347 research outputs found

    Fermion Mass Matrices in term of the Cabibbo-Kobayashi-Maskawa Matrix and Mass Eigenvalues

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    A parameter free, model independent analysis of quark mass matrices is carried out. We find a representation in terms of a diagonal mass matrix for the down (up) quarks and a suitable matrix for the up (down) quarks, such that the mass parameters only depend on the six quark masses and the three angles and phase appearing in the Cabibbo-Kobayashi-Maskawa matrix. The results found may also be applied to the Dirac mass matrices of the leptons.Comment: 7 pages LaTeX, no figures. Title changed, Particle Data Group parametrization of CKM matrix used in equation (8), numerical values in table 1 evaluated using the quark mass values at the Z^o mass scale, equation (21) eliminated and 2 references change

    Redifferentiation of iodine-refractory metastatic thyroid cancer: from bench to bedside, through a network analysis

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    BACKGROUND: Radioiodine-refractory (RAIR) differentiated thyroid cancers (DTC) lose the ability to efficiently concentrate iodide, rendering RAI (iodine-131; I-131) ineffective. Few studies have shown improved RAI uptake after MEK inhibitors (MEKi) and/or BRAF inhibitors (BRAFi). MicroRNA (miRNA) role in redifferentiation process has been poorly investigated. METHODS: We retrospectively evaluated RAIR DTC patients treated with redifferentiation therapy using kinase inhibitor (KI) therapy with single-agent or combination MEKi and/or BRAFi. Our primary objectives were the percentage of patients with uptake on diagnostic (Dx) and post-treatment (post-Tx) whole body scan (WBS), and the radiologic response to I-131 achieved over that seen with KI. We exploited a bioinformatic approach (SWItchMiner, SWIM) to identify the key genes (switch genes) involved in BRAF-mediated carcinogenesis. MicroRNA Enrichment TURned NETwork (Mienturnet) was used to find the most important miRNAs able to regulate these switch genes. We validated our results by in vitro experiments. RESULTS: A total of 41 patients with RAIR, advanced DTC (76% BRAF V600E mutant cancer) were included in the study. At post treatment scan, there was uptake, either optimal or suboptimal, in 95% of patients. After I-131, 73% of patients were deemed treatment successes, reaching stable or partial response, that lasted at least one year without treatment on systemic therapy. The median PFS was 29 months from the start of KI and the median TTP was 20 months from RAI administration. The investigation of mutational landscape of BRAF mutated papillaty thiroid cancer (PTC) by SWIM allowed to identify a subset of switch genes (227), 30% of which is regulated by hsa-miR-335-5p. In vitro experiments showed that miRNA-335-5p is lost in primary or continuous BRAF mutated cell lines. Its over-expression in thyroid tumor cell lines harboring BRAF mutation induces the activation of NIS protein and increases intra-cellular iodide uptake. CONCLUSIONS: Redifferentiation therapy with MEKi and/or BRAFi resensitizes a subset of RAIR DTC patients to RAI and may result in prolonged stable disease off KI. Hsa-miR-335-5p may have a role in redifferentiation of RAIR BRAF-mutated papillary thyroid cancer. MiR-335-5p over-expression may contribute to restoring RAI responsiveness

    Anti epidermal growth factor receptor therapy in small bowel adenocarcinoma

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    Rationale:Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal cancer, thus limited data about treatment for advanced disease are available. The lack of specific guidelines has justified the use of therapeutic protocols usually applied in advanced colorectal cancer. Few and preliminary data have suggested possible clinical benefit from the use of target therapy such as bevacizumab and cetuximab.Patient concerns:We present the case of a young woman who was admitted to the emergency department for acute abdominal pain, nausea, and vomiting related to a jejunal stenosis.Diagnoses:An enteroscopy with jejunal biopsy showed poorly differentiated cancerous cells suggestive for primary intestinal cancer. There were no signs of metastatic disease at radiological evaluation. A jejunal resection was subsequently carried out and the diagnosis of mucinous adenocarcinoma of the jejunum was confirmed.Interventions:The computed tomography scan performed 1 month after surgery showed metastatic disease. Therefore, the patient received combined protocols of chemotherapy and either bevacizumab or the anti-epidermal growth factor receptor (EGFR) panitumumab.Outcomes:A partial response (PR) was achieved with Folfox plus panitumumab and a maintenance therapy with panitumumab is being conducted with a mild toxicity and a progression free survival of 19 months since the beginning of panitumumab.Lessons:This is, to the best of our knowledge, the first report in the literature of a patient with SBA who has benefitted from panitumumab with an overall survival of 83 months

    Psychology in Argentina: european imprint and national character

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    El trabajo se propone revisar algunas de las relevantes visitas de pensadores europeos a la Argentina ocurridas en las primeras décadas del siglo XX. El estudio se basa en comunicaciones científicas presentadas y publicadas en Buenos Aires (/AR), muchas de ellas en español, priorizando el análisis de sus efectos en el desarrollo de la ciencia psicológica en Argentina y en la conformación de un pensamiento autóctono y nacional. Entre las visitas de pensadores europeos que llegaron a nuestro país se toman en esta oportunidad a P. Janet (1859-1947), G. Dumas (1866-1946), W. Khöler (1887-1967), y F. Krueger (1874-1948). Desde el punto de vista metodológico el artículo se basa en el análisis de documentos de primera fuente en bibliotecas y archivos.This paper aims to review some visits to Argentina of remarkable intellectuals during the first half of the 20thcentury. The study is based upon scientific publications presented and published in Buenos Aires (many of them in Spanish) with emphasis on their effect on the configuration of national thinking. Among then numerous outstanding European thinkers that came to our country, we have selected P. Janet (1859-1947), G. Dumas (1866-1946), W. Khöler (1887-1967), and F. Krueger (1874-1948). From a methodological stand point, the paper is based on the analysis of primary source documents from libraries and archives.Facultad de Psicologí

    The role of stereotactic body radiation therapy in oligometastatic colorectal cancer

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    Rationale: Regorafenib is the new standard third-line therapy in metastatic colorectal cancer (mCRC). However, the reported 1-year overall survival rate does not exceed 25%. Patient concerns: A 55-year-old man affected by mCRC, treated with regorafenib combined with stereotactic body radiotherapy (SBRT), showing a durable response. Interventions: After 6 months of regorafenib, a PET/CT scan revealed a focal uptake in a solid lung nodule which was treated with SBRT, whereas continuing regorafenib administration. Fourteen months later, the patient had further progression in a parasternal lymph node, but treatment with regorafenib was continued. The regorafenib-associated side effects, such us the hand-foot syndrome, were favorable managed by reducing the dose from 160 to 120 mg/day. Outcomes: Patient-reported outcome was characterized by a progression-free survival of approximately 3 years. Lessons: in presence of oligometastatic progression, a local SBRT while retaining the same systemic therapy may be a better multidisciplinary approach. Moreover, disease progression is no longer an absolute contraindication for continuing the regorafenib treatment

    A sustainable revolution: Let's go sustainable to get our globe cleaner

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    The concept of sustainability is a clear blue sea, a snowy mountain, a flowery meadow, in which there is resource sharing that allows us to satisfy human needs without damaging natural resources. The challenge is complex, and we hope to support the decarbonization of our society and mitigate climate changes. This Special Issue aims to outline different approaches in several sectors with a common point of view: seeing our world with a green perception and encouraging a sustainable revolution to provide a cleaner world

    Is thyroid nodule location associated with malignancy risk?

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    PURPOSE: Nodules located in the upper pole of the thyroid may carry a greater risk for malignancy than those in the lower pole. We conducted a study to analyze the risk of malignancy of nodules depending on location. METHODS: The records of patients undergoing thyroid-nodule fine-needle aspiration cytology (FNAC) at an academic thyroid cancer unit were prospectively collected. The nodules were considered benign in cases of a benign histology or cytology report, and malignant in cases of malignant histology. Pathological findings were analyzed based on the anatomical location of the nodules, which were also scored according to five ultrasonographic classification systems. RESULTS: Between November 1, 2015 and May 30, 2018, 832 nodules underwent FNAC, of which 557 had a definitive diagnosis. The prevalence of malignancy was not significantly different in the isthmus, right, or left lobe. Among the 227 nodules that had a precise longitudinal location noted (from 219 patients [155 females], aged 56.2±14.0 years), malignancy was more frequent in the middle lobe (13.2%; odds ratio [OR], 9.74; 95% confidence interval [CI], 1.95 to 48.59). This figure was confirmed in multivariate analyses that took into account nodule composition and the Thyroid Imaging, Reporting, and Data System (TIRADS) classification. Using the American College of Radiologists TIRADS, the upper pole location also demonstrated a slightly significant association with malignancy (OR, 6.92; 95% CI, 1.02 to 46.90; P=0.047). CONCLUSION: The risk of thyroid malignancy was found to be significantly higher for mid-lobar nodules. This observation was confirmed when suspicious ultrasonographic features were included in a multivariate model, suggesting that the longitudinal location in the lobe may be a risk factor independently of ultrasonographic appearance

    Strategies for Psychiatric Rehabilitation and their Cognitive Outcomes in Schizophrenia: Review of Last Five-year Studies

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    Background: Cognitive deficits are core features of Schizophrenia, showing poor response to antipsychotic treatment, therefore non-pharmacological rehabilitative approaches to such a symptom domain need to be identified. However, since not all patients with Schizophrenia exhibit the same cognitive impairment profile, individualized rehabilitative approaches should be set up. Objectives: We explored the last five-year literature addressing the issue of cognitive dysfunction response to rehabilitative methodologies in Schizophrenia to identify possible predictors of response and individualized strategies to treat such a dysfunction. Conclusion: A total of 76 studies were reviewed. Possible predictors of cognitive rehabilitation outcome were identified among patient-specific and approachspecific variables and a general overview of rehabilitative strategies used in the last five years has been depicted. Studies suggest the existence of multifaced and multi-domain variables that could significantly predict pro-cognitive effects of cognitive rehabilitation, which could also be useful for identifying individual-specific rehabilitation trajectories over time. An individualized rehabilitative approach to cognitive impairment in Schizophrenia is possible if taking into account both patient and approach specific predictors of outcomes
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