presence of G*E interactions, particularly if residual variability is also heterogeneous across environments. The objective of this study was to infer upon the existence of G*E interactions for tick resistance of cattle based on various models with different assumptions of genetic and residual variability. Methods: Data were collected by the Delta G Connection Improvement program and included 10,673 records of tick counts on 4363 animals. Twelve models, including three traditional animal models (AM) and nine different hierarchical Bayesian reaction norm models (HBRNM), were investigated. One-step models that jointly estimate environmental covariates and reaction norms and two-step models based on previously estimated environmental covariates were used to infer upon G*E interactions. Model choice was based on the deviance criterion information. Results: The best-fitting model specified heterogeneous residual variances across 10 subclasses that were bounded by every decile of the contemporary group (CG) estimates of tick count effects. One-step models generally had the highest estimated genetic variances. Heritability estimates were normally higher for HBRNM than for AM. Onestep models based on heterogeneous residual variances also usually led to higher heritability estimates. Estimates of repeatability varied along the environmental gradient (ranging from 0.18 to 0.45), which implies that the relative importance of additive and permanent environmental effects for tick resistance is influenced by the environment. Estimated genetic correlations decreased as the tick infestation level increased, with negative correlations between extreme environmental levels, i.e., between more favorable (low infestation) and harsh environments (high infestation). Conclusions: HBRNM can be used to describe the presence of G*E interactions for tick resistance in Hereford and Braford beef cattle. The preferred model for the genetic evaluation of this population for tick counts in Brazilian climates was a one-step model that considered heteroscedastic residual variance. Reaction norm models are a powerful tool to identify and quantify G*E interactions and represent a promising alternative for genetic evaluation of tick resistance, since they are expected to lead to greater selection efficiency and genetic progress. [ABSTRACT FROM AUTHOR]

Background: Biodiesel industry wastes were evaluated as supplements for lipase production by Moniliella spathulata R25L270, which is newly identified yeast with great lipolytic potential. Macaúba cake (MC), used for the first time in this work as inducer to produce lipases, and residual oil (RO) were mixed to maximise enzyme production. The lipase secreted was biochemically characterised. Results: The best ratio for the mixture (MC:RO) was 0.66:0.34 and the fitted values for lipase activity and total protein concentration were 0.98 U mL-1 and 0.356 mg mL-1, respectively. Maximum activity obtained (2.47 U mL-1) was achieved at 31.5°C and pH 6.7, and the enzyme was stable in this condition. A novel enzyme was purified and identified for the first time by mass spectrometry. The lipase efficiently hydrolysed different natural oils and exhibited selectivity in the production of eicosapentaenoic acid from fish oil. Conclusion: The use of MC and RO as a supplement to produce the new lipase from M. spathulata R25L270 may be one alternative for reducing lipase production costs and simultaneously adding value to biodiesel industry residues. The potential application of the lipase in the oleochemical industry was demonstrated by its pH and temperature stabilities and selective hydrolysis. [ABSTRACT FROM AUTHOR]

Background: Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models. Results: We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IId (CaMKIId) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophicsignaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases. Conclusions: These results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) is an essential signal transduction element involved in the regulation of several cellular activities and it is required at various key stages of the cell cycle. Intracellular Ca2+ is crucial for the orderly cell cycle progression and plays a vital role in the regulation of cell proliferation. Recently, it was demonstrated by in vitro and in vivo studies that nucleoplasmic Ca2+ regulates cell growth. Even though the mechanism by which nuclear Ca2+ regulates cell proliferation is not completely understood, there are reports demonstrating that activation of tyrosine kinase receptors (RTKs) leads to translocation of RTKs to the nucleus to generate localized nuclear Ca2+ signaling which are believed to modulate cell proliferation. Moreover, nuclear Ca2+ regulates the expression of genes involved in cell growth. This review will describe the nuclear Ca2+ signaling machinery and its role in cell proliferation. Additionally, the potential role of nuclear Ca2+ as a target in cancer therapy will be discussed. [ABSTRACT FROM AUTHOR]

Purinergic receptors participate, in almost every cell type, in controlling metabolic activities and many physiological functions including signal transmission, proliferation and differentiation. While most of P2Y receptors induce transient elevations of intracellular calcium concentration by activation of intracellular calcium pools and forward these signals as waves which can also be transmitted into neighboring cells, P2X receptors produce calcium spikes which also include activation of voltage-operating calcium channels. P2Y and P2X receptors induce calcium transients that activate transcription factors responsible for the progress of differentiation through mediators including calmodulin and calcineurin. Expression of P2X2 as well as of P2X7 receptors increases in differentiating neurons and glial cells, respectively. Gene expression silencing assays indicate that these receptors are important for the progress of differentiation and neuronal or glial fate determination. Metabotropic receptors, mostly P2Y1 and P2Y2 subtypes, act on embryonic cells or cells at the neural progenitor stage by inducing proliferation as well as by regulation of neural differentiation through NFAT translocation. The scope of this review is to discuss the roles of purinergic receptor-induced calcium spike and wave activity and its codification in neurodevelopmental and neurodifferentiation processes. [ABSTRACT FROM AUTHOR]

Background: Adenosine triphosphate (ATP) is secreted from hepatocytes under physiological conditions and plays an important role in liver biology through the activation of P2 receptors. Conversely, higher extracellular ATP concentrations, as observed during necrosis, trigger inflammatory responses that contribute to the progression of liver injury. Impaired calcium (Ca2+) homeostasis is a hallmark of acetaminophen (APAP)-induced hepatotoxicity, and since ATP induces mobilization of the intracellular Ca2+ stocks, we evaluated if the release of ATP during APAP-induced necrosis could directly contribute to hepatocyte death. Results: APAP overdose resulted in liver necrosis, massive neutrophil infiltration and large non-perfused areas, as well as remote lung inflammation. In the liver, these effects were significantly abrogated after ATP metabolism by apyrase or P2X receptors blockage, but none of the treatments prevented remote lung inflammation, suggesting a confined local contribution of purinergic signaling into liver environment. In vitro, APAP administration to primary mouse hepatocytes and also HepG2 cells caused cell death in a dose-dependent manner. Interestingly, exposure of HepG2 cells to APAP elicited significant release of ATP to the supernatant in levels that were high enough to promote direct cytotoxicity to healthy primary hepatocytes or HepG2 cells. In agreement to our in vivo results, apyrase treatment or blockage of P2 receptors reduced APAP cytotoxicity. Likewise, ATP exposure caused significant higher intracellular Ca2+ signal in APAP-treated primary hepatocytes, which was reproduced in HepG2 cells. Quantitative real time PCR showed that APAP-challenged HepG2 cells expressed higher levels of several purinergic receptors, which may explain the hypersensitivity to extracellular ATP. This phenotype was confirmed in humans analyzing liver biopsies from patients diagnosed with acute hepatic failure. Conclusion: We suggest that under pathological conditions, ATP may act not only an immune system activator, but also as a paracrine direct cytotoxic DAMP through the dysregulation of Ca2+ homeostasis. [ABSTRACT FROM AUTHOR]

The article presents research on the biomass pretreatment through biotechnological routes. Topics discussed include the significance of biomass pretreatment, the envisaged biorefinery model, the types of biomass pretreatment, the biomass pretreatment selection, and the advantages and disadvantages of pretreatments.

Background: There is limited evidence for the comparative effectiveness of analgesic medicines for adults with low back pain. This systematic review and network meta-analysis aims to determine the analgesic effect, safety, acceptability, effect on function, and relative rank according to analgesic effect, safety, acceptability, and effect on function of a single course of [an] analgesic medicine(s) or combination of these medicines for people with low back pain. Methods: We will include published and unpublished randomised trials written in any language that compare an analgesic medicine to either another medicine, placebo/sham, or no intervention in adults with low back pain, grouped according to pain duration: acute (fewer than 6 weeks), sub-acute (6 to 12 weeks), and chronic (greater than 12 weeks). The co-primary outcomes are pain intensity following treatment and safety (adverse events). The secondary outcomes are function and acceptability (all-cause dropouts). We will perform a network meta-analysis to compare and rank analgesic medicines. We will form judgements of confidence in the results using the Confidence in Network Meta-Analysis (CINeMA) methodology. Discussion: This network meta-analysis will establish which medicine, or combination of medicines, is most effective for reducing pain and safest for adults with low back pain. Systematic review registration: PROSPERO CRD42019145257 [ABSTRACT FROM AUTHOR]

Gestational Diabetes (GDM) is a prevalent health challenge in Mexico, affecting 10-14% of pregnancies but detected in only about 5.1% of cases, highlighting a critical gap in the healthcare system. This underdiagnosis poses severe health risks to mothers and children and reflects broader systemic healthcare failures. The disparity in detection rates points to insufficient screening protocols and uneven access to care, particularly affecting rural areas. Additionally, a lack of integrated digital health solutions exacerbates these issues, leading to inconsistent management and follow-up of diagnosed cases. The current reactive healthcare policies fail to prioritize early intervention and comprehensive patient education, crucial for effective GDM management. This paper calls for immediate and coordinated policy action to standardize GDM screening using updated protocols across all healthcare settings, bolster digital health infrastructure for better surveillance and management, and launch an extensive public health campaign focused on GDM awareness and education. These measures should be rigorously evaluated and adapted based on ongoing research and feedback to ensure they meet the needs of all segments of the population. Addressing these challenges head-on will improve health outcomes for mothers and children and reduce long-term healthcare costs associated with GDM complications., Competing Interests: Declarations. Ethics and approval and consent to participate: This study uses publicly available data. No ethical approval was required. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: Myopia is a prevalent disease influenced by both genetic and environmental factors. This study aims to explore myopia risk factors, including the association between night-time reading habits under low illumination in children., Methods: A cross-sectional survey was conducted in Argentina as part of the "Myopia Awareness Campaign" in June 2024. A total of 1,298 children aged 7-15 years were included. Data on self-reported myopia, reading habits, illumination levels, type of housing, outdoor time, and parental high myopia were collected through a 23-question Google Forms survey disseminated by ophthalmologists. Multiple logistic regression was used to assess the association between these factors and self-reported myopia., Results: The prevalence of self-reported myopia in children was 23.7%. Significant risk factors for myopia included older age (odds ratio, OR: 1.15; 95% Confidence Intervals, CI:1.08-1.23), high-intensity reading (OR: 1.69; 95% CI:1.12-2.55), parental high myopia (OR: 2.88; 95% CI:2.07-4.00), less outdoor time (OR: 0.98; 95% CI: 0.97-0.999), and living in a house without a garden (OR:1.49; 95% CI:1.12-2.00). While initial unadjusted analysis suggested that reading at night in the dark was associated with myopia, the association lost significance after adjusting for age., Conclusions: This study highlights the importance of environmental factors and lifestyle choices in myopia development. Although reading at night in the dark appeared as a potential risk factor, further research is needed to clarify its role in myopia development and progression. The existence of accessible outdoor areas may increase the time children spent outdoors helping to mitigate myopia incidence., Competing Interests: Declarations. Ethics approval and consent to participate: The questionnaire included an explanation of the anonymity and did not collect other demographic data except age and sex of the children. The Ethics Committee of the Argentine Council of Ophthalmology was consulted for this study, and the authorities stated that for studies based on population surveys with no intervention and anonymity, the ethical approval was waived. All participants who answered the questionnaire gave informed consent to participate in the study. Consent for publication: N/A. Competing interests: Leonardo Fernández Irigaray and Rafael Iribarren report personal fees from NOVAR outside the submitted work. Virginia Zanutigh is president of the Argentinian Council of Ophthalmology. Carla Lanca reports personal fees from Eyerising International outside the submitted work. Andrzej Grzybowski: Grants outside the submitted work from Alcon, Bausch&Lomb, Zeiss, Teleon, J&J, CooperVision, Hoya, Essilor, Thea, Polpharma, Viatris, and Lectures for Thea, Polpharma, Viatris, Eyerising, Essilor, Alcon; Member of Advisory Boards: Nevakar, GoCheckKids and Thea., (© 2025. The Author(s).)

Background: Dogs are the main domestic reservoir host of the parasite Trypanosoma cruzi, the causative agent of Chagas disease, and they are considered sentinel animals for the detection of new cases of human infection. Canis familiaris is also a well-established experimental T. cruzi infection model, but little is known about the progression of Chagas disease in naturally-infected dogs, especially during the acute phase in these hosts. Triatomine species infected with discrete typing units (DTUs) I, II and III of T. cruzi have been previously found in many of the municipalities of the state of Rio Grande do Norte. The current study describes the clinical, hematological, biochemical, cardiological and parasitological characteristics of a single dog during the acute phase of its naturally-acquired T. cruzi infection, and characterizes the isolate obtained from this individual host using biological, molecular and phylogenetic methods., Results: A  juvenile dog exhibiting discomfort during defecation, itchy skin, and enlarged popliteal lymph nodes showed a prolonged period of patent parasitemia, with normocytic and hypochromic anemia. In addition, cardiac damage was suggested by high concentrations of the biomarkers cardiac troponin I and NT-ProBNP, as well as Doppler echocardiography, which showed qualitative segmental hypokinesia. The parasites isolated from this individual canine were genotyped, using three molecular markers and phylogenetic analysis, as the DTU TcIII. First detected in sylvatic environments, our current observations also demonstrate the presence of this DTU in domestic/ peridomestic locations., Conclusions: The cardiac alterations that we observed in a naturally-T. cruzi-infected dog contribute to expanding our knowledge of both Chagas disease in Canis familiaris, and the epidemiological scenario in locations where Triatoma brasiliensis is the main triatomine vector of T. cruzi., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by Ethics Committee on the Use of Animals/UFRN, protocol no.134.062/2018 and no.138.066/2018. The dog owner was informed about the research and gave written informed consent before samples were collected. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Globally, one in six people have disabilities. They often experience health inequities and many of them arise from system-level failures. This study aimed to assess the inclusion of people with disabilities in the health system of Chile and define recommendations for improvement on the basis of the evidence., Methods: A health system assessment was conducted between June and November 2023 following the Missing Billion Disability-Inclusive Health Systems Framework and System Level Assessment Toolkit. The assessment was led by the Ministry of Health and conducted by a task team, including organizations of people with disabilities. Mixed methods were used to collect data on nine system-level and service delivery components for a set of 33 indicators, including through a health policy review, systematic review, key informant interviews and a scoping review. Scores were assigned to indicators, components and the overall health system. With this assessment, key recommendations were developed and agreed upon on the basis of a prioritization analysis of impact and feasibility during workshops., Results: The Chilean health system was assessed to have a low progress towards disability-inclusive health. Among system-level components, intermediate progress has been made in governance, health financing and data and evidence. However, progress in leadership on disability seems low. Among service delivery components, the accessibility of health facilities and rehabilitation and assistive technology showed the best results. However, there were notable gaps in the autonomy and awareness and ability to afford care by people with disabilities, and the capacity of human resources to support this group. The task team defined priority actions in governance, leadership, and human resources., Conclusions: Short-term actions for the country should involve foundational governance on inclusive health, strengthened leadership of people with disabilities, and mandatory training of healthcare workers to improve healthcare access among this population. Future reassessments should be conducted to monitor and evaluate progress on effective healthcare coverage and health status among people with disabilities., Competing Interests: Declarations. Ethics approval and consent to participate: This study obtained ethical approval by the Ethics Committee of London School of Hygiene and Tropical Medicine (no. 28068) and the Ethics Committee of Research with Human Beings of the Faculty of Medicine, of University of Chile (no. 152-2022). Informed consent was obtained from participants of key informant interviews. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Homeobox A9 promoter methylation (HOXA9) has been reported as a biomarker for early lung adenocarcinoma patients' prognosis. We aim to evaluate its prognostic value, regardless of disease stage. Using droplet digital PCR, we measured HOXA9 methylation in a cohort comprising 161 Brazilian patients. Low HOXA9 methylation was associated with higher cancer-specific survival but showed no significance after adjustment for clinical covariates. While low HOXA9 methylation was associated with earlier stages, no survival association was observed in this subset of patients. Overall, HOXA9 promoter methylation is not an independent prognostic biomarker of cancer-specific survival in Brazilian lung adenocarcinomas patients., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted according to Brazilian national and institutional ethical policies. The present study was previously approved by the Barretos Cancer Hospital IRB (Project #630/2012) and informed consent was waived. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: To test the effects of a physical activity intervention program on symptoms of mental disorders among adolescents., Methods: This study is a 12-week cluster randomized controlled trial. The sample consisted of 306 adolescents (45,8% male, age: 13,6 [0,72] years; 54.2% female, age: 13.5 [0.69] years), randomized into an intervention group (N = 165) and a control group (N = 141). The physical activity program involved sessions including muscle strengthening and cardiorespiratory exercises and lifestyle guidance. The mental health indicators analyzed were: anxiety, depression, sleep, and psychological well-being. Intervention effects were analyzed by generalized estimating equations., Results: After 12 weeks, no significant improvements were observed in the intervention group for sleep; anxiety; depression, and psychological well-being. In the subgroup analysis, significant group×time interactions were observed for adolescents who were classified with moderate symptoms of depression (mean difference: -0.97, p = 0.002) and anxiety (mean difference: -3.03, p = 0.01) with favorable effects for intervention group., Conclusion: After the 12-week intervention period, it can be concluded that 12 weeks of school-based physical activity intervention significantly reduced symptoms of anxiety and depression in adolescents with moderate/severe symptoms. Furthermore, the intervention contributed to the maintenance of psychological well-being, since the control group showed a significant reduction in this mental health indicator., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by the Human Research Ethics Committee of the State University of Northern of Parana, Brazil (no: 4.452.513). All procedures applied in the research study were in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants and their literate legal guardian. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Parkinson's disease (PD) can cause postural instability, which may result in falls. These issues have been associated with motor and non-motor symptoms (NMS), including cognitive dysfunction. Several techniques have been employed to investigate the underlying neural mechanisms involved in postural control in PD. These include behavioural studies assessing associations between cognition and postural control, functional neuroimaging studies, and resting-state neural correlates. This review provides an overview of these emerging bodies of research. Scopus, PubMed, and ProQuest were searched and detailed the brain-imaging technique, cohort, and postural control measures. A total of 79 studies were identified. Findings supported the notion of cortical involvement in postural control function to compensate for subcortical damage resulting from PD. Future studies should standardise their outcome measures and data analysis to allow comparisons of results across studies and ensure more comprehensive and robust data collection to enhance the reliability and validity of these findings., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: β-Caryophyllene, a sesquiterpenoid, holds considerable potential in pharmaceutical, nutraceutical, cosmetic, and chemical industries. In order to overcome the limitation of β-caryophyllene production by the extraction from plants or chemical synthesis, we aimed the microbial production of β-caryophyllene in non-conventional yeast Yarrowia lipolytica in this study., Results: Two genes, tHMG1 from S. cerevisiae to boost the mevalonate pool and QHS1 from Artemisia annua, were expressed under different promoters and copy numbers in Y. lipolytica. The co-expression of 8UAS pEYK1-QHS1 and pTEF-tHMG1 in the obese strain yielded 165.4 mg/L and 201.5 mg/L of β-caryophyllene in single and double copies, respectively. Employing the same combination of promoters and genes in wild-type-based strain with two copies resulted in a 1.36-fold increase in β-caryophyllene. The introduction of an additional three copies of 8UAS pEYK1-tHMG1 further augmented the β-caryophyllene, reaching 318.5 mg/L in flask fermentation. To maximize the production titer, we optimized the carbon source ratio between glucose and erythritol as well as fermentation condition that led to 798.1 mg/L of β-caryophyllene., Conclusions: A biosynthetic pathway of β-caryophyllene was firstly investigated in Y. lipolytica in this study. Through the modulation of key enzyme expression, we successfully demonstrated an improvement in β-caryophyllene production. This strategy suggests its potential extension to studies involving the microbial production of various industrially relevant terpenes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This paper evaluates and compares different fine-tuned variations of generative large language models (LLM) in the zero-shot named entity recognition (NER) task for the clinical domain. As part of the 8th Biomedical Linked Annotation Hackathon, we examined Llama 2 and Mistral models, including base versions and those that have been fine-tuned for code, chat, and instruction-following tasks. We assess both the number of correctly identified entities and the models' ability to retrieve entities in structured formats. We used a publicly available set of clinical cases labeled with mentions of diseases, symptoms, and medical procedures for the evaluation. Results show that instruction fine-tuned models perform better than chat fine-tuned and base models in recognizing entities. It is also shown that models perform better when simple output structures are requested., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To analyze the temporal and territorial relationship between health system financing fragmentation and maternal mortality in the last two decades in Mexico., Methods: We conducted an ecological-longitudinal study of the maternal mortality ratio (MMR) in the 32 states of Mexico during the period 2000-2022. Annual MMRs were estimated at the national and state levels according to health insurance. We compared the distribution of individual attributes and place of residence between deceased women with and without social security to identify overrepresented demographic profiles. Finally, we mapped state disparities in MMR by health insurance for the last four political administrations., Findings: MMR in Mexico decreased from 59.3 maternal deaths per hundred thousand live births in 2000 to 47.3 in 2018. However, from 2019 onwards, MMR increased from 48.7 in 2019 to 72.4 in 2022. Seven out of ten maternal deaths occurred in the population without social security from 2000 to 2018, then decreasing to six out of ten from 2020. Maternal deaths in the population without social security were more frequent among younger women, with less schooling, unmarried, and residing in rural areas, with higher Indigenous presence and greater social marginalization. From 2019 onwards, the MMR was higher in the population with social security., Conclusion: The results of this study confirm the close relationship between maternal mortality and social inequalities, and suggest that affiliation with social security has ceased to be a differentiating factor in recent years. Understanding the evolution of maternal mortality between the population with and without social security in Mexico allows us to quantify the gap in maternal deaths attributed to inequalities in access to maternal health services, which can contribute to the design of policies that mitigate these gaps., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. This study involved no human participants and was approved by the Research, Ethics, and Biosecurity Committees of the National Institute of Public Health of Mexico (ID:2358/1826/S21-2022). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study aimed to investigate the relationship of psychological empowerment and enjoyment of physical activity with changes in physical activity levels, sleep quality, and muscular endurance following a high-intensity interval training (HIIT) program in physically inactive young women., Methods: A total of 61 physically inactive young women (age: 20.1 ± 2.7 y) were recruited to participate in a six-month HIIT intervention delivered via a smartphone app. Outcome measures included physical activity levels (MET-min/week), muscular endurance (plank test), and sleep quality through the Pittsburgh Sleep Quality Index (PSQI). The Healthy Lifestyle and Personal Control Questionnaire (HLPCQ) and the Physical Activity Enjoyment Scale (PACES) were used to assess psychological empowerment and enjoyment, respectively. Repeated measures ANOVA and covariate analyses were performed to evaluate the impact of the intervention and the role of psychological empowerment and enjoyment., Results: At 6 months, significant improvements in physical activity (p < 0.001; η p ²=0.336) and muscular endurance (p = 0.005; η p ²=0.085) were observed, with large and moderate effect sizes, respectively. The PACES showed a significant interaction with time for MET-min/week (F = 11.67, p = 0.001, η p ²=0.129), suggesting that enjoyment influenced the increase in physical activity. No significant differences in sleep quality were observed (p > 0.05)., Conclusion: Enjoyment plays a crucial role in the response to HIIT programs among physically inactive young women, particularly in improving weekly physical activity levels. Psychological training showed no significant relationship with the outcomes studied., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of University of Valencia (1944476, 5 May 2022). The trial protocol has been registered on the Clinical Trials Registry (NCT05467280). Informed consent was obtained from all subjects involved in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Asymptomatic carriers significantly influence the transmission dynamics of C. difficile. This study aimed to assess the prevalence of toxigenic C. difficile asymptomatic colonization (tCDAC) and investigate its heterogeneity across different populations. We searched MEDLINE, Web of Science, and Scopus for articles published between 2000 and 2023 on tCDAC. Studies including asymptomatic adults with laboratory-confirmed tCDAC were eligible. We performed a random-effects meta-analysis to estimate the pooled prevalence by clinical characteristics, settings, and geographic areas. In addition, we used outlier analyses and meta-regression to explore sources of prevalence variability., Results: Fifty-one studies involving 39,447 patients were included. The tCDAC prevalence ranged from 0.5 to 51.5%. Among pooled estimates, a high prevalence was observed in patients with cystic fibrosis, outbreak settings, and cancer patients, whereas the lowest rates were found in healthy individuals and healthcare workers. Similar colonization rates were observed between admitted and hospitalized patients. Our meta-regression analysis revealed lower rates in healthy individuals and higher rates in cystic fibrosis patients and studies from North America. Additionally, compared with that among healthy individuals, the prevalence significantly increased by 15-47% among different populations and settings., Conclusion: Our study revealed that tCDAC is a common phenomenon. We found high prevalence estimates that showed significant variability across populations. This heterogeneity could be partially explained by population characteristics and settings, supporting their role in the pathogenesis and burden of this disease. This highlights the need to identify high-risk groups to improve infection control strategies, decrease transmission dynamics, and better understand the natural history of this disease., Competing Interests: Declarations. Potential conflicts of interest: All authors report no conflicts of interest relevant to this article., (© 2024. The Author(s).)

Background: Both maximal muscle strength and muscle power are independently important for karatekas. However, the relationship between strength and power in elite male kumite karatekas is under researched. This study aimed to determine the relationship between back-leg-chest (BLC) isometric muscle strength with sprint and jump variables in elite male karatekas., Methods: Male elite/international level (tier 4) kumite karatekas (n = 14; age, 20.79 ± 1.67 year; height, 1.77 ± 0.06 m; weight, 72.21 ± 5.20 kg) were recruited. BLC strength, sprint and jump values were measured with a dynamometer, a photocell, and an application, respectively. Pearson correlation (trivial r < 0.1; small r < 0.3; moderate r < 0.5; large r < 0.7; very large r < 0.9; nearly perfect/perfect r ≥ 0.9) and linear regression analyses were performed to determine the relationship and shared variance between BLC strength, sprint, and jump performance., Results: There were large to very large correlations between BLC strength and sprint time (r = - 0.930, p < 0.01), velocity (r = 0.918; p < 0.01), acceleration (r = 0.913; p < 0.01) and running momentum (r = 0.721; p < 0.01). Additionally, BLC strength correlated with jump height (moderate, r = 0.550, p < 0.05), peak anaerobic power (moderate, r = 0.672, p < 0.01) and power to body mass ratio (moderate, r = 0.545, p < 0.05). BLC strength and sprint variables showed an r 2  = 0.52-0.86 (p < 0.01), while BLC strength and jump variables showed an r 2  = 0.29-0.45 (p < 0.05)., Conclusions: BLC strength is related to jump and sprint performance in male elite karate athletes. This relationship underscores the importance of including strength training that targets BLC muscle strength in training programs for coaches and athletes., Competing Interests: Declarations. Ethics approval and consent to participate: All the procedures implemented in this study were approved by the Ethics Committee of the Inonu University, (approval number: 2024/1802). Informed consent forms were signed after the participants were informed of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: IgG4-related cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC) are chronic fibro-inflammatory hepatobiliary conditions, with genetic, environmental, and immunologic risk factors, in which epigenetic alterations may provide insights into pathophysiology and novel biomarkers. This study is the first to assess methylation signatures in IgG4-SC., Results: Whole blood DNA methylation profiling and genotyping was performed in 264 individuals; 47 with IgG4-SC, 65 with PSC, 64 with ulcerative colitis (UC), and 88 healthy controls. We identified 19 significant methylation differences between IgG4-SC and controls and 38 between PSC and controls. IgG4-SC and PSC shared 8 probes. Inflammatory genes (including CEP97, IFNAR1, TXK, HERC6, C5orf36, PYY, and MTRNR2L1) were predominantly involved in dysregulated methylation. Epigenetic age acceleration was observed in patients with IgG4-SC, but not in those with PSC or UC. meQTL analyses to identify genetic determinants of methylation revealed a strong human leucocyte antigen (HLA) signal in both PSC and IgG4-SC (HLA-DQB2, HLA-DPA1, HLA-F and HLA-DRA)., Conclusions: We identify novel epigenetic alterations in IgG4-SC and PSC, with biological age acceleration in IgG4-SC, providing insights into disease pathogenesis, and highlight the role of genetic variation especially within the HLA region in shaping the methylome., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for the study was obtained from the Research Ethics Committee Oxfordshire (10/H0604/51) and the Oxford Radcliffe Biobank (19/SC/0173). Competing interests: EC provides educational material and consults for Amgen (Horizon Therapeutics), Zenus BioPharma, Falk Pharma, Ipsen, Mirum, Intercept, Advance Therapeutics and Moderna. JS has received lecture fees from Takeda and from the Falk Foundation., (© 2024. The Author(s).)

Background: Crocetin is a multifunctional apocarotenoid natural product derived from saffron, holding significant promises for protection against various diseases and other nutritional applications. Historically, crocetin has been extracted from saffron stigmas, but this method is hindered by the limited availability of high-quality raw materials and complex extraction processes. To overcome these challenges, metabolic engineering and synthetic biology can be applied to the sustainable production of crocetin., Results: We constructed a Yarrowia lipolytica strain using hybrid promoters and copy number adjustment, which was able to produce 2.66 g/L of β-carotene, the precursor of crocetin. Next, the crocetin biosynthetic pathway was introduced, and we observed both the production and secretion of crocetin. Subsequently, the metabolite profiles under varied temperatures were studied and we found that low temperature was favorable for crocetin biosynthesis in Y. lipolytica. Therefore, a two-step temperature-shift fermentation strategy was adopted to optimize yeast growth and biosynthetic enzyme activity, bringing a 2.3-fold increase in crocetin titer. Lastly, fermentation media was fine-tuned for an optimal crocetin output of 30.17 mg/L, bringing a 51% higher titer compared with the previous highest report in shake flasks. Concomitantly, we also generated Y. lipolytica strains capable of achieving substantial zeaxanthin production, yielding 1575.09 mg/L, doubling the previous highest reported titer., Conclusions: Through metabolic engineering and fermentation optimization, we demonstrated the first de novo biosynthesis of crocetin in the industrial yeast Yarrowia lipolytica. In addition, we achieved a higher crocetin titer in flasks than all our known reports. This work not only represents a high production of crocetin, but also entails a significant simultaneous zeaxanthin production, setting the stage for sustainable and cost-effective production of these valuable compounds., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The widely implemented prevention program in Brazil, PROERD (a translated version of the DARE-kiR program), showed no evidence of effect in preventing drug use in a recent trial. The lack of cultural adaptation and instructors' deviations from the curriculum were identified as potential reasons for its ineffectiveness. This study aims to identify points of inadequacy of the PROERD program for the Brazilian culture, suggesting strategies for revising the curriculum to improve implementation., Methods: We triangulated data obtained from three different groups of study participants: semi-structured interviews with the law enforcement officer who implemented the program, focus groups with students who participated in the program, and questionnaires completed by external experts in the prevention field who evaluated the program's manuals. Data was analyzed using thematic analysis based on the Ecological Validity Model theory, which encompasses three main axes: methodology, content, and language to identify the main points for cultural adaptation., Results: Regarding the program's methodology, there is an excess of activities with little interactivity involving literacy skills that do not match Brazilian students' cognitive development and require equipment unavailable in Brazilian public schools. Regarding content, activities were considered appropriate for evidence-based prevention; however, there were some contradictions related to the drug content. The language presented in the program's manuals was considered inappropriate for the culture of Brazilian youth (vocabulary, examples, and images)., Conclusions: In conclusion, this study strongly recommends revising the PROERD curriculum Caindo na Real, ensuring it will align with the international prevention standards and Brazilian Culture., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures complied with institutional and national research committee ethical standards, the 1964 Declaration of Helsinki, and subsequent amendments or comparable ethical standards. The study protocol was approved by the Research Ethics Committee of the Federal University of São Paulo (nº: 1327/2018 and 1292/2020). Informed consent was obtained from all participants. Consent for publication: Consent for publication was obtained from all participants. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The exogenous application of phytohormones to manipulate weed seed germination and emergence is a potential avenue for exploring alternative integrated weed management strategies. Greenhouse and field experiments were conducted to investigate the effects of exogenous applications of the phytohormones gibberellic acid (GA3) and abscisic acid (ABA) on waterhemp (Amaranthus tuberculatus [Moq.]) emergence., Results: In the greenhouse study, all waterhemp populations in sandy soil and three out of five populations in clay soil demonstrated a positive response to increased GA3; however, the response was small, leading to an increase in waterhemp emergence of up to 10% points, and weak (R 2  < 0.3). Only one population exhibited a small (up to 10 points) and weak (R adj  < 0.3). Only one population exhibited a small (up to 10 points) and weak (R 2 adj  = 0.1) reduction in emergence in response to increased ABA in clay soil. The field studies demonstrated no differences in waterhemp and soybean emergence in response to application of GA3 and ABA., Conclusions: Despite the low to absent efficacy of the exogenous application of GA3 and ABA in manipulating waterhemp emergence in these experiments, our findings provide foundation information for future research on this concept, particularly supporting further research investing the use of GA3 in lighter textured soils., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Ehrlichiosis and anaplasmosis are vector-borne bacterial diseases produced by intracellular rickettsial species of the genus Ehrlichia and Anaplasma. Ehrlichia canis and Anaplasma spp. (A. platys and A. phagocytophilum) have reported cases of zoonotic transmision and are the main bacterial agents of canine ehrlichiosis and anaplasmosis. They normally present an asymptomatic or mild course in domestic and wild animals with some lethal cases reported. The main vector of these diseases in Europe are the castor bean tick (Ixodes ricinus) and the brown dog tick (Rhipicephalus sanguineus), although only in the latter, the main host is the domestic dogs. The aim of this work is to apply an integrative approach to convert ecological niche models (ENMs) into potential transmission risk models and understand the relative contribution of the two potential vectors (R. sanguineus and I. ricinus) to spread both diseases in the Iberian Peninsula and Balearic Islands., Results: Two ENMs meeting all criteria were successfully generated for R. sanguineus and I. ricinus with human footprint being the most relevant explanatory variable. The novelty of the study lies in the combination of independent ENMs for both species to estimate the disease transmission risk of specific bacteria (E. canis, A. platys and A. phagocytophilum). Only the transmission risk maps that had higher contribution of R. sanguineus than I. ricinus showed relevant and positive significant correlations between risk and seroprevalence in either of the two species of bacteria (R ≥ 0.4; p < 0.05). Regarding Anaplasma spp., the map having 10% contribution of I. ricinus (10I) and 90% of R. sanguineus (90R) inferred 47.4% of infected dogs in very high-risk areas. In the case of E. canis, the model showing a proportion of 25I-75R showed better validation power (53.4% of infected dogs in very high-risk areas)., Conclusion: The validation approach used in this study produced a good approximation to understand the relative contribution of the two tick species in bacterial disease transmission in dogs in the Iberian Peninsula and Balearic Islands. Rhipicephalus sanguineus appears as the main transmitter of both diseases in the study area (90% and 75% for anaplasmosis and ehrlichiosis respectively), in accordance with its higher abundance and host preference. This estimate may help veterinary staff, clinicians and owners to optimize the control of these diseases in certain vulnerable areas, and thus reduce the risk of infection in risk areas., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: None. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: To validate the Compassion Fatigue Inventory in Spanish-speaking health personnel, its psychometric properties were tested, and the influencing factors were investigated., Method: This was a cross-sectional validation study. Information was collected through a survey of 733 nurses, physician and medical residents using the Compassion fatigue Inventory (CFI), Secondary Traumatic Stress Questionnaire (CETS), The physician burnout syndrome scale (PhBS), the quality-of-life index (SQL -sp) and the reduced Moral Stress Scale (MMDHPr). The psychometric properties of the CFI were tested via exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and internal consistency analysis. The final version of the translated CFI was correlated with other scales., Results: An EFA was performed to evaluate the translated CFI, resulting in 15 items in three dimensions, as reported in the literature: reduced compassion, social life, and workplace. The CFA showed good fit indices and psychometric values (Cronbach´s alpha = 0.87, Omega = 0.87, Comparative Fit Index = 0.99, Tucker Lewis = 0.99, root mean square error of approximation = 0.045, Standardized Root Mean Square Residual = 0.05). The CFI had a negative correlation with the SQL-sp and a positive correlation with the other subscales. Work experience is predictive of a small reduction in CFI scores., Conclusion: The adaptation of the CFI in a sample of Latino health professionals shows satisfactory psychometric indices in the evaluation of compassion fatigue and can be proposed as a specific inventory to differentiate compassion fatigue from other occupational syndromes., Competing Interests: Declarations Ethics approval and consent to participate Ethics approval of the protocol was obtained from the Local Ethics Committee No. 13018 of the 'Unidad Médica de Alta Especialidad, Hospital de Especialidades, Centro Médico Nacional de Occidente, Lic. Ignacio García Téllez,' which belongs to the social security network 'Instituto Mexicano del Seguro Social' (IMSS), with the government registration number COFEPRIS 17 CI 14 039 114, CONBIOETICA 14 CEI 20190123 and was registered as R-2024–1301-043. Electronic consent was obtained from all participants before starting the survey. No personal data that would allow identification were collected. Before signing the electronic consent form, they were informed of the handling of confidential data. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Visceral leishmaniasis (VL) is a zoonotic disease caused by Leishmania infantum and transmitted by the sand fly Lutzomyia longipalpis. Dogs are the major domestic reservoir of L. infantum. To prevent the spread of the disease, dog collars impregnated with 4% deltamethrin have been effectively used in VL endemic areas. However, this approach may contribute to the emergence of insecticide resistance in sand flies. Therefore, it is important to characterize the susceptibility of different populations of Lu. longipalpis to deltamethrin in areas where insecticide-impregnated dog collars are used., Methods: Six field sand fly populations from Brazil were exposed to deltamethrin in CDC bottle bioassays at the diagnostic doses (DD) of 21.9 μg/bottle and 30 μg/bottle. For the dose-response (DR) experiments, doses of 1, 3, 5, 7, 9 and 11 μg/bottle of deltamethrin were used to impregnate bottles; control group bottles were impregnated with acetone only. Each bottle contained an average of 20 sand flies, both male and female, and they were exposed to either deltamethrin or acetone for 60 min., Results: Based on the DD of 21.9 μg/bottle, three populations were susceptible to deltamethrin. In contrast, two populations collected from the states of Ceará and Minas Gerais exhibited mortality rates of 94.9% and 95.7%, indicating possible resistance, and one population from the state of Ceará showed resistance, with a mortality rate of 87.1%. At the DD of 30 μg/bottle, two populations from the states of Ceará and Piauí showed possible resistance, while the other four populations were susceptible. The resistance ratio (RR 50 ) ranged from 2.27 to 0.54, and RR 95 ranged from 4.18 to 0.33, indicating a low resistance intensity., Conclusions: This study established a DD for Lu. longipalpis using the CDC bottle bioassay. We found that Lu. longipalpis populations in three Brazilian states where insecticide-impregnated dog collars were used for VL control were susceptible to deltamethrin. However, one population in Ceará State was classified as resistant to deltamethrin. These results contribute to the current knowledge on sand fly resistance and surveillance, and highlight the need for a better understanding of the resistance mechanisms of Lu. longipalpis in areas where insecticide-impregnated dog collars have been widely used., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The first outbreaks of coronavirus CoV, SARS-CoV and MERS-CoV have occurred in China and Saudi Arabia over the past decade, respectively. From the end of 2019, a great battle began by the world scientific community against SARS-CoV-2, the virus that caused COVID-19, a pathology that generated devastating consequences on all existing continents. Several mutations have already been detected in the structure of the virus, which have been responsible for the generation of many types of variants since the detection of the first COVID-19 virus identified in China. The worrisome mutations arising from the first genome of SARS-CoV-2 have been intensively studied. Some mutations increase the transmissibility of the disease through Spike, the protein responsible for binding the virus in the human cell. Among the numerous strains, the most discussed are called by the WHO as "variants of concern". This study aims to review if COVID-19 severity may be variant dependent. Our study found tree publications that associate severity of COVI-19 symptoms to different SARS-CoV-2 variants. The most part of publications do not establish which variant is being expressed during studies. More studies with this focus are needed for a better understanding of the disease and respective variants., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hospital-associated functional decline affects nearly one-third of the hospitalized older adults. The aim of this trial is to investigate the effect of a cognitive stimulation intervention provided via immersive virtual reality (IVR), with or without a multicomponent physical exercise intervention (ME) in hospitalized patients aged 75 or older with severe functional dependency at admission (Barthel Index < 60 points)., Methods: This clinical randomized controlled trial will be conducted in the Acute Geriatric Unit of a tertiary hospital in Spain. A total of 212 acute patients will be enrolled according to the following criteria: age ≥ 75, Barthel Index < 60, able to collaborate, expected length of stay ≥ 5 days, absence of clinical instability and severe dementia (Global Deterioration Scale 7) or other end-stage disease. Patients will be randomly assigned to a control group (CG) or any of the three intervention groups (IG): IVR, ME, or IVR + ME. The IVR group will watch ad-hoc videos showing Spanish regional landscapes and villages, approximately 4 min per day for three consecutive days. The ME group will undergo aerobic and strength exercise for progressive training of the upper and lower limbs. The IVR + ME group will do both cognitive and physical intervention. The primary outcomes will be cognitive and physical measures at discharge. Mood, quality of life, isometric strength, and acceptance of IVR will be also assessed., Discussion: This project has the potential to enhance physical and psychological well-being of patients with severe functional dependency hospitalized for acute conditions, using technology. Virtual reality is expected to be favourably perceived by hospitalized older adults. This intervention represents a novelty in the geriatric patients' care, comprising IVR and/or ME dispensed within the patient's room, and including patients who are commonly excluded from research clinical trials., Trial Registration: This study was approved by the Navarra Clinical Research Ethics Committee on May 17th, 2023 (PI&#95;2023/60). The trial is registered at ClinicalTrials.gov, registration number NCT06340282, 24th May 2024., (© 2024. The Author(s).)

Background: Brazil has the highest number of HTLV-1 infection in Latin America, with around one million cases spread unevenly across regions. However, there is a limited number of studies on this infection in the general population. This cross-sectional study aimed to estimate the prevalence of HTLV as well as identify types, and subtypes of HTLV among the urban population of Campo Grande, capital of Mato Grosso do Sul state (MS)., Results: Between July 2023 and March 2024, all information was obtained from self-reported interviews, and blood samples were collected and screened for anti-HTLV-1/2 by immunoassay and confirmed using the immunoblot method. The proviral DNA of HTLV-1/2 in positive samples was quantified by real-time PCR (qPCR) and genotyped by nucleotide sequencing (Sanger's method). The study enrolled 611 participants, with the majority being women (90.54%), mixed race (46.32%), heterosexual (87.64%), and with a median age of 39 years. The prevalence rate of anti-HTLV-1 infection was 0.82% (CI 95% 0.34-1.96). All positive samples (n = 5) were identified as belonging to the Cosmopolitan subtype, one belonging to Japanese and four to Transcontinental subgroups. Among the five positive individuals, two presented symptoms associated with HTLV-1 infection., Conclusion: This study highlights an intermediate prevalence of HTLV-1 in the urban population of Campo Grande, Mato Grosso do Sul, and provides epidemiological information that could help bridge the gaps in the distribution of HTLV in the general population. Also, medical care was provided for individuals presenting clinical manifestations who were previously unaware of their serological status., (© 2024. The Author(s).)

Background: The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019., Results: The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF., Conclusion: This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services., (© 2024. The Author(s).)

Background: Surf therapy is gaining popularity for improving mental health. However, there is limited research evidence to substantiate these claims. Therefore, this systematic review aimed to assess randomized or non-randomized studies analyzing the efficacy of surf therapy in improving symptoms of mental illness compared to non-exercising controls and/or alternative intervention, and to identify evidential gaps to inform future research., Methods: PRISMA 2020 reporting guidelines were followed. Eligibility criteria included participants of any age and sex, explicitly diagnosed with any mental health disorder, while exposed to surf therapy and compared to non-exercising controls and/or alternative interventions. The primary outcome consisted of changes in symptoms of mental illness scored from baseline to post-intervention. Any randomized or non-randomized trial design was considered. We searched Cochrane Library, CINAHL, EMBASE, PubMed, Scopus, SPORTDiscus and Web of Science databases (December 7, 2023), without language or publication date restrictions and without filters. Risk of bias was assessed using RoB 2. A meta-analysis could not be conducted due to heterogeneity of the studies; therefore, a narrative synthesis of individual study results was performed., Results: Of 5,666 records, three randomized controlled studies were included in the review. Overall, the findings of the three studies suggest no robust consistent evidence of improvement in mental health symptoms when comparing surf therapy to wait-list control groups or other nature-based exercise interventions (hike therapy). Certainty of evidence should be considered very low, as it is based on three randomized controlled trials., Conclusion: Although we believe that surf therapy provides an interesting approach, robust evidence is scarce. Routes for future well-designed, controlled studies are discussed., Other: No funding to report., Registration: PROSPERO CRD42021277060., (© 2024. The Author(s).)

Purpose: This scoping review aims to explore the current applications of ChatGPT in the retina field, highlighting its potential, challenges, and limitations., Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, MEDLINE, and Embase, to identify relevant articles published from 2022 onwards. The inclusion criteria focused on studies evaluating the use of ChatGPT in retinal healthcare. Data were extracted and synthesized to map the scope of ChatGPT's applications in retinal care, categorizing articles into various practical application areas such as academic research, charting, coding, diagnosis, disease management, and patient counseling., Results: A total of 68 articles were included in the review, distributed across several categories: 8 related to academics and research, 5 to charting, 1 to coding and billing, 44 to diagnosis, 49 to disease management, 2 to literature consulting, 23 to medical education, and 33 to patient counseling. Many articles were classified into multiple categories due to overlapping topics. The findings indicate that while ChatGPT shows significant promise in areas such as medical education and diagnostic support, concerns regarding accuracy, reliability, and the potential for misinformation remain prevalent., Conclusion: ChatGPT offers substantial potential in advancing retinal healthcare by supporting clinical decision-making, enhancing patient education, and automating administrative tasks. However, its current limitations, particularly in clinical accuracy and the risk of generating misinformation, necessitate cautious integration into practice, with continuous oversight from healthcare professionals. Future developments should focus on improving accuracy, incorporating up-to-date medical guidelines, and minimizing the risks associated with AI-driven healthcare tools., (© 2024. The Author(s).)

Purpose: To assess the accuracy of High-Resolution OCT in detecting biomarkers associated with central serous chorioretinopathy (CSC) compared to standard OCT., Methods: We conducted a cross-sectional study involving CSC patients who underwent High-Resolution and standard OCT during the same visit. Using the SPECTRALIS High-Res OCT device (Heidelberg Engineering, Heidelberg, Germany), macular B-scans were obtained and compared with those acquired using a SPECTRALIS HRA + OCT device (Heidelberg Engineering, Heidelberg, Germany). Qualitative assessments were performed, and statistical analyses compared the performance of both OCT modalities., Results: Thirty-one patients diagnosed with CSC were included with a mean age of 56.3 years (± 10.2). Among them, 29% (n = 9) were classified as acute CSC (aCSC), while 71% (n = 22) had chronic CSC (cCSC). High-Resolution OCT outperformed standard OCT in detecting microstructural changes in the outer retinal layers, including a higher prevalence of disrupted interdigitation zone (IZ) (29% vs. 6%, p = 0.003) and retinal pigment epithelium (RPE) disruption (12% vs. 2%, p = 0.0024). Intergrader agreement was high (Cohen's Kappa = 0.85)., Conclusion: High-Resolution OCT demonstrates promise in identifying critical biomarkers associated with CSC, particularly disruptions in the IZ and RPE. Further validation in larger cohorts is required to confirm their clinical relevance in patients with CSC., (© 2024. The Author(s).)

Background: Sperm cryopreservation is widely used in the cattle industry, as it allows for disassociating the localization of sires and the collection of semen from the timing of artificial insemination. While freeze-thawing is known to impair sperm DNA integrity, whether the damage induced consists of single- (SSB) or double-strand breaks (DSB) has not been determined. In addition, no previous study has addressed if DNA breaks preferentially reside in specific genome regions such as those forming the toroid linker regions, or are rather spread throughout the regions linked to protamines. The main aim of the present work, therefore, was to elucidate the type and localization of the DNA damage generated by cryopreservation and to evaluate its impact on artificial insemination outcomes in cattle., Results: The incidence of SSB and DSB was evaluated in 12 ejaculates before and after cryopreservation with the Comet assay, and the localization of the DNA breaks was assessed using pulsed-field gel electrophoresis (PFGE). Before cryopreservation, the incidence of SSB was 10.99% ± 4.62% and involved 20.56% ± 3.04% of sperm cells, whereas these figures significantly (P < 0.0001) increased up to 34.11% ± 3.48% and 53.36% ± 11.00% in frozen-thawed sperm. In contrast, no significant differences in the incidence of DSB were observed (P > 0.990) before and after cryopreservation (before: incidence of 13.91% ± 1.75% of sperm DNA affecting 56.04% ± 12.49% of sperm cells; after: incidence of 13.55% ± 1.55% of sperm DNA involving 53.36% ± 11.00% of sperm cells). Moreover, PFGE revealed that the percentage of sperm DNA fragments whose length was shorter than a toroid (< 31.5 kb) was greater (P < 0.0001) after (27.00% ± 4.26%) than before freeze-thawing (15.57% ± 4.53%). These differences indicated that the DNA breaks induced by cryopreservation affect the regions condensed in protamines, which are structured in toroids. On the other hand, in vivo fertility rates were associated to the incidence of SSB and DSB in frozen-thawed sperm (P = 0.032 and P = 0.005), but not with the size of the DNA fragments resulting from these breaks (P > 0.05)., Conclusion: Cryopreservation of bovine sperm generates single-strand DNA breaks, which are mainly located in protamine-condensed toroidal regions. The incidence of DNA breaks in cryopreserved sperm has an impact on cattle fertility, regardless of the size of generated fragments., (© 2024. The Author(s).)

Background: To analyze the associations among autonomous motivation, self-efficacy, satisfaction of basic psychological needs, social support and perceived environment with physical activity practice of adolescents aged between 12 and 15 years; and to test autonomous motivations and self-efficacy as potential mediators of the associations between these environmental factors and physical activity practice., Methods: We evaluated 553 adolescents, that participated in the ActTeens Program. Physical activity was assessed using the Physical Activity Questionnaire for Adolescents. Autonomous motivation, self-efficacy, satisfaction of basic psychological needs, parents' social support and perceived environment were assessed using specifics questionnaires. Linear regression models were used to test the associations., Results: Parents' support (β = 0.32), satisfaction of basic psychological needs of colleagues (β = 0.21) and teachers (β = 0.12), and perceived environment (β = 0.10) had significant associations with physical activity (p < 0.05). The direct effect value was reduced when autonomous motivation was added as a mediator of the association between parents' support and physical activity (β = 0.24), with a 25% mediated effect. Autonomous motivation was mediator of the relationship between basic psychological needs of colleagues (β = 0.13; EM = 38%), teachers (β = 0.02; EM = 83%), and perceived environment (β = 0.03; EM = 70%) with physical activity., Conclusion: Self-efficacy was not associated with physical activity and autonomous motivation was an important mediator of adolescents' physical activity., (© 2024. The Author(s).)