Intraoperative ultrasound-guided breast-conserving surgery: A performance analysis on the basis of novel cancer lesion classification and patients' cosmetic satisfaction.

Background: Intraoperative ultrasound-guided breast-conserving surgery guarantees real-time direct visualization of tumor and resection margins. We compared surgical, oncologic, and cosmetic outcomes between intraoperative ultrasound-guided breast-conserving surgery and traditional (palpation- or wire-guided) surgery across all breast cancer lesion types.

Methods: This prospective observational cohort study was conducted at the Veneto Institute of Oncology between January 2021 and October 2022.

Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study.

Purpose: The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND.

Methods: The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.

Mobility Gaps of Hydrogenated Amorphous Silicon Related to Hydrogen Concentration and Its Influence on Electrical Performance.

This paper presents a comprehensive study of hydrogenated amorphous silicon (a-Si)-based detectors, utilizing electrical characterization, Raman spectroscopy, photoemission, and inverse photoemission techniques. The unique properties of a-Si have sparked interest in its application for radiation detection in both physics and medicine. Although amorphous silicon (a-Si) is inherently a highly defective material, hydrogenation significantly reduces defect density, enabling its use in radiation detector devices.

Surgery Plays a Leading Role in Breast Cancer Treatment for Patients Aged ≥90 Years: A Large Retrospective Cohort Study.

Background: The population aged ≥90 years is increasing worldwide, yet nearly 50% of elderly breast cancer (BC) patients receive suboptimal treatments, resulting in high rates of BC-related mortality. We analyzed clinical and survival outcomes of nonagenarian BC patients to identify effective treatment strategies.

Methods: This single-institution retrospective cohort study analyzed patients aged ≥90 years diagnosed with stage I-III BC between 2007 and 2018.

Dosimetry of microbeam radiotherapy by flexible hydrogenated amorphous silicon detectors.

Detectors that can provide accurate dosimetry for microbeam radiation therapy (MRT) must possess intrinsic radiation hardness, a high dynamic range, and a micron-scale spatial resolution. In this work we characterize hydrogenated amorphous silicon detectors for MRT dosimetry, presenting a novel combination of flexible, ultra-thin and radiation-hard features.Two detectors are explored: an n-type/intrinsic/p-type planar diode (NIP) and an NIP with an additional charge selective layer (NIP + CSC).

Strained Silicon Technology: Non-Destructive High-Lateral-Resolution Characterization Through Tip-Enhanced Raman Spectroscopy.

The semiconductor industry is undergoing a transformative phase, marked by the relentless drive for miniaturization and a constant demand for higher performance and energy efficiency. However, the reduction of metal-oxide-semiconductor field-effect transistor sizes for advanced technology nodes below 10 nm presents several challenges. In response, strained silicon technology has emerged as a key player, exploiting strain induction in the silicon crystal lattice to improve device performance.

Toward the nanoscale chemical and physical probing of milk-derived extracellular vesicles using Raman and tip-enhanced Raman spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) is an advanced technique to perform local chemical analysis of the surface of a sample through the improvement of the sensitivity and the spatial resolution of Raman spectroscopy by plasmonic enhancement of the electromagnetic signal in correspondence with the nanometer-sized tip of an atomic force microscope (AFM). In this work, TERS is demonstrated to represent an innovative and powerful approach for studying extracellular vesicles, in particular bovine milk-derived extracellular vesicles (mEVs), which are nanostructures with considerable potential in drug delivery and therapeutic applications. Raman spectroscopy has been used to analyze mEVs at the micrometric and sub-micrometric scales to obtain a detailed Raman spectrum in order to identify the 'signature' of mEVs in terms of their characteristic molecular vibrations and, therefore, their chemical compositions.

Characterization of a flexible a-Si:H detector for in vivo dosimetry in therapeutic x-ray beams.

Background: The increasing use of complex and high dose-rate treatments in radiation therapy necessitates advanced detectors to provide accurate dosimetry. Rather than relying on pre-treatment quality assurance (QA) measurements alone, many countries are now mandating the use of in vivo dosimetry, whereby a dosimeter is placed on the surface of the patient during treatment. Ideally, in vivo detectors should be flexible to conform to a patient's irregular surfaces.

Discovery and Structure-Activity Relationships of Novel DAF-12 Receptor Modulators.

The nuclear receptor DAF-12 has been recognized as the key molecular player regulating the life cycle of the nematode parasite . DAF-12 ligands permit the receptor to function as an on/off switch modulating infection, making it vulnerable to therapeutic intervention. In this study, we report the design and synthesis of a set of novel dafachronic acid derivatives, which were used to outline the first structure-activity relationship targeting the DAF-12 receptor and to unveil hidden properties shared by the molecular shape of steroidal ligands that are relevant to the receptor binding and modulation.

Chemical exploration of TGR5 functional hot-spots: Synthesis and structure-activity relationships of C7- and C23-Substituted cholic acid derivatives.

The activation of TGR5 bestows on bile acids the ability to modulate nongenomic signaling pathways, which are responsible of physiological actions including immunosuppressive and anti-inflammatory properties as well as the regulation of glucose metabolism and energy homeostasis. TGR5 agonists have therefore emerged in drug discovery and preclinical appraisals as promising compounds for the treatment of liver diseases and metabolic syndrome. In this study, we have been devising site-selected chemical modifications of the bile acid scaffold to provide novel chemical tools able to modulate the functions of TGR5 in different tissues.

Intraoperative Ultrasound-Guided Conserving Surgery for Breast Cancer: No More Time for Blind Surgery.

Background: Breast-conserving surgery (BCS) still remains a blind surgery despite all available tumor localization methods. Intraoperative ultrasound (IOUS) allows real-time visualization during all resection phases.

Methods: This was a prospective observational cohort study conducted at the Veneto Institute of Oncology between January 2021 and June 2022.

Hydrogenated amorphous silicon high flux x-ray detectors for synchrotron microbeam radiation therapy.

. Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field.

Novel 1,4-Dihydropyridine Derivatives as Mineralocorticoid Receptor Antagonists.

The mineralocorticoid receptor (MR) belongs to the steroid receptor subfamily of nuclear receptors. MR is a transcription factor key in regulating blood pressure and mineral homeostasis. In addition, it plays an important role in a broad range of biological and pathological conditions, greatly expanding its interest as a pharmacological target.

Novel pyridine-containing histone deacetylase inhibitors strongly arrest proliferation, induce apoptosis and modulate miRNAs in cancer cells.

After over 30 years of research, the development of HDAC inhibitors led to five FDA/Chinese FDA-approved drugs and many others under clinical or preclinical investigation to treat cancer and non-cancer diseases. Herein, based on our recent development of pyridine-based isomers as HDAC inhibitors, we report a series of novel 5-acylamino-2-pyridylacrylic- and -picolinic hydroxamates and 2'-aminoanilides 5-8 as anticancer agents. The hydroxamate 5d proved to be quite HDAC3/6-selective exhibiting IC values of 80 and 11 nM, respectively, whereas the congener 5e behaved as inhibitor of HDAC1-3, -6, -8, and -10 (class I/IIb-selective inhibitor) at nanomolar level.

A Study of the Radiation Tolerance and Timing Properties of 3D Diamond Detectors.

We present a study on the radiation tolerance and timing properties of 3D diamond detectors fabricated by laser engineering on synthetic Chemical Vapor Deposited (CVD) plates. We evaluated the radiation hardness of the sensors using Charge Collection Efficiency (CCE) measurements after neutron fluences up to 1016 n/cm2 (1 MeV equivalent.) The radiation tolerance is significantly higher when moving from standard planar architecture to 3D architecture and increases with the increasing density of the columnar electrodes.

High-Resolution Photoemission Study of Neutron-Induced Defects in Amorphous Hydrogenated Silicon Devices.

In this paper, by means of high-resolution photoemission, soft X-ray absorption and atomic force microscopy, we investigate, for the first time, the mechanisms of damaging, induced by neutron source, and recovering (after annealing) of p-i-n detector devices based on hydrogenated amorphous silicon (a-Si:H). This investigation will be performed by mean of high-resolution photoemission, soft X-Ray absorption and atomic force microscopy. Due to dangling bonds, the amorphous silicon is a highly defective material.

Farnesoid X receptor activation by the novel agonist TC-100 (3α, 7α, 11β-Trihydroxy-6α-ethyl-5β-cholan-24-oic Acid) preserves the intestinal barrier integrity and promotes intestinal microbial reshaping in a mouse model of obstructed bile acid flow.

The intestinal tract hosts the gut microbiota (GM), actively shaping health. Bile acids(BAs) are both digestive and signaling molecules acting as hormones via the activation of farnesoid X receptor (FXR). Obstruction of bile flow initiates a cascade of pathological events ultimately leading to intestinal mucosal injury.

Development of 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulfate sodium salt (INT-767): Process optimization, synthesis and characterization of metabolites.

Herein we report our synthetic efforts in supporting the development of the bile alcohol sulfate INT-767, a FXR/TGR5 dual agonist with remarkable therapeutic potential for liver disorders. We describe the process development to a final route for large scale preparation and analogues synthesis. Key sequences include Grignard addition, a one-pot two-step shortening-reduction of the carboxylic side chain, and the final sulfation reaction.

First-in-Class Inhibitors of the Ribosomal Oxygenase MINA53.

MINA53 is a JmjC domain 2-oxoglutarate-dependent oxygenase that catalyzes ribosomal hydroxylation and is a target of the oncogenic transcription factor -MYC. Despite its anticancer target potential, no small-molecule MINA53 inhibitors are reported. Using ribosomal substrate fragments, we developed mass spectrometry assays for MINA53 and the related oxygenase NO66.

Synthesis and biological activity of cyclopropyl Δ7-dafachronic acids as DAF-12 receptor ligands.

The four cyclopropyl stereoisomers of Δ7-dafachronic acids were prepared from the bile acid hyodeoxycholic acid and employed as chemical tools to exploit the importance of the orientation and spatial disposition of the carboxyl tail and the C25-methyl group for the binding at the DAF-12 receptor. The synthesis route was based on (a) Walden inversion and stereoselective PtO-hydrogenation to convert the L-shaped 5β-cholanoid scaffold into the planar 5α-sterol intermediate; (b) two-carbon homologation of the side chain by Wittig and cyclopropanation reaction; and (c) formation of the 3-keto group and Δ7 double bond. The synthesized isomers were isolated and tested for their activity as DAF-12 ligands by AlphaScreen assays.

Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients' Lives, and Reduce Costs.

Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients' lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption.

A Study of the Radiation Tolerance of CVD Diamond to 70 MeV Protons, Fast Neutrons and 200 MeV Pions.

We measured the radiation tolerance of commercially available diamonds grown by the Chemical Vapor Deposition process by measuring the charge created by a 120 GeV hadron beam in a 50 μm pitch strip detector fabricated on each diamond sample before and after irradiation. We irradiated one group of samples with 70 MeV protons, a second group of samples with fast reactor neutrons (defined as energy greater than 0.1 MeV), and a third group of samples with 200 MeV pions, in steps, to (8.