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Abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

Ao observar a configuração atual da área portuária de Santos (São Paulo), mais especificamente do Paquetá e adjacências, o desenho da Avenida Perimetral ganha destaque e se apresenta nitidamente como um elemento central, além do mais óbvio, nas investigações sobre a relação porto/cidade neste município. Porém, a área do Porto Organizado excede o eventual limite físico que representa a Avenida Perimetral, ao abarcar um conjunto de áreas não afetas às operações portuárias imersas sobre a malha urbana da cidade. Condição que exacerba conflitos de usos que a administração municipal tenta remediar via regramento legal que apresenta incentivos e/ou restrições a determinados usos e atividades. O presente artigo propõe observar tal relação dicotômica através da análise de um conjunto de peças técnicas que variam entre legislações, Planos de Desenvolvimento e Zoneamento do Porto de Santos, o atual e seu antecessor, o Plano de Investimentos Mínimos da Ferrovia Interna do Porto de Santos e o documento relativo ao Estudo de Viabilidade Técnica, Econômica e Ambiental, da área recentemente arrendada no Paquetá, o STS 11. Por meio de tais documentos e de leituras desse território foi possível investigar a condição atual e os cenários futuros da relação porto/ cidade, que apontam para a intensificação da fragmentação da área do Porto Organizado e de sua cisão com a cidade, além do avanço das atividades retroportuárias sobre a malha urbana e da dissolução de paisagens.

Abstract The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. “European Registry on H. pylori Management (Hp-EuReg)” data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18–59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p

Background. First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. Materials and methods. Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. Results. Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. Conclusion. Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.

Abstract Lemongrass (Cymbopogon citratus) is an aromatic plant of great significance in industries due to its essential oil characteristic aroma. Essential oils are concentrated plant extracts that evaporate when in contact with air and have low chemical stability, which can improve encapsulation techniques. This study aimed to evaluate the seasonal influence in the concentration of the predominant component citral of the essential oil of C. citratus and develop microparticles by spray drying containing this vegetal matrix. The lemongrass leaves were collected in the four seasons, and the essential oil was extracted by hydrodistillation. The chemical composition was determined by gas chromatography coupled with the mass spectrometry technique (GC-MS). Different proportions of arabic and guar gums were evaluated as encapsulating agents. Physicochemical analyses characterized the microparticle powder. GC-MS showed higher citral in the spring and summer (84.89% and 79.39%, respectively), and it was possible to identify a high amount of citral in the microparticles. Field-emission scanning electron microscopy showed agglomerate and collapsed microparticles. Fourier transform infrared spectroscopy suggested the essential oil encapsulation due to a band at 1675 cm-1 used as a reference, related to the acyclic monoterpenes of citral. X-ray diffraction showed the amorphous structure of the microparticles. Thermogravimetric curves of microparticles showed higher Tonset in microparticles than those observed for pure lemongrass essential oil, inferring that microencapsulation improved the thermal stability. This result confirms the lemongrass essential oil microencapsulation and its potential application in food products, drugs, or cosmetics.

A legislação educacional brasileira, na atualidade, determina o atendimento das pessoas com deficiência, incluindo autistas, em classes comuns do ensino regular, oportunizando aos arquitetos refletirem sobre as necessidades espaciais desses usuários, as quais, ao incorporarem estratégias pedagógicas inclusivas, apresentam novas demandas ao processo de projeto. Desta forma, este artigo tem o objetivo de trazer contribuições sobre a importância do espaço físico em edifícios escolares no processo de ensino-aprendizagem de estudantes autistas, por meio da apresentação de resultados de pesquisa sobre o tema. Para tanto, é apresentada uma revisão bibliográfica e documental de marcos legais da educação especial e da educação inclusiva, com foco nas pessoas com deficiência, sobretudo autistas, seguida por uma problematização de bases conceituais que fundamentam essa temática, assim como do processo de elaboração de programas de necessidades arquitetônicos, alinhando-o ao compromisso com a cidadania e a dimensão ético-política. Espera-se com essa pesquisa contribuir para ações comprometidas com nossas responsabilidades como cidadãos e mais especificamente para a construção de parâmetros projetuais que favoreçam o ingresso e a permanência com qualidade de pessoas autistas no ensino regular.

The case shows the difficulties faced by a social business to become financially viable. Talita Peixoto is an African-Brazilian woman enterprising for the first time. Together with her husband, she created Clubinho Preto, a Brazilian subscription club for children that delivered boxes with books, clothing, and accessories to educate children in a positive Afrocentric culture. After two years, they are struggling financially. Looking for alternatives, Talita planned to expand her business by adding schools as clients. Her business partners opposed the idea, believing that not every manager would truly commit to the racial cause. Talita needed the money, but not at any cost. How can she transform her purpose into a product? To answer this question, it is necessary to align purpose, value creation, and a business model. This case can be taught in executive training programs and undergraduate classes on marketing and consumer behavior, social entrepreneurship, and business purposes. We invite teachers and students to include the discussion on diversity, equity, and inclusion in all these disciplines.

Resumo Este estudo investiga o percurso das transformações da violência presente na relação homem-animal, em múltiplos períodos do tempo, recorrendo a expressões artísticas, de forma a trazer contribuições para esta temática. O estudo utiliza uma abordagem multidisciplinar dos campos das Artes, História e Filosofia buscando contribuições à literatura de marketing e comportamento do consumidor. A análise crítica visual é a metodologia utilizada na análise de seis obras de artes de diferentes períodos históricos e compreensão da relação homem-animal no tempo. Os achados sugerem formas de violência que estão presentes nessa relação e se transformam. A pesquisa desafia o domínio da discussão sobre a relação homem-animal no campo do marketing, circunscrita a experiências positivas com animais de companhia; traz interpretações dos caminhos da violência na relação homem-animal ao longo do tempo para melhor compreender significados e práticas do presente; adiciona elementos visando discussões e reflexões, necessárias a pesquisadores e profissionais de marketing, sobre a relação homem-animal e violência.

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the “most important” variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013–2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin–clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth–quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin–amoxicillin–metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Serrated polyposis syndrome (SPS) is one of the most frequent polyposis syndromes characterized by an increased risk for developing colorectal cancer (CRC). Although SPS etiology has been mainly associated with environmental factors, germline predisposition to SPS could also be relevant for cases with familial aggregation or a family history of SPS/CRC. After whole-exome sequencing of 39 SPS patients from 16 families, we identified a heterozygous germline frameshift variant in the POLD1 gene (c.1941delG, p.(Lys648fs*46)) in a patient with SPS and CRC. Tumor presented an ultra-hypermutated phenotype and microsatellite instability. The POLD1 germline variant segregated in three additional SPS-affected family members. We attempted to create yeast and cellular models for this variant but were no viable. Alternatively, we generated patient-derived organoids (PDOs) from healthy rectal tissue of the index case, as well as from a control donor. Then, we challenged PDOs with a DNA-damaging agent to induce replication stress. No significant differences were observed in the DNA damage response between control and POLD1-Lys648fs PDOs, nor specific mutational signatures were observed. Our results do not support the pathogenicity of the analyzed POLD1 frameshift variant. One possible explanation is that haplosufficiency of the wild-type allele may be compensating for the absence of expression of the frameshift allele. Overall, future work is required to elucidate if functional consequences could be derived from POLD1 alterations different from missense variants in their proofreading domain. To our knowledge, our study presents the first organoid model for germline POLD1 variants and establishes the basis for its use as a model for disease in SPS, CRC and other malignancies.

Background and study aims Artificial intelligence is currently able to accurately predict the histology of colorectal polyps. However, systems developed to date use complex optical technologies and have not been tested in vivo. The objective of this study was to evaluate the efficacy of a new deep learning-based optical diagnosis system, ATENEA, in a real clinical setting using only high-definition white light endoscopy (WLE) and to compare its performance with endoscopists. Methods ATENEA was prospectively tested in real life on consecutive polyps detected in colorectal cancer screening colonoscopies at Hospital Clínic. No images were discarded, and only WLE was used. The in vivo ATENEA’s prediction (adenoma vs non-adenoma) was compared with the prediction of four staff endoscopists without specific training in optical diagnosis for the study purposes. Endoscopists were blind to the ATENEA output. Histology was the gold standard. Results Ninety polyps (median size: 5 mm, range: 2–25) from 31 patients were included of which 69 (76.7 %) were adenomas. ATENEA correctly predicted the histology in 63 of 69 (91.3 %, 95 % CI: 82 %–97 %) adenomas and 12 of 21 (57.1 %, 95 % CI: 34 %–78 %) non-adenomas while endoscopists made correct predictions in 52 of 69 (75.4 %, 95 % CI: 60 %–85 %) and 20 of 21 (95.2 %, 95 % CI: 76 %–100 %), respectively. The global accuracy was 83.3 % (95 % CI: 74%–90 %) and 80 % (95 % CI: 70 %–88 %) for ATENEA and endoscopists, respectively. Conclusion ATENEA can accurately be used for in vivo characterization of colorectal polyps, enabling the endoscopist to make direct decisions. ATENEA showed a global accuracy similar to that of endoscopists despite an unsatisfactory performance for non-adenomatous lesions.

Gastric cancer (GC) is a major public health problem worldwide, with high mortality rates due to late diagnosis and limited treatment options. Biomarker research is essential to improve the early detection of GC. Technological advances and research methodologies have improved diagnostic tools, identifying several potential biomarkers for GC, including microRNA, DNA methylation markers, and protein-based biomarkers. Although most studies have focused on identifying biomarkers in biofluids, the low specificity of these markers has limited their use in clinical practice. This is because many cancers share similar alterations and biomarkers, so obtaining them from the site of disease origin could yield more specific results. As a result, recent research efforts have shifted towards exploring gastric juice (GJ) as an alternative source for biomarker identification. Since GJ is a waste product during a gastroscopic examination, it could provide a “liquid biopsy” enriched with disease-specific biomarkers generated directly at the damaged site. Furthermore, as it contains secretions from the stomach lining, it could reflect changes associated with the developmental stage of GC. This narrative review describes some potential biomarkers for gastric cancer screening identified in gastric juice.

This work analyzes an index of thermal comfort adaptable to the summer period in the city of Pelotas - RS. Daily data for 9h, 15h, and 21h (local time) of meteorological variables (air temperature and relative humidity) were used, from 1985 to 2015, obtained byAgroclimatological Station of Embrapa (Brazilian Company of Agricultural Research). In order to represent daily thermal comfort, twobiometeorological indexes were analyzed: Heat Index (HI) and Humidex Index (HU), during the mornings, afternoons and evenings. The results showed that the Humidex Index presented, on most days, heat stress, mainly in January, considering all periods of the day(mornings, afternoons and nights), while the Heat Index presented, the condition of thermal stress only in the afternoon.

Pancreatic ductal adenocarcinoma is one of the most aggressive forms of cancer, and the third leading cause of cancer-related mortality in the United States. Although important advances have been made in the last decade, the mortality rate of pancreatic ductal adenocarcinoma has not changed appreciably. This review summarizes a rapidly emerging model of pancreatic cancer research, focusing on 3-dimensional organoids as a powerful tool for several applications, but above all, representing a step toward personalized medicine.

Gastric cancer is one of the most common cancers worldwide, with a bad prognosis associated with late-stage diagnosis, significantly decreasing the overall survival. This highlights the importance of early detection to improve the clinical course of these patients. Although screening programs, based on endoscopic or radiologic approaches, have been useful in countries with high incidence, they are not cost-effective in low-incidence populations as a massive screening strategy. Additionally, current biomarkers used in daily routine are not specific and sensitive enough, and most of them are obtained invasively. Thus, it is imperative to discover new noninvasive biomarkers able to diagnose early-stage gastric cancer. In this context, liquid biopsy is a promising strategy. In this review, we briefly discuss some of the potential biomarkers for gastric cancer screening and diagnosis identified in blood, saliva, urine, stool, and gastric juice.