Unveiling the Brazilian kefir microbiome: discovery of a novel Lactobacillus kefiranofaciens (LkefirU) genome and in silico prospection of bioactive peptides with potential anti-Alzheimer properties.

BACKGROUND: Kefir is a complex microbial community that plays a critical role in the fermentation and production of bioactive peptides, and has health-improving properties. The composition of kefir can vary by geographic localization and weather, and this paper focuses on a Brazilian sample and continues previous work that has successful anti-Alzheimer properties. In this study, we employed shotgun metagenomics and peptidomics approaches to characterize Brazilian kefir further. RESULTS: We successfully assembled the novel genome of Lactobacillus kefiranofaciens (LkefirU) and conducted a comprehensive pangenome analysis to compare it with other strains. Furthermore, we performed a peptidome analysis, revealing the presence of bioactive peptides encrypted by L. kefiranofaciens in the Brazilian kefir sample, and utilized in silico prospecting and molecular docking techniques to identify potential anti-Alzheimer peptides, targeting ß-amyloid (fibril and plaque), BACE, and acetylcholinesterase. Through this analysis, we identified two peptides that show promise as compounds with anti-Alzheimer properties. CONCLUSIONS: These findings not only provide insights into the genome of L. kefiranofaciens but also serve as a promising prototype for the development of novel anti-Alzheimer compounds derived from Brazilian kefir.

DockThor-VS: A Free Platform for Receptor-Ligand Virtual Screening.

The DockThor-VS platform (https://dockthor.lncc.br/v2/) is a free protein-ligand docking server conceptualized to facilitate and assist drug discovery projects to perform docking-based virtual screening experiments accurately and using high-performance computing. The DockThor docking engine is a grid-based method designed for flexible-ligand and rigid-receptor docking. It employs a multiple-solution genetic algorithm and the MMFF94S molecular force field scoring function for pose prediction. This engine was engineered to handle highly flexible ligands, such as peptides. Affinity prediction and ranking of protein-ligand complexes are performed with the linear empirical scoring function DockTScore. The main steps of the ligand and protein preparation are available on the DockThor Portal, making it possible to change the protonation states of the amino acid residues, and include cofactors as rigid entities. The user can also customize and visualize the main parameters of the grid box. The results of docking experiments are automatically clustered and ordered, providing users with a diverse array of meaningful binding modes. The platform DockThor-VS offers a user-friendly interface and powerful algorithms, enabling researchers to conduct virtual screening experiments efficiently and accurately. The DockThor Portal utilizes the computational strength of the Brazilian high-performance platform SDumont, further amplifying the efficiency and speed of docking experiments. Additionally, the web server facilitates and enhances virtual screening experiments by offering curated structures of potential targets and compound datasets, such as proteins related to COVID-19 and FDA-approved drugs for repurposing studies. In summary, DockThor-VS is a dynamic and evolving solution for docking-based virtual screening to be applied in drug discovery projects.

Cardiovascular and Renal Effects Induced by Alpha-Lipoic Acid Treatment in Two-Kidney-One-Clip Hypertensive Rats.

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.

Plant diversity darkspots for global collection priorities.

More than 15% of all vascular plant species may remain scientifically undescribed, and many of the > 350 000 described species have no or few geographic records documenting their distribution. Identifying and understanding taxonomic and geographic knowledge shortfalls is key to prioritising future collection and conservation efforts. Using extensive data for 343 523 vascular plant species and time-to-event analyses, we conducted multiple tests related to plant taxonomic and geographic data shortfalls, and identified 33 global diversity darkspots (those 'botanical countries' predicted to contain most undescribed and not yet recorded species). We defined priority regions for future collection according to several socio-economic and environmental scenarios. Most plant diversity darkspots are found within global biodiversity hotspots, with the exception of New Guinea. We identify Colombia, Myanmar, New Guinea, Peru, Philippines and Turkey as global collection priorities under all environmental and socio-economic conditions considered. Our study provides a flexible framework to help accelerate the documentation of global plant diversity for the implementation of conservation actions. As digitisation of the world's herbaria progresses, collection and conservation priorities may soon be identifiable at finer scales.

A Novel Kunitz Trypsin Inhibitor from Enterolobium gummiferum Seeds Exhibits Antibiofilm Properties against Pathogenic Yeasts.

Plant peptidase inhibitors play crucial roles in plant defence mechanisms and physiological processes. In this study, we isolated and characterised a Kunitz trypsin inhibitor from Enterolobium gummiferum seeds named EgPI (E. gummiferum peptidase inhibitor). The purification process involved two chromatography steps using size exclusion and hydrophobic resins, resulting in high purity and yield. EgPI appeared as a single band of ~20 kDa in SDS-PAGE. Under reducing conditions, the inhibitor exhibited two polypeptide chains, with 15 and 5 kDa. Functional characterisation revealed that EgPI displayed an inhibition stoichiometry of 1:1 against trypsin, with a dissociation constant of 8.4 × 10-9 mol·L-1. The amino-terminal sequencing of EgPI revealed the homology with Kunitz inhibitors. Circular dichroism analysis provided insights into the secondary structure of EgPI, which displayed the signature typical of Kunitz inhibitors. Stability studies demonstrated that EgPI maintained the secondary structure necessary to exhibit its inhibitory activity up to 70 °C and over a pH range from 2 to 8. Microbiological screening revealed that EgPI has antibiofilm properties against pathogenic yeasts at 1.125 µmol·L-1, and EgPI reduced C. albicans biofilm formation by 82.7%. The high affinity of EgPI for trypsin suggests potential applications in various fields. Furthermore, its antibiofilm properties recommended its usefulness in agriculture and antimicrobial therapy research, highlighting the practical implications of our research.

Descriptive study of perineuronal net in enteric nervous system of humans and mice.

Perineuronal nets (PNN) are highly specialized structures of the extracellular matrix around specific groups of neurons in the central nervous system (CNS). They play functions related to optimizing physiological processes and protection neurons against harmful stimuli. Traditionally, their existence was only described in the CNS. However, there was no description of the presence and composition of PNN in the enteric nervous system (ENS) until now. Thus, our aim was to demonstrate the presence and characterize the components of the PNN in the enteric nervous system. Samples of intestinal tissue from mice and humans were analyzed by RT-PCR and immunofluorescence assays. We used a marker (Wisteria floribunda agglutinin) considered as standard for detecting the presence of PNN in the CNS and antibodies for labeling members of the four main PNN-related protein families in the CNS. Our results demonstrated the presence of components of PNN in the ENS of both species; however its molecular composition is species-specific.

Three biomarkers (HER2, PD-L1, and microsatellite status) in a large cohort of metastatic gastroesophageal adenocarcinomas: The MD Anderson Cancer Center experience.

Human epidermal growth factor receptor-2 (HER2), programmed death-ligand 1 (PD-L1), and microsatellite (MS) status are well-established biomarkers in gastroesophageal adenocarcinomas (GEAs). However, it is unclear how the combination of these biomarkers is associated with clinicopathological factors and prognosis. This retrospective study included baseline metastatic GEA patients who were tested for all three biomarkers (HER2, PD-L1, and MS status) at the MD Anderson Cancer Center between 2012 and 2022. Stratification was performed according to the combination of biomarker profiles: triple negative (TN), single positive (SP), and multiple positive (MP). Comparative analyses of clinicopathological factors and survival using combinations of biomarkers were performed. Among the 698 GEA patients analyzed, 251 (36.0%) were classified as TN, 334 (47.9%) as SP, and 113 (16.1%) as MP. The MP group showed a significant association with tumors located in the esophagus (p < .001), well to moderate differentiation (p < .001), and the absence of signet ring cells (p < .001). In the survival analysis, MP group had a significantly longer overall survival (OS) compared to the other groups (MP vs. TN, p < .001 and MP vs. SP, p < .001). Multivariate Cox regression analysis revealed that MP serves as an independent positive prognostic indicator for OS (hazard ratio = 0.63, p < .01). Our findings indicate that MP biomarkers are associated with a favorable prognosis in metastatic GEA. These results are reflective of clinical practice and offer valuable insights into how therapeutics and future biomarkers could influence therapy/prognosis.

The somatic mutation profile of estrogen receptor-positive HER2-negative metastatic breast cancer in Brazilian patients.

Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity. Methods: We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering PIK3CA, AKT1, ESR1, ERBB2, BRCA1, BRCA2, PALB2, TP53, but not PTEN) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]). Results: Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in PIK3CA and 1.8% in AKT1. Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the PIK3CA mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2, or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases. Conclusion: We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives.

Oral Treatment with the Pectin Fibre Obtained from Yellow Passion Fruit Peels Worsens Sepsis Outcome in Mice by Affecting the Intestinal Barrier.

The biological activities of plant-derived soluble dietary fibres (SDFs) have been widely investigated. Pectin from yellow passion fruit (YPF-peSDF) peels was suggested as a protective macromolecule in ulcers and colitis due to its antioxidant and anti-inflammatory properties. Sepsis has high mortality and morbidity and is characterised by inflammatory and oxidative stress imbalances. Evidence suggests that pectins may aid sepsis treatment; however, the effects of YPF-peSDF on sepsis remain unclear. Herein, polymicrobial sepsis was induced by cecal-ligation and puncture in mice treated with YPF-peSDF (1 and 10 mg/kg; gavage). YPF-peSDF accelerated mortality, reaching 100% in 24 h. Inflammation was present in the colons and small intestines (SI) of both vehicle- and fibre-treated mice. Although crypt depth and width, and villus height were preserved in the SI of septic mice administered YPF-peSDF, they exhibited exacerbated muscle layer atrophy and mucosa and submucosa hypertrophy, along with shortened enterocytes. Larger crypts and shorter enterocytes were noted in their colons in comparison with vehicle-controls. YPF-peSDF also reduced inflammatory cell numbers and exacerbated IL-6 levels in peritoneal lavage fluid (PELF) samples. YPF-peSDF modulated SI but not colon cytokines. Lipoperoxidation and antioxidant capacity levels were attenuated in PELF samples. Overall, in contrast to previous evidence, YPF-peSDF worsened polymicrobial sepsis outcomes in mice.

Nursing care regarding the psycho-emotional aspects of women submitted to mastectomy / Assistência de enfermagem frente aos aspectos psicoemocionais de mulheres mastectomizadas

Breast cancer, or breast neoplasm, is one of the most frequent types of cancer, and one of the most prevalent among women. The diagnosis and specific treatments, such as mastectomy surgery, lead women to experience different feelings, with the most predominant negative thoughts. In this way, the objective of this study is to describe the importance of nursing care in the face of the psycho-emotional aspects of women after mastectomy. This is an integrative literature review study, developed in electronic Medline and Lilacs databases. The following terms were used: Breast neoplasm; Nursing; Emotions; Mastectomy. A total of 2,314 articles were found, of which eight were selected. The results and discussions were divided into two thematic axes: The first deals with the emotions of women after mastectomy, whose feelings arising from the diagnosis of the disease start to affect different areas, such as personality, sexuality, family, and social relationships. Furthermore, the second deals with nursing care after mastectomy, which must be conducted integrally, aiming at restoring physical and emotional health. Nursing is the vehicle capable of planning and collaborating with these women, promoting humanized treatment and assistance, oriented and aimed at a better quality of life, and stimulating self-help, self-esteem, and acceptance of their body.

O câncer de mama ou neoplasia da mama, é um dos tipos de cânceres mais frequentes, e um dos mais prevalentes entre as mulheres. O diagnóstico e determinados tratamentos, como a cirurgia de mastectomia, levam as mulheres a vivenciarem diferentes sentimentos, sendo os pensamentos negativos os mais predominantes. Desta maneira, o objetivo deste estudo é descrever a importância da assistência do enfermeiro frente aos aspectos psicoemocionais de mulheres mastectomizadas. Trata-se de um estudo de revisão integrativa da literatura, desenvolvida nas bases eletrônicas de dados Medline e Lilacs. Foram utilizados os seguintes descritores: Neoplasias da mama; Enfermagem; Emoções; Mastectomia. Foram encontrados 2314 artigos, dos quais foram selecionados oito. Os resultados e discussões foram divididos em dois eixos temáticos: O primeiro trata das emoções das mulheres mastectomizadas, cujos sentimentos advindos com o diagnóstico da doença passam a afetar diferentes aspectos psicoemocionais, como personalidade, sexualidade, família e relações sociais. E o segundo trata da assistência de enfermagem após a mastectomia, a qual deve se dar de maneira integral, visando tanto o restabelecimento da saúde física quanto emocional. A enfermagem pode desempenhar um cuidado diferenciado e voltado para as necessidades psicoemocionais das mulheres, promovendo tratamento e assistência humanizados, orientados e voltados a uma melhor qualidade de vida, e com o fim de estimular a autoajuda, a autoestima e a aceitação de seu corpo.

A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain.

Neuropathic pain arises from injuries to the nervous system in diseases such as diabetes, infections, toxicity, and traumas. The underlying mechanism of neuropathic pain involves peripheral and central pathological modifications. Peripheral mechanisms entail nerve damage, leading to neuronal hypersensitivity and ectopic action potentials. Central sensitization involves a neuropathological process with increased responsiveness of the nociceptive neurons in the central nervous system (CNS) to their normal or subthreshold input due to persistent stimuli, leading to sustained electrical discharge, synaptic plasticity, and aberrant processing in the CNS. Current treatments, both pharmacological and non-pharmacological, aim to alleviate symptoms but often face challenges due to the complexity of neuropathic pain. Neuromodulation is emerging as an important therapeutic approach for the treatment of neuropathic pain in patients unresponsive to common therapies, by promoting the normalization of neuronal and/or glial activity and by targeting cerebral cortical regions, spinal cord, dorsal root ganglia, and nerve endings. Having a better understanding of the efficacy, adverse events and applicability of neuromodulation through pre-clinical studies is of great importance. Unveiling the mechanisms and characteristics of neuromodulation to manage neuropathic pain is essential to understand how to use it. In the present article, we review the current understanding supporting dorsal root ganglia and spinal cord neuromodulation as a therapeutic approach for neuropathic pain.

Mapping of metals contamination in coastal sediments around the world in the last decades: A bibliometric analysis and systematic review.

The quality of coastal sediments contaminated by metals has been discussed for decades worldwide. However, there is a lack of information on the current situation and trends in this research field. For this reason, this is the first study to present an integrated analysis of bibliometric mapping and systematic review, using the Scopus database. The subject has grown exponentially, with a notable increase in citations and predicted increases for the coming years. The Chinese Academy of Sciences and Chinese authors were highlighted. The main areas of study were the Yellow Sea, Adriatic Sea and Persian Gulf. The main metals related were Cu, Pb, Zn, Cr and Cd, linked to anthropogenic sources such as agriculture, domestic sewage and mining and industry activities. The IGEO proved to be the main index for assessing pollution. This research is useful for pointing out the needs of future research, supporting the development of this topic.

Synthesis and pharmacological evaluation of novel N-aryl-cinnamoyl-hydrazone hybrids designed as neuroprotective agents for the treatment of Parkinson's disease.

Molecular hybridization between structural fragments from the structures of curcumin (1) and resveratrol (2) was used as a designing tool to generate a new N-acyl-cinnamoyl-hydrazone hybrid molecular architecture. Twenty-eight new compounds were synthesized and evaluated for multifunctional activities related to Parkinson's disease (PD), including neuroprotection, antioxidant, metal chelating ability, and Keap1/Nrf2 pathway activation. Compounds 3b (PQM-161) and 3e (PQM-164) were highlighted for their significant antioxidant profile, acting directly as induced free radical stabilizers by DPPH and indirectly by modulating intracellular inhibition of t-BOOH-induced ROS formation in neuronal cells. The mechanism of action was determined as a result of Keap1/Nrf2 pathway activation by both compounds and confirmed by different experiments. Furthermore, compound 3e (PQM-164) exhibited a significant effect on the accumulation of α-synuclein and anti-inflammatory activity, leading to an expressive decrease in gene expression of iNOS, IL-1ß, and TNF-α. Overall, these results highlighted compound 3e as a promising and innovative multifunctional drug prototype candidate for PD treatment.

Is there a superiority between arthrocentesis and stabilizing occlusal splint for the treatment of anterior disc displacement with reduction and intermittent block and anterior disc displacement without reduction in TMJ? Randomized clinical trial.

INTRODUCTION: Anterior displacement of the temporomandibular joint (TMJ) disc is a disorder in which the articular disc is dislocated from its correct position relative to the mandibular condyle and mandibular fossa. Traditionally, the initial treatment of disc displacements involves various conservative measures, including the use of a stabilizing interocclusal splint. However, in cases where there is associated limited mouth opening, as in the case of anterior disc displacement with reduction and intermittent block (ADDwRIB), and anterior disc displacement without reduction (ADDw/oR), arthrocentesis has been suggested as another modality of initial treatment due to its faster effect in preventing disease progression to a more advanced stage, as well as reducing the chances of pain chronification and central sensitization. OBJECTIVES: This study aimed to analyze whether there is a preponderance in efficacy between treatments with a stabilizing interocclusal splint or arthrocentesis in these patients. METHODS: A randomized, prospective, longitudinal clinical trial was conducted. The sample was obtained by convenience, between June 2021 and January 2023. Twenty-four patients with diagnoses of ADDwRIB and ADDw/oR were included. The diagnosis and clinical evaluations followed the DC/TMD criteria, and TMJ MRI was performed. Patients were randomly allocated to 2 treatment groups. Group 1 (n = 13): stabilizing interocclusal splint. Group 2 (n = 11): arthrocentesis. Patients were evaluated after 1, 2, 3, and 6 months for clinical parameters of pain, functionality, and psychosocial status. RESULTS: Both treatments were effective in reducing pain levels, with no statistically significant differences. Group 1 showed significantly greater mouth-opening levels compared to Group 2 (P = .041). CONCLUSION: Both groups showed significant improvements in various parameters evaluated throughout the study, indicating they are equally effective in pain control and most functional and quality of life parameters. However, the stabilizing interocclusal splint treatment was superior in restoring mouth opening.

First Case Report of Bilateral Parotid Lymphoepithelial Carcinoma.

Background/Aim: The parotid is the largest salivary gland and is located anteriorly to the sternocleidomastoid muscle and laterally to the ramus of the mandible. Neoplasms in this gland are relatively rare, with 80% being benign and 20% malignant, primarily represented by mucoepidermoid carcinoma. In the head and neck region, lymphoepithelial carcinoma (LEC) accounts for 0.4% of malignant salivary gland tumors. Case Report: A 35-year-old man with no previous comorbidities was admitted to a Head and Neck Surgery Specialty Service for a painless right cervical mass of uncertain growth. Extensive diagnostic investigation revealed involvement of the contralateral parotid, associated with systemic lymph node enlargement. Thus, adjuvant radiotherapy was decided by the treating team. Conclusion: This case confirms the heterogeneous features and distinctive behavior that the disease can present, as seen with bilateral parotid LEC.

ANN-Based LiDAR Positioning System for B5G.

This work reports the development of an efficient and precise indoor positioning system utilizing two-dimensional (2D) light detection and ranging (LiDAR) technology, aiming to address the challenging sensing and positioning requirements of the beyond fifth-generation (B5G) mobile networks. The core of this work is the implementation of a 2D-LiDAR system enhanced by an artificial neural network (ANN), chosen due to its robustness against electromagnetic interference and higher accuracy over traditional radiofrequency signal-based methods. The proposed system uses 2D-LiDAR sensors for data acquisition and digital filters for signal improvement. Moreover, a camera and an image-processing algorithm are used to automate the labeling of samples that will be used to train the ANN by means of indicating the regions where the pedestrians are positioned. This accurate positioning information is essential for the optimization of B5G network operation, including the control of antenna arrays and reconfigurable intelligent surfaces (RIS). The experimental validation demonstrates the efficiency of mapping pedestrian locations with a precision of up to 98.787%, accuracy of 95.25%, recall of 98.537%, and an F1 score of 98.571%. These results show that the proposed system has the potential to solve the problem of sensing and positioning in indoor environments with high reliability and accuracy.

Retrospective Study of Claudin 18 Isoform 2 Prevalence and Prognostic Association in Gastric and Gastroesophageal Junction Adenocarcinoma.

PURPOSE: Claudin 18 isoform 2 (CLDN18.2) is an emerging biomarker and therapeutic target in gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. This study aimed to obtain deeper understanding of CLDN18.2 positivity patterns, prognostic implications, and associations with various demographic, clinical, and molecular characteristics in G/GEJ adenocarcinoma. METHODS: Archived tumor tissue samples from 304 patients with G/GEJ adenocarcinoma in the United States were assessed for CLDN18.2 positivity by immunohistochemistry. CLDN18.2 positivity was defined as ≥50% or ≥75% of tumor cells with CLDN18 staining intensity ≥2+. CLDN18.2 positivity patterns were analyzed for association with prognosis and clinicopathologic/demographic characteristics. Where possible, CLDN18.2 positivity was analyzed for matched tissue samples to assess concordance between primary and metastatic tumors and concordance before and after chemotherapy. RESULTS: The overall prevalence of CLDN18.2-positive tumors (with ≥75% cutoff) was 44.4% (n = 135 of 304). CLDN18.2-positive tumors had a prevalence of 51.4% (n = 91 of 177) in gastric and 34.6% (n = 44 of 127) in GEJ adenocarcinoma. With a ≥50% cutoff, the prevalence of CLDN18.2-positive tumors was 64.4% (n = 114 of 177) in gastric adenocarcinoma and 44.9% (n = 57 of 127) in GEJ adenocarcinoma. There was no association between overall survival and CLDN18.2 positivity using either threshold. Statistically significant associations were noted between CLDN18.2 positivity and sex, histologic type of G/GEJ adenocarcinoma, and adenocarcinoma subtype (≥75% cutoff), and metastasis site and tumor grade (≥50% cutoff). The overall concordance of CLDN18.2 positivity (≥75% cutoff) was 73% (27 of 37) for matched primary versus metastatic tumor samples and 74% (29 of 39) for matched samples before and after chemotherapy. CONCLUSION: This study demonstrated that CLDN18.2 positivity did not correlate with survival in G/GEJ adenocarcinoma, consistent with published data. On the basis of matched sample analysis, CLDN18.2 appears to demonstrate >70% concordance as a biomarker. Observed correlations with certain patient/tumor characteristics warrant further study.

SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel.

BACKGROUND: The clinical impact of SMARCA4 mutations (SMARCA4ms) in gastroesophageal adenocarcinoma (GEA) remains underexplored. This study aimed to examine the association of SMARCA4ms with clinical outcomes and co-occurrence with other gene mutations identified through a next-generation sequencing (NGS) panel in GEA patients. METHODS: A total of 256 patients with metastatic or recurrent GEA who underwent NGS panel profiling at the MD Anderson Cancer Center between 2016 and 2022 were included. Comparative analyses were performed to assess clinical outcomes related to SMARCA4ms. The frequency and types of SMARCA4ms and their co-occurrence with other gene mutations were also examined. RESULTS: SMARCA4ms were identified in 19 patients (7.4%). These SMARCA4ms were significantly associated with non-signet ring cell subtype (p = 0.044) and PD-L1 positive expression (p = 0.046). No difference in survival between the SMARCA4m and SMARCA4-normal group was observed (p = 0.84). There were significant associations between SMARCA4ms and FANCA, IGF1R, KRAS, FANCL, and PTEN alterations. Notably, 15 of the 19 SMARCA4m cases involved SNV missense mutations, with frequent co-occurrences noted with TP53, KRAS, ARID1A, and ERBB2 mutations. CONCLUSIONS: These results serve as the first comprehensive examination of the relationship between SMARCA4ms and clinical outcomes in GEA.

Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas: A Phase I/II Single-Arm Study.

Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24-31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel.

Profile of Notifications of Deaths Due to Acute Myocardial Infarction in the I GERES Municipalities of Pernambuco, 2018-2021 / Perfil das Notificações das Mortes por Infarto Agudo do Miocárdio nos Municípios da I GERES de Pernambuco, 2018-2021

In Brazil and around the world, cardiovascular diseases are responsible for thousands of deaths every year. Among these, those related to ischemic heart disease stand out. From this perspective, to assist in the development of effective and timely health strategies and policies, this study aimed to analyze deaths from Acute Myocardial Infarction (AMI) reported in municipalities belonging to the I Regional Health Management (GERES) of Pernambuco in the years 2018 to 2021. This is a retrospective ecological study, carried out using data from the Mortality Information System. The variables used to describe deaths from AMI were: municipality of coverage, sex, age, color/race, education, marital status and place of death. The results showed a reduction in deaths due to heart attacks in the municipalities and years investigated. The variables studied showed a statistically significant association with the rates of deaths from AMI. The predominant profile of deaths from heart attacks was among residents of the reef, male, mixed race, with one to three years of education, aged 75 and over and married. This study makes important contributions by describing the profile of deaths due to AMI in the I GERES municipalities of Pernambuco and can help guide public health strategies. (AU)

No Brasil e no Mundo, as doenças cardiovasculares são responsáveis por milhares de mortes todos os anos. Entre tais, destacam-se aqueles relacionados à doença isquêmica do coração. Nesta perspectiva, para auxiliar na elaboração de estratégias e políticas de saúde eficazes e oportunas, este estudo teve como objetivo analisar as mortes por Infarto Agudo do Miocárdio notificadas nos municípios pertencentes à I Gerência Regional de Saúde (GERES) de Pernambuco nos anos de 2018 a 2021. Trata-se de um estudo ecológico retrospectivo, realizado através de dados do Sistema de Informação de Mortalidade. A variáveis utilizadas para a descrição das mortes por IAM foram: município de abrangência, sexo, idade, cor/raça, escolaridade, estado civil e local de ocorrência do óbito. Os resultados mostraram redução dos óbitos por Infarto nos municípios e anos investigados. As variáveis estudadas apresentaram associação estatisticamente significativa com as taxas de mortes por IAM. O perfil predominante das mortes por infarto foi entre os residentes do recife, sexo masculino, pardos, escolaridade de um a três anos, com faixa etária de 75 anos e mais e com estado civil casado. Este estudo traz contribuições importantes ao descrever o perfil dos óbitos por IAM nos municípios da I GERES de Pernambuco, podendo auxiliar no direcionamento de estratégias em saúde pública. (AU)