Pan-KRAS inhibitors BI-2493 and BI-2865 display potent anti-tumor activity in tumors with KRAS wild-type allele amplification.

KRASG12C selective inhibitors, such as sotorasib and adagrasib, have raised hopes of targeting other KRAS mutant alleles in cancer patients. We report that KRAS wild-type amplified tumor models are sensitive to treatment with the small molecule KRAS inhibitors BI-2493 and BI-2865. These pan-KRAS inhibitors directly target the "OFF" state of KRAS and result in potent anti-tumor activity in pre-clinical models of cancers driven by KRAS mutant proteins.

Proposal for a Ramsey Neutron-Beam Experiment to Search for Ultralight Axion Dark Matter at the European Spallation Source.

High-intensity neutron beams, such as those available at the European Spallation Source (ESS), provide new opportunities for fundamental discoveries. Here, we discuss a novel Ramsey neutron-beam experiment to search for ultralight axion dark matter through its coupling to neutron spins, which would cause the neutron spins to rotate about the velocity of the neutrons relative to the dark matter halo. We estimate that experiments at the HIBEAM beamline with a 50 m free flight path at the ESS can improve the sensitivity to the axion-neutron coupling compared to the current best laboratory limits by up to 2-3 orders of magnitude over the axion mass range 10^{-22}  eV-10^{-16}  eV.

Translation, cross-cultural adaptation, and validation of the Italian version of the Parkinson's disease caregiver burden questionnaire (PDCB-I).

Background: To translate and cross-culturally adapt the Parkinson's Disease Caregiver Burden questionnaire (PDBC) into Italian language and to evaluate the psychometric properties of the Italian version in terms of test-retest reliability, internal consistency, and construct validity.

Methods: The PDBC-I was developed by forward-backward translation to establish correspondence with the original English latest version. Psychometric properties were estimated in a sample of primary caregivers of individuals with Parkinson's disease.

Multiomic Profiling and Neuroprotective Bioactivity of Hairy Root-Derived Extracellular Vesicles in a Cellular Model of Parkinson's Disease.

Purpose: Extracellular vesicles (EVs) are promising tools for nanomedicine and nanobiotechnology. The purification of mammalian-derived EVs involves intensive processes, and their therapeutic application raises multiple safety and regulatory issues. Plants have the potential to serve as nonconventional sources of therapeutically relevant EVs.

(L.) Hill extracts: phytochemical characterization and exploitation of its biological activities by loading into nanoformulation.

Introduction: The current investigation presents a two-fold approach to rediscovering the potential of as a wild edible plant, both in its raw extract form and as a nanoformulated product. Furthermore, the study aimed to promote the valorization of traditional dishes and contribute to biodiversity conservation and sustainable use of , thus enhancing economic profits.

Methods: Liquid chromatography-mass spectrometry analyses were conducted to characterize the metabolite profile of the raw and cooked leaf extracts, and the extract from discarded leaves.

Physical model of neutron scattering by clathrate hydrate and C60hosting paramagnetic oxygen molecules.

This paper describes the physical modelling of neutron scattering in two polycrystalline inclusion compounds, fully deuterated clathrate hydrate andC60, each with paramagnetic oxygen as guest molecules. For studying the suitability of these materials for neutron moderation to very low energies, the model includes, in addition to the magnetic neutron scattering by the oxygen, the nuclear scattering by all constituents. The theoretical total cross sections are calculated based on the phonon density of states obtained by density functional theory and molecular dynamics simulations.

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study.

Background: Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia.

Neutron instrument concepts for a high intensity moderator at the European spallation source.

In the course of the Horizon 2020 project HighNESS, a second moderator concept has been developed for the European Spallation Source, which complements the currently built moderator and is optimized for high intensity with a large viewable surface area. In this work we introduce conceptual designs for neutron instruments for condensed matter research designed to make optimal use of the capabilities of this moderator. The focus is on two concepts for small-angle neutron scattering and one neutron imaging instrument, which are intended to complement corresponding instruments that are already under construction at the European Spallation Source.

Unleashing the potential of metaphors: a categorization system for exploring return to work after maternity.

Purpose: Return to work after maternity leave represents a radical change in women's lives. This paper aims to present a new metaphor categorization system based on two studies, which could assist working mothers in expressing the nuances of their experience when returning to work after maternity leave.

Methods: We carried out the analysis of the metaphors according to the method for thematic analysis, through a multistep, iterative coding process.

Exploring Influence of Production Area and Harvest Time on Specialized Metabolite Content of Leaves and Evaluation of Antioxidant and Anti-Aging Properties.

Calabrian is one of the most appreciated licorice varieties worldwide, and its leaves are emerging as a valuable source of bioactive compounds. Nevertheless, this biomass is usually discarded, and its valorization could contribute to boost the economic value of the licorice production chain. In this study, the effects of production area and harvest time on the specialized metabolite content of leaves (GGL) and also the antioxidant and anti-aging properties are evaluated to explore the potential of this untapped resource and to select the most optimal harvesting practices.

Reverse engineering in forensic investigations: a new approach to bite mark analysis.

The study of bite marks provides crucial elements that contribute towards identifying the biter. In many cases, it assumes importance when bite marks are detected on the body of a victim of violence, but it could also be relevant when the bite marks are seen on food substances at the crime scene. In both circumstances, comparing the bite marks with a suspect's dentition can be decisive in confirming or excluding the culpability.

Search for Evidence of Baryogenesis and Dark Matter in B^{+}→ψ_{D}+p Decays at BABAR.

A new dark sector antibaryon, denoted ψ_{D}, could be produced in decays of B mesons. This Letter presents a search for B^{+}→ψ_{D}+p (and the charge conjugate) decays in e^{+}e^{-} annihilations at 10.58 GeV, using data collected in the BABAR experiment.

Phosphorus Acquisition Efficiency and Transcriptomic Changes in Maize Plants Treated with Two Lignohumates.

Lignohumates are increasing in popularity in agriculture, but their chemistry and effects on plants vary based on the source and processing. The present study evaluated the ability of two humates (H1 and H2) to boost maize plant performance under different phosphorus (P) availability (25 and 250 μM) conditions in hydroponics, while understanding the underlying mechanisms. Humates differed in chemical composition, as revealed via elemental analysis, phenol and phytohormone content, and thermal and spectroscopic analyses.

Child abuse and neglect: oral and dental signs and the role of the dentist.

Historically, the law, dental and forensic literature has included numerous articles concerning abused children. The orofacial structures are injured frequently in the maltreated child. Injuries of the neck, head, face, and oral cavity represent the most affected areas of the victim's body that routinely sustain physical trauma in child maltreatment cases.

An Interesting Case of Neonatal AKI: What Is the Time to Consider Anuria Irreversible?

Acute kidney injury is a frequent complication for critical newborns. Its management is a significant challenge, especially in extremely low-birth-weight (ELBW) infants. Currently, peritoneal dialysis (PD) is the most manageable treatment.

A novel, integrated approach for understanding and investigating Healthcare Associated Infections: A risk factors constellation analysis.

Introduction: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are major public health threats in upper- and lower-middle-income countries. Electronic health records (EHRs) are an invaluable source of data for achieving different goals, including the early detection of HAIs and AMR clusters within healthcare settings; evaluation of attributable incidence, mortality, and disability-adjusted life years (DALYs); and implementation of governance policies. In Italy, the burden of HAIs is estimated to be 702.

Design of an Herbal Preparation Composed by a Combination of L. and L. Extracts, Magnolol and Diosmetin to Address Chronic Venous Diseases through an Anti-Inflammatory Effect and AP-1 Modulation.

Chronic venous disease (CVD) is an often underestimated inflammatory pathological condition that can have a serious impact on quality of life. Many therapies have been proposed to deal with CVD, but unfortunately the symptoms recur with increasing frequency and intensity as soon as treatments are stopped. Previous studies have shown that the common inflammatory transcription factor AP-1 (activator protein-1) and nuclear factor kappa-activated B-cell light chain enhancer (NF-kB) play key roles in the initiation and progression of this vascular dysfunction.

PEGylated Liposomes Loaded with Carbamate Inhibitor ANP0903 Trigger Apoptosis by Enhancing ER Stress in HepG2 Cancer Cells.

Liver cancer is one of the most common causes of cancer death worldwide. In recent years, substantial progress has been made in the development of systemic therapies, but there is still the need for new drugs and technologies that can increase the survival and quality of life of patients. The present investigation reports the development of a liposomal formulation of a carbamate molecule, reported as ANP0903, previously tested as an inhibitor of HIV-1 protease and now evaluated for its ability to induce cytotoxicity in hepatocellular carcinoma cell lines.

Psychological Distress of Healthcare Workers in 4 Hospitals Compared to General Population During the First Italian Wave of COVID-19 Pandemic.

COVID-19 caused important consequences on public health, economy, physical, and mental health of people. The aim of this study was to evaluate the impact of COVID-19 on frontline workers, comparing them with their colleagues who had no contact with the patients and with the general population, by administering an online questionnaire based on the Distress Questionnaire-5 (DQ5). The study was carried out during the first Italian wave of COVID-19 pandemic from 1st to 30th of April.

Rhanteriol, a New Desf. Lignan with Pharmacological Potential as an Inhibitor of Enzymes Involved in Neurodegeneration and Type 2 Diabetes.

Several specialized plant metabolites are reported to be enzyme inhibitors. In this investigation, the phytochemical composition and the biological activity of Desf. were studied.