POLE mutations in endometrial carcinoma: Clinical and genomic landscape from a large prospective single-center cohort.

Background: To date, 11 DNA polymerase epsilon (POLE) pathogenic variants have been declared "hotspot" mutations. Patients with endometrial cancer (EC) characterized by POLE hotspot mutations (POLEmut) have exceptional survival outcomes. Whereas international guidelines encourage deescalation of adjuvant treatment in early-stage POLEmut EC, data regarding safety in POLEmut patients with unfavorable characteristics are still under investigation.

Melt electrowriting of hydrophilic/hydrophobic multiblock copolymers for bone tissue regeneration.

Bone-healing complications can occur due to large bone defects or an insufficient bone regeneration capacity. Melt electrowriting (MEW) is a potential candidate for manufacturing synthetic scaffolds that may resolve bone-healing complications. MEW can exploit various biocompatible polymers with a wide range of tissue engineering applications.

Actionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort.

Background: According to the European Society for Clinical Oncology (ESMO) guidelines, the therapeutic algorithm for early-stage epithelial ovarian carcinoma (EOC) is primarily based on grading and histotype. Adjuvant chemotherapy is usually recommended for high-grade tumors and for the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IC; however, overtreatment remains a concern. Conversely, patients truly at higher risk of recurrence currently lack access to additional therapeutic strategies.

Enthesitis on Chip - A Model for Studying Acute and Chronic Inflammation of the Enthesis and its Pharmacological Treatment.

Enthesitis, the inflammation of the enthesis, which is the point of attachment of tendons and ligaments to bones, is a common musculoskeletal disease. The inflammation often originates from the fibrocartilage region of the enthesis as a consequence of mechanical overuse or -load and consequently tissue damage. During enthesitis, waves of inflammatory cytokines propagate in(to) the fibrocartilage, resulting in detrimental, heterotopic bone formation.

Uni- and Multivariate Analyses of Cancer Risk in Cytologically Indeterminate Thyroid Nodules: A Single-Center Experience.

Every year in Italy, about 60,000 new cases of nodular thyroid pathology are diagnosed, of which almost 30% are cytologically indeterminate (TIR3A/3B). The risk of malignancy reported in the literature on thyroid nodules ranges from 5% to 15% for TIR3A and from 15% to 30% for TIR3B. It is suspected that these percentages are higher in practice.

Microfluidically Aligned Collagen to Maintain the Phenotype of Tenocytes In Vitro.

Tendon is a highly organized tissue that transmits forces between muscle and bone. The architecture of the extracellular matrix of tendon, predominantly from collagen type I, is important for maintaining tenocyte phenotype and function. Therefore, in repair and regeneration of damaged and diseased tendon tissue, it is crucial to restore the aligned arrangement of the collagen type I fibers of the original matrix.

Conjunctival melanoma following cornea transplant from a cancer donor: A case report.

Purpose: Conjunctival melanoma is a rare ocular tumor. We report a case of ocular conjunctival melanoma during topical immunosuppression, after a corneal transplant from a donor with metastatic melanoma.

Observation: A 59-year-old white male presented with a progressive nonpigmented conjunctival lesion in his right eye.

A Computational Framework for Comprehensive Genomic Profiling in Solid Cancers: The Analytical Performance of a High-Throughput Assay for Small and Copy Number Variants.

In January 2022, our institution launched a comprehensive cancer genome profiling program on 10 cancer types using a non-IVD solution named the TruSight Oncology 500 Assay provided by Illumina. The assay analyzes both DNA and RNA, identifying Single-Nucleotide Variants (SNV)s and Insertion-Deletion (InDel) in 523 genes, as well as known and unknown fusions and splicing variants in 55 genes and Copy Number Alterations (CNVs), Mutational Tumor Burden (MTB) and Microsatellite Instability (MSI). According to the current European IVD Directive 98/79/EC, an internal validation was performed before running the test.

Integrating a Comprehensive Cancer Genome Profiling into Clinical Practice: A Blueprint in an Italian Referral Center.

The implementation of cancer molecular characterization in clinical practice has improved prognostic re-definition, extending the eligibility to a continuously increasing number of targeted treatments. Broad molecular profiling technologies better than organ-based approaches are believed to serve such dynamic purposes. We here present the workflow our institution adopted to run a comprehensive cancer genome profiling in clinical practice.

Experience on the Management of Patients with Asthma or Chronic Obstructive Pulmonary Disease During the COVID-19 Pandemic: the NEUMOBIAL Study.

Introduction: Chronic obstructive pulmonary disease (COPD) and asthma are treatable but greatly underdiagnosed disorders. Telemedicine made it possible to continue diagnosis, follow-up visits and treatment modifications during the COVID-19 pandemic. The present study describes the management of patients with COPD and asthma, and their treatments during the pandemic from the pulmonologist's perspective.

Solvent influence on manufacturability, phase behavior and morphology of amorphous solid dispersions prepared via bead coating.

Bead coating or fluid-bed coating serves as an auspicious solvent-based amorphous solid dispersion (ASD) manufacturing technique in respect of minimization of potential physical stability issues. However, the impact of solvent selection on the bead coating process and its resulting pellet formulation is, to the best of our knowledge, never investigated before. This study therefore aims to investigate the influence of the solvent on the bead coating process itself (i.

Patients with epilepsy during the COVID-19 pandemic: Depressive symptoms and their association with healthcare access.

Background: The coronavirus disease 2019 (COVID-19) outbreak impacted the lives of worldwide people with epilepsy (PWE) in various aspects, particularly in those countries most significantly affected by this pandemic, such as Brazil. We aimed to investigate the prevalence of depressive symptoms in PWE and their correlation with epilepsy features and access to treatment.

Methods: PWE were invited to answer a cross-sectional online-based survey to assess and rate depressive symptoms using the NDDI-E during the first year of the COVID-19 pandemic and its relation to multiple lifestyles epilepsy clinical aspects.

Relativistic Bell Test within Quantum Reference Frames.

A still widely debated question in the field of relativistic quantum information is whether entanglement and the degree of violation of Bell's inequalities for massive relativistic particles are frame independent or not. At the core of this question is the effect that spin gets entangled with the momentum degree of freedom at relativistic velocities. Here, we show that Bell's inequalities for a pair of particles can be maximally violated in a special-relativistic regime, even without any postselection of the momentum of the particles.

The novel Mechanical Ventilator Milano for the COVID-19 pandemic.

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests.

Author Correction: Quantum clocks and the temporal localisability of events in the presence of gravitating quantum systems.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20105-3.

Quantum clocks and the temporal localisability of events in the presence of gravitating quantum systems.

The standard formulation of quantum theory relies on a fixed space-time metric determining the localisation and causal order of events. In general relativity, the metric is influenced by matter, and is expected to become indefinite when matter behaves quantum mechanically. Here, we develop a framework to operationally define events and their localisation with respect to a quantum clock reference frame, also in the presence of gravitating quantum systems.

Relativistic Quantum Reference Frames: The Operational Meaning of Spin.

The spin is the prime example of a qubit. Encoding and decoding information in the spin qubit is operationally well defined through the Stern-Gerlach setup in the nonrelativistic (i.e.

Quantum mechanics and the covariance of physical laws in quantum reference frames.

In physics, every observation is made with respect to a frame of reference. Although reference frames are usually not considered as degrees of freedom, in all practical situations it is a physical system which constitutes a reference frame. Can a quantum system be considered as a reference frame and, if so, which description would it give of the world? Here, we introduce a general method to quantise reference frame transformations, which generalises the usual reference frame transformation to a "superposition of coordinate transformations".

Histomorphometric analysis of osteocyte lacunae in human and pig: exploring its potential for species discrimination.

In recent years, several studies have focused on species discrimination of bone fragments by histological analysis. According to literature, the most consistent distinguishing features are Haversian canal and Haversian system areas. Nonetheless, there is a consistent overlap between human and non-human secondary osteon dimensions.

Entanglement of quantum clocks through gravity.

In general relativity, the picture of space-time assigns an ideal clock to each world line. Being ideal, gravitational effects due to these clocks are ignored and the flow of time according to one clock is not affected by the presence of clocks along nearby world lines. However, if time is defined operationally, as a pointer position of a physical clock that obeys the principles of general relativity and quantum mechanics, such a picture is, at most, a convenient fiction.

Development of a synthetic tissue engineered three-dimensional printed bioceramic-based bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro.

Over the last decade there have been increasing efforts to develop three-dimensional (3D) scaffolds for bone tissue engineering from bioactive ceramics with 3D printing emerging as a promising technology. The overall objective of the present study was to generate a tissue engineered synthetic bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro, thereby mimicking the advantageous properties of autogenous bone grafts and facilitating usage for reconstructing segmental discontinuity defects in vivo. To this end, 3D scaffolds were developed from a silica-containing calcium alkali orthophosphate, using, first, a replica technique - the Schwartzwalder-Somers method - and, second, 3D printing, (i.

Feasibility, efficacy and safety of stent insertion as a palliative treatment for malignant strictures in the cervical segment of the esophagus and the hypopharynx.

Background: 50% of esophageal cancers are inoperable at the time of diagnosis, and around 15% involve the cervical esophagus. The hypopharynx is often involved by these malignancies as well. Palliation of cervical esophageal malignancies through stent insertion is considered limited due to technical challenges, poor patient tolerance and high complication rate.

A PHACES syndrome unmasked by propranolol interruption in a tetralogy of Fallot patient: case report and extensive review on new indications of beta blockers.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and usually they don't require specific therapy. In 10-20% of cases IHs are able to generate complication and medical/surgical intervention is needed. For many decades standard treatment consisted in oral or intralesional corticosteroids until Leaute-Labreze and colleagues published the first report on the efficacy of propranolol for cutaneous infantile hemangiomas in 2008.