Compartmental analysis of dynamic nuclear medicine data: models and identifiability

Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the first of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. Specifically, here we discuss the identifiability problem for a general n-dimension compartmental system and provide uniqueness results in the case of two-compartment and three-compartment compartmental models. The second paper will utilize this framework in order to show how non-linear regularization schemes can be applied to obtain numerical estimates of the tracer coefficients in the case of nuclear medicine data corresponding to brain, liver and kidney physiology

Was du nicht sagst! – ¡No me digas! Überraschung! Analyse deutscher und spanischer emotiver Formeln

Als Routineformeln werden einzelne Wörter oder feste Wortketten betrachtet, die zur Durchführung eines Sprechaktes dienen. Ziel dieses Beitrags ist es, eine Gruppe von Routineformeln zu erforschen, denen die phraseologische Forschung bisher eine begrenzte Aufmerksamkeit gewidmet hat, und zwar emotive Formeln. Deutsche und spanische Routineformeln, die den Sprechakttyp EIN GEFÜHL ÄUßERN bzw. AUSDRÜCKEN realisieren, werden untersucht und durch eine kontrastive Analyse verglichen. Insbesondere kommen Einheiten in Betracht, die Überraschung bzw. Erstaunen – und ihre jeweiligen Gefühlsnuancen – äußern bzw. ausdrücken können. Ein vorherrschend pragmalinguistisches Tertium Comparationis wird festgelegt, in dem der Kontext sich jeweils als auschlaggebend erweist, um die Bedeutung und den Intensivierungsgrad der einzelnen Wortketten bestimmen zu können

Mujeres víctimas, fetos públicos, úteros aislados: tecnologías de género, tensiones y desplazamientos en las representaciones visuales sobre aborto en Chile

Considering images as gender technologies, this article aims to explore the campaigns and visual representation of feminist activism in the current dispute for abortion in Chile. We analyse visual initiatives and performances of the feminist, lesbian-feminist and sexual dissidence activism that show a displacement and problematisation in respect to certain visual and representational politics that we consider ‘humanitarian’ and victimizer - from those against abortion and hegemonic feminisms.  In particular, we focus on the construction of three political signs: women as victims, isolated uterus and public foetuses.  A partir de considerar las imágenes como tecnologías de género, este artículo busca explorar las campañas y representaciones visuales de activismos feministas en torno a la actual disputa por el derecho al aborto en Chile.. Analizaremos diversas iniciativas visuales y de performance del activismo feminista, lesbofeminista y de la disidencia sexual, dando cuenta de las problematizaciones y desplazamientos que desde estos sectores se ha hecho a ciertas políticas visuales y representacionales que consideramos como humanitaristas y victimizantes - tanto las contrarias al aborto como algunas de feminismos hegemónicos-. Nos interesa particularmente cómo han sido construidos y dislocados tres signos políticos: las mujeres como víctimas, los úteros aislados y los fetos públicos.

Die Wunschformeln: eine kontrastive Analyse zwischen Standardspanischem und -deutschem

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Primary Resistance to Immunotherapy-Based Regimens in First Line Hepatocellular Carcinoma: Perspectives on Jumping the Hurdle

Simple Summary Immune checkpoint inhibitors (ICIs) had been explored extensively in patients affected by unresectable hepatocellular carcinoma. These agents were expected to be the keystones of the disease's first-line treatment because they were theoretically able to revert the immune suppressive tumor microenvironment of the cancerous liver, and because of their manageable safety profile. However, when used as monotherapies, they showed important activity and efficacy limitations. In this mini-review, we summarize the characteristics of the different ICIs-based regimens which constitute the present gold standard of first-line treatment, then, moving from their shortcomings, we discuss the rationale supporting the strategies currently under investigation: systemic triplets and new paradigms of immune-therapeutic agents such as CAR-T and vaccines. Immune checkpoint inhibitors (ICIs) are a key component of different stages of hepatocellular carcinoma (HCC) treatment, particularly in the first line of treatment. A lesson on the primary resistance which hampers their efficacy and activity was learned from the failure of the trials which tested them as first-line mono-therapies. Despite the combination of anti-PD(L)1 agents with anti-VEGF, anti CTLA4, or TKIs demonstrating relevant improvements in efficacy, the "doublets strategy" still shows room for improvement, due to a limited overall survival benefit and a high rate of progressive disease as best response. In this review, we discuss the results from the currently tested doublet strategies (i.e., atezolizumab+bevacizumab, durvalumab+tremelimumab with a mention to the newly presented ICIs/TKIs combinations), which highlight the need for therapeutic improvement. Furthermore, we examine the rationale and provide an overview of the ongoing trials testing the treatment intensification strategy with triplet drugs: anti-PD1+anti-CTLA4+anti-VEGF/TKIs and anti-PD1+anti-VEGF+alternative immunity targets. Lastly, we report on the alternative strategy to integrate ICIs into the new paradigm of immune therapeutics constituted by CAR-T and anti-cancer vaccines. This review provides up-to-date knowledge of ongoing clinical trials of the aforementioned strategies and critical insight into their mechanistic premises

Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice

The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice

Mammary gland, skin and soft tissue tumors in pet cats: findings of the feline tumors collected from 2002 to 2022

IntroductionCancer is a leading cause of death in cats, and the rate of such disease has been increasing recently. Nonetheless, feline oncology represents an important area of study not only for the health and wellbeing of cats but also for human health since various types of cancer in cats share similarities to those found in humans. Therefore, epidemiological studies on feline oncology may suggest environmental and genetic factors contributing to cancer in cats, which can eventually be translated to improve human cancer care.MethodTo provide an initial understanding of the epidemiology of feline neoplasms, a descriptive study was undertaken using a dataset documenting cases of feline cancer gathered from the Liguria region (northwest Italy) spanning from 2002 to 2022. The database includes tumor location, morphological codes of the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3), feline's breed, sex, neuter status, date of birth, date of diagnosis, national territorial unit code of the town of the owner's residence, and an alphanumeric string uniquely identifying the owner's surname.Results and discussionThe dataset involves a population of 4,399 cats, including 3,195 females (1,425 neutered) and 1,204 males (750 neutered). Our results indicate that mammary gland tumors are the most represented tumors in the female population, while soft tissue and skin cancers appear to have a higher abundance in the male population during the periods investigated (2002–2022). Moreover, Poisson regression analysis showed that not neutered female cats have a significantly increased risk of developing mammary gland tumors compared to the neutered female population [proportional morbidity ratio (PMR) neutered vs. not neutered = 0.58, 95% CI: 0.47–0.72]; meanwhile, for both sexes, for soft tissue and skin tumors, being neutered appears to be a risk factor (PMR neutered vs. not neutered = 2.26, 95% CI: 1.86–2.73; PMR neutered vs. not neutered = 1.16, 95% CI: 0.89–1.51). Finally, the evaluation of the Ligurian municipalities pollution, based on wild boars data (i.e., biomonitors), which coexisted with cats, was correlated to cancer development for all the tumors investigated (in polluted areas, estimated PMRs ranged from 42.61 to 80.13, 95% CI: 29.94–105.11). Overall, the data presented here suggest the use of the feline population as a possible animal model for human health, i.e., sentinel

The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

Background and aims: The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods: This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results: A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12-76.3) and 6.8 months (95% CI 2.7-24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3 versus >31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. Conclusions: PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC

Predictive significance of circulating histones in hepatocellular carcinoma patients treated with sorafenib

Background: Predictive biomarkers for advanced hepatocellular carcinoma are lacking. EZH2 drives sorafenib resistance through H3K27me3 and is counteracted by SETD2, which catalyzes H3K36me3. The authors tested the predictive power of circulating H3K27me3 and H3K36me3 in advanced hepatocellular carcinoma patients treated with sorafenib. Methods: A total of 80 plasma samples were tested for histone variants by ELISA. Changes from baseline to best response or progressive disease were correlated with patient survival. Results: A higher EZH2/SETD2 ratio predicted worse prognosis in this setting. H3K27me3 and H3K36me3 decreased from baseline to best response. The H3K27me3/H3K36me3 ratio increased from baseline to progressive disease. Higher ratios at best response were associated with shorter progression-free survival. Conclusion: The authors suggest that circulating H3K27me3/H3K36me3 ratio level acts as a predictive biomarker for sorafenib treatment outcomes in patients with advanced hepatocellular carcinoma