Possible observation of parametrically amplified coherent phasons in K0.3MoO3 using time-resolved extreme-ultraviolet ARPES

We use time- and angle-resolved photoemission spectroscopy (tr-ARPES) in the Extreme Ultraviolet (EUV) to measure the time- and momentum-dependent electronic structure of photo-excited K0.3MoO3. Prompt depletion of the Charge Density Wave (CDW) condensate launches coherent oscillations of the amplitude mode, observed as a 1.7-THz-frequency modulation of the bonding band position. In contrast, the anti-bonding band oscillates at about half this frequency. We attribute these oscillations to coherent excitation of phasons via parametric amplification of phase fluctuations.Comment: 4 figure

Activity of platinum and cetuximab in cutaneous squamous cell cancer not amenable to curative treatment

Background: Unresectable or metastatic cutaneous squamous cell cancers (cSCCs) are rare but potentially life-threatening diseases. In this setting, systemic therapy has a palliative intent with limited benefit, but there is no established consensus regarding the proper management of this tumour. This retrospective study aimed to review outcomes in patients with non-curable cSCC treated with platinum-based chemotherapy and cetuximab. Methods: We considered 12 consecutive patients treated between June 2010 and March 2016. All patients had received previous treatment for the local disease. Results: The overall response rate was 50%, and the disease control rate was 67%. Median progression-free survival and overall survival were 6.6 (95% confidence interval [CI]: 1.9-8.4) and 14.6 (95% CI: 9.4-20.1) months, respectively. The median duration of response was 4.8 months (95% CI: 1.2-5.9). The most frequent toxicities were skin reactions (58%; grade 3: 25%) and anaemia (10%). No grade 4 toxicities were observed. Conclusions: Cetuximab and platinum-based chemotherapy were shown to be feasible and active in cSCC, with an acceptable toxicity profile, even if with a limited duration of response

Ambiguity in mean-flow-based linear analysis

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Efeito de herbicidas sobre a taxa de transporte de elétrons e o acúmulo de matéria seca em tomateiro.

Objetivou-se com este trabalho avaliar o efeito dos herbicidas metribuzin e carfentrazone sobre a taxa de transporte de elétrons (ETR) do fotossistema II (FSII) e o acúmulo de matéria seca em tomateiro.CD-ROM. Suplemento. Trabalho apresentado no 51. Congresso Brasileiro de Olericultura, Viçosa, MG

Bone fracture as a novel immune-related adverse event with immune checkpoint inhibitors: Case series and large-scale pharmacovigilance analysis

Although immune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), the potential effect on the skeleton is poorly defined albeit biologically plausible and assessable through pharmacovigilance. We described a case series of patients experiencing skeletal fractures while on ICIs at the National Cancer Institute of Milan. To better characterize the clinical features of skeletal irAEs reported with ICIs, we queried the FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis by means of reporting odds ratios (RORs), deemed significant by a lower limit of the 95% confidence interval (LL95% CI) &gt; 1. Bone AEs emerging as significant were scrutinized in terms of demographic and clinical data, including concomitant irAEs or drugs affecting bone resorption or causing bone damage. Four patients with skeletal events while on ICIs were included in our case series, of which three exhibited vertebral fractures. In FAERS, 650 patients with bone and joint injuries and treated with ICIs were retrieved, accounting for 822 drug-event pairs. Statistically significant ROR was found for eight, two and one bone AEs respectively with PD-1, PD-L1 and CTLA-4 inhibitors, being pathological fracture (N = 46; ROR = 3.17; LL95%CI = 2.37), spinal compression fracture (42; 2.51; 1.91), and femoral neck fracture (26; 2.38; 1.62) the most common. Concomitant irAEs or drugs affecting bone metabolism were poorly reported. The increased reporting of serious vertebral fractures in patients without concomitant irAEs and no apparent preexisting risk factors could suggest a possible cause-effect relationship and calls for close clinical monitoring and implementation of dedicated guidelines

Mining of self-organizing map gene-expression portraits reveals prognostic stratification of HPV-positive head and neck squamous cell carcinoma

Patients (pts) with head and neck squamous cell carcinoma (HNSCC) have different epidemiologic, clinical, and outcome behaviors in relation to human papillomavirus (HPV) infection status, with HPV-positive patients having a 70% reduction in their risk of death. Little is known about the molecular heterogeneity in HPV-related cases. In the present study, we aim to disclose the molecular subtypes with potential biological and clinical relevance. Through a literature review, 11 studies were retrieved with a total of 346 gene-expression data points from HPV-positive HNSCC pts. Meta-analysis and self-organizing map (SOM) approaches were used to disclose relevant meta-gene portraits. Unsupervised consensus clustering provided evidence of three biological subtypes in HPV-positive HNSCC: Cl1, immune-related; Cl2, epithelial\u2013mesenchymal transition-related; Cl3, proliferation-related. This stratification has a prognostic relevance, with Cl1 having the best outcome, Cl2 the worst, and Cl3 an intermediate survival rate. Compared to recent literature, which identified immune and keratinocyte subtypes in HPV-related HNSCC, we confirmed the former and we separated the latter into two clusters with different biological and prognostic characteristics. At present, this paper reports the largest meta-analysis of HPV-positive HNSCC studies and offers a promising molecular subtype classification. Upon further validation, this stratification could improve patient selection and pave the way for the development of a precision medicine therapeutic approach

Ectopic hbox12 Expression Evoked by Histone Deacetylase Inhibition Disrupts Axial Specification of the Sea Urchin Embryo

Dorsal/ventral patterning of the sea urchin embryo depends upon the establishment of a Nodal-expressing ventral organizer. Recently, we showed that spatial positioning of this organizer relies on the dorsal-specific transcription of the Hbox12 repressor. Building on these findings, we determined the influence of the epigenetic milieu on the expression of hbox12 and nodal genes. We find that Trichostatin-A, a potent and selective histone-deacetylases inhibitor, induces histone hyperacetylation in hbox12 chromatin, evoking broad ectopic expression of the gene. Transcription of nodal concomitantly drops, prejudicing dorsal/ventral polarity of the resulting larvae. Remarkably, impairing hbox12 function, either in a spatially-restricted sector or in the whole embryo, specifically rescues nodal transcription in Trichostatin-A-treated larvae. Beyond strengthen the notion that nodal expression is not allowed in the presence of functional Hbox12 in the same cells, these results highlight a critical role of histone deacetylases in regulating the spatial expression of hbox12

The effects of COVID-19 pandemic on elective post-bariatric surgery waiting list. A single plastic surgery center investigation

Objective: After massive weight loss, patients that meet specific criteria can be inserted in an ad-hoc post-bariatric surgery list in order to be subjected to body contouring procedures. During COVID-19 pandemic, the Italian National Health System has been overwhelmed by the continue load of life-threatening patients that needed medical assistance. Plastic surgery practice enormously scaled back during this period and this fact greatly affected elective procedures waiting lists. The aim of our study is to analyze how the lockdown and its related sanitary policies affected post-bariatric patients' behaviors towards the delay of their procedure. Patients and methods: A 7-item questionnaire was administered to all patients. Change in the desire to be subjected to body contouring procedures was recorded. Smoking status, level of training during quarantine and psychological co-morbidities were also evaluated. Results: 124 patients completed the questionnaire. Data analysis showed that none of them encountered a decrease of the desire to be subjected to post-bariatric plastic surgery procedures. Conclusions: The present study showed that all the patients in the waiting list did not modify their interest in being subjected to post-bariatric surgery procedures, even though the waiting time increased

The sea urchin sns5 chromatin insulator settles a gene therapy vector into an independent domain of expression in the vertebrate genome

One of the critical aspects of introducing a transgene into the eukaryotic genome is the great variability of gene expression due to position effects (1). Chromatin-dependent repressive states could be overcome by incorporation in the transgene of chromatin insulators, functioning to establish and delimit domains of expression. We have previously demonstrated that the sea urchin sns5 DNA element has the typical features of an insulator: by acting as enhancer blocker, it shields promoters from neighboring regulatory elements, and by acting as barrier it buffers a transgene from the propagation of condensed chromatin (2,3). We have investigated the use of sns5 in the field of gene therapy. Our preliminary studies shown that the inclusion of sns5 in \uf0e3-retroviral vectors allows position-independent expression in erythroid cells (4). Moreover, transcription factors and histone modifications mark the sns5 chromatin at the integration site (4), suggesting that sns5 displays mechanisms of action common to other well characterized insulators. Here we show that sns5 increases the likelihood and the expression of a \uf062-globin/lentiviral vector integrated as a single copy in both murine cell clones and in a mouse model of \uf062-thalassemia. It has been proposed that two copies of insulators may direct the formation of a chromatin loop by interaction among protein complexes assembled on their sequences (5). Intriguingly, by using the 3C technology, we found that sns5-flanked vectors integrated at a single copy in the resident genome are specifically organized into an independent chromatin structure. Our findings highlight that sns5 could be a promising tool for improving the performance of vectors in the field of gene therapy. 1. Gaszner and Felsenfeld (2006). Nat Rev Genet 7:703-13 2. Palla et al (1997). PNAS USA 94:2272-7 3. Cavalieri et al (2009). Nucleic Acids Res 37:7407-15 4. D'Apolito et al (2009). Mol Ther 17:1434-41 5. Wallace and Felsenfeld (2007). Curr Op Genet Dev 17:400-