Exploration of degrons and their ability to mediate targeted protein degradation.

Degrons are short amino acid sequences that can facilitate the degradation of protein substrates. They can be classified as either ubiquitin-dependent or -independent based on their interactions with the ubiquitin proteasome system (UPS). These amino acid sequences are often found in exposed regions of proteins serving as either a tethering point for an interaction with an E3 ligase or initiating signaling for the direct degradation of the protein.

Lazertinib: breaking the mold of third-generation EGFR inhibitors.

Small molecules targeting activating mutations within the epidermal growth factor receptor (EGFR) are efficacious anticancer agents, particularly in non-small cell lung cancer (NSCLC). Among these, lazertinib, a third-generation tyrosine kinase inhibitor (TKI), has recently gained FDA approval for use in combination with amivantamab, a dual EGFR/MET-targeting monoclonal antibody. This review delves into the discovery and development of lazertinib underscoring the improvements in medicinal chemistry properties, especially in comparison with osimertinib.

Massive subcutaneous filariosis by in beech marten () in Italy.

The beech marten () is a small-size mustelid endangered according to the IUCN Red List. Despite the plethora of parasites potentially affecting its population decline, subcutaneous filarioids are occasionally reported in martens and their competent arthropod vectors are to date unknown. Therefore, from January 2023 to August 2024, this study investigated the presence of subcutaneous filarioids and ectoparasites of road-killed beech martens ( = 7) from southwestern Italy.

Circulating tumor DNA in head and neck squamous cell carcinoma-current status and future prospects.

Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck. Stagnating survival rates in recent decades, despite advances in the treatment paradigms, surveillance technologies, and multidisciplinary care, leave clinicians with a need for better options for screening, risk-stratifying, and monitoring patients. A growing proportion of patients with HPV-associated SCC have improved outcomes but continue to have a heterogenous response to treatment.

Landscapes-a lens for assessing sustainability.

Context: There are urgent calls to transition society to more sustainable trajectories, at scales ranging from local to global. Landscape sustainability (LS), or the capacity for landscapes to provide equitable access to ecosystem services essential for human wellbeing for both current and future generations, provides an operational approach to monitor these transitions. However, the complexity of landscapes complicates how and what to consider when assessing LS.

MITIGATING OVER-SATURATED FLUORESCENCE IMAGES THROUGH A SEMI-SUPERVISED GENERATIVE ADVERSARIAL NETWORK.

Multiplex immunofluorescence (MxIF) imaging is a critical tool in biomedical research, offering detailed insights into cell composition and spatial context. As an example, DAPI staining identifies cell nuclei, while CD20 staining helps segment cell membranes in MxIF. However, a persistent challenge in MxIF is saturation artifacts, which hinder single-cell level analysis in areas with over-saturated pixels.

Ketamine Infusion as an Adjunct to Opioid Analgesia in Pediatric Patients with High-Risk Neuroblastoma Undergoing Treatment with Dinutuximab: Adverse Effects and Safety in a Non-ICU Setting.

Introduction: Anti-GD2 immunotherapy has improved outcomes for children with high-risk neuroblastoma (HRNBL). Dinutuximab promotes complement-mediated reaction against disialoganglioside GD2, which is expressed in peripheral nerves and over-expressed in neuroblastoma. Dinutuximab is associated with ≥grade 3 neuropathic pain.

Healthcare Resource Utilization Among Patients With Generalized Pustular Psoriasis: The Impact of Flares and Disease Severity.

Background: Generalized pustular psoriasis (GPP) is a rare, chronic, often unpredictable, severe multisystemic autoinflammatory skin disease from which patients can experience flares, episodes of widespread eruptions of painful, sterile pustules often accompanied by systemic symptoms. The impact of GPP flares and underlying GPP severity on the healthcare resource utilization (HCRU) is not well characterized.

Objective: To quantify HCRU among US GPP patients by flare status and underlying severity.

Mapping Trends and Hotspots Regarding the Use of Lung Ultrasound in the Field of Anesthesiology: A Bibliometric Analysis of Global Research.

Purpose: Lung ultrasound (LUS) is increasingly utilized in the field of anesthesiology due to its focused, quick application and the advantage of not exposing patients to ionizing radiation. This study aims to analyze the status and trends in this area from a macroscopic perspective.

Methods: A bibliometric analysis was conducted using the Web of Science (WoS) Core Collection.

Use of Coronary CTA to Triage Patients With Low to Intermediate Risk for CADs in an Acute Care Facility Can Help Lower Healthcare Costs When Compared With the Current Standard of Care: A Retrospective Study.

Acute chest pain is one of the most common reasons for ED visits in the United States. Most patients are eventually admitted to the hospital to "rule out ACS" even when there are no significant EKG abnormalities or elevated cardiac enzymes. In addition to undergoing expensive tests while in the hospital, patients are also exposed to iatrogenic harm thereby worsening the overall healthcare costs.

Intermittent Sinus Pause/Asystole in the Setting of Anticholinergic Overdose.

Anticholinergic toxicity typically presents with symptoms of cutaneous vasodilation, delirium, mydriasis, urinary retention, hyperthermia, anhidrosis, and tachycardia. This case report presents a 68-year-old female patient who exhibited some of these signs and symptoms after ingesting an unknown quantity of dicyclomine. However, she displayed one notable exception to the classic toxidrome.

Descriptions of one hundred new species of Hesperiidae.

A century and a half since the time of Hewitson, we are experiencing a renaissance in species discovery fueled by whole genome sequencing. A large-scale genomic analysis of Hesperiidae Latreille, 1809 (Lepidoptera), including primary type specimens, reveals a deluge of species new to science. One hundred of them (one in a new genus) are described here from the New World (type localities are given in parenthesis): () Grishin, (Ecuador: Napo), Grishin, (Ecuador: Esmeraldas), Grishin, (Panama: Panama), () Grishin, (Ecuador: Zamora-Chinchipe), () Grishin, (Panama: Darien), () Grishin, (Ecuador: Napo), () Grishin, (Panama: Panama), () Grishin, (Ecuador: Pastaza), Grishin, (Panama: Colón), Grishin, (Ecuador: Napo), Grishin, (Ecuador: Esmeraldas), Grishin, (Guyana), Grishin, (Peru: Cuzco), Grishin, (Peru: Cuzco), Grishin, (Panama: Panama), Grishin, (Brazil: Mato Grosso), () Grishin, (Brazil: Rondônia), () Grishin, (Panama: Panama), () Grishin, (Ecuador: Napo), Grishin, (Brazil: Rondônia), Grishin, (Peru: Loreto), Grishin, (Suriname: Para), Grishin, (Brazil: Santa Catarina), Grishin, (Panama: Panama), Grishin, (Brazil: Santa Catarina), Grishin, (Ecuador: Orellana), Grishin, (Venezuela: Aragua), Grishin, (Guatemala), Grishin, (Guyana), () Grishin, (Panama: Darien), () Grishin, (Mexico: Guerrero.

Outcomes of Combined Left Atrial Appendage Occlusion and Transcatheter Mitral Edge-to-Edge Repair: The WATCH-TEER Study.

Background: Up to 50% of patients undergoing mitral transcatheter edge-to-edge repair (MTEER) have an indication for left atrial appendage occlusion (LAAO). However, prospective evaluation of this strategy is lacking.

Objectives: The aim of the study was to prospectively evaluate the outcomes of combined LAAO and MTEER.

A health-equity framework for tailoring digital non-pharmacological interventions in aging.

If designed with health equity in mind, digital non-pharmacological interventions (NPIs) represent a cost-effective, scalable means of reducing health disparities associated with age-related mental health disorders in older adults in the USA. However, disparities in technological access, literacy and effectiveness can limit the impact of these interventions in older adults from disadvantaged groups. We present a health-equity-promoting framework for the development of digital NPIs for age-related mental health disorders and provide an example from the literature that highlights how interventions can be targeted at specific groups to increase technological access, literacy and effectiveness to ensure that these interventions can meet their potential of reducing health disparities.

Sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and myocardial infarction undergoing percutaneous coronary intervention: A systematic review and meta-analysis.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown benefits in improving cardiovascular (CV) outcomes in patients with heart failure (HF) and may mitigate symptom progression in myocardial infarction (MI). However, their effectiveness in patients with type 2 diabetes and MI undergoing percutaneous coronary intervention (PCI) is unclear.

Methods: To identify eligible studies, a comprehensive search of electronic databases, PubMed, Cochrane Library, Scopus and Embase, was conducted from inception until May 2024.

Reducing off-target expression of mRNA therapeutics and vaccines in the liver with microRNA binding sites.

Lipid nanoparticles (LNPs) are often liver tropic, presenting challenges for LNP-delivered mRNA therapeutics intended for other tissues, as off-target expression in the liver may increase side effects and modulate immune responses. To avoid off-target expression in the liver, miR-122 binding sites have been used by others in viral and non-viral therapeutics. Here, we use a luciferase reporter system to compare different copy numbers and insertion locations of miR-122 binding sequences to restrict liver expression.

Investigating a hybrid mixed population leads to recognizing a new species of (Ericaceae).

While investigating the potential for species to hybridize in the mixed populations of Point Sal and Burton Mesa in Santa Barbara County, California, we discovered that from the Nipomo Mesa (San Luis Obispo County), formerly considered a northern population of , are genetically and morphologically distinct. We name this new taxon after the ytt (Northern Chumash language) word for the Nipomo Mesa region. For morphological and molecular analyses, we sampled 54 plants, focusing on , , and from multiple species and comparative single species populations.

"Do all bisexuals have this power?": An exploratory study of "crippling nicotine addiction," identity, and other emergent themes in vaping messages on QueerTok.

Nicotine and tobacco use disproportionally affects sexual and gender minority (SGM) populations in the United States. Social media narratives may contribute to these disparities. This qualitative study delineated perceptions and experiences depicted in SGM-related videos about nicotine vaping on TikTok.

Intimate partner sexual violence is associated with unhealthy alcohol use among Kenyan women engaged in sex work.

Aim: Unhealthy alcohol use is often correlated with experiences of intimate partner violence (IPV). We investigated how different types of IPV (sexual, physical, emotional, and financial) were associated with unhealthy alcohol use among women engaged in sex work in Mombasa, Kenya.

Methods: This cross-sectional study included 283 HIV-negative women who engaged in sex work recruited from an ongoing cohort study.

First, Do No Harm (to the One You Train).

Unlabelled: or "first, do no harm" is perhaps the most well-known aphorism in the culture of medical education. While its application to patients is well known, the injunction can also be read with medical trainees in mind. Teaching physicians have an obligation to recognize their role as moral teachers and coaches, who must consider "first, do no harm" not only when considering their patients but also when weighing the moral formation of their trainees, especially in a season in which medical educators are attempting to clarify the "harms" of medical training.