Transformers meets neoantigen detection: a systematic literature review.

Cancer immunology offers a new alternative to traditional cancer treatments, such as radiotherapy and chemotherapy. One notable alternative is the development of personalized vaccines based on cancer neoantigens. Moreover, Transformers are considered a revolutionary development in artificial intelligence with a significant impact on natural language processing (NLP) tasks and have been utilized in proteomics studies in recent years. In this context, we conducted a systematic literature review to investigate how Transformers are applied in each stage of the neoantigen detection process. Additionally, we mapped current pipelines and examined the results of clinical trials involving cancer vaccines.

Road traffic noise exposure and its impact on health: evidence from animal and human studies-chronic stress, inflammation, and oxidative stress as key components of the complex downstream pathway underlying noise-induced non-auditory health effects.

In heavily urbanized world saturated with environmental pollutants, road traffic noise stands out as a significant factor contributing to widespread public health issues. It contributes in the development of a diverse range of non-communicable diseases, such as cardiovascular diseases, metabolic dysregulation, cognitive impairment, and neurodegenerative disorders. Although the exact mechanisms behind these non-auditory health effects remain unclear, the noise reaction model centres on the stress response to noise. When exposed to noise, the body activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to the secretion of stress hormones like catecholamines and cortisol. Prolonged exposure to noise-induced stress results in chronic inflammation and oxidative stress. This review underscores the role of inflammation and oxidative stress in the progression of noise-induced vascular dysfunction, disruption of the circadian rhythm, accelerated aging, neuroinflammation, and changes in microbiome. Additionally, our focus is on understanding the interconnected nature of these health outcomes: These interconnected factors create a cascade effect, contributing to the accumulation of multiple risk factors that ultimately lead to severe adverse health effects.

The study of galactomannans with different molecular weights and their ability to form microparticles suitable for pulmonary delivery.

The influence of locust bean gum (LBG) galactomannans (GMs) molecular weight (Mw) to assemble microparticulate systems was evaluated, and carriers for deep lung delivery were developed. A commercial batch of LBG with a mannose/galactose (M/G) ratio of 2.4 (batch 1) was used to study the influence of different microwave partial acid hydrolysis conditions on carbohydrate composition, glycosidic linkages, and aqueous solutions viscosity. The microwave treatment did not affect the composition, presenting 4-Man (36-42 %), 4,6-Man (27-35 %), and T-Gal (24-25 %) as the main glycosidic linkages. Depolymerization led to a viscosity reduction (≤0.005 Pa·s) with no major impact on polysaccharide debranching. The structural composition of the LBG galactomannans were further elucidated with sequence-specific proteins using carbohydrate microarray technologies. A second batch of LBG (M/G 3.3) was used to study the impact of GMs with different Mw on microparticle assembling, characteristics, and insulin release kinetics. The low-Mw GMs microparticles led to a faster release (20 min) than the higher-Mw (40 min) ones, impacting the release kinetics. All microparticles exhibited a safety profile to cells of the respiratory tract. However, only the higher-Mw GMs allowed the assembly of microparticles with sizes suitable for this type of administration.

Molecular Surveillance of Artemisinin-Resistant Plasmodium falciparum Parasites in Mining Areas of the Roraima Indigenous Territory in Brazil.

Multidrug- and artemisinin-resistant (ART-R) Plasmodium falciparum (Pf) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region (pfk13) gene allows tracking mutations in parasite resistance to artemisinin. The increase in illegal miners in the Roraima Yanomami indigenous land (YIL) could favor ART-R parasites. Thus, this study aimed to investigate ART-R in patients from illegal gold mining areas in the YIL of Roraima, Brazil. A questionnaire was conducted, and blood was collected from 48 patients diagnosed with P. falciparum or mixed malaria (Pf + P. vivax). The DNA was extracted and the pfk13 gene was amplified by PCR. The amplicons were subjected to DNA-Sanger-sequencing and the entire amplified fragment was analyzed. Among the patients, 96% (46) were from illegal mining areas of the YIL. All parasite samples carried the wild-type genotypes/ART-sensitive phenotypes. These data reinforce the continued use of artemisinin-based combination therapies (ACTs) in Roraima, as well as the maintenance of systematic monitoring for early detection of parasite populations resistant to ART, mainly in regions with an intense flow of individuals from mining areas, such as the YIL. This is especially true when the achievement of falciparum malaria elimination in Brazil is planned and expected by 2030.

Restoring the epigenome in Alzheimer's disease: advancing HDAC inhibitors as therapeutic agents.

Current treatment options for Alzheimer's disease (AD) focus on symptom relief rather than halting disease progression. In this context, targeting histone deacetylation emerges as a promising therapeutic alternative. Dysregulation of histone deacetylase (HDAC) activity is present in AD, contributing to cognitive decline. Pharmacological HDAC inhibition has shown benefits in preclinical models, namely reduced amyloid beta plaque formation, lower phosphorylation and aggregation of tau protein, greater microtubule stability, less neuroinflammation, and improved metabolic homeostasis and cell survival. Nonetheless, clinical trials evidenced limitations such as insufficient selectivity or blood-brain barrier penetration. Hence, future innovative strategies are required to enhance their efficacy/safety.

Increased TGFß1, VEGF and IFN-γ in the Sputum of Severe Asthma Patients With Bronchiectasis.

BACKGROUND: Bronchiectasis is one of the most common comorbidities in severe asthma. However, the mechanisms by which asthma promotes the development and progress of this condition are not well defined. This study aimed to analyze the inflammatory phenotypes and quantify the expression of proinflammatory and remodeling cytokines in asthma patients with and without bronchiectasis. METHODS: The study sample comprised individuals with severe asthma and bronchiectasis (group AB, n=55) and a control population of individuals with severe asthma without bronchiectasis (group AC, n=45). Induced sputum samples were obtained and cell types determined by differential cell count. Proinflammatory and bronchial remodeling cytokines (IL-8, neutrophilic elastase, TGFß1, VEGF, IFN-γ, TNF-α, and GM-CSF) were analyzed by immunoassay in sputum supernatant. RESULTS: Neutrophilic inflammation was the primary phenotype in both asthma groups. Higher levels of TGFß1, VEGF and IFN-γ were observed in asthma patients with bronchiectasis (group AB) than in controls (group AC) (15 vs 24pg/ml, p=0.014; 183 vs 272pg/ml, p=0.048; 0.85 vs 19pg/ml, p<0.001, respectively). Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were significantly lower in the AB group than in the AC group (1.2 vs 4.4pg/ml, p<0.001). IL-8, neutrophil elastase and TNF-α did not present significant differences between the groups. CONCLUSIONS: Raised levels of TGFß1 and VEGF cytokines may indicate airway remodeling activation in asthma patients with bronchiectasis. The type of inflammation in asthma patients did not differ according to the presence or absence of bronchiectasis.

Trauma-informed systems change training has transcultural, transcontinental transformative healing power: An analysis of leaders in the United States and Angola, Africa.

The Institute for Trauma-Informed Systems Change (ITISC) facilitated a 2-day, 12-hr trauma-informed workshop, delivered virtually, using the Training for Change curriculum. The workshop took place in Portuguese in September 2021 with a group of Angolan leaders (N = 51) and in May 2022, in English, with neonatal intensive care unit (NICU) workers from the United States (N = 73). Surveys were administered before (Time [T] 0) and after the workshop (T1) and consisted of demographic questions and the Survey for Trauma-Informed Systems Change (STISC), which assesses system-wide knowledge and attitudes about trauma-informed systems change and the intersection of culture, safety, and acceptance in the workplace. At T1, 18 (35.3%) participants in the Angolan leaders' group and 46 (63.0%) in the NICU group completed the surveys. Mean scores on the STISC Self-Assessed Knowledge and Attitudes subscale and STISC System-Wide Knowledge and Attitudes subscale increased significantly in both groups after the training. Effect sizes were large for self-assessed knowledge and attitudes, Angolan leaders: d = 1.11, NICU: d = 1.97, and small-to-medium for system-wide knowledge and attitudes, Angolan leaders: d = 0.52, NICU: d = 0.38. Limitations include the relatively small sample size and low participation rates for survey responses. Future research should examine the efficacy of the curriculum in larger samples that include individuals from diverse professions and additional countries. Together, the findings provide initial support that this training can be directly translated and implemented on a global scale.

Relapsing Plasmodium vivax malaria in a 12-year-old Brazilian girl: A case report.

Plasmodium vivax causes the vast majority of malaria cases in Brazil. The lifecycle of this parasite includes a latent stage in the liver, the hypnozoite. Reactivation of hypnozoites induces repeated relapses. We report a case of two relapses of vivax malaria in a teenage girl after conventional treatment with chloroquine and primaquine. Chloroquine prophylactic treatment for three months was prescribed with a favourable outcome of the case.

A compared histopathological study on kidneys and eye bulbs in distinct clinical presentations of canine leishmaniasis by Leishmania infantum.

Canine leishmaniasis (CanL) caused by Leishmania infantum commonly progresses with renal and ophthalmic lesions associated with active systemic disease. As chronic inflammation related to immune complex deposits is a pathophysiological factor in the development of both glomerulonephritis and uveitis, we aimed to evaluate renal and ocular histopathological lesions and analyze whether they were related to each other and the clinical degree of the disease. For that, we evaluated 15 dogs from CanL-endemic areas. L. infantum PCR-positive dogs were studied according to disease severity into two different groups: Group-1 (G1) had data from seven dogs with mild to moderate CanL and no history of treatment, and G2 was formed with eight dogs with severe to terminal disease that had not responded to CanL treatment. Histopathological analysis of kidneys showed higher frequencies and intensities of glomerular basement membrane thickening (p = 0.026), deposits in glomeruli (p = 0.016), epithelial necrosis (p = 0.020), tubular dilatation (p = 0.003) and interstitial fibrosis (p = 0.04) in G2 dogs than in G1 dogs. Surprisingly, the histopathology of eye bulbs showed a higher frequency and intensity of retinitis (p = 0.019) in G1 dogs than in G2 dogs. The comparative analysis showed that there was no correspondence between histopathological findings in kidneys versus eyes in milder or more severe CanL. Our findings suggested that (1) clinically undetectable eye alterations can be more precocious than those in kidneys in the development of CanL, and (2) the lower frequency of eye lesions and higher frequency of renal lesions in dogs with terminal disease even after treatment indicate that therapy may have been effective in reducing CanL-associated ophthalmic disease but not proportionally in reducing kidney disease.

Factors associated with frailty among older individuals with chronic diseases: A multicenter study.

Objective: Frailty is a syndrome that predisposes older individuals to adverse health outcomes, such as disability, dependence, falls, hospitalization, post-operative complications, and poor health in general. This study aimed to identify factors associated with frailty in older people with chronic diseases in Colombia. Methods: A cross-sectional study was conducted with a nonprobabilistic sample of 230 older people (aged ⩾ 60 years) from four Colombian cities. Frailty was based on Fried's phenotype (frail defined as having ⩾3 criteria). Comorbidities were classified based on Charlson's Comorbidity Index and key questionnaires for activities of daily living (ADLs) were evaluated. Results: Most were female (57.8%) with a mean ± SD age of 71.9 ± 8 years. Among them, 27.4% were frail and 58.7% were prefrail. Female gender, age ⩾ 75 years, low educational and socioeconomic level, dependence on ADLs, and cognitive impairment were associated with higher odds of prefrailty/frailty. Conclusions: Prefrailty and frailty are common among older people with chronic diseases in Colombia. This syndrome is associated with social and health-related conditions, which should be addressed when providing care for these patients.

Feline Leishmaniasis: Evidence-based Treatments and Challenges to be Solved.

Leishmaniasis is a neglected tropical disease caused by protozoa parasites from the Leishmania genus. Vertebrate hosts acquire the infection through the bite of a female sandfly, initiating a complex parasite development cycle. Contrary to previous beliefs regarding cats' resistance, these animals have recently been identified as potential reservoirs for leishmaniasis. Clinical symptoms in cats can manifest in diverse forms, including cutaneous, mucocutaneous, and visceral manifestations. The diagnosis of feline leishmaniasis is complicated by nonspecific symptoms and the relatively lower specificity of serological tests. The recommended treatment for feline leishmaniasis involves the administration of medications; however, success varies in each cat. This review aims to present cases of feline leishmaniasis, highlighting clinical symptoms, diagnostic methods, therapy schedules, and outcomes. Among the 24 cases documented in the available literature, 12 achieved successful treatment without relapses, resulting in a reduced parasite load and improved symptoms. Three cases responded well but presented persistent sequelae. Two feline leishmaniasis cases initially had treatment success but later experienced recurrences. Finally, no response was observed in seven cases, leading to the euthanasia of cats due to ineffectiveness or irregularities along the therapy. Conventional treatments, despite potential hepatotoxicity and nephrotoxicity, exhibit a high efficacy in reducing parasitic load, thereby improving clinical symptoms and increasing the life expectancy of affected cats. Nevertheless, consistent adherence is crucial, as interruptions may render the therapy ineffective and contribute to parasite resistance. Therefore, addressing the challenges associated with feline leishmaniasis treatment necessitates the development of new strategies to ensure a more effective and sustained approach.

A template wizard for the cocreation of machine-readable data-reporting to harmonize the evaluation of (nano)materials.

Making research data findable, accessible, interoperable and reusable (FAIR) is typically hampered by a lack of skills in technical aspects of data management by data generators and a lack of resources. We developed a Template Wizard for researchers to easily create templates suitable for consistently capturing data and metadata from their experiments. The templates are easy to use and enable the compilation of machine-readable metadata to accompany data generation and align them to existing community standards and databases, such as eNanoMapper, streamlining the adoption of the FAIR principles. These templates are citable objects and are available as online tools. The Template Wizard is designed to be user friendly and facilitates using and reusing existing templates for new projects or project extensions. The wizard is accompanied by an online template validator, which allows self-evaluation of the template (to ensure mapping to the data schema and machine readability of the captured data) and transformation by an open-source parser into machine-readable formats, compliant with the FAIR principles. The templates are based on extensive collective experience in nanosafety data collection and include over 60 harmonized data entry templates for physicochemical characterization and hazard assessment (cell viability, genotoxicity, environmental organism dose-response tests, omics), as well as exposure and release studies. The templates are generalizable across fields and have already been extended and adapted for microplastics and advanced materials research. The harmonized templates improve the reliability of interlaboratory comparisons, data reuse and meta-analyses and can facilitate the safety evaluation and regulation process for (nano) materials.

Implementation of the My Abilities First Tool: A qualitative study on the perceptions of professionals, caregivers, children, and adolescents with disabilities.

OBJECTIVE: To analyze the perceptions of professionals, caregivers, children, and adolescents with disabilities regarding the implementation of the My Abilities First (MAF) tool in Specialized Child Rehabilitation Centers (CERs). METHOD: This is a qualitative research based on Reflexive Thematic Analysis (RTA). The study involved twenty-seven intentionally selected individuals, comprising 12 physiotherapists, 4 occupational therapists, 11 caregivers, 9 children and 2 adolescents. Participants completed sociodemographic and clinical questionnaires and took part in semi-structured online interviews, focusing on two themes: Positive health approaches and the MAF tool. The study was approved by the local ethics committee (opinion 4.779.175). RESULTS: Reflexive Thematic Analysis of the interviews resulted in two themes: (1) Perceptions regarding the MAF tool as an educational and contributory process to enhance the inclusion and participation of children and adolescents with disabilities, and (2) Barriers and facilitators for the implementation process of the MAF tool. The implementation of MAF was identified as a driving factor in promoting equity and increased participation of children and adolescents with disabilities in various settings, including health, education, and leisure. Interviewees highlighted the need to confront attitudinal, communication, and social barriers that may hinder the implementation of the tool. CONCLUSION: The implementation of the MAF tool was perceived as an innovation due to its focus on the abilities of individuals with disabilities. However, there is a need to restructure it to broaden its scope and access to different contexts in order to confront barriers and enhance the inclusion and participation of children and adolescents with disabilities.

Effect of UV-C disinfection and copper plating on healthcare-associated infections in a NICU with high ESBL infections.

INTRODUCTION: Healthcare-associated infections (HCAIs) in neonates are frequent and highly lethal, in particular those caused by extended spectrum beta-lactamase (ESBL) producing bacteria. We evaluated the beneficial effects of ultraviolet C (UV-C) disinfection and copper adhesive plating on HCAIs in the Neonatal Intensive Care Unit (NICU) of a third level paediatric hospital in Mexico City, both in combination of hand-hygiene (HH) and prevention bundles. METHODS: All NICU patients were included. There were 4 periods (P): P1: HH monitoring and prevention bundles; P2: P1+UV-C disinfection; P3: P2+Copper adhesive plating on frequent-contact surfaces and P4: Monitoring of P3 actions. RESULTS: 552 neonates were monitored during 15,467 patient days (PD). HCAI rates decreased from 11.03/1000 PD in P1 to 5.35/1000 PD in P4 (p=0.006). HCAIs with bacterial isolates dropped from 5.39/1000 PD in PI to 1.79/1000 PD in P4 (p=0.011). UV-C and copper were associated with significant HCAI prevention (RR 0.49, CI95% 0.30-0.81, p=0.005) and with lesser HCAIs with bacterial isolates (RR 0.33, CI95% 0.14-0.77, p=0.011). CONCLUSIONS: Copper adhesive plating combined with UV-C disinfection were associated with a drop in HCAI rates and with the elimination of ESBL-caused HCAIs. Hence, we propose that these strategies be considered in MDRO proliferation preventions.

The dispersant Corexit 9500 and (dispersed) oil are lethal to coral endosymbionts.

Endosymbionts (Symbiodiniaceae) play a vital role in the health of corals. Seawater pollution can harm these endosymbionts and dispersants used during oil spill cleanup can be extremely toxic to these organisms. Here, we examined the impact of oil and a specific dispersant, Corexit-9500, on two representative endosymbionts - Symbiodinium and Cladocopium - from the Southwestern endemic coral Mussismilia braziliensis. The survival and photosynthetic potential of the endosymbionts decreased dramatically after exposure to the dispersant and oil by ~25 % after 2 h and ~50 % after 7 days. Low concentrations of dispersant (0.005 ml/l) and dispersed oil (Polycyclic Aromatic Hydrocarbons, 1132 µg/l; Total Petroleum Hydrocarbons, 595 µg/l) proved highly toxic to both Symbiodinium and Cladocopium. These levels triggered a reduction in growth rate, cell size, and cell wall thickness. After a few hours of exposure, cellular organelles were damaged or destroyed. These acute toxic effects underline the fragile nature of coral endosymbionts.

Teaching Population Panel Management: A Patient Outreach Activity in a Family Medicine Clerkship.

BACKGROUND AND OBJECTIVES: The delivery of population health education in medical school can be challenging. We developed a patient outreach activity for third-year students to teach them the role of population panel management in primary care. METHODS: The family medicine undergraduate medical education and population health teams collaborated to develop an educational patient outreach toolkit. After an orientation, family medicine clerkship students were assigned to call patients on their faculty adviser's patient panel to discuss care gaps and identify barriers and potential strategies to improve care. After the experience, students completed reflection questions, which we analyzed. RESULTS: From February to August 2022, 82 third-year medical students participated in the patient outreach activity during their 6-week clerkship. Of the 1,235 total attempted calls, 24% of the patients scheduled their appointments afterward. After analyzing the reflective student feedback, we identified six main takeaways, which focused on the importance of population health, the identification of barriers to care, positive and negative feelings that students experienced when making calls, student self-identified areas of growth, and the fragmentation/inefficiency of the health care system. CONCLUSIONS: An opportunity exists to continue to teach students about how to communicate with patients about their health and how to address and improve social determinants of health. This curricular activity can be a step toward efforts to align population health and clinical practice and a way for medical students to add value by educating patients.

Alternative Treatments to Pharmacological Therapy in Pediatric Populations With Attention-Deficit/Hyperactivity Disorder (ADHD): A Scoping Review.

In recent years, there has been an increase in the prevalence of the diagnosis of attention-deficit/hyperactivity disorder (ADHD), a cognitive and behavioral disorder in which individuals present with inattention and impulsivity, in the pediatric population. With an increase in diagnoses, there is also increasing concern regarding overdiagnosis and overtreatment with medications for ADHD. The objective of this study was to map out and compile the recent literature pertaining to alternative therapies (e.g., physical activity, diet, mindfulness, and computer-based interventions) for children and adolescents diagnosed with ADHD in an attempt to reduce or replace the use of pharmacological therapy. This scoping review searched articles from multiple databases (PubMed, ScienceDirect, Web of Science, Directory of Open Access Journals, Scopus, and CINAHL). Using search terms "children with ADHD," "alternative treatment," and "cognitive behavioral therapy," articles were identified that were specific to the research question. The inclusion criteria were patients under the age of 18 with a previous diagnosis of ADHD, no other comorbid illnesses, alternative treatments, and was limited to studies published between 2012 and 2022. After removing duplicates, screening for eligibility criteria, and conducting a critical appraisal of the articles, 16 articles were retained for the final review. The main alternative therapeutic domains that emerged were (1) physical activity, (2) diet, (3) mindfulness, (4) computer-based interventions, and (5) miscellaneous interventions. Seven articles assessed the effect of physical activity on executive and cognitive function in children and adolescents with ADHD. Most findings showed improvement with increased physical activity. Two articles explored the effect of diet on the improvement of ADHD symptoms and reported a positive impact. The two articles that evaluated the effects of mindfulness on ADHD symptoms reported a reduction in ADHD symptoms. Two studies evaluated the use of computer-based interventions as an adjunct treatment in children and adolescents with ADHD; improvements in symptoms were reported. One study each evaluated interventions based on music and nerve stimulation. These showed an improvement in attention, memory, and executive function. With the increasing prevalence of ADHD diagnosis in children and adolescents, alternative and/or adjunctive treatments may be a viable and valuable alternative to pharmaceutical interventions. The findings from this review suggest that multiple non-pharmacological interventions effectively reduce symptoms of ADHD in children and adolescents, including diet, exercise, mindfulness, computer-based interventions, music, and nerve stimulation. While there are implications for alternatives to be used in the future, more research is warranted using larger samples with controlled trials.

Acquired tracheomalacia due to SARS-CoV-2 pneumonia.

INTRODUCTION: Several studies mentioned parenchymal findings after SARS-CoV-2 pneumonia, but few studies have mentioned alterations in the airways. The aim of this study was to estimate the prevalence of tracheomalacia and to analyse the clinical characteristics in a cohort of patients with SARS-CoV-2. METHODS: The study population consisted of all patients with SARS-CoV-2 admitted a hospital serving a population of 500 000 inhabitants. Patients were visited between 2 and 6 months after hospital discharge. In this visit, all patients were subjected to an exhaustive clinical questionnaire and underwent clinical examination, pulmonary function tests and chest CT. RESULTS: From February 2020 to August 2021, 1920 patients were included in the cohort and tracheomalacia was observed in 15 (0.8%) on expiratory HRCT imaging. All patients with tracheomalacia also presented ground glass opacities in the CT scan and 12 patients had airway sequelae. CONCLUSIONS: Tracheomalacia is an exceptional sequela of SARS-CoV-2 survivors.