The Stromal and Immune Landscape of Colorectal Cancer Progression during Anti-EGFR Therapy

The EGFR antibodies cetuximab and panitumumab are used in patients with EGFR-expressing, KRAS, or NRAS wild-type metastatic colorectal cancer (mCRC) either in combination with standard chemotherapy, for first-line treatment, or as single agents when tumors become resistant to prior cytotoxic regimens. However, only 20% of individuals experience tumor regressions, and only an additional 30% have some extent of clinical benefit in terms of disease stabilization (Douillard et al., 2013). This relatively low response rate is compounded by the dismal reality that subjects who initially respond typically become refractory to treatment in a period of months. In this issue of Cancer Cell, Woolston et al., 2019 offer a comprehensive picture of the identifying traits of primary and acquired resistance to cetuximab in a cohort of 35 mCRC patients (Figure 1). In a difference from previous studies, mostly conducted in a retrospective manner and focused on a small number of candidate biomarkers, here the authors embarked on a prospective trial whereby biopsies collected before initiation of single-agent cetuximab and at the time of disease progression were subjected to whole-exome and RNA-sequencing analyses and immunophenotyping

MinerAlert: an hybrid approach for web mining detection

The introduction of new memory-based crypto-mining techniques and the rise of new web technologies like WebAssembly, made the use of browsers for crypto-currencies mining more and more convenient and popular. That, in turn, originated a new form of computer piracy, called cryptojacking, which is rapidly gaining ground on the web. A cryptojacking site exploits its visitors’ hardware resources to secretly mine crypto-currencies. This paper analyzes current web-based cryptojacking detection methods in order to propose a novel hybrid strategy. Current detection methods are found to require either considerable computer administration skills or execution privileges usually not available to common users. In this view, a method, named MinerAlert, has been designed and proposed, aiming at detecting in real-time sites performing cryptojacking. To address the limitations of current methods, the method implementation has been achieved through a browser extension. The present paper describes the method’s details and its implementation. It also reports the experimental results of its utilization, showing its positive performances in terms of ease of use, successful detections and speed

Immunogenomics of Colorectal Tumors: Facts and Hypotheses on an Evolving Saga

Different mutational burden only partially explains the different response of MSI and MSS CRCs to immunotherapy. Neoantigen load, as measured using available prediction algorithms, is not sufficiently accurate for implementation into clinical decision making. Abundant immune infiltration in the tumor tissue is likely to have high prognostic value, but not an equally high predictive value in terms of response to immunotherapy. The intrinsic characteristics of MSI and MSS CRCs determine differences in their evolutionary paths, which inevitably influence the way the immune system sculpts tumor clonal and subclonal dynamics. Immunotherapy with immune checkpoint inhibitors is an approved treatment option for a subpopulation of patients with colorectal cancers that display microsatellite instability. However, not all individuals within this subgroup respond to immunotherapy, and molecular biomarkers for effective patient stratification are still lacking. In this opinion article, we provide an overview of the different biological parameters that contribute to rendering colorectal cancers with microsatellite instability potentially sensitive to immunotherapy. We critically discuss the reasons why such parameters have limited predictive value and the implications therein. We also consider that a more informed knowledge of response determinants in this tumor subtype could help understand the mechanisms of immunotherapy resistance in microsatellite stable tumors. We conclude that the dynamic nature of the interactions between cancer and immune cells complicates conventional biomarker development and argue that a new generation of adaptive metrics, borrowed from evolutionary genetics, may improve the effectiveness and reliability of clinical decision making

Monitoring Epiphytic Lichen Biodiversity to Detect Environmental Quality and Air Pollution: the Case Study of Roccamonfina Park (Campania Region - Italy)

In this study, lichen distribution was examined in a district of Campania region to monitor the evolution of air quality at landscape scale. A new methodological approach was tried by overlapping the results of biomonitoring samplings to land cover maps, in order to highlight the relations between air pollution and land use patterns. The main objectives of this work were the following: i) to evaluate air quality on the studied area with the aid of IBL index, and reporting geo-referenced data on a thematic map; ii) to relate lichen distribution and biodiversity to land use spatial patterns; iii) to put the basis for a comparative analysis focussed on changes induced by the present socio-economic evolution of the plain, from agriculture to industrial and tertiary; iv) to provide a reproducible protocol for monitoring air quality, identifying clusters of lichen species linked to particular land use models and formulating previsions about environmental quality on areas characterized by similar dynamics

I reinterventi nell’iperparatiroidismo

reinterventi in chirurgia paratiroidea rappresentano una sfida impegnativa per il chirurgo che deve valutare attentamente i dati operatori e istologici del primo intervento, usare una diagnostica accurata preoperatoria con ecografia e scintigrafia con sestamibi e avere ben presente l’anatomia e l’embriologia delle ghiandole paratiroidee. Elementi fondamentali per ottenere un successo chirurgico sono l’uso del dosaggio intraoperatorio del paratormone e una grande esperienza del chirurgo. Seguendo tali principi si arriva a ottenere una remissione del quadro iperparatiroideo nell’85-90% per l’HPT I e nel 70% per l’HPT II e III. Gli Autori presentano la loro casistica di 75 reinterventi dopo HPT I e di 85 reinterventi dopo HPT II e III, su una casistica totale di 2072 interventi di paratiroidectomia eseguiti fra gennaio 1975 e ottobre 2009

Weyl-Gauging and Conformal Invariance

Scale-invariant actions in arbitrary dimensions are investigated in curved space to clarify the relation between scale-, Weyl- and conformal invariance on the classical level. The global Weyl-group is gauged. Then the class of actions is determined for which Weyl-gauging may be replaced by a suitable coupling to the curvature (Ricci gauging). It is shown that this class is exactly the class of actions which are conformally invariant in flat space. The procedure yields a simple algebraic criterion for conformal invariance and produces the improved energy-momentum tensor in conformally invariant theories in a systematic way. It also provides a simple and fundamental connection between Weyl-anomalies and central extensions in two dimensions. In particular, the subset of scale-invariant Lagrangians for fields of arbitrary spin, in any dimension, which are conformally invariant is given. An example of a quadratic action for which scale-invariance does not imply conformal invariance is constructed.Comment: Extended version including discussion of arbitrary spin in any dimensions. References adde

Male fetal loss in the U.S. following the terrorist attacks of September 11, 2001

Background: The secondary sex ratio (i.e., the odds of a male birth) reportedly declines following natural disasters, pollution events, and economic collapse. It remains unclear whether this decline results from an excess of male fetal loss or reduced male conceptions. The literature also does not converge as to whether the terrorist attacks of September 11, 2001 induced "communal bereavement", or the widespread feeling of distress among persons who never met those directly involved in the attacks. We test the communal bereavement hypothesis among gravid women by examining whether male fetal deaths rose above expected levels in the US following September 11, 2001. Methods: We apply interrupted time-series methods to all fetal deaths at or greater than the 20(th) week of gestation in the US from 1996 to 2002. Time-series methods control for trends, seasonality, and other forms of autocorrelation that could induce spurious associations. Results: Results support the hypothesis in that the fetal death sex ratio (i.e., the odds of a male fetal death) increased above its expected value in September 2001. Additional analysis of the secondary sex ratio indirectly supports that the terrorist attacks may have threatened the gestation of male more than female fetuses. Conclusions: Societal responses to events such as September 11, 2001 do not appear confined only to persons who have ever met the deceased. The fetal death sex ratio in the US population may serve as a sentinel indicator of the degree to which pregnant women react to population stressors