Mesenchymal stromal cells promote the formation of lung cancer organoids via Kindlin-2.

Background: Patient-derived lung cancer organoids (PD-LCOs) demonstrate exceptional potential in preclinical testing and serve as a promising model for the multimodal management of lung cancer. However, certain lung cancer cells derived from patients exhibit limited capacity to generate organoids due to inter-tumor or intra-tumor variability. To overcome this limitation, we have created an in vitro system that employs mesenchymal stromal cells (MSCs) or fibroblasts to serve as a supportive scaffold for lung cancer cells that do not form organoids.

Neoadjuvant or concurrent atezolizumab with chemoradiation for locally advanced cervical cancer: a randomized phase I trial.

Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC.

Deep learning model to identify and validate hypotension endotypes in surgical and critically ill patients.

Background: Hypotension is associated with organ injury and death in surgical and critically ill patients. In clinical practice, treating hypotension remains challenging because it can be caused by various underlying haemodynamic alterations. We aimed to identify and independently validate endotypes of hypotension in big datasets of surgical and critically ill patients using unsupervised deep learning.

Comparing Patient Care Models at a Local Free Clinic vs an Insurance-Based University Medical Center.

More than 30 million Americans lack access to affordable health care, and many seek medical services such as dermatologic care at free clinics. In this study, we analyzed the dermatology patient populations at the Birmingham Free Clinic (BFC) and the University of Pittsburgh Medical Center (UPMC), both in Pittsburgh, Pennsylvania. A retrospective chart review of 76 BFC dermatology patients and a time-matched sample of 322 UPMC dermatology patients was performed for the period from January 2020 to May 2022.

Restrictive or Liberal Blood Transfusion in Patients with Myocardial Infarction and CKD.

Background: Chronic kidney disease (CKD) is associated with higher risk of myocardial infarction and anemia. Among patients with anemia and CKD who experience myocardial infarction, it remains uncertain if a liberal red blood cell transfusion threshold strategy (hemoglobin cutoff [Hgb] < 10 g/dL) is superior to a restrictive transfusion threshold (Hgb 7-8 g/dL) strategy.

Methods: Among the 3,504 patients enrolled in the Myocardial Ischemia and Transfusion (MINT) trial with non-missing creatinine, we compared baseline characteristics and 30-day and 6-month outcomes of patients without CKD (N = 1279), CKD with eGFR 30-60 mL/min/1.

Prehospital endotracheal intubation success rates for critical care nurses versus paramedics.

Objectives: Prehospital endotracheal intubation (ETI) is a lifesaving procedure with known complications. To reduce ETI-associated morbidity and mortality, organizations prioritize first-pass success (FPS). However, there are few data evaluating the association of FPS with clinician licensure.

Children's executive functioning and health behaviors across pediatric life stages and ecological contexts.

Executive functioning (EF) has been linked to chronic disease risk in children. Health behaviors are thought to partially explain this association. The current cross-sectional study evaluated specific domains of EF and varied health behaviors in three pediatric life stages.

Pain Coping Skills Training for Patients Receiving Hemodialysis: The HOPE Consortium Randomized Clinical Trial.

Importance: Chronic pain is common among individuals with dialysis-dependent kidney failure.

Objective: To evaluate the effectiveness of pain coping skills training (PCST), a cognitive behavioral intervention, on pain interference.

Design, Setting, And Participants: This multicenter randomized clinical trial of PCST vs usual care was conducted across 16 academic centers and 103 outpatient dialysis facilities in the US.

Biomarkers.

Background: This research introduces a novel method for quantifying aggregated tau in body fluids, specifically cerebrospinal fluid (CSF), aiming to enhance the diagnosis and monitoring of neurodegenerative diseases, with a focus on Alzheimer's disease (AD).

Method: By combining tau protein amplification with a highly sensitive single-molecule array (Simoa) immunoassay using an anti-tau antibody CT19.1 in a homogenous manner, the approach enables precise measurements of tau aggregates in CSF.

Biomarkers.

Background: The association between [F]Flortaucipir (FTP) and [F]MK6240, two commonly used tau-PET tracers in Alzheimer's disease (AD), varies due to distinct binding properties and off-target signal regions. Our study aims to elucidate the biological factors influencing this association and evaluate the applicability of a common equation across different on-target regions.

Method: 113 individuals from the HEAD dataset (11 young, 58 cognitively unimpaired elderly, and 44 cognitively impaired) underwent [F]MK6240, [F]FTP and Aβ-PET scans.

Biomarkers.

Background: In the context of Alzheimer's disease (AD), blood-based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD.

Biomarkers.

Background: [F]MK-6240 was developed for PET imaging of AD tau pathology, but the exact molecular signature of specific binding remains unclear. This study quantified levels of four phospho-tau forms and total tau in postmortem brain tissues from [F]MK-6240 imaged cases to investigate associations with antemortem [F]MK-6240 PET.

Methods: This study included four participants from the Wisconsin ADRC or WRAP with antemortem [F]MK-6240 and [C]PiB PET imaging and postmortem brain tissue obtained on average 32-months after imaging (Table 1).

Biomarkers.

Background: The detection and monitoring of Alzheimer's disease (AD) biomarkers in plasma are crucial for early diagnosis and prognosis. However, the stability of plasma AD biomarkers can be compromised by the degradation caused by endogenous proteases present in blood. The efficacy of protease inhibitors in mitigating this degradation is yet to be established.

Biomarkers.

Background: Alzheimer's disease (AD) blood biomarkers alone can detect amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ-positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Biomarkers.

Background: Differences between on- and off-target retention characteristics between [F]MK6240 and [F]Flortaucipir (FTP) complicate the harmonization across tracers. Our objective here was to separate the impact of the reference region by evaluating correlations between [F]MK6240 (MK) and [F]FTP standard uptake values (SUVs).

Method: Participants (Figure 1, n=90) received an amyloid-β (Aβ) PET scan ([C]PIB or [F]NAV4694) and two tau-PET scans: [F]MK (90-110 minutes post-injection) and [F]FTP (80-100 minutes post-injection).

Biomarkers.

Background: Alzheimer's disease (AD) pathology occurs in the brain before manifestation of significant cognitive decline. Growing evidence suggests that brain networks such as default mode network (DMN) or salience network, identified through resting-state functional magnetic resonance imaging (MRI), are affected by AD pathology. In this study, we investigated the relationship between network segregation and the key in vivo AD pathologies including beta-amyloid (Aβ) and tau deposition in old adults with no cognitive impairment.

Biomarkers.

Background: Little is known about how plasma Alzheimer's disease (AD) biomarkers relate to neuroimaging biomarkers of cerebral small vessel disease (cSVD) in the context of neurodegeneration and AD pathology in late life.

Method: This cross-sectional study included 251 Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers (Aβ42/Aβ40, GFAP, NfL, p-tau181, p-tau217, p-tau231; Quanterix SIMOA), MRI (neurodegeneration and cSVD), PiB (amyloid) PET, and UDSv3-based adjudicated cognitive status (69% cognitively normal, 27% MCI, 4% probable dementia) data at the Wake Forest site. Multivariable models examined relationships among cognitive status, plasma, and neuroimaging biomarkers (covariates: age, education, race, gender, smoking status, kidney function [eGFR], APOE-ε4, BMI; significance at p<.

Biomarkers.

Background: In older adults, greater amyloid (Aβ) and tau positron emission tomography (PET) binding is associated with cognitive decline and dementia. However, the association of early amyloid and tau PET accumulation with cognition at midlife remains unclear. The goal of the current study was to evaluate the associations of Aβ and tau PET with cognition in a predominately middle-aged community-based cohort, as well as to examine the factors that may modify these associations.

Biomarkers.

Background: Brain age (BA) prediction models have emerged as valuable tools for understanding individual differences in trajectories of brain aging. These models aim to estimate overall brain health by predicting BA based on structural MRI data. To enhance the specificity of existing BA models, we introduce a deep learning-based BA prediction model.

Biomarkers.

Background: Emerging evidence underscores the importance of neuroinflammation in the progression of Alzheimer's disease (AD) pathophysiology. Recent studies indicate the involvement of the inflammatory mechanisms both in amyloid- β (Aβ) and tau deposition in the brain. Nevertheless, due to the complexity of the immune responses and the intricate interplay between the peripheral and the central nervous systems, identifying biomarkers that reflect the brain´s inflammatory state in AD has been a challenge.

Biomarkers.

Background: Trisomy 21 in Down syndrome (DS) is associated with an earlier accumulation of beta-amyloid (Aβ) plaques and a higher rate of Alzheimer's Disease due to the triplication of the amyloid precursor protein gene. In this study we compare accumulation rates of Aβ measured with [C-11]PiB PET between large longitudinal cohorts of DS and neurotypical (NT) participants at a single site.

Methods: Participants imaged at the University of Wisconsin with ≥2 PiB scans and ≥2 years between scans were included in this study.

Biomarkers.

Background: Studies of aging in non-human primates are important to elucidate primate-specific mechanisms underlying human aging, including pathological trajectories like Alzheimer's disease (AD). Evidence of AD-like brain aging has been reported across the primate order including amyloid beta (AB) deposits, but blood-based biomarkers are less well-studied. The goal of this project was to explore the use of validated assays for plasma biomarkers in two new non-human primate species: coppery titi monkeys (Plecturocebus cupreus) and brown capuchins (Sapajus apella).

Biomarkers.

Background: To evaluate the in vitro binding properties of [C]PiB and [F]NAV4694 head-to-head in post-mortem human brain tissue.

Method: Autoradiography was used to assess uptake of [C]PiB and [F]NAV4694 in control (CN) and Alzheimer's disease (AD) autopsy-confirmed brain tissues. The study focuses on the analysis of the prefrontal cortex, inferior parietal cortex, posterior cingulate cortex and hippocampus sections in 11 CN and 11 AD cases.