Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

Sequential intranasal booster triggers class switching from intramuscularly primed IgG to mucosal IgA against SARS-CoV-2.

The persistent emergence of COVID-19 variants and recurrent waves of infection worldwide underscores the urgent need for vaccines that effectively reduce viral transmission and prevent infections. Current intramuscular (IM) COVID-19 vaccines inadequately protect the upper respiratory mucosa. In response, we have developed a nonadjuvanted, interferon-armed SARS-CoV-2 fusion protein vaccine with IM priming and intranasal (IN) boost sequential immunization.

EMPOWER PKD: Patient, Caregiver, and Researcher Priorities for Research in Polycystic Kidney Disease.

Background: Patient involvement in research can help to ensure that the evidence generated aligns with their needs and priorities. In the Establishing Meaningful Patient-Centered Outcomes With Relevance for Patients with Polycystic Kidney Disease (EMPOWER PKD) project we aimed to identify patient-important outcomes and discuss the impact of PKD on patients.

Methods: Nine focus groups were held with adult patients with PKD, caregivers, and clinical or research experts in PKD.

The Association Between COVID-19 Vaccination Uptake and Information-Seeking Behaviors Using the Internet: Nationwide Cross-Sectional Study.

Background: The COVID-19 pandemic, declared in March 2020, profoundly affected global health, societal, and economic frameworks. Vaccination became a crucial tactic in combating the virus. Simultaneously, the pandemic likely underscored the internet's role as a vital resource for seeking health information.

Timing of neuroprognostication in the ICU.

Purpose Of Review: Neuroprognostication after acute brain injury (ABI) is complex. In this review, we examine the threats to accurate neuroprognostication, discuss strategies to mitigate the self-fulfilling prophecy, and how to approach the indeterminate prognosis.

Recent Findings: The goal of neuroprognostication is to provide a timely and accurate prediction of a patient's neurologic outcome so treatment can proceed in accordance with a patient's values and preferences.

Injury induced endotheliopathy: overview, diagnosis, and management.

Purpose Of Review: This review aims to examine recent advances in the understanding of injury-induced endotheliopathy and therapeutics to mitigate its development in critically injured patients.

Recent Findings: Clinical studies have clearly demonstrated that syndecan-1 ectodomains can be found in circulation after various types of trauma and injury and correlates with worse outcomes. As the mechanisms of endotheliopathy are better understood, pathologic hyperadhesive forms of von Willebrand factor, along with a relative deficiency of its cleaving enzyme, a disintegrin and metalloprotease with thrombospondin type I motifs, member 13 (ADAMTS13), have emerged as additional biomarkers.

Electronic Patient-Reported Outcome System Implementation in Outpatient Cardiovascular Care: A Randomized Clinical Trial.

Importance: The integration of patient-reported outcome (PRO) assessments in cardiovascular care has encountered considerable obstacles despite their established clinical relevance.

Objective: To assess the impact of a physician- and patient-friendly electronic PRO (ePRO) monitoring system on the quality of cardiovascular care in clinical practice.

Design, Setting, And Participants: This open-label, multicenter, pilot randomized clinical trial was phase 2 of a multiphase study that was conducted from October 2022 to October 2023 and focused on the implementation and evaluation of an ePRO monitoring system in outpatient clinics in Japan.

Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement.

Importance: Osteoporotic fractures are associated with psychological distress, subsequent fractures, loss of independence, reduced ability to perform activities of daily living, and death.

Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for osteoporosis to prevent fractures in adults 40 years or older with no known diagnosis of osteoporosis or history of fragility fracture.

Population: Adults 40 years or older without known osteoporosis or history of fragility fractures.

Mycotoxin exposure through the consumption of processed cereal food for children (< 5 years old) from rural households of Oshana, a region of Namibia.

Mycotoxin exposure from contaminated food is a significant global health issue, particularly among vulnerable children. Given limited data on mycotoxin exposure among Namibian children, this study investigated mycotoxin types and levels in foods, evaluated dietary mycotoxin exposure from processed cereal foods in children under age five from rural households in Oshana region, Namibia. Mycotoxins in cereal-based food samples (n = 162) (mahangu flour (n = 35), sorghum flour (n = 13), mahangu thin/thick porridge (n = 54), oshikundu (n = 56), and omungome (n = 4)) were determined by liquid chromatography-tandem mass spectrometry.

[C]MK-6884 PET imaging reveals lower M muscarinic acetylcholine receptor availability following cocaine self-administration in male rats.

Background: Cocaine Use Disorder (CUD) remains a significant problem in the United States, with high rates of relapse and no present FDA-approved treatment. The acetylcholine neurotransmitter system, specifically through modulation of muscarinic acetylcholine receptor (mAChR) function, has shown promise as a therapeutic target for multiple aspects of CUD. Enhancement of the M mAChR subtype via positive allosteric modulation has been shown to inhibit the behavioral and neurochemical effects of cocaine across several rodent models of CUD.

Clinical utility of tumor-infiltrating lymphocyte evaluation by two different methods in breast cancer patients treated with neoadjuvant chemotherapy.

Purpose: The aim of this study was to examine the clinical utility of tumor-infiltrating lymphocytes (TILs) evaluated by "average" and "hot-spot" methods in breast cancer patients.

Methods: We examined 367 breast cancer patients without neoadjuvant chemotherapy (NAC) by average and hot-spot methods to determine the consistency of TIL scores between biopsy and surgical specimens. TIL scores before NAC were also compared with the pathological complete response (pCR) rate and clinical outcomes in 144 breast cancer patients that received NAC.

Tetraspanins CD63 and CD81 as potential prognostic biomarkers in breast cancer.

Exosome markers, CD63 and CD81, belong to the tetraspanin family and are expressed in solid tumors. It has been reported that these tetraspanin family members are prognostic factors in some cancers. However, the expression of CD63 and CD81 in pathological breast cancer specimens has not been reported.

Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity.

To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.

Non small cell lung cancer with SMARCA4 deficiency harboring rare EGFR mutations exhibited significant tumor response when treated with afatinib: a case report.

SMARCA4-deficient non small cell lung cancer (SMARCA4-dNSCLC) has recently garnered increasing attention due to its high malignancy and poor prognosis. The literature suggests that in non small cell lung cancer (NSCLC), the loss of SMARCA4 frequently co-occurs with mutations in KRAS, KEAP1, and STK11 rather than in EGFR, ALK, and ROS1. Herein, we present the first documented case of SMARCA4-dNSCLC accompanied with rare mutations of EGFR exon 20 S768I and exon 18 G719X.

Novel Protective Role for Gut Microbiota-derived Metabolite PAGln in Doxorubicin-induced Cardiotoxicity.

Purpose: Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of phenylacetylglutamine (PAGln), a novel gut microbiota metabolite, in Dox-induced cardiotoxicity (DIC).

Methods: DIC models were established in vivo and in vitro, and a series of experiments were performed to verify the cardioprotective effect of PAGln.

Advanced Markers for Hemodynamic Monitoring in Cardiogenic Shock and End-Stage Heart Failure: A Mini Review.

Right heart catheterization (RHC) provides critical hemodynamic insights by measuring atrial, ventricular, and pulmonary artery pressures, as well as cardiac output (CO). Although the use of RHC has decreased, its application has been linked to improved outcomes. Advanced hemodynamic markers such as cardiac power output (CPO), aortic pulsatility index (API), pulmonary artery pulsatility index (PAPi), right atrial pressure to pulmonary capillary wedge pressure ratio (RAP/PCWP) and right ventricular stroke work index (RVSWI) have been introduced to enhance risk stratification in cardiogenic shock (CS) and end-stage heart failure (HF) patients.

Standard: Human gastric organoids.

Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications.

Ketamine Infusion for Complex Regional Pain Syndrome Treatment: A Narrative Review.

Purpose Of Review: Complex Regional Pain Syndrome (CRPS) is a neuropathic pain disorder characterized by pain disproportionate to the inciting event that is constant for an extended duration. Numerous treatment options for this condition have been explored with unsatisfactory results in many cases. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist typically used as an anesthetic and analgesic, presents a promising potential treatment for CRPS in patients who fail to respond to traditional therapies.

Successful staged surgery for advanced esophageal cancer after conversion pancreatoduodenectomy with pancreaticogastrostomy.

Background: Complex surgery during initial cancer treatment can limit surgical options when planning management of a secondary malignancy. Subtotal esophagectomy and pancreatoduodenectomy are the most invasive and difficult procedures in gastroenterological surgery. Surgical cases in which subtotal esophagectomy was performed after pancreatoduodenectomy with pancreaticogastrostomy are extremely rare and challenging procedures due to the resulting complicated anatomical changes.

Analysis of macular retinal thickness in polyarteritis nodosa using spectral domain optical coherence tomography.

Purpose: To identify the macular retinal layer thickness changes in polyarteritis nodosa (PAN) patients without pathological findings appearing in color fundus photography (CFP), and to investigate the correlations with disease durations.

Methods: A total of 24 PAN patients who had been for 3 years or more and underwent SD-OCT were recruited from the UK Biobank, with exclusions for diabetes, eye disease, or abnormal CFP findings. Only the right eyes were included, with each PAN patient paired one-to-one with a control matched for age, sex, and ethnicity.

Machine learning validation of a simple prediction model for the correlation between advanced age and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage.

Adverse effects of advanced age and poor initial neurological status on outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH) have been documented. While a predictive model of the non-linear correlation between advanced age and clinical outcome has been reported, no previous model has been validated. Therefore, we created a prediction model of the non-linear correlation between advanced age and clinical outcome by machine learning and validated it using a separate cohort.