Covalent Modification of p53 by ()-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one.

is commonly mutated in cancer, giving rise to loss of wild-type tumor suppressor function and increases in gain-of-function oncogenic roles. Thus, inhibition of mutant p53 and reactivation of wild-type function represents a potential means to target diverse tumor types. ()-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one (NSC59984), first identified from a high-throughput screen, induces wild-type p53 signaling and antiproliferative effects while inhibiting mutant p53 gain-of-function activities.

How difficult is titanium plate and screw implant removal? A retrospective case series.

Introduction: Titanium implants are commonly used for surgical fixation in orthopedic trauma, and have many benefits compared to stainless steel implants. Despite these benefits, some orthopedic surgeons remain hesitant to use titanium implants due to concerns of difficulty with future implant removal, given concerns with cold-welding and screw strippage. The objective of this study was to assess difficulties associated with titanium plate and screw implant removal.

Urinary Incontinence Medications: Patient-Initiated Concerns in Primary Care.

Importance: Guideline-recommended medications for overactive bladder and urge urinary incontinence (OAB/UUI) are effective but have high costs and side effects. Little is known about patient concerns regarding these medications when prescribed by their primary care providers (PCPs).

Objective: The aim of the study was to describe PCP-patient interactions when prescribing medications for OAB/UUI, specifically clinical concerns, cost and authorization issues, and mode of communication for these interactions.

Pain and Post-traumatic Stress Disorder Symptoms: Dyadic Relationships Between Canadian Armed Forces Members/Veterans With Chronic Pain and Their Offspring.

Chronic pain and mental health issues occur at higher rates in Veterans than the general population. One widely recognized mental health issue faced by Veterans is post-traumatic stress disorder (PTSD). Trauma symptoms and pain frequently co-occur and are mutually maintained due to shared mechanisms.

Investigation of Two Zr-p-NOBn-DOTA Isomers via NMR and Quantum Chemical Studies.

A combination of NMR studies and quantum chemical calculations were employed to investigate the structure and energetics of Zr chelates of pNOBn-DOTA. We have demonstrated that two discrete regioisomeric chelates are generated during the complex formation. The nitrobenzyl substituent can adopt either an equatorial corner or side position on the macrocyclic ring.

IMPROVER (Involving Men with Prostate Cancer in Engaged Research): Assessing Patient Experience With Testing, Diagnosis, And Surveillance.

Background: Our understanding of patient experiences with prostate cancer testing for diagnosis and surveillance is limited. The aim of this study was to collaborate with patients and clinicians to understand their lived experience and unmet needs around the early detection, diagnosis and monitoring (active surveillance) of prostate cancer.

Methods: Two focus groups were held with patients (n = 20) and healthcare professionals (n = 16), to identify the main challenges in prostate cancer detection, diagnosis, and monitoring.

Parametric investigation of ultrashort pulsed laser surface texturing on aluminium alloy 7075 for hydrophobicity enhancement.

Unlabelled: Hydrophobicity plays a pivotal role in mitigating surface fouling, corrosion, and icing in critical marine and aerospace environments. By employing ultrafast laser texturing, the characteristic properties of a material's surface can be modified. This work investigates the potential of an advanced ultrafast laser texturing manufacturing process to enhance the hydrophobicity of aluminium alloy 7075.

Challenges and approaches to calibrating patient phenotype as evidence for cancer gene variant classification under ACMG/AMP guidelines.

Since first publication of the American College of Medical Genetics and Genomics/Association for Medical Pathology (ACMG/AMP) variant classification guidelines, additional recommendations for application of certain criteria have been released (https://clinicalgenome.org/docs/), to improve their application in the diagnostic setting. However, none have addressed use of the PS4 and PP4 criteria, capturing patient presentation as evidence towards pathogenicity.

Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors.

Herein, we describe the global comparison of miRNAs in human pancreatic cancer tumors, adjacent normal tissue, and matched patient-derived xenograft models using microarray screening. RNA was extracted from seven tumor, five adjacent normal, and eight FI PDX tumor samples and analyzed by Affymetrix GeneChip miRNA 4.0 array.

Structural Optimization and Anticancer Activity of Polo-like Kinase 1 (Plk1) Polo-Box Domain (PBD) Inhibitors and Their Prodrugs.

Polo-like kinase 1 (Plk1), a mitotic kinase whose activity is widely upregulated in various human cancers, is considered an attractive target for anticancer drug discovery. Aside from the kinase domain, the C-terminal noncatalytic polo-box domain (PBD), which mediates the interaction with the enzyme's binding targets or substrates, has emerged as an alternative target for developing a new class of inhibitors. Various reported small molecule PBD inhibitors exhibit poor cellular efficacy and/or selectivity.

Impact of the COVID-19 pandemic on cancer care in Ireland - Perspectives from a COVID-19 and Cancer Working Group.

Upon the COVID-19 pandemic onset in Ireland, cancer service disruptions occurred due to prioritisation of COVID-19 related care, redeployment of staff, initial pausing of screening, diagnostic, medical and surgical oncology procedures, staff shortages due to COVID-19 infection and impacts on the physical and mental health of cancer healthcare workers. This was coupled with reluctance among people with symptoms suspicious for cancer to attend for clinical evaluation, due to concerns of contracting the virus. This was further compounded by a cyber-attack on national health service IT systems on May 14th 2021.

Area-Selective Deposition of AlO and Al-Silicate for Fully Self-Aligned Via Integration.

The rush for better-performing electronics, and manufacturing processes that heavily rely on "top-down" patterning techniques, is making the integration of "self-aligned" fabrication methods, such as area-selective deposition (ASD), a critical objective for continued device scaling. The fully self-aligned via (FSAV) scheme is broadly proposed as a "killer application" to determine whether ASD can shift from an R&D process to high-volume manufacturing. Nevertheless, the lack of a suitable low-κ deposition process has prevented the realization of FSAV by dielectric-on-dielectric ASD.

Structure-Activity Studies of 1-Imidazo[4,5-]quinolin-4-amine Derivatives as A Adenosine Receptor Positive Allosteric Modulators.

We previously reported 1-imidazo[4,5-]quinolin-4-amines as A adenosine receptor (AAR) positive allosteric modulators (PAMs). AAR agonists, but not PAMs, are in clinical trials for inflammatory diseases and liver conditions. We synthesized new analogues to distinguish 2-cyclopropyl antagonist (orthosteric interaction demonstrated by binding and predicted computationally) from PAMs (derivatives with large 2-alkyl/cycloalkyl/bicycloalkyl groups).

Prioritising Informed Health Choices Key Concepts for those impacted by cancer: a protocol.

Few areas of health have been as insidiously influenced by misinformation as cancer. Thus, interventions that can help people impacted by cancer reduce the extent to which they are victims of misinformation are necessary. The Informed Health Choices (IHC) initiative has developed Key Concepts that can be used in the development of interventions for evaluating the trustworthiness of claims about the effects of health treatments.

Fabrication of High-κ Dielectric Metal Oxide Films on Topographically Patterned Substrates: Polymer Brush-Mediated Depositions.

Fabrication of ultrathin films of dielectric (with particular reference to materials with high dielectric constants) materials has significance in many advanced technological applications including hard protective coatings, sensors, and next-generation logic devices. Current state-of-the-art in microelectronics for fabricating these thin films is a combination of atomic layer deposition and photolithography. As feature size decreases and aspect ratios increase, conformality of the films becomes paramount.

Approaches to Safety Evaluation of Baby Wipes.

Unlabelled: Disposable baby wipes manufactured by Procter & Gamble, soft sheets bearing lotion that is balanced to maintain natural skin pH, are convenient for cleaning the diaper area and a quick cleanup on baby's face and hands.

Objective: Develop a rigorous safety assessment process to ensure that baby wipes are safe and gentle to skin. This process is built-in from the start of product research and development.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Aim: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.

Methods: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.

Lentzeacins A-E, New Bacterial-Derived 2,5- and 2,6-Disubstituted Pyrazines from a BGC-Rich Soil Bacterium sp. GA3-008.

Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide range of biological effects including antineoplastic, antidiabetic and antibiotic activities. As part of a project investigating the secondary metabolites present in understudied and chemically rich Actinomycetes, we isolated a series of six pyrazines from a soil-derived sp. GA3-008, four of which are new.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Aim: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.

Methods: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Aim: This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.

Methods: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Aim: This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.

Methods: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Aim: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients.

Methods: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered.

Intronic Breakpoint Signatures Enhance Detection and Characterization of Clinically Relevant Germline Structural Variants.

The relevance of large copy number variants (CNVs) to hereditary disorders has been long recognized, and population sequencing efforts have chronicled many common structural variants (SVs). However, limited data are available on the clinical contribution of rare germline SVs. Here, a detailed characterization of SVs identified using targeted next-generation sequencing was performed.

Vertirhodins A-F, C-Linked Pyrrolidine-Iminosugar-Containing Pyranonaphthoquinones from sp. B15-008.

Six novel pyranonaphthoquinones, vertirhodins A-F (-), were discovered from a soil-derived sp. B15-008. Their chemical structures and absolute configurations were determined using nuclear magnetic resonance and comparison of experimental and theoretical electronic circular dichroism spectra.