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The present works focuses on the theoretical analysis of the Italian temporal particle ancora, in its aspectual (ancora/still) and non-aspectual (ancora/again) temporal uses. The gist of this proposal is that the additive component of the meaning of ancora comes about as an obligatory inference derived via exhaustification, rather than being presupposed. The interpretation of ancora under negation is subject to another instance of Exh, which operates on the alternatives triggered by the Rise-Fall intonation in Italian, similar to other focus particles like solo (only) and anche (also).

IntroductionCutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment.MethodsA431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2.ResultsThe rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model’s utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI.DiscussionThis model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

BackgroundVisceral adiposity, more so than overall adiposity, is associated with chronic disease and mortality. There has been, to our knowledge, little research exploring the association between diet quality and visceral adipose tissue (VAT) among a mulitethnic population aged 18-80 y.ObjectiveThe primary objective of this cross-sectional analysis was to examine the association between diet quality [Healthy Eating Index-2010 (HEI-2010) scores] and VAT among a multiethnic population of young, middle, and older aged adults in the United States. Secondary objectives were to repeat these analyses with overall adiposity and blood-based biomarkers for type 2 diabetes and cardiovascular disease risk as outcome measures.MethodsA total of 540 adults (dropped out: n = 4; age: 18-40 y, n = 220; 40-60 y, n = 183; 60-80 y, n = 133) were recruited across 3 sites (Honolulu County, San Francisco, and Baton Rouge) for the Shape Up! Adults study. Whole-body DXA, anthropometry, fasting blood draw, and questionnaires (food frequency, physical activity, and demographic characteristics) were completed. Linear regression was used to assess the associations between HEI-2010 tertiles and VAT and secondary outcome measures among all participants and age-specific strata, while adjusting for known confounders.ResultsVAT, BMI (kg/m2), body fat percentage, total body fat, trunk fat, insulin, and insulin resistance were inversely related to diet quality (all P values

Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1–2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55–82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18–1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0–0.48 ng/mL). Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

Abstract Entanglement is assuming a central role in modern quantum many-body physics. Yet, for lattice gauge theories its certification remains extremely challenging. A key difficulty stems from the local gauge constraints underlying the gauge theory, which separate the full Hilbert space into a direct sum of subspaces characterized by different superselection rules. In this work, we develop the theoretical framework of entanglement witnessing for lattice gauge theories that takes this subtlety into account. We illustrate the concept at the example of a U(1) lattice gauge theory in 2+1 dimensions, without and with dynamical fermionic matter. As this framework circumvents costly state tomography, it opens the door to resource-efficient certification of entanglement in theoretical studies as well as in laboratory quantum simulations of gauge theories.

Abstract Disinformation about science can impose enormous economic and public health burdens. A recently proposed strategy to help online users recognise false content is to follow the techniques of professional fact checkers, such as looking for information on other websites (lateral reading) and looking beyond the first results suggested by search engines (click restraint). In two preregistered online experiments (N = 5387), we simulated a social media environment and tested two interventions, one in the form of a pop-up meant to advise participants to follow such techniques, the other based on monetary incentives. We measured participants’ ability to identify whether information was scientifically valid or invalid. Analysis of participants’ search style reveals that both monetary incentives and pop-up increased the use of fact-checking strategies. Monetary incentives were overall effective in increasing accuracy, whereas the pop-up worked when the source of information was unknown. Pop-up and incentives, when used together, produced a cumulative effect on accuracy. We suggest that monetary incentives enhance content relevance, and could be combined with fact-checking techniques to counteract disinformation.

Alzheimer's disease (AD) is the leading neurodegenerative pathology in aged individuals, but many questions remain on its pathogenesis, and a cure is still not available. Recent research efforts have generated measurements of multiple omics in individuals that were healthy or diagnosed with AD. Although machine learning approaches are well-suited to handle the complexity of omics data, the models typically lack interpretability. Additionally, while the genetic landscape of AD is somewhat more established, the proteomic landscape of the diseased brain is less well-understood. Here, we establish a deep learning method that takes advantage of an ensemble of autoencoders (AEs) -- EnsembleOmicsAE-to reduce the complexity of proteomics data into a reduced space containing a small number of latent features. We combine brain proteomic data from 559 individuals across three AD cohorts and demonstrate that the ensemble autoencoder models generate stable latent features which are well-suited for downstream biological interpretation. We present an algorithm to calculate feature importance scores based on the iterative scrambling of individual input features (i.e., proteins) and show that the algorithm identifies signaling modules (AE signaling modules) that are significantly enriched in protein-protein interactions. The molecular drivers of AD identified within the AE signaling modules derived with EnsembleOmicsAE were missed by linear methods, including integrin signaling and cell adhesion. Finally, we characterize the relationship between the AE signaling modules and the age of death of the patients and identify a differential regulation of vimentin and MAPK signaling in younger compared with older AD patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Although some of the novel systemic treatments, especially the group of tyrosine kinase inhibitors, have shown a durable central nervous system response, ionizing radiation remains the mainstay in the management of brain metastases (BM). Recent technological advancements have enabled the replacement of whole-brain radiotherapy with localized stereotactic radiotherapy (SRT) for treating up to 10 BM, either as a primary or combined treatment, reducing neurotoxicity and improving local control (LC). The delivered target dose and patient selection play a crucial role in enhancing treatment efficacy. However, there is still limited evidence supporting which factors most affect LC and which patients derive the greatest benefit from SRT. This retrospective single-institutional study evaluated treatment outcomes in a heterogeneous patient population treated with Linac-based SRT, with the aim of identifying potential dosimetric and clinical prognostic factors to better inform the decision-making process. Background/Objectives: To report on predictive factors in Linac-based SRT for single and multiple BM. Methods: Consecutive patients receiving either one or three fractions of single-isocenter coplanar VMAT SRT were retrospectively included. The GTV-PTV margin was 1–2 mm. The delivered target dose was estimated by recalculating the original plans on roto-translated CT according to errors recorded by post-treatment CBCT. The Kaplan–Meier method estimated local progression-free survival (LPFS), intracranial progression-free survival (IPFS), and overall survival (OS). Log-rank and Wilcoxon–Mann–Whitney tests evaluated inter-group differences, whereas Cox regression analysis assessed prognostic factors. Results: Fifty females and fifty males, with a median age of 69 years, received 107 SRTs. A total of 213 BM (range, 1–10 per treatment) with a median volume of 0.22 cc were irradiated with a median minimum BED of 59.5 Gy. The median delivered GTV D95 reduction was −0.3%. The median follow-up was 11 months. Nineteen LP events and a 1-year LC rate of 90.1% were observed. The GTV coverage did not correlate with LC, while the GTV volume was a risk factor for LP, with the 1-year rate dropping to 73% for volumes ≥ 0.88 cc. The median LPFS, IPFS, and OS were 6, 5, and 7 months, respectively. Multivariate analysis showed that patients with melanoma histology and those receiving a second or subsequent systemic therapy line had the worst outcomes, whereas patients with adenocarcinoma histology and mutations showed better results. Conclusions: The accuracy and efficacy of the Linac-based SRT approach for BM were confirmed, but the dose distribution alone failed to predict the treatment response, suggesting that other factors must be considered to maximize SRT outcomes. [ABSTRACT FROM AUTHOR]

Background: There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines. Objective: To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1. Materials and methods: Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow‐up closure date was September 1, 2021. Curative‐intent surgery, curative‐intent radiotherapy, or palliative care was undertaken. Endpoints included five‐year overall, disease‐specific, and disease‐free survival from the date of treatment. Results: Five‐year Kaplan–Meier overall survival was 61.9% (95% CI 46.2%–74.3%), with disease‐specific survival of 74.6% (95% CI 58.8%–85.3%), and disease‐free survival 62.1% (95% CI 46.5%–74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease‐specific survival of 94.1% at 5 years with 82.5% disease‐free survival. Discussion: Five‐year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative‐intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival. Conclusion: Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1. [ABSTRACT FROM AUTHOR]

This article supplements our earlier article on the Nutbush dance, ‘Doing the Nutbush’. After that was published, there was a media frenzy which resulted in many comments on The Guardian site and on the ABC Facebook site. We also received a number of emails. All these contributions have helped fine-tune the history of the dance that we have been examining. Two key things became clear. Around 1970 there was a push in state education departments across Australia to substitute the American line dance, the Madison, for bush dances as a way of updating and making more relevant dance for primary school children. Meanwhile, during the 1960s, another American dance, the Alley Cat, had been becoming popular mostly with children but to some extent also with adults. Around 1975 the Alley Cat started to be danced to Ike and Tina Turner’s Nutbush City Limits in primary school physical education (PE) classes. As this was happening, a few more energetic steps were added to the dance. The result was a dance named after the song, the Nutbush. This then became a popular dance in state primary schools across the country. With the aid of the new information, we have been given, this supplementary article traces this history. [ABSTRACT FROM AUTHOR]