A Case of Success: Complete Response to Radium-223 in Metastatic Castration-Resistant Prostate Cancer.

Radium-223 dichloride (Ra223) is the first targeted alpha agent approved for treating metastatic castration-resistant prostate cancer (mCRPC) with bone-exclusive disease. A benefit in overall survival and time to the first symptomatic skeletal-related event was shown in the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. However, this trial did not describe a bone scan response to Ra223, and there is no universal consensus about how it should be monitored. Furthermore, a scintigraphy flare phenomenon may lead to false-positive tracer uptake in responsive cases, thereby misleading the interpretation of imaging results.  We present the case of a 67-year-old male with mCRPC and exclusive bone disease treated with Ra223. The bone scintigraphy after the end of the treatment showed an apparent aggravation of the lesions, corresponding to a flare phenomenon, with an almost complete resolution after three months. The patient maintained a scintigraphic response for seven months.

The challenging approach of a young patient with a primary intimal sarcoma of the heart: a case report.

Background: Primary intimal sarcomas of the heart are extremely rare and have a dismal prognosis. Their management represents a complex clinical challenge since complete surgical resection is the only reliable possibility of cure but is only possible in 50% of patients. In non-resectable disease, anthracycline-based therapy is the most effective treatment, but pazopanib may be used in patients unfit to receive anthracyclines. Case summary: A 38-year-old man presented with acute right heart failure symptoms due to a primary intimal sarcoma of the heart. A definite diagnosis was made after cardiac surgery. Multi-modality cardiac imaging showed early recurrence of disease with mitral valve and pulmonary veins' invasion, and the patient was deemed inoperable. Due to chronic kidney disease and previous heart failure symptoms, he was started on first-line pazopanib palliative treatment. After 11 months of chemotherapy, there was good clinical tolerance and no evidence of disease progression, which occurred after 13 months. Discussion: This case highlights the value of a multi-modality imaging approach for cardiac masses. Most importantly, it reports the successful treatment of a young patient with a primary intimal sarcoma of the heart who was started on palliative pazopanib, with a significantly higher progression-free survival than is reported in the literature. This finding may support pazopanib as a good alternative as first-line treatment when there is contraindication for anthracycline-based chemotherapy.

Exploring Caenorhabditis elegans as Parkinson's Disease Model: Neurotoxins and Genetic Implications.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, the first being Alzheimer's disease. Patients with PD have a loss of dopaminergic neurons in the substantia nigra of the basal ganglia, which controls voluntary movements, causing a motor impairment as a result of dopaminergic signaling impairment. Studies have shown that mutations in several genes, such as SNCA, PARK2, PINK1, DJ-1, ATP13A2, and LRRK2, and the exposure to neurotoxic agents can potentially increase the chances of PD development. The nematode Caenorhabditis elegans (C. elegans) plays an important role in studying the risk factors, such as genetic factors, aging, exposure to chemicals, disease progression, and drug treatments for PD. C. elegans has a conserved neurotransmission system during evolution; it produces dopamine, through the eight dopaminergic neurons; it can be used to study the effect of neurotoxins and also has strains that express human α-synuclein. Furthermore, the human PD-related genes, LRK-1, PINK-1, PDR-1, DJR-1.1, and CATP-6, are present and functional in this model. Therefore, this review focuses on highlighting and discussing the use of C. elegans an in vivo model in PD-related studies. Here, we identified that nematodes exposed to the neurotoxins, such as 6-OHDA, MPTP, paraquat, and rotenone, had a progressive loss of dopaminergic neurons, dopamine deficits, and decreased survival rate. Several studies have reported that expression of human LRRK2 (G2019S) caused neurodegeneration and pink-1, pdr-1, and djr-1.1 deletion caused several effects PD-related in C. elegans, including mitochondrial dysfunctions. Of note, the deletion of catp-6 in nematodes caused behavioral dysfunction, mitochondrial damage, and reduced survival. In addition, nematodes expressing α-synuclein had neurodegeneration and dopamine-dependent deficits. Therefore, C. elegans can be considered an accurate animal model of PD that can be used to elucidate to assess the underlying mechanisms implicated in PD to find novel therapeutic targets.

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer: A case report.

BACKGROUND: In patients with metastatic colorectal cancer (mCRC), the treatment options are limited and have been proved to be affected by rat sarcoma virus (RAS) mutational status. In RAS wild-type (wt) patients, the combination of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with chemotherapy (CT) is more effective than CT alone. On the other hand, RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies. CASE SUMMARY: Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022. At the time of cell-free DNA determination, five patients had undergone one CT line, five patients had undergone two CT lines, and one patient had undergone three CT lines (all in combination with bevacizumab). At the second and third treatment lines [second line (2L), third line (3L)], patients with neo-RAS wt received a combination of CT and cetuximab. In neo-RAS wt patients treated with anti-EGFR, our findings indicated an increase in progression-free survival for both 2L and 3L (14.5 mo, P = 0.119 and 3.9 mo, P = 0.882, respectively). Regarding 2L overall survival, we registered a slight increase in neo-RAS wt patients treated with anti-EGFR (33.6 mo vs 32.4 mo, P = 0.385). At data cut-off, two patients were still alive: A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR (ongoing). CONCLUSION: Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Prognostic value of flow-status in severe aortic stenosis patients undergoing percutaneous intervention.

PURPOSE: Low-flow status is a mortality predictor in severe aortic stenosis (SAS) patients, including after transcatheter aortic valve implantation (TAVI) treatment. However, the best parameter to assess flow is unknown. Recent studies suggest that transaortic flow rate (FR) is superior to currently used stroke volume index (SVi) in defining low-flow states. Therefore, we aimed to evaluate the prognostic value of FR and SVi in patients undergoing TAVI. METHODS: A single-centre retrospective analysis of all consecutive patients treated with TAVI for SAS between 2011 and 2019 was conducted. Low-FR was defined as < 200 mL/s and low-SVi as < 35 mL/m2. Primary endpoint was all-cause five-year mortality, analyzed using Kaplan-Meier curves and Cox regression models. Secondary endpoint was variation of NYHA functional class six months after procedure. Patients were further stratified according to ejection fraction (EF < 50%). RESULTS: Of 489 cases, 59.5% were low-FR, and 43.1% low-SVi. Low-flow patients had superior surgical risk, worse renal function, and had a higher prevalence of coronary artery disease. Low-FR was associated with mortality (hazard ratio 1.36, p = 0.041), but not after adjustment to EuroSCORE II. Normal-SVi was not associated with survival, despite a significative p-trend for its continuous value. No associations were found for flow-status and NYHA recovery. When stratifying according to preserved and reduced EF, both FR and SVi did not predict all-cause mortality. CONCLUSION: In patients with SAS undergoing TAVI, a low-FR state was associated with higher mortality, as well as SVi, but not at a 35 mL/m2 cut off.

Construção e validação de um modelo de decisão para a canulação da fistula arteriovenosa em hemodiálise / Arteriovenous fistula cannulation in hemodialysis: Constructing and validating a decision-making model / Construcción y validación de un modelo de decisión para la canulación de fístulas arteriovenosas en hemodiálisis

Resumo Enquadramento: A fístula arteriovenosa é considerada como o acesso vascular de eleição para hemodiálise, a sua utilização pode ser realizada através de quatro técnicas de canulação distintas: Escada, Botoeira, MuST ou Área. Objetivo: Construir e validar um instrumento de apoio à decisão para a técnica de canulação ideal da fistula arteriovenosa em hemodiálise. Metodologia: Estudo metodológico em duas etapas mediante a realização da técnica de Delphi entre outubro 2021 e fevereiro de 2022 através de 27 juízes peritos. O instrumento de apoio ao modelo de decisão para a canulação foi segmentado em quatro blocos: avaliação física, avaliação ecográfica, esquema fotográfico com dermopigmentação e observações. Para análise, utilizou-se o índice de validade de conteúdo ≥ 0,90. Resultados: Obteve-se consenso final de juízes através de uma concordância unânime na estrutura do instrumento e um índice de validade de conteúdo global de 0,94. Conclusão: O instrumento em estudo revelou-se válido em aparência e conteúdo para aplicação em consulta de enfermagem.

Abstract Background: The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. Four different cannulation techniques can be used: Rope Ladder (RL), Buttonhole (BH), Multiple Single cannulation Technique (MuST), or Area Puncture (AP). Objective: To build and validate a decision-making instrument for the optimal AVF cannulation technique in hemodialysis. Methodology: This two-stage methodological study using the Delphi method was conducted between October 2021 and February 2022 with 27 experts. The decision-making instrument for choosing the cannulation technique was divided into four blocks: physical assessment, ultrasound assessment, vascular access graphical representation, and observations. The content validity index ≥ 0.90 was used in the analysis. Results: The instrument's structure obtained the unanimous agreement of the experts and an overall content validity index of 0.94. Conclusion: The instrument under analysis proved to have the face and content validity for nursing consultations.

Resumen Marco contextual: La fístula arteriovenosa se considera el acceso vascular de preferencia para la hemodiálisis y puede realizarse mediante cuatro técnicas de canulación diferentes, escalera, ojal, MuST o área. Objetivo: Construir y validar una herramienta de apoyo a la decisión para la técnica ideal de canulación de la fístula arteriovenosa en hemodiálisis. Metodología: Estudio metodológico en dos etapas mediante la técnica Delphi entre octubre de 2021 y febrero de 2022 con 27 jueces expertos. El instrumento de apoyo al modelo de decisión para la canulación se segmentó en cuatro bloques: evaluación física, evaluación ecográfica, esquema fotográfico con dermopigmentación y observaciones. Para el análisis, se utilizó el índice de validez de contenido ≥ 0,90. Resultados: El consenso final de los jueces se obtuvo mediante un acuerdo unánime sobre la estructura del instrumento y un índice de validez de contenido global de 0,94. Conclusión: El instrumento estudiado demostró ser válido en apariencia y contenido para aplicarlo en la consulta de enfermería.

Polyphenol Composition by HPLC-DAD-(ESI-)MS/MS and Bioactivities of Extracts from Grape Agri-Food Wastes.

BACKGROUND: Grape agri-food wastes, such as skin, seeds, and other discarded by-products, contain phytochemical compounds that offer potential health benefits. METHODS: This study aimed to investigate the polyphenol composition and bioactivities of different extracts obtained from grape marc and seeds, with the goal of exploring their potential for application as natural food additives. RESULTS: Regardless of the extraction method used (dynamic maceration, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE)), all extracts exhibited relatively high concentrations of phenolic compounds. The chemical characterization of the extracts revealed the presence of specific compounds and chemical groups associated with each extraction methodology. Moreover, the extracts displayed satisfactory antioxidant activities, especially in inhibiting lipoperoxidation as assessed by the TBARS assay. Additionally, the extracts demonstrated effective inhibition against different strains of bacteria and fungi known as food contaminants. Taken together, these findings indicate that those extracts have the potential to be tested as natural antioxidants and preservatives with sustainable origins in food and beverage systems. Among the extraction methods evaluated, traditional maceration and UAE provided extracts with the highest antioxidant and antimicrobial activities. CONCLUSIONS: Our results suggest the opportunity to explore grape marc and seeds discarded by the winery industry in Portugal as natural sources of bioactive compounds, which could be employed as functional food ingredients or technological additives. The valorization of grape biowastes offers a promising strategy to reduce waste and harness their potential health benefits.

Skin pigmentation as landmark for arteriovenous fistula cannulation in hemodialysis.

BACKGROUND: The cannulation of the arteriovenous fistula (AVF) for hemodialysis (HD) has traditionally depended on the nurse's tactile sensation, which has been associated with suboptimal needle placement and detrimental effects on vascular access (VA) longevity. While the introduction of ultrasound (US) has proven beneficial in mapping the AVF outflow vein and assisting in cannulation planning, aneurysmal deformations remain a common occurrence resulting from various factors, including inadequate cannulation techniques. Within this context, the utilization of skin pigmentation as a clinical landmark has emerged as a potential approach to enhance cannulation planning in HD. METHODS: A prospective longitudinal study was undertaken to investigate the correlation between the occurrence of venous morphological deformations and the cannulation technique guided by skin pigmentation after a 2-month period of implementation. RESULTS: Thirty patients were enrolled in the study with 433 cannulations being described within the first 2 months of AVF use. The overall rate of cannulation-related adverse events was 21.9%. Comparative analysis demonstrated a statistically significant relationship (p < 0.001) between aneurysmal deformation and non-compliance with the proposed cannulation technique, resulting in cannulation outside the designated points. Non-compliance was primarily attributed to nurse's decision (57.1%). CONCLUSION: The integration of US mapping of the AVF outflow vein and the utilization of skin pigmentation as a guiding tool have shown promising results in enhancing cannulation planning over time. Consistent adherence to a cannulation technique other than the area technique has been found to reduce the risk of AVF morphological deformation. These findings underscore the potential benefits of incorporating skin pigmentation as a clinical landmark in cannulation practices, highlighting its ability to impact positively cannulation outcomes.

Chemical and Bioactive Screening of Green Polyphenol-Rich Extracts from Chestnut By-Products: An Approach to Guide the Sustainable Production of High-Added Value Ingredients.

Opportunities for the valorisation of agro-industrial residues of the chestnut (Castanea sativa Mill.) production chain have been fostered with the production of multifunctional polyphenol-rich extracts with the potential to be introduced as natural additives or active components in several products. Nonetheless, it is crucial to explore the feasibility of different extracts from the various by-products for these applications through the exhaustive study of their composition and bioactivities without losing sight of the sustainable character of the process. This work aimed at the screening of the phenolic compound composition and bioactivities of different green extracts of chestnut burs, shells and leaves, as the first step to establish their potential application as natural ingredients, primarily as food preservatives. To this end, maceration (MAC) as a conventional extraction method besides ultrasound and microwave-assisted extractions (UAE and MAE) was employed to obtain the extracts from chestnut by-products using water (W) and hydroethanolic solution (HE) as solvents. Phenolic compounds were analysed by HPLC-DAD-(ESI-)MS/MS; the antioxidant capacity was assessed by colourimetric assays, and the antimicrobial activity was evaluated against several strains of food-borne bacteria and fungi. The leaf extracts obtained by MAC-HE and UAE-HE presented the highest concentration of phenolic compounds (70.92 ± 2.72 and 53.97 ± 2.41 mg.g-1 extract dw, respectively), whereas, for burs and shells, the highest recovery of total phenolic compounds was achieved by using UAE-HE and UAE-W (36.87 ± 1.09 and 23.03 ± 0.26 mg.g-1 extract dw, respectively). Bis-HHDP-glucose isomers, chestanin and gallic acid were among the most abundant compounds. Bur extracts (MAC-HE and UAE-HE) generally presented the highest antioxidant capacity as measured by TBARS, while the best results in DPPH and reducing power assays were found for shell extracts (MAE-W and MAC-HE). Promising antibacterial activity was noticed for the aqueous extracts of burs, leaves and hydroethanolic extracts of shells, with emphasis on the MAE-W extract of burs that showed bactericidal activity against E. cloacae, P. aeruginosa and S. aureus (MBC 5 mg.mL-1). Overall, it can be concluded that chestnut by-products, including burs, shells and leaves, are sources of polyphenolic compounds with significant antioxidant and antimicrobial activities. The choice of extraction method and solvent greatly influenced the composition and bioactivity of the extracts. These findings highlight the potential of chestnut by-products for the development of natural additives, particularly for food preservation, while also emphasizing the importance of sustainable utilization of agricultural waste materials. Further research is warranted to optimize extraction techniques and explore additional applications for these valuable bioactive compounds.

Anthracyclines versus No Anthracyclines in the Neoadjuvant Strategy for HER2+ Breast Cancer: Real-World Evidence.

BACKGROUND AND OBJECTIVES: Deescalation strategies omitting anthracyclines (AC) have been explored in early human epidermal growth factor receptor 2-positive breast cancer (HER2+ EBC), showing similar efficacy regarding pathological complete response (pCR) and long-term outcomes as AC-containing regimens. The standard treatment for this tumor subtype is based on chemotherapy and dual HER2 blockade with trastuzumab and pertuzumab, with AC-containing regimens remaining a frequent option for these patients, even in non-high-risk cases. The primary aim of this study was to assess and compare the effectiveness of neoadjuvant regimens with and without AC used in the treatment of HER2+ EBC in the clinical practice according to the pCR achieved with each. METHODS: This retrospective multicentric study included patients with HER2+ EBC from Portuguese, Spanish, and Chilean hospitals (January 2018-December 2021). Patients receiving neoadjuvant therapy (NAT) with dual HER2 blockade (trastuzumab and pertuzumab), followed by surgery, were included. Statistical analysis used chi-squared/Fisher's exact test for associations, multivariate logistic regression for pCR, and Kaplan-Meier method for event-free survival (EFS). IBM SPSS Statistics 29.0 analyzed the data. RESULTS: The study included 371 patients from eight hospitals. Among them, 237 received sequential AC and taxane-based chemotherapy with 4 cycles of trastuzumab and pertuzumab, while 134 received 6 cycles of TCHP (docetaxel, carboplatinum, trastuzumab, and pertuzumab). The average age of the patients was 52.8 years and 52.7 years, respectively. Omitting AC from the neoadjuvant approach did not preclude achieving pCR [p = 0.246, 95% confidence interval (CI) 0.235-0.257] and was safe regardless of patient characteristics. Relapse rates were 6.8% (16 patients) in the AC group and 4.5% (6 patients) in the TCHP group. Over a median follow-up of 2.9 years, the estimated 3-year EFS was 92.5% in the AC group and 95.4% in the TCHP group (hazard ratio 0.602, 95% CI 0.234-1.547, p = 0.292, favoring TCHP). CONCLUSION: This study reports real-world evidence showing similar pCR and EFS outcomes with treatment regimens with and without AC and raises awareness of possible overtreatment and long-term toxicity in some patients with HER2+ EBC with the use of AC.

Ovule Transcriptome Analysis Discloses Deregulation of Genes and Pathways in Sexual and Apomictic Limonium Species (Plumbaginaceae).

The genus Limonium Mill. (sea lavenders) includes species with sexual and apomixis reproductive strategies, although the genes involved in these processes are unknown. To explore the mechanisms beyond these reproduction modes, transcriptome profiling of sexual, male sterile, and facultative apomictic species was carried out using ovules from different developmental stages. In total, 15,166 unigenes were found to be differentially expressed with apomictic vs. sexual reproduction, of which 4275 were uniquely annotated using an Arabidopsis thaliana database, with different regulations according to each stage and/or species compared. Gene ontology (GO) enrichment analysis indicated that genes related to tubulin, actin, the ubiquitin degradation process, reactive oxygen species scavenging, hormone signaling such as the ethylene signaling pathway and gibberellic acid-dependent signal, and transcription factors were found among differentially expressed genes (DEGs) between apomictic and sexual plants. We found that 24% of uniquely annotated DEGs were likely to be implicated in flower development, male sterility, pollen formation, pollen-stigma interactions, and pollen tube formation. The present study identifies candidate genes that are highly associated with distinct reproductive modes and sheds light on the molecular mechanisms of apomixis expression in Limonium sp.

Caenorhabditis elegans as a Prediction Platform for Nanotechnology-Based Strategies: Insights on Analytical Challenges.

Nanotechnology-based strategies have played a pivotal role in innovative products in different technological fields, including medicine, agriculture, and engineering. The redesign of the nanometric scale has improved drug targeting and delivery, diagnosis, water treatment, and analytical methods. Although efficiency brings benefits, toxicity in organisms and the environment is a concern, particularly in light of global climate change and plastic disposal in the environment. Therefore, to measure such effects, alternative models enable the assessment of impacts on both functional properties and toxicity. Caenorhabditis elegans is a nematode model that poses valuable advantages such as transparency, sensibility in responding to exogenous compounds, fast response to perturbations besides the possibility to replicate human disease through transgenics. Herein, we discuss the applications of C. elegans to nanomaterial safety and efficacy evaluations from one health perspective. We also highlight the directions for developing appropriate techniques to safely adopt magnetic and organic nanoparticles, and carbon nanosystems. A description was given of the specifics of targeting and treatment, especially for health purposes. Finally, we discuss C. elegans potential for studying the impacts caused by nanopesticides and nanoplastics as emerging contaminants, pointing out gaps in environmental studies related to toxicity, analytical methods, and future directions.

Closed-incision negative-pressure wound therapy (ciNPWT) to minimize wound-related complications in lower limb reconstruction after bone tumor resection: preliminary proof-of-concept study.

AIMS: The purpose of this study was to compare the impact of postoperative closed-incision negative-pressure wound therapy (ciNPWT) and conventional dressings in wound-related complications after bone tumor resection and reconstruction. PATIENTS AND METHODS: A total of 50 patients with bone tumors and clinical indication for wide resection and reconstruction were included and divided into two groups (A and B). Bone defect reconstructions were achieved with modular endoprosthesis or biologic techniques, mainly involving allografts with free vascularized fibula. Group A received ciNPWT, and Group B conventional dressings. Wound-related complications, including wound dehiscence, persistent wound leakage, surgical site infections (SSIs), and causes for surgical revision, were assessed. RESULTS: Nineteen patients were included in Group A and 31 in Group B. No significant differences were found between groups regarding epidemiologic and clinical presentation features, contrarily to reconstructive options, which were significantly different between both (Fisher = 10,100; p = 0.005). Additionally, Group A presented lower wound dehiscence rate (0 vs. 19.4%; χ2(1) = 4.179; p = 0.041), SSI rate (0 vs. 19.4%; χ2(1) = 4.179; p = 0.041), and surgical revision rate (5.3% vs. 32.3%; χ2(1) = 5.003; p = 0.025) compared to Group B. CONCLUSIONS: This is the first study reporting the impact of ciNPWT after bone tumor resection and reconstruction, and its results support a potential role for this technique in diminishing postoperative wound complications and SSIs. A multicentric randomized controlled trial may help clarify the role and impact of ciNPWT after bone tumor resection and reconstruction.

Overexpression of Water-Responsive Genes Promoted by Elevated CO2 Reduces ROS and Enhances Drought Tolerance in Coffea Species.

Drought is a major constraint to plant growth and productivity worldwide and will aggravate as water availability becomes scarcer. Although elevated air [CO2] might mitigate some of these effects in plants, the mechanisms underlying the involved responses are poorly understood in woody economically important crops such as Coffea. This study analyzed transcriptome changes in Coffea canephora cv. CL153 and C. arabica cv. Icatu exposed to moderate (MWD) or severe water deficits (SWD) and grown under ambient (aCO2) or elevated (eCO2) air [CO2]. We found that changes in expression levels and regulatory pathways were barely affected by MWD, while the SWD condition led to a down-regulation of most differentially expressed genes (DEGs). eCO2 attenuated the impacts of drought in the transcripts of both genotypes but mostly in Icatu, in agreement with physiological and metabolic studies. A predominance of protective and reactive oxygen species (ROS)-scavenging-related genes, directly or indirectly associated with ABA signaling pathways, was found in Coffea responses, including genes involved in water deprivation and desiccation, such as protein phosphatases in Icatu, and aspartic proteases and dehydrins in CL153, whose expression was validated by qRT-PCR. The existence of a complex post-transcriptional regulatory mechanism appears to occur in Coffea explaining some apparent discrepancies between transcriptomic, proteomic, and physiological data in these genotypes.

Eco-physiological Responses of Aquatic Fungi to Three Global Change Stressors Highlight the Importance of Intraspecific Trait Variability.

Anthropogenic change at a global scale is affecting life on Earth with impacts on freshwaters. Aquatic hyphomycetes are fungi that drive organic matter decomposition in freshwaters and mediate energy transfer to higher trophic levels. Intraspecific trait variability affects ecological processes and can account for species adaptations to environmental change. To ascertain how aquatic hyphomycetes respond to global change related stressors, we selected 20 strains (7 species), based on their co-occurrence in streams and phylogenetic relatedness. We measured fungal growth rates at different temperatures (7 levels), nutrient concentrations (6 levels) and medium moisture (6 levels). Our results indicate that all stressors affected fungal growth, and responses to nutrient enrichment and moisture were strain specific. Fungal responses to the stressors were not explained by their phylogenetic relatedness. In the absence of stressors, interspecific diversity best explained the variance in fungal traits, while the increase in the stress gradient increased the importance of intraspecific diversity.

Estado, racismo e ações afirmativas para promoção da igualdade racial: dilemas no capitalismo / Estado, racismo y acciones afirmativas para promover de la igualdad racial: dilemas en el capitalismo / State, racism and affirmative actions to promote racial equality: dilemmas in capitalism

Resumo O presente artigo tem como objetivo desenvolver uma discussão materialista-histórica a respeito das contradições entre o Estado e as políticas de ação afirmativa no modo de produção capitalista. Para tanto, consideramos as dinâmicas reais e concretas entre o capital, os movimentos sociais, as conjunturas políticas e econômicas, que interferem na ação do Estado, bem como o entendimento das relações sociais de classe e raça como centrais para uma análise da formação social brasileira, sem a qual não conseguimos ter melhor compreensão do tempo presente. Apresentamos brevemente algumas formulações da tradição marxista a respeito do Estado e das Relações Raciais e discutimos acerca de alguns dilemas que envolvem as políticas de ação afirmativa no Brasil, uma vez que se revelam enquanto conquista da classe trabalhadora, ao mesmo tempo em que possibilitam a manutenção da ordem do Capital.

Resumen Este artículo tiene como objetivo desarrollar una discusión materialista histórica sobre las contradicciones entre el Estado y las Políticas de Acción Afirmativa en el modo de producción capitalista. Consideramos las dinámicas reales y concretas entre el capital, los movimientos sociales, las coyunturas políticas y económicas, que interfieren en la acción del Estado, así como la comprensión de las relaciones sociales de classe y raza como centrales para un análisis del contexto social brasileño, sin la cual no podemos tener una mejor comprensión del tiempo presente. Presentamos brevemente algunas formulaciones de la tradición marxista sobre el Estado y las Relaciones Raciales y discutimos algunos dilemas que envuelven las Políticas de Acción Afirmativa en Brasil, ya que se revelan como una conquista de la clase obrera, al mismo tiempo que posibilitan el mantenimiento de la misma. el orden del Capital.

Abstract The purpose of this article is to develop a historical materialist discussion about the contradictions between State and Affirmative Action policies in the capitalist mode of production. For this purpose, we consider the real and concrete dynamics between capital, social movements, political and economic conjunctures, that they interfere in the State's action, in addition to theories about social relations of class and race, which are central to an analysis of Brazilian social formation, without which we cannot have a better understanding of the present time. We briefly present some formulations of the Marxist tradition regarding State and racial relations and discuss some dilemmas that involve Affirmative Action policies in Brazil, considering that they are conquests of the working class, at the same time that they make it possible to maintain the order of Capital.

Salt Stress Tolerance in Casuarina glauca: Insights from the Branchlets Transcriptome.

Climate change and the accelerated rate of population growth are imposing a progressive degradation of natural ecosystems worldwide. In this context, the use of pioneer trees represents a powerful approach to reverse the situation. Among others, N2-fixing actinorhizal trees constitute important elements of plant communities and have been successfully used in land reclamation at a global scale. In this study, we have analyzed the transcriptome of the photosynthetic organs of Casuarina glauca (branchlets) to unravel the molecular mechanisms underlying salt stress tolerance. For that, C. glauca plants supplied either with chemical nitrogen (KNO3+) or nodulated by Frankia (NOD+) were exposed to a gradient of salt concentrations (200, 400, and 600 mM NaCl) and RNA-Seq was performed. An average of ca. 25 million clean reads was obtained for each group of plants, corresponding to 86,202 unigenes. The patterns of differentially expressed genes (DEGs) clearly separate two groups: (i) control- and 200 mM NaCl-treated plants, and (ii) 400 and 600 mM NaCl-treated plants. Additionally, although the number of total transcripts was relatively high in both plant groups, the percentage of significant DEGs was very low, ranging from 6 (200 mM NaCl/NOD+) to 314 (600 mM NaCl/KNO3+), mostly involving down-regulation. The vast majority of up-regulated genes was related to regulatory processes, reinforcing the hypothesis that some ecotypes of C. glauca have a strong stress-responsive system with an extensive set of constitutive defense mechanisms, complemented by a tight mechanism of transcriptional and post-transcriptional regulation. The results suggest that the robustness of the stress response system in C. glauca is regulated by a limited number of genes that tightly regulate detoxification and protein/enzyme stability, highlighting the complexity of the molecular interactions leading to salinity tolerance in this species.

Genomic Profiling of Sarcomas: A Promising Weapon in the Therapeutic Arsenal.

Sarcomas are rare malignant mesenchymal neoplasms, and the knowledge of tumor biology and genomics is scarce. Chemotherapy is the standard of care in advanced disease, with poor outcomes. Identifying actionable genomic alterations may offer effective salvage therapeutic options when previous lines have failed. Here, we report a retrospective cohort study of sarcoma patients followed at our center and submitted to comprehensive genomic profiling between January 2020 and June 2021. Thirty patients were included, most (96.7%) with reportable genomic alterations. The most common alterations were linked to cell cycle regulation (TP53, CDKN2A/B, and RB1 deletions and CDK4, MDM2, and MYC amplifications). Most patients (96.7%) had microsatellite stability and low tumor mutational burden (≤10 muts/megabase (Mb); median 2 Muts/Mb). Two-thirds of patients had actionable mutations for targeted treatments, including five cases with alterations amenable to targeted therapies with clinical benefit within the patient's tumor type, ten cases with targetable alterations with clinical benefit in other tumor types, and five cases with alterations amenable to targeting with drugs under investigation in a clinical trial setting. A significant proportion of cases in this study had actionable genomic alterations with available targeted drugs. Next-generation sequencing is a feasible option for identifying molecular drivers that can provide therapeutic options for individual patients. Molecular Tumor Boards should be implemented in the clinical practice to discuss genomic findings and inform clinically relevant targeted therapies.

On the Relevance of Soft Tissue Sarcomas Metabolic Landscape Mapping.

Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a "fit for all" principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors.

Assessment of nutritional status of oncology patients at hospital admission: A Portuguese real-world study.

Background: Nutritional status in patients with cancer has a determining role in the evolution of the disease and tolerance to treatments. Severity of undernutrition impacts morbidity and mortality in cancer patients and can limit patient response to the optimal therapies if nutritional issues are not appropriately addressed and managed. Despite the importance of malnutrition for the clinical evolution of oncology patients, there is not yet a universally accepted standard method for evaluating malnutrition in such patients. The aim of this study was to stratify the nutritional status of inpatients at an Oncology Department. Methods: This is an observational study with 561 cancer patients, assessed at admission to a Medical Oncology Department from November 2016 to February 2020. All patients were considered eligible. Non-compliant and/or comatose patients were excluded. Nutritional status was assessed using the PG-SGA, BMI classified with the WHO criteria, and calculation of the percentage of weight loss in the previous 3-6 months. Results: A total of 561 patients (303 F: 258 M; mean age 65 ± 13 years) were included. One-third of the patients, n=191/561 (34%), lost 6% of their weight in the month prior to admission and 297/561 (53%) patients lost 10.2% of weight in the previous 6 months. Mean BMI was 24.1 ± 5.8 kg/m2; N = 280/561 (50%) patients had regular BMI according to the WHO criteria. N = 331/561 (59%) patients reported eating less in the month prior to admission. N = 303/561 (54%) had moderate/severe deficits of muscle and adipose compartments. The PG-SGA identified 499/561 (89%) patients as moderately/severely malnourished, of which 466/561 (83%) patients scored ≥9 points, meeting criteria for a critical need for nutritional support. Fifteen percent of patients scored >4 points, indicating a need for directed therapy for symptom control and only 1% scored <2 points (maintenance nutritional counseling). Conclusion: In this oncological setting, a higher proportion of patients were nutritionally-at-risk or with moderate/severe malnutrition. The large majority of patients in this study presented with a critical need for nutritional intervention. These findings highlight the need for an integrated assessment of nutritional status at patient referral. This will allow early and timely nutrition care, which is recommended to prevent or reverse further deterioration of the condition and to optimize treatment administration.