Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Depletion of myeloid-derived suppressor cells sensitizes murine multiple myeloma to PD-1 checkpoint inhibitors.

Background: Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts the efficacy of ICB therapy.

Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma.

Background: Siglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) and to evaluate its potential antitumor effects in several preclinical renal cancer models.

Early treatment discontinuation in patients with deficient mismatch repair or microsatellite instability high metastatic colorectal cancer receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy.

Salient Voice Symptoms in Primary Muscle Tension Dysphonia.

Introduction: Patients with primary muscle tension dysphonia (pMTD) commonly report symptoms of vocal effort, fatigue, discomfort, odynophonia, and aberrant vocal quality (eg, vocal strain, hoarseness). However, voice symptoms most salient to pMTD have not been identified. Furthermore, how standard vocal fatigue and vocal tract discomfort indices that capture persistent symptoms-like the Vocal Fatigue Index (VFI) and Vocal Tract Discomfort Scale (VTDS)-relate to acute symptoms experienced at the time of the voice evaluation is unclear.

Prognostic Value of Response Evaluation Using PSMA PET/CT in Patients with Metastatic Prostate Cancer (RECIP 1.0): A Systematic Review and Meta-analysis.

Rationale And Objectives: Recently, the Response Evaluation Using PSMA PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer (RECIP 1.0) was proposed to better evaluate treatment response in prostate cancer patients using PET/CT with prostate-specific membrane antigen (PSMA) than more traditional approaches like metabolic PET evaluation response criteria in solid tumor (PERCIST 1.0).

Early outcomes following local salvage treatment with MRI-assisted low-dose rate brachytherapy (MARS) for MRI-visible postsurgical bed recurrences and focal intraprostatic recurrences.

Background: To determine outcomes of MRI-assisted radiosurgery (MARS) for salvage brachytherapy using the radioisotope Pd after various upfront treatments including surgery, external beam radiotherapy, and brachytherapy.

Methods: We retrospectively reviewed data for patients who underwent salvage MARS for intraprostatic lesions or prostate bed recurrences from 2016 to 2022. Biochemical recurrence, prostate cancer-specific, and overall survival, and the cumulative incidences of toxicities, were determined by Kaplan-Meier estimates.

The public health risks of counterfeit pills.

Synthetic illicit drugs, such as nitazenes and fentanyls, are becoming commonplace in countries around the world, including in Europe, Australia, and Latin America, which raises concern for overdose crises like those seen in North America. An important dimension of the risk represented by synthetic drugs is the fact that they are increasingly packaged in counterfeit pill form. These pills-often indistinguishable from authentic pharmaceuticals-have substantially widened the scope of populations susceptible to synthetic drug overdose in North America (eg, among adolescents experimenting with pills or tourists from the USA seeking psychoactive medications from pharmacies in Mexico).

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

A Guide to Pediatric Antibiotic Allergy Testing: A Report from the United States Drug Allergy Registry.

Pediatric antibiotic labels are common, and unnecessary antibiotic avoidance is associated with negative personal and public health outcomes; as a result, there is an increasing emphasis on the importance of pediatric antibiotic allergy evaluations. Different testing strategies have been advised, including skin testing and challenge testing with varied doses and duration. Established consensus testing protocols are lacking.

Defining the optimal radiation-induced lymphopenia metric to discern its survival impact in esophageal cancer.

Background: A detrimental association between radiation-induced lymphopenia (RIL) and oncologic outcomes in esophageal cancer patients has been established. However, an optimal metric for RIL remains undefined, but is important for application of this knowledge in clinical decision-making and trial designs. The aim of this study was to find the optimal RIL metric discerning survival.

Convolutional Neural Networks for the segmentation of hippocampal structures in postmortem MRI scans.

Background: The hippocampus plays a crucial role in memory and is one of the first structures affected by Alzheimer's disease. Postmortem MRI offers a way to quantify the alterations by measuring the atrophy of the inner structures of the hippocampus. Unfortunately, the manual segmentation of hippocampal subregions required to carry out these measures is very time-consuming.

Prognostic significance of diastolic wall strain as a predictor of remodeling and poor outcomes in heart failure and pulmonary embolism: A systematic review.

Background: Diastolic wall strain (DWS), also referred to as right ventricular (RV) dysfunction, is a significant predictor of pulmonary embolism (PE) and heart failure (HF). Rooted in linear elastic theory, DWS reflects decreased wall thinning during diastole, indicating reduced left ventricular (LV) compliance and increased diastolic stiffness. Elevated diastolic stiffness is associated with worse outcomes, particularly in PE and HF with preserved ejection fraction (HFpEF).

Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2- metastatic breast cancer in the US real-world setting.

Background: Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.

Automatic and strategic components of bilingual lexical alignment.

Second-language speakers are more likely to strategically reuse the words of their conversation partners (Zhang & Nicol, 2022). This study investigates if this is also the case for lower-proficiency bilinguals from a bilingual community, who use language more implicitly, and if there is more alignment with lower than with higher proficiency, provided the words to be aligned to are all highly familiar. In two experiments, Spanish-English bilinguals took turns with a confederate to name and match pictures in Spanish.

Detecting novel plant pathogen threats to food system security by integrating the Plant Reactome and remote sensing.

Plant diseases constantly threaten crops and food systems, while global connectivity further increases the risks of spreading existing and exotic pathogens. Here, we first explore how an integrative approach involving plant pathway knowledgegraphs, differential gene expression data, and biochemical data informing Raman spectroscopy could be used to detect plant pathways responding to pathogen attacks. The Plant Reactome (https://plantreactome.

Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells.

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226.

Development and refinement of the Cardiovascular Health Equity through Food (CHEF) intervention for childhood cancer survivors.

Purpose: The aim of this study was to develop and refine Cardiovascular Health Equity through Food (CHEF), an intervention to address food insecurity (FI) in early childhood cancer survivors (CCS).

Methods: Single-center mixed-methods pilot study of a novel "food is medicine" intervention evaluating acceptability, satisfaction, and opportunities for refinement. CHEF participants were provided: (1) meal-kit delivery for 3 household meals/week for 3 months and (2) application assistance for federal nutrition benefits.

Coronary Intervention Outcomes in Patients with Liver Cirrhosis.

Purpose Of Review: This review assesses the outcomes of coronary interventions in patients with liver cirrhosis and coronary artery disease (CAD), focusing on the clinical challenges posed by cirrhosis-related hemodynamic and coagulopathic changes. It highlights essential considerations for managing these patients, who have an increased risk of adverse events during coronary procedures.

Recent Findings: Recent studies have shown that patients with liver cirrhosis undergoing PCI experience significantly higher mortality rates compared to non-cirrhotic patients, particularly in the context of STEMI and NSTEMI.

Correlations Between Spirituality, Anxiety, and Depression in Hemodialysis Patients in Saudi Arabia: A Cross-Sectional Study.

Spirituality is widely recognized as a potential moderator of the adverse effects of hemodialysis on mental health. Understanding its impact on mental health in Saudi Arabia and the Arab world, however, remains a significant research gap. Hence, this study aims to explore the correlations between spirituality, anxiety, and depression among Saudi Arabian patients undergoing hemodialysis.