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Global agricultural production must double by 2050 to meet the demands of an increasing world human population but this challenge is further exacerbated by climate change. Environmental stress, heat, and drought are key drivers in food security and strongly impacts on crop productivity. Moreover, global warming is threatening the survival of many species including those which we rely on for food production, forcing migration of cultivation areas with further impoverishing of the environment and of the genetic variability of crop species with fall out effects on food security. This review considers the relationship of climatic changes and their bearing on sustainability of natural and agricultural ecosystems, as well as the role of omics-technologies, genomics, proteomics, metabolomics, phenomics and ionomics. The use of resource saving technologies such as precision agriculture and new fertilization technologies are discussed with a focus on their use in breeding plants with higher tolerance and adaptability and as mitigation tools for global warming and climate changes. Nevertheless, plants are exposed to multiple stresses. This study lays the basis for the proposition of a novel research paradigm which is referred to a holistic approach and that went beyond the exclusive concept of crop yield, but that included sustainability, socio-economic impacts of production, commercialization, and agroecosystem management.

Objetivo: avaliar o efeito da intervenção educativa no conhecimento da equipe de enfermagem sobre o suporte básico de vida para o atendimento à parada cardiorrespiratória de adultos no ambiente intra-hospitalar. Método: estudo transversal com abordagem quantitativa, realizado com 25 profissionais de enfermagem em dois hospitais de região oeste de Santa Catarina - Brasil. Avaliou-se por meio da aplicação de um pré-teste, intervenção educativa e pós-teste. Resultados: houve aumento significativo no conhecimento dos profissionais. O hospital A obteve a média de acertos de 7,23 no pré-teste, elevando para 11,33 no pós-teste, com valor de p ≤ 0,0001. Já o hospital B pontuou 6,07 no pré-teste, progredindo para 11,15 no pós-teste, valor de p ≤ 0,0006. Conclusão: a intervenção realizada demonstrou ser uma estratégia eficaz, visto que os resultados pré-teste demostravam déficit significativo de conhecimento, e após a intervenção educativa, mostraram melhoria na maioria dos itens avaliados em relação ao atendimento específico.

Este artigo tem por objetivo descrever e analisar as interações de um grupo de estudantes do Ensino Fundamental com applets do GeoGebra, desenvolvidos a partir de uma proposta de construção de conceitos de Matemática através da exploração de fractais. A pesquisa considera a necessidade de desenvolver uma compreensão detalhada dos percursos cognitivos e das diversas possibilidades que surgem com a utilização de recursos digitais amplamente acessíveis na atu-alidade. O referencial teórico aborda a abstração reflexionante de Jean Piaget, além de estudos sobre as potencialidades dos ambientes de geometria dinâmica e dos fractais na construção de conceitos matemáticos. A metodologia contempla uma abordagem qualitativa, com dados coletados por meio de atividades no GeoGebra, vídeos dos encontros com os participantes, notas de campo e protocolos de observação, com intervenções inspiradas no método clínico de Jean Piaget. Os resultados enfatizam a importância de uma análise detalhada das interações dos estudantes com os applets, suas estratégias e como demonstram progressos con-ceituais ao longo do processo, observadas sob diferentes perspectivas. As elaborações dos estudantes em resposta a atividades significativas e desafiadoras evi-denciam as implicações do processo de abstração reflexionante e suas contribuições no que se refere aos avanços na construção de conceitos relacionados às prin-cipais características dos fractais.

Work and intellectually fatiguing environments can significantly influence the health of individuals, which is strictly bound to motor efficiency. In particular, desk workers and university students may have a sedentary lifestyle and a condition of mental fatigue caused by daily routine, which could impair motor efficiency. The assessment is a starting point for enhancing awareness of the individual’s psychophysical condition through the perception of one’s body motor efficiency, motivating to move towards improvement. This way, a submaximal test based on perceived exertion was developed (Cubo Fitness Test, CFT) and validated in previous studies. Hence, two further studies were employed to enhance the consistency and accuracy of this instrument in different conditions. The first study investigated the internal responsiveness of CFT, evaluating if mental fatigue could affect motor efficiency. The second study investigated which perceived intensity (weak, moderate, strong, or absolute maximum) could be more reliable for applying the CFT (as previous research focused the investigation only on moderate intensity). In the first investigation, participants assessed two stimuli (mental fatigue induced with a Stroop color-word task and a neutral condition based on the vision of a documentary) lasting 60 min each. The quality of psychophysical recovery (total quality recovery) and the mood state (Italian Mood State questionnaire) were evaluated before the stimuli. After the fatiguing or the neutral task, the mood state was newly assessed, together with the evaluation of the workload’s characteristics (Nasa TLX) and the CFT motor efficiency. In the second investigation, participants had to perform CFT twice for each at different intensities of Borg’s Scale of perceived exertion. Researchers successfully requested to fill out the NASA TLX questionnaire regarding the perceived workload characteristics of CFT, and the reliability of each intensity was assessed. Results seem to enhance the consistency and the accuracy of the instrument. Indeed, findings evidenced that CFT is not influenced by mental fatigue conditions typical of the intellectual work of desk workers and university students for which this test was specifically conceived. Moreover, moderate and strong perceived intensity are the most adequate conditions to assess motor efficiency in these populations.

ABSTRACT Objective: To assess mothers’ knowledge on sun exposure related to serum vitamin D levels in the neonatal period. Methods: Observational, analytical and cross-sectional study, carried out from August 2020 to May 2021 through a questionnaire directed to mothers of newborns, in a maternity hospital in Southern Brazil. Results: From 141 interviewees, 132 (93.6%) believe it is important to expose the neonate to sun, 101 (71.6%) think this exposure can increase vitamin D levels, 86 (61%) received such information from a doctor, 108 (76.6%) believe there are no risks of sun exposure, 88 (62.4%) claim it isn´t necessary to use any kind of protection, 96 (68.1%) said that only exposure to the sun was necessary to maintain adequate levels of vitamin D during the neonatal period. Only two mothers (1.4%) claim that you should not exposure the neonate to the sun, and only one (0.7%) stated that sun expose can cause skin problems. Conclusions: Most mothers lack satisfactory knowledge about sun exposure related to serum vitamin D levels in the neonatal period. The need to inform and clarify the population about sun exposure during this period is remarkable, in addition to disseminating the proper way to maintain serum levels of vitamin D.

The preparation of bridged bicyclooctadienes through the dearomatization of simple arenes is an interesting synthetic tool to access a vast chemical space of elegant molecular architectures from a wide range of simple and cheap building blocks. However, the energetic toll due to the loss of the aromatic stabilization has greatly limited the development of para-cycloadditions, especially with respect to intermolecular processes. We report herein the first general approach for the selective dearomatization of simple naphthalene. The visible-light-promoted reaction occurs under mild conditions over an ample range of substrates and it involves the initial sensitization of an acylallenamide. Moreover, complete control on the difunctionalization of either the internal or the terminal C–C double bond is observed depending on the substrate functionalization.

Justificativa e Objetivos: no decorrer dos atendimentos aos usuários acometidos pela COVID-19, observaram-se sinais e sintomas persistentes ou o desenvolvimento de sintomas tardios, denominados de condições pós-COVID. Dessa forma, torna-se necessário promover práticas de Educação Permanente em Saúde para o atendimento das condições pós-COVID. Com isso, o objetivo do estudo é construir um manual para auxiliar profissionais de saúde da Atenção Primária à Saúde (APS) no manejo das condições pós-COVID. Métodos: adotou-se, para a construção do manual, o método proposto por Echer, que prevê seis etapas para a estruturação de um manual. Ademais, o presente estudo utilizou somente cinco delas, sendo que a sexta etapa consiste na validação do manual. Além disso, estabeleceram-se os seguintes eixos norteadores: objetividade, formulação autoexplicativa, abordagem pedagógica problematizadora inspirada em Bordenave e Pereira e na Política Nacional de Educação Permanente em Saúde. Resultados: o estudo resultou na construção de um manual que compreende 25 condições pós-COVID, apresentadas de forma didática, com seleção de conteúdo e ajuste da linguagem considerando o público-alvo, com ilustrações e fluxogramas facilitadores na condução da linha de raciocínio clinico, bem como a inclusão de casos clínicos visando à aproximação com a pratica clínica. Conclusão: a construção do manual possibilita que o profissional ofereça ao usuário acometido uma assistência de qualidade e resolutiva, minimizando os danos na qualidade de vida do mesmo. Ademais, espera-se que o manual alcance uma ampla divulgação nos mais distintos espaços de saúde, fornecendo subsídios aos profissionais de saúde.

Abstract The current study focuses on the investigation of AVPR2 (VTR2C) protein-coupled receptor variants specific to different primate taxa. AVPR2 is activated by the neurohormone AVP, which modulates physiological processes, including water homeostasis. Our findings reveal positive selection at three AVPR2 sites at positions 190, 250, and 346. Variation at position 250 is associated with human Congenital Nephrogenic Diabetes Insipidus (cNDI), a condition characterized by excessive water loss. Other 13 functional sites with potential adaptive relevance include positions 185, 202, 204, and 252 associated with cNDI. We identified SH3-binding motifs in AVPR2’s ICL3 and N-terminus domains, with some losses observed in clades of Cercopithecidae, Callitrichinae, and Atelidae. SH3-binding motifs are crucial in regulating cellular physiology, indicating that the differences may be adaptive. Co-evolution was found between AVPR2 residues and those in the AVP signal peptide/Neurophysin-2 and AQP2, other molecules in the same signaling cascade. No significant correlation was found between these Primates’ taxon-specific variants and the bioclimatic variables of the areas where they live. Distinct co-evolving amino acid sequences in functional sites were found in Platyrrhini and Catarrhini, which may have adaptive implications involving glucocorticoid hormones, suggesting varied selective pressures. Further studies are required to confirm these results.

Abstract The relationship between chromosomal and morphological variation in mammals is poorly understood. We analyzed the cranial size and shape variation in Ctenomys lami concerning to the geographic variation in their chromosome numbers. This subterranean rodent occurs in a narrow range of sand-dunes in the Coastal Plain of southern Brazil. This species presents a high karyotypic variation with diploid numbers varying from 2n = 54 to 2n = 58, involving the fission and fusion of chromosome pairs 1 and 2. Due to different chromosome rearrangement frequencies along their geographic distribution, four karyotypic blocks were proposed. This study, explored cranium shape and size variation in geographical, chromosomal polymorphism, and chromosome rearrangements contexts to test whether the four karyotypic blocks reflect morphologically distinct units. For this, we measured 89 craniums using geometric morphometrics and used uni and multivariate statistics to discriminate the predicted groups and test for an association among chromosomal and morphological variation. Our results show the size and shape of sexual dimorphism, with males larger than females, and support the existence of four karyotypic blocks for Ctenomys lami based on morphological variation. However, our results do not support a direct relationship between chromosomal and cranial morphological variation in C. lami.

El presente artículo expone los resultados preliminares del relevamiento realizado en el marco del proyecto "Movimentos socioterritoriais em perspectiva comparativa" (UNESP, Brasil, 2019-2022), implementado en distintas universidades de América Latina, cuyo objetivo es el estudio y la comparación de los movimientos socioespaciales y socioterritoriales a partir del análisis de sus acciones colectivas. Lxs autorxs de este trabajo pertenecemos a la Universidad Nacional de La Plata, y la información a presentar se encuadra en contextos urbanos de la Argentina durante el año 2021. A partir de su relevamiento se construye una matriz de información, en la que se organizan y clasifican bajo distintos criterios de agregación los datos obtenidos. Con los resultados preliminares de dicha base, realizamos un recorte teórico que permitió enfocarnos en aquellas acciones colectivas vinculadas a la lucha por la vivienda y el hábitat en diferentes regiones del país, a partir de las cuales se realizaron mapas y gráficos que dan cuenta de la distribución de dicha conflictividad. A su vez, nos propusimos identificar dentro de este entramado aquellas estrategias que responden a formas mercantilizadas y desmercantilizadas de producción del hábitat, formas que creemos que conviven y entran en tensión al interior del repertorio de acción al que nos referimos. Presentaremos el análisis de dos casos que, creemos, pueden ayudarnos a echar luz sobre estas tensiones, para finalizar con algunas conclusiones en torno a los resultados obtenidos del análisis de las acciones relevadas, en combinación con reflexiones teóricas del cuerpo de autores elegido.

ObjectivesTo approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.DesignRetrospective cohort study.SettingClinics across North America.ParticipantsThe study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.MethodsPhenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.ResultsAmong 1032 patients, 58 (5.6%) reported a family history of myasthenia gravis. A history of autoimmune diseases was present in 26.6% of patients and in 28.4% of their family members.DiscussionThe familial rate of myasthenia gravis was higher than would be expected for a sporadic disease. Furthermore, a high proportion of patients had a personal or family history of autoimmune disease. Taken together, these findings suggest a genetic contribution to the pathogenesis of myasthenia gravis.

Selected case studies of precipitating ice clouds at Dome C (Antarctic Plateau) were used to test a new approach for the estimation of ice cloud reflectivity at 24 GHz (12.37 mm wavelength) using ground-based far infrared spectral measurements from the REFIR-PAD Fourier transform spectroradiometer and backscattering/depolarization lidar profiles. The resulting reflectivity was evaluated with the direct reflectivity measurements provided by a co-located micro rain radar (MRR) operating at 24 GHz, that was able to detect falling crystals with large particle size, typically above 600 µm. To obtain the 24 GHz reflectivity, we used the particle effective diameter and the cloud optical depth retrieved from the far infrared spectral radiances provided by REFIR-PAD and the tropospheric co-located backscattering lidar to calculate the modal radius and the intercept of the particle size distribution. These parameters spanned in the wide ranges between 570–2400 µm and 10−2–104 cm−5, respectively. The retrieved effective sizes and optical depths mostly varied in the ranges 70–250 µm and 0.1–5, respectively. From these parameters, the theoretical reflectivity at 24 GHz was obtained by integrating the size distribution over different cross sections for various habit crystals provided by Eriksson et al. (2018) databases. From the comparison with the radar reflectivity measurements, we found that the hexagonal column-like habits, the columnar crystal aggregates, and the 5/6 branches bullet rosettes showed the best agreement with the MRR observations. The dispersion coefficient of the crystal particle size distribution was assumed in the range 0–2 according to the temperature dependence found in previous studies. The retrieved values of the intercept and slope were found in good agreement with these studies. The presence of the inferred habits was confirmed by the crystal images taken by the ICE-CAMERA, operating in proximity of REFIR-PAD and the MRR. In particular, the occurrence of hexagonal column-like ice crystals was confirmed by the presence of 22∘ solar halos, detected by the HALO-CAMERA. The average crystal lengths obtained from the retrieved size distribution were also compared to those estimated from the ICE-CAMERA images. The agreement between the two results confirmed that the retrieved parameters of the particle size distributions correctly reproduced the observations.

Key Clinical Message Concurrent polycystic liver disease and echinococcus infection can hinder diagnosis. Surgery may be needed for accurate diagnosis and treatment. Multidisciplinary collaboration is crucial. Abstract Cystic echinococcosis, caused by Echinococcus granulosus eggs, is a parasitic zoonosis that typically affects humans through accidental ingestion. Polycystic liver disease is a condition characterized by the presence of multiple liver cysts and is often associated with polycystic kidney disease. Here, we present a case of a man in his 70s with a pre‐existing diagnosis of polycystic liver disease. Radiological findings of a suspicious cyst in the S4 segment initially lacked serological evidence of echinococcosis; however, intraoperative confirmation revealed the presence of an echinococcal cyst. This article aims to explore both clinical conditions and highlight the therapeutic considerations for their management. Moreover, we discuss the significance of this unique case, emphasizing the possibility of the coexistence of these two pathologies.

Classical singers train intensively for many years to achieve a high level of vocal control and specific sound characteristics. However, the actual span of singers’ activities often includes venues other than opera halls and requires performing in styles outside their strict training (e.g., singing pop songs at weddings). We examine classical singers’ ability to adjust their vocal productions to other styles, in relation with their formal training. Twenty-two highly trained female classical singers (aged from 22 to 45 years old; vocal training ranging from 4.5 to 27 years) performed six different melody excerpts a cappella in contrasting ways: as an opera aria, as a pop song and as a lullaby. All melodies were sung both with lyrics and with a /lu/ sound. All productions were acoustically analyzed in terms of seven common acoustic descriptors of voice/singing performances and perceptually evaluated by a total of 50 lay listeners (aged from 21 to 73 years old) who were asked to identify the intended singing style in a forced-choice lab experiment. Acoustic analyses of the 792 performances suggest distinct acoustic profiles, implying that singers were able to produce contrasting sounding performances. Furthermore, the high overall style recognition rate (78.5% Correct Responses, hence CR) confirmed singers’ proficiency in performing in operatic style (86% CR) and their versatility when it comes to lullaby (80% CR) and pop performances (69% CR), albeit with occasional confusion between the latter two. Interestingly, different levels of competence among singers appeared, with versatility (as estimated based on correct recognition in pop/lullaby styles) ranging from 62 to 83% depending on the singer. Importantly, this variability was not linked to formal training per se. Our results indicate that classical singers are versatile, and prompt the need for further investigations to clarify the role of singers’ broader professional and personal experiences in the development of this valuable ability.

As queimaduras são traumas de importante relevância, não somente pela frequência com que ocorrem, mas, sobretudo pela capacidade de provocar sequelas, prolongar o tempo de internação e impactar negativamente na qualidade de vida. A terapia de fotobiomodulação é um tratamento promissor para auxiliar na cicatrização de feridas agudas ou crônicas, estimulando a microcirculação, reduzindo a inflamação, edema, dor e a carga bacteriana, com consequente redução dos custos relacionados às coberturas, antibióticos e tempo de internação. Mapear as evidências disponíveis a respeito da fotobiomodulação no processo de cicatrização de queimaduras: uma revisão integrativa. Revisão integrativa de literatura, descrita por Whittemore e Knafl. Após acesso às bases de dados e aplicação dos critérios de inclusão e exclusão, foram selecionados 07 artigos, publicados entre 2013 e 2023. A partir da análise dos artigos, emergiram três categorias: Aumento da proliferação celular, organização das fibras de colágeno, neoangiogênese e diminuição da inflamação mediadas pela fotobiomodulação; fotobiomodulação na redução da carga bacteriana em feridas por queimaduras infectadas; e associação de terapias na cicatrização de queimaduras. Conclui-se que a fotobiomodulação oferece uma abordagem não invasiva e promissora no tratamento de queimaduras, acelerando a cicatrização, reduzindo a inflamação e melhorando a aparência estética. Com mais pesquisas e avanços tecnológicos, espera-se que essa terapia se torne cada vez mais eficaz e amplamente utilizada no cuidado de pacientes com queimaduras.

ABSTRACT Epstein-Barr virus (EBV) is associated with 10% of human gastric carcinomas, which are distinguished by a CpG island methylator phenotype. In gastric carcinoma tumors and cell lines, the EBV genome also exhibits a high degree of 5-methyl cytosine (5mC) marks, which are propagated by host DNA methyltransferases (DNMT) with each cell cycle. Therefore, we sought to determine the effect of DNMT inhibition by the small molecule Decitabine (DCB) on EBV genomic 5mC and chromatin structure in two tumor-derived gastric cancer cell lines, YCCEL1 and SNU719. Decitabine effects on EBV genomic 5mC, chromatin structure, and viral gene expression were profiled by reduced representation bisulfite sequencing, ATAC-seq, and RNA-seq, respectively. Decitabine treatment resulted in global viral genome hypomethylation and a global increase in open chromatin. The most striking finding resulted from analyzing the methylation pattern from single RRBS sequencing reads, showing that the EBV genome contains a heterogeneous pool of epigenetic states, each of which is eroded upon Decitabine treatment. We observed heterogeneous 5mC epiallele patterns around EBV genomic CTCF binding sites and lytic gene transcriptional start sites. These results highlight the importance of 5mC in maintaining EBV genomic chromatin structure and latency. Furthermore, the presence of 5mC epialleles suggests EBV+ gastric cancers harbor transcriptionally distinct EBV episomes, which may exert distinct functional roles in maintaining latency and driving tumorigenesis. IMPORTANCE Epstein-Barr virus (EBV) latency is controlled by epigenetic silencing by DNA methylation [5-methyl cytosine (5mC)], histone modifications, and chromatin looping. However, how they dictate the transcriptional program in EBV-associated gastric cancers remains incompletely understood. EBV-associated gastric cancer displays a 5mC hypermethylated phenotype. A potential treatment for this cancer subtype is the DNA hypomethylating agent, which induces EBV lytic reactivation and targets hypermethylation of the cellular DNA. In this study, we identified a heterogeneous pool of EBV epialleles within two tumor-derived gastric cancer cell lines that are disrupted with a hypomethylating agent. Stochastic DNA methylation patterning at critical regulatory regions may be an underlying mechanism for spontaneous reactivation. Our results highlight the critical role of epigenetic modulation on EBV latency and life cycle, which is maintained through the interaction between 5mC and the host protein CCCTC-binding factor.

PurposeProne cross-table lateral x-ray (CTLxR) and colostogram aid surgical planning for anorectal malformations (ARMs) without perineal fistulas. We suggest objective imaging tools to classify ARMs.MethodsThree observers prospectively evaluated CTLxR and colostograms of male ARM patients (2012–2022) without perineal fistulas. The level of the rectal pouch was estimated with pubococcygeal (PC) and ischiatic (I) lines. On CTLxR, we described the “pigeon sign”, defined as the rectal pouch ending with a beak-like image, suspicious for a rectourinary fistula. ARM was defined as rectobulbar when the rectal pouch was below the I line, rectoprostatic when between PC and I lines, and rectovesical when above the PC line. Concordance was assessed with Fleiss' kappa. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the “pigeon sign” were calculated.ResultsThirteen patients were included in this study. The interobserver agreement on CTLxR was 69.2% (k = 0.54) on pouch ending, 84.6% (k = 0.69) on the “pigeon sign”, and 76.9% (k = 0.69) on diagnosis; concordance between observers and intraoperative diagnosis was 66.6% (k = 0.56). The “pigeon sign” had 75% sensitivity, 100% specificity, 100% PPV, and 50% NPV. The interobserver agreement on colostograms was 84.6% (k = 0.77) on pouch ending and 89.7% (k = 0.86) on diagnosis; concordance between observers and intraoperative diagnosis was 92.3% (k = 0.90).ConclusionPC and I lines and the “pigeon sign” are useful tools in examining CTLxR and colostograms. Adequate CTLxR interpretation may modify surgical strategy.

ObjectiveDementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission.Materials and methodsSixty-five demented patients (Alzheimer’s disease, AD, n = 44; frontotemporal disease, FTD, n = 13; vascular disease, VaD, n = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants.ResultsDemented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) (p = 0.03 to

BackgroundThymic epithelial tumors are rare malignant neoplasms that are frequently associated with paraneoplastic syndromes, especially myasthenia gravis. GTF2I is an oncogene mutated in a subgroup of thymomas that is reputed to drive their growth. However, for GTF2I wild-type tumors, the relevant mutations remain to be identified.MethodsWe performed a meta-analysis and identified 4,208 mutations in 339 patients. We defined a panel of 63 genes frequently mutated in thymic epithelial tumors, which we used to design a custom assay for next-generation sequencing. We sequenced tumor DNA from 67 thymomas of patients with myasthenia gravis who underwent resection in our institution.ResultsAmong the 67 thymomas, there were 238 mutations, 83 of which were in coding sequences. There were 14 GTF2I mutations in 6 A, 5 AB, 2 B2 thymomas, and one in a thymoma with unspecified histology. No other oncogenes showed recurrent mutations, while sixteen tumor suppressor genes were predicted to be inactivated. Even with a dedicated assay for the identification of specific somatic mutations in thymic epithelial tumors, only GTF2I mutations were found to be significantly recurrent.ConclusionOur evaluation provides insights into the mutational landscape of thymic epithelial tumors, identifies recurrent mutations in different histotypes, and describes the design and implementation of a custom panel for targeted resequencing. These findings contribute to a better understanding of the genetic basis of thymic epithelial tumors and may have implications for future research and treatment strategies.

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP’s prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child–Pugh class B–C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child–Pugh class B–C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.