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BACKGROUND: Schizophrenia is a disorder associated with neurocognitive deficits that adversely affect daily functioning and impose an economic burden. Cognitive rehabilitation interventions, particularly during the early phases of illness, have been shown to improve cognition, functionality, and quality of life. The Feuerstein Instrumental Enrichment (FIE) program, based on the Mediated Learning Experience and the Structural Cognitive Modifiability theory, has been applied in various disorders, but its applicability in schizophrenia has not yet been clarified. OBJECTIVE: This study aims to investigate the effects of the FIE program on the functionality of patients with first-episode schizophrenia. METHODS: In total, 17 patients will be recruited for an open-label intervention consisting of twice-weekly sessions for 10 weeks. The primary outcome measure will be changes in the Goal Achievement Scale score. Maze task performance from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery will serve as a secondary outcome measure. At the same time, changes in Positive and Negative Syndrome Scale scores and other MATRICS domains will be analyzed as exploratory outcomes. Assessments will be administered before and after the intervention, with a follow-up period of 6 months. RESULTS: This trial was preregistered in The Brazilian Registry of Clinical Trials (RBR-4gzhy4s). By February 2024, 11 participants were enrolled in the training. Recruitment is expected to be completed by May 2024. Data analysis will be conducted between May and September 2024. The results are expected to be published in January 2025. CONCLUSIONS: This study may establish a protocol for the FIE program that uses mediation techniques for individuals in the early stages of schizophrenia. The results will add to the knowledge about strategies to promote cognitive skills and functional impairment in daily life. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57031.

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Trastornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/rehabilitación , Esquizofrenia/complicaciones , Trastornos Psicóticos/terapia , Adulto , Masculino , Femenino , Adulto Joven , Brasil , Adolescente

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Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography-mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA.

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BACKGROUND: The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis. METHODS: A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves. RESULTS: Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds. CONCLUSIONS: In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis.

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Causas de Muerte , Fallo Renal Crónico , Nomogramas , Diálisis Renal , Calcificación Vascular , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Calcificación Vascular/mortalidad , Calcificación Vascular/diagnóstico por imagen , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Diálisis Renal/mortalidad , Medición de Riesgo , Factores de Tiempo , Anciano , Factores de Riesgo , Resultado del Tratamiento , Diabetes Mellitus/mortalidad , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/sangre , Adulto , Valor Predictivo de las Pruebas , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/sangre , Técnicas de Apoyo para la Decisión , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia

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Background: The early stages of psychotic disorders correspond to the early phases of the disease and include the prodromal phase and first-episode psychosis; they constitute a period at high risk of suicidal behaviour. A long duration of untreated psychosis (DUP) is among the risk factors of suicidal behaviour identified in this early period. Many studies have shown the effectiveness of early interventions on the overall prognosis of psychotic disorders in the early stages, and early intervention strategies have been developed and tested worldwide. Several authors reported an improvement in suicidal behaviours; however, all these data have not been systematically analysed yet. The main objective of this systematic review was to collect evidence on the effect on suicidal behaviour of early interventions for patients in the early stages of psychotic disorders. Methods: We will carry out a systematic review of the literature according to the PRISMA criteria by searching articles in five databases (PubMed, Cochrane, PsycINFO, Scopus, EMBASE), without restriction on the publication date. The selection criteria are: articles (any type; e.g. prospective, retrospective, controlled or uncontrolled, and literature reviews) on early interventions for psychotic disorders in the early stages with data on suicide attempts, death by suicide, suicidal ideation; articles written in English or French. Exclusion criteria are: articles on suicidal behaviours in patients with psychotic disorders in the early stages, but without early intervention, and articles on early-stage psychotic disorders without data on suicidal behaviours. Discussion: If this review confirms the effectiveness on suicidal behaviours of early interventions for young patients with psychotic disorders, the development/implementation of such intervention programmes should be better promoted. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021237833.

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The brain's abnormal and uncontrollable cell partitioning is a severe cancer disease. The tissues around the brain or the skull induce this tumor to develop spontaneously. For the treatment of a brain tumor, surgical techniques are typically preferred. Deep learning models in the biomedical field have recently attracted a lot of attention for detecting and treating diseases. This article proposes a new Ensemble Deep Learning Network (EDLNet) model. This research uses the Modified Faster RCNN approach to classify brain MRI scan images into cancerous and non-cancerous. A deep recurrent convolutional neural network (DRCNN)-based diagnostic method for early-stage brain tumor segmentation is presented. The evaluation outcomes show that the proposed tumor classification and segmentation model's performance accurately segments tissues from MRI images. For the analysis of the proposed model, two different publicly available datasets (D1&D2) are used. For D1 and D2 datasets, a total of 99.76% and 99.87% accuracies are achieved by the proposed model. The performance results of the proposed model are more effective than the state-of-the-art network models as per the experimental results.Communicated by Ramaswamy H. Sarma.

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INTRODUCTION: Surveillance is the standard management in low-risk cN0 penile squamous cell carcinoma (peSCC) patients. However, no previous analysis focused on early and long-term outcomes of these patients. We report on main oncological outcomes of a large series of low-risk cN0 peSCC patients. PATIENTS AND METHODS: Between 1980 and 2017 included, 93 evaluable consecutive low-risk (ie, pT1a G1 cN0M0) peSCC patients underwent primary tumor surgery and either observation (74) or dynamic sentinel node biopsy (DSNB) (19) following a clinical diagnosis of T1 in 66 (71%), T2 in 15 (16.1%) and Tx in 12 (12.9%) patients, respectively. The statistical significance of differences in medians and proportions was tested with the Kruskal-Wallis and chi-square tests. Kaplan-Meier plots illustrated 5-year inguinal relapse (IR)-free survival rates. RESULTS: Median age was 60 years (IQR: 50-69 years). Median follow-up was 92 months (IQR 54-133 months). Surveillance was more frequently adopted in clinical (c)T1 than in cT2 tumors (79.7% vs. 36.8%). None of 19 patients who had DSNB had nodal metastasis. Overall, 7 (7.5%) out of 93 pT1aG1cN0 peSCC patients had IR after a median interval of 9 months. Of note, 1 patient only relapsed after 12 months of surveillance. After stratification according to IR, relapses occurred more frequently in younger patients (59 vs. 64 years, P < .001). The 5-year IR-free survival rates for the entire cohort was 92% (95% Confidence interval [CI] 87-98%). CONCLUSIONS: Observation is a safe and effective management for low-risk peSCC patients. Younger patients may be offered a mini-invasive staging as an alternative.

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Carcinoma de Células Escamosas , Neoplasias del Pene , Masculino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias del Pene/patología , Carcinoma de Células Escamosas/patología , Estadificación de Neoplasias

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INTRODUCTION: Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ). MATERIAL AND METHODS: A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny. RESULTS: Patients with SCZ showed lower CR than those in the ESP (p<0.001). CR correctly classified 79.6% of the cases (p<0.001; Exp(B)=1.062). In ESP group, CR was related to working memory (p=0.030) and negative symptoms (p=0.027). CR (t=3.925, p<0.001) and cannabis use (t=2.023, p=0.048) explained 26.7% of the variance on functioning (p=0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R2=0.091, p=0.001) and functioning (R2=0.074, p=0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p=0.037) was mediated by CR level (p=0.003). CONCLUSIONS: The implications of CR depend on the stage of the disease (ESP vs. SCZ), with a greater effect on neurocognition and negative symptoms in patients with chronic SCZ.

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Reserva Cognitiva , Estilo de Vida , Esquizofrenia , Humanos , Masculino , Reserva Cognitiva/fisiología , Femenino , Adulto , Enfermedad Crónica/psicología , Adulto Joven , Persona de Mediana Edad

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Based mainly on their personal experience, the authors try to describe the origin of cardiovascular disease (CVD) epidemiology and the problems and difficulties practitioners attempted to tackle and solve during the first few decades of this discipline, which started around the middle of the last century. Beyond identifying the characteristics of those who became CVD epidemiologists, a description is given of the initial structures of the involved studies, participation rates, risk factors measurements and standardization, clinical measurements and diagnostic criteria, mortality data collection and coding, data loading and analysis, plus a number of problems still unsolved at the beginning of the 2000s. Despite many obstacles, and the initial hostility of the medical-scientific establishment, CVD epidemiology represented a revolution in researching in the bio-medical field. In the end, it also affected clinical research introducing the use of the quantitative approach bound to mathematical-statistical procedures. After decades of hard work and the development of a number of innovative tools, CVD epidemiology received its deserved recognition, eventually being accepted as a reputable and independent scientific discipline. Yet, in several countries, especially those from Southern Europe, an academic recognition of CVD epidemiology is still lacking.

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Introducción: El cáncer de pulmón representa la causa más común de muerte por enfermedades malignas en el mundo. La tasa de respuesta al tratamiento es pobre aún en estadios iniciales y depende de varios elementos. Objetivo: Evaluar la respuesta a la quimiorradioterapia en carcinomas de pulmón en estadios iniciales según hábito de fumar, histología y etapa clínica al diagnóstico. Materiales y métodos: Se realizó un estudio de evaluación, analítico, transversal, retrospectivo. El universo estuvo constituido por los 45 pacientes con diagnóstico citohistológico de cáncer de pulmón de células no pequeñas en etapas desde la IA a la IIIA, que recibieron tratamiento de primera línea con quimiorradioterapia, atendidos en el Centro Oncológico Provincial de Matanzas, en el período de enero de 2017 a diciembre de 2019. Resultados: Se obtuvo respuesta completa en un 36,6 % de los no fumadores y en el 25 % de los fumadores. En cuanto a respuesta completa a la quimiorradioterapia de los tumores de pulmón según histología, en los adenocarcinomas fue del 10 %; en los epidermoides, 22,6 %, y en los adenoescamosos, 50 %. En etapas IA-IB presentó respuesta completa el 50 % de los casos, en las IIA-IIB el 37,5 %, mientras que en la IIIA predominó la respuesta parcial. Conclusiones: Los mejores porcientos de respuesta completa se obtuvieron en los no fumadores, con tipo histológico adenoescamoso y en etapas IA-IB.

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Introduction: Lung cancer is the most common cause of death from malignant diseases in the world. The response rate to treatment is poor even in the initial stages and depends on several elements. Objective: To evaluate the response to chemoradiotherapy in lung carcinomas in early stages according to smoking habit, histology and clinical stage at diagnosis. Materials and method: An analytical, cross-sectional, retrospective evaluation study was carried out; the universe consisted of 45 patients with a cytohistological diagnosis of non-small cell lung cancer in stages from IA to IIIA, who received first-line treatment with chemoradiotherapy, attended at the Provincial Cancer Center of Matanzas, in the period of January 2017 to December 2019. Results: A complete response was obtained in 36.6% of non-smokers and in 25% of smokers. Regarding complete response to chemoradiotherapy of lung tumors according to histology, in adenocarcinomas it was 10%, in epidermoids, 22.6%, and in adenosquamous cell, 50%. In stages IA-IB, 50% of the cases presented a complete response, in stages IIA-IIB, 37.5%, while in IIIA partial response predominated. Conclusions: The best percentages of complete response were obtained in non-smokers, with adenosquamous histology type and in stages IA-IB.

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OBJECTIVE: To study the phenomenon of impulsivity, its components and aggression in patients at risk for schizophrenia at the stage of remission after the first depressive episode. MATERIAL AND METHODS: Forty-eight male patients (mean age 19.4±2.9 years) with the first depressive episode (ICD-10 F32.1, F32.2) with attenuated positive, negative and/or disorganized symptoms were examined. According to the severity of impulsivity, the patients were divided into the clinical group (n=26) with pathological impulsivity and the comparison group (n=27) without it. The control group consisted of 41 mentally healthy young men, students of higher education of 1-3 courses, (mean age 19.7±1.6 years). HDRS, SOPS, SANS, Barratt Impulsiveness Scale (BIS-11) and Buss Perry Aggression Questionnaire (BPAQ) were used. Statistical analysis was carried out using the Statistica 12 software. RESULTS: The differences between the clinical group and the comparison group were determined by the total score of the subscale of general symptoms of SOPS at admission (53 [41.75; 56] and 45.5 [41.75; 51.25], respectively) (U=187.5; p=0.037) and at discharge (28 [19; 37] and 25 [17.75; 29.25] points respectively) (U=166.5; p=0.012), according to the total HDRS score at admission (35 [31; 38] and 29 [26; 34.25]) (U=191.0; p=0.046). In the clinical group, the motor component of impulsivity and the factor of general impulsivity on the BIS-11 correlated with the severity of aggression on the BPAQ (r=0.395, p<0.05 and r=0.635, p<0.05, respectively). Significant differences were revealed in the clinical group depending on the presence of negative symptoms on the corresponding SOPS subscale according to the total BPAQ score (p=0.01). Correlation analysis showed numerous connections: positive between the total aggressiveness score and the duration of depression (p<0.05), negative between the factors of self-control, consistency, attention, and total scores on the SANS and SOPS (p<0.05). CONCLUSION: We identify the differences in the structure of impulsivity in patients at risk of developing schizophrenia at the stage of remission after the first depressive state, the comparison group and the control group, as well as the relationship of impulsivity factors with individual clusters of psychopathological disorders.

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Agresión , Esquizofrenia , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Pacientes , Estado de Salud , Conducta Impulsiva

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Individuals at clinical high risk for psychosis (CHR-P) present as help-seeking individuals with social deficits as well as cognitive and functional impairment and have a 23-36% risk of transition to first-episode psychosis. The therapeutic role of intranasal oxytocin (ΟΤ) in psychiatric disorders has been widely studied during the last decades, concerning its effects on social behavior in humans. A literature search was conducted via Pubmed and Scopus, using the search terms "oxytocin" and "psychosis." Six studies were included in the current review. There were differences in terms of demographics, intervention type, and outcome measures. ΟΤ may affect the social cognition skills of people at prodromal and early stages of psychosis, but its effect on clinical symptoms is ambiguous. Because of the high level of heterogeneity of existing studies, more original studies are needed to examine and clarify whether OT improves high-risk and early psychosis populations.

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BACKGROUND: Diabetes is the leading cause of chronic kidney disease (CKD) and contributes to an elevated incidence of diastolic dysfunction in the early stages of CKD. Intracardiac vortex is a novel hemodynamic index for perceiving cardiac status. Here, we visualized left ventricular (LV) vortex characteristics using vector flow mapping (VFM) in type 2 diabetic patients with early CKD. METHODS: This cross-sectional study included 67 controls and 89 type 2 diabetic patients with stages 2-3a CKD. All subjects underwent transthoracic echocardiographic examination. LV anterior vortex during early diastole (E-vortex), atrial contraction (A-vortex) and systole (S-vortex) were assessed using VFM in the apical long-axis view. Its relation to glycemia or LV filling echocardiographic parameters were further analyzed using correlation analysis. RESULTS: Type 2 diabetic patients with early CKD had a small area (439.94 ± 132.37 mm2 vs. 381.66 ± 136.85 mm2, P = 0.008) and weak circulation (0.0226 ± 0.0079 m2/s vs. 0.0195 ± 0.0070 m2/s, P = 0.013) of E-vortex, but a large area (281.52 ± 137.27 mm2 vs. 514.83 ± 160.33 mm2, P ˂ 0.001) and intense circulation (0.0149 ± 0.0069 m2/s vs. 0.0250 ± 0.0067 m2/s, P < 0.001) of A-vortex compared to controls. CKD patients with poorly controlled hyperglycemia had stronger A-vortex (area: 479.06 ± 146.78 mm2 vs. 559.96 ± 159.27 mm2, P = 0.015; circulation: 0.0221 ± 0.0058 m2/s vs. 0.0275 ± 0.0064 m2/s, P < 0.001) and S-vortex (area: 524.21 ± 165.52 mm2 vs. 607.87 ± 185.33 mm2, P = 0.029; circulation: 0.0174 ± 0.0072 m2/s vs. 0.0213 ± 0.0074 m2/s, P = 0.015), and a longer relative duration of S-vortex (0.7436 ± 0.0772 vs. 0.7845 ± 0.0752, P = 0.013) than those who had well-controlled hyperglycemia. Glycemia, and E/A (a LV filling parameter) were respectively found to had close correlation to the features of A-vortex and S-vortex (all P < 0.05). CONCLUSIONS: Abnormal LV vortices were detected in type 2 diabetic patients with early CKD using VFM, especially in those who neglected hyperglycemic control. LV vortex might be a promising parameter to slow or halt the hyperglycemia-induced diastolic dysfunction in early CKD.

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Diabetes Mellitus Tipo 2 , Hiperglucemia , Insuficiencia Renal Crónica , Humanos , Estudios Transversales , Atrios Cardíacos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico

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INTRODUCTION: Progressive advanced non-small cell lung cancer (NSCLC) accounts for about 80-85% of all lung cancers. Approximately 10-50% of patients with NSCLC harbor targetable activating mutations, such as in-frame deletions in Exon 19 (Ex19del) of EGFR. Currently, for patients with advanced NSCLC, testing for sensitizing mutations in EGFR is mandatory prior to the administration of tyrosine kinase inhibitors. PATIENTS AND METHODS: Plasma was collected from patients with NSCLC. We carried out targeted NGS using the Plasma-SeqSensei™ SOLID CANCER IVD kit on cfDNA (circulating free DNA). Clinical concordance for plasma detection of known oncogenic drivers was reported. In a subset of cases, validation was carried out using an orthogonal OncoBEAMTM EGFR V2 assay, as well as with our custom validated NGS assay. Somatic alterations were filtered, removing somatic mutations attributable to clonal hematopoiesis for our custom validated NGS assay. RESULTS: In the plasma samples, driver targetable mutations were studied, with a mutant allele frequency (MAF) ranging from 0.00% (negative detection) to 82.25%, using the targeted next-generation sequencing Plasma-SeqSensei™ SOLID CANCER IVD Kit. In comparison with the OncoBEAMTM EGFR V2 kit, the EGFR concordance is 89.16% (based on the common genomic regions). The sensitivity and specificity rates based on the genomic regions (EGFR exons 18, 19, 20, and 21) were 84.62% and 94.67%. Furthermore, the observed clinical genomic discordances were present in 25% of the samples: 5% in those linked to the lower of coverage of the OncoBEAMTM EGFR V2 kit, 7% in those induced by the sensitivity limit on the EGFR with the Plasma-SeqSensei™ SOLID CANCER IVD Kit, and 13% in the samples linked to the larger KRAS, PIK3CA, BRAF coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit. Most of these somatic alterations were cross validated in our orthogonal custom validated NGS assay, used in the routine management of patients. The concordance is 82.19% in the common genomic regions (EGFR exons 18, 19, 20, 21; KRAS exons 2, 3, 4; BRAF exons 11, 15; and PIK3CA exons 10, 21). The sensitivity and specificity rates were 89.38% and 76.12%, respectively. The 32% of genomic discordances were composed of 5% caused by the limit of coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit, 11% induced by the sensitivity limit of our custom validated NGS assay, and 16% linked to the additional oncodriver analysis, which is only covered by our custom validated NGS assay. CONCLUSIONS: The Plasma-SeqSensei™ SOLID CANCER IVD kit resulted in de novo detection of targetable oncogenic drivers and resistance alterations, with a high sensitivity and accuracy for low and high cfDNA inputs. Thus, this assay is a sensitive, robust, and accurate test.

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BACKGROUND: Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder. METHODS: The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status. RESULTS: Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001). CONCLUSIONS: Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent.

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Trastornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/tratamiento farmacológico , Factores de Riesgo , Progresión de la Enfermedad , Cognición

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Accurate identification of the early stages of coal-fire combustion is important for effectively controlling the spread of coal fires. CO2 and CO, as characteristic gases in the early stage of coal fire combustion, can be effectively monitored by in-situ monitoring near the surface. However, in the previous in-situ monitoring methods, the influence of surface meteorological and soil factors on the release law of characteristic gases is often ignored. Therefore, this paper considers the complexity of the geological conditions in the coal fire area, a system, and equipment for obtaining the near-surface CO2 and CO variation laws in the early stage of coal fire combustion proposed by the concentration gradient method (CGM). The system and equipment realize the simultaneous online coupling of multi-area and multi-parameter data and conduct field investigations on the Wuda coal fire area. The results show that in the early stage of coal combustion, the change patterns of CO2 and CO concentrations in different regions are anomalous, and the CO2 concentration was higher than the CO concentration. The CO2 and CO concentrations in shallow soil increased with the increase of soil depth, and compared with other areas, the CO2 and CO concentration was the highest. The shallow soil and CO2 were identified as the key areas and characteristic gases for identifying the early stage of coal-fire combustion. The CO2 flux (CF) of different shallow soil depths decreased with increased soil layer depth. Variation of soil-surface CO2 flux (S-SCF) estimated by flux extrapolation method (FLEM). The change of S-SCF is controlled by meteorological and soil factors, and there is a certain connection between it and the "respiration phenomenon" in the fissure area. Thus, this study provides a theoretical basis for effectively identifying the early stages of coal-fire combustion.

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Suelo , Combustión Espontánea , Dióxido de Carbono/análisis , Carbón Mineral , Gases

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Background: The genus Cyclocosmia Ausserer, 1871 previously included ten species from North America and Asia, six of which have been recorded from China. New information: A new species, Cyclocosmiaruyi Yu & Zhang sp. n., is described and diagnosed, based on both sexes from Guangxi Province, China. Morphological characters for the early stages of juveniles of the new species are also provided.

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Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. Although current treatments can control the progression of DR to a certain extent, there is no effective treatment for early DR. Apart from vascular endothelial growth factor, it has been noted that the apelin/APJ system contributes to the pathogenesis of DR. We used a high-fat diet/streptozotocin-induced type 2 diabetic mouse model. The mice were divided into a lentivirus control group (LV-EGFP), an apelin-overexpression group (LV-Apelin+), and an apelin-knockdown group (LV-Apelin-), all of which were administrated intravitreal injections. LV-Apelin+ ameliorated the loss of pericytes in DR mice, whereas LV-Apelin- aggravated the loss of pericytes. Similarly, LV-Apelin+ reduced the leakage of retinal vessels, whereas LV-Apelin- exacerbated it. The genes and signaling pathway related to cell adhesion molecules were downregulated, whereas the cell-cell tight junctions and anti-apoptotic genes were upregulated in response to apelin overexpression. However, the alterations of these same genes and signaling pathways were reversed in the case of apelin knockdown. Additionally, LV-Apelin+ increased ZO-1 and occludin levels, whereas LV-Apelin- decreased them. Our results suggest that apelin can reduce vascular leakage by protecting pericytes, which offers a promising new direction for the early treatment of DR.

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Apelina , Diabetes Mellitus , Retinopatía Diabética , Animales , Ratones , Retinopatía Diabética/genética , Pericitos/metabolismo , Vasos Retinianos/metabolismo , Estreptozocina , Factor A de Crecimiento Endotelial Vascular/metabolismo , Apelina/genética

RESUMEN

BACKGROUND: The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Based on published studies, accelerated partial breast irradiation (APBI) is recommended for strictly selected patients. The aim of this single-institution prospective randomized study was to compare the targeted APBI delivered by stereotactic approach with the currently more commonly used accelerated whole breast irradiation with the boost to the tumor bed in terms of feasibility, safety, tolerance, and cosmetic effects. MATERIALS AND METHODS: Early-stage breast cancer patients after partial mastectomy were screened for eligibility. The inclusion criteria were age > 50 years, non-lobular carcinoma histology, size 2cm, negative margins 2mm, L0, ER-positive, BRCA negative. Enrolled patients were equally randomized into two arms according to radiotherapeutic regiment - external APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67 Gy + 5× 2 Gy). These preliminary results of the ongoing study evaluated the first 57 from 84 planned patients. RESULTS: The median age was 65 years. The tumors were of grade 1 in 60 % of patients, the median size of 9mm and 70 % were classified as invasive ductal carcinoma. Statistical significant differences between the groups in baseline characteristics were not observed. A total of 29 patients was enrolled in the APBI group by the end of 2020. All enrolled patients were evaluated one month after RT. A total of 40 (70,2 %) a 33 (58 %) had examinations 3 and 6 months after RT, respectively. Toxicity evaluation showed statistically significantly fewer acute adverse events in the APBI group in terms of skin erythema, desquamation, skin tenderness, dryness, edema, pigmentation, breast pain and fatigue. Late toxicity evaluated in 3 and 6 months after RT was significantly higher in the control group. The cosmetic effect (independently evaluated by a physician, nurse and patient) was more favorable to the APBI group. CONCLUSION: The technique using the principles of targeted radiotherapy turned out to be a less toxic and easier feasible approach for adjuvant radiation of early-stage breast cancer patients. Consequently, the presented study increases the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.

Asunto(s)

Neoplasias de la Mama , Humanos , Anciano , Persona de Mediana Edad , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Estudios Prospectivos , Mastectomía , Adyuvantes Inmunológicos , Radioterapia Adyuvante

RESUMEN

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers. Objectives: The aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms. Methods: Clinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers. Results: A total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82; P = 0.019) and remained significant after adjusting for sex, age, ATTR-CM type, and estimated glomerular filtration rate (HR: 0.18; 95% CI: 0.06-0.55; P = 0.002). Conclusions: After a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.