A phase II trial of hepatic ablation of metastases to modulate and enhance immunotherapy response in non-small cell lung cancer (HAMMER-NSCLC).

Background: Anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-[L]1) immunotherapy promotes systemic anti-tumor immunity through expanding neoantigen-specific CD8 + T cells, but it is less effective in patients with liver metastases. Nearly 20% of non-small cell lung cancer (NSCLC) patients develop liver metastases, and these patients are characterized by fewer and less active effector T cells. Preclinical work has shown that liver metastases cause systemic immunosuppression through siphoning neoantigen-specific CD8 + T cells from systemic circulation with subsequent macrophage-mediated intrahepatic death.

Integrated histopathologic modeling of detailed tumor subtypes and actionable biomarkers.

Accurate cancer subtyping with accompanying molecular characterization is critical for precision oncology. While machine learning approaches have been applied to both digital pathology and cancer genomics, previous work has been limited in sample size and has typically aggregated granular cancer subtypes into coarse groupings , likely obfuscating informative molecular and prognostic associations and phenotypic variation of more detailed tumor subtypes. Accordingly, we collated 378,123 hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) with matched targeted DNA clinical sequencing results and OncoTree detailed cancer subtypes from a real-world cohort of 71,142 patients.

Modeling dynamic inflow effects in fMRI to quantify cerebrospinal fluid flow.

Cerebrospinal fluid (CSF) flow in the brain is tightly regulated and essential for brain health, and imaging techniques are needed to quantitatively establish the properties of this flow system. Flow-sensitive fMRI has recently emerged as a tool to measure large scale CSF flow dynamics with high sensitivity and temporal resolution; however, the measured signal is not quantitative. Here, we developed a dynamic model to simulate fMRI inflow signals based on time-varying flow velocities.

The temporal specificity of BOLD fMRI is systematically related to anatomical and vascular features of the human brain.

The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter which blurs rapid changes. However, the shape and timing of hemodynamic responses are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of functional MRI (fMRI) signals, or the ability of fMRI to preserve fast information, could also vary substantially across the cortex.

Visual stimulus-evoked blood velocity responses in individual human posterior cerebral arteries measured with dynamic phase-contrast functional MR angiography.

Functional MRI (fMRI) tracks brain activity through the associated hemodynamic changes via neurovascular coupling. Neurons communicate with the microvessels of the parenchyma to initiate a hemodynamic response, and these microvessels then communicate with upstream arterioles and arteries. The role of the larger feeding arteries-far upstream from the site of neuronal activity-in coordinating this response is incompletely understood, yet is important for the interpretation of fMRI.

Improving therapeutic strategies for triple-negative breast cancer: synergistic effects of DKC1 inhibition and paclitaxel.

Background: Paclitaxel (PTX) is a standard treatment for triple-negative breast cancer (TNBC), but its effectiveness is often compromised by toxicity at therapeutic doses. Dyskerin pseudouridine synthase 1 (DKC1), a telomerase subunit, is overexpressed in TNBC and associated with poor prognosis. This study investigates whether combining PTX with R1D2-10, a novel DKC1 inhibitor developed by our group, enhances cytotoxicity while reducing required PTX dosages.

A Comprehensive Dataset for Activity of Daily Living (ADL) Research Compiled by Unifying and Processing Multiple Data Sources.

: Activities of Daily Living (ADLs) are essential tasks performed at home and used in healthcare to monitor sedentary behavior, track rehabilitation therapy, and monitor chronic obstructive pulmonary disease. The Barthel Index, used by healthcare professionals, has limitations due to its subjectivity. Human activity recognition (HAR) is a more accurate method using Information and Communication Technologies (ICTs) to assess ADLs more accurately.

Comparative Evaluation of Automatic Detection and Classification of Daily Living Activities Using Batch Learning and Stream Learning Algorithms.

Activities of Daily Living (ADLs) are crucial for assessing an individual's autonomy, encompassing tasks such as eating, dressing, and moving around, among others. Predicting these activities is part of health monitoring, elderly care, and intelligent systems, improving quality of life, and facilitating early dependency detection, all of which are relevant components of personalized health and social care. However, the automatic classification of ADLs from sensor data remains challenging due to high variability in human behavior, sensor noise, and discrepancies in data acquisition protocols.

Doping and Annealing Conditions Strongly Influence the Water Oxidation Performance of Hematite Photoanodes.

Hematite (α-FeO) is one of the most promising semiconductors for solar water splitting due to its high theoretical efficiency and low cost. However, its poor electronic properties strongly limit its performance. Furthermore, the impact of composition and processing conditions on such properties, and on the water splitting efficiency, is poorly understood.

Disparities in receipt of palliative-intent treatment among disaggregated Hispanic populations with breast, lung, and prostate cancer in the United States.

Background: Despite palliative-intent interventions' ability to improve the quality of life of patients, significant inequalities persist in uptake. Such disparities are characterized by racial, socioeconomic, and geographic factors. However, less is known among disaggregated Hispanic populations.

Outcomes After Radiation for Oligoprogressive Disease Sites in Patients With -Mutant Lung Cancer Treated With Osimertinib.

Purpose: Oligoprogressive disease (OPD) commonly occurs in patients with advanced mutation-positive non-small cell lung cancer (EGFR+ LC) on systemic therapy. While radiation therapy (XRT) to treat OPD can improve outcomes, the clinical and genomic predictors of benefit from local therapy for oligoprogression on osimertinib are unclear.

Methods: We conducted a single-center retrospective analysis of 81 patients with EGFR+ LC on osimertinib who received XRT for OPD (defined as progression in ≤5 lesions) between January 2014 and December 2022.

GDF8 and activin A blockade protects against GLP-1-induced muscle loss while enhancing fat loss in obese male mice and non-human primates.

Glucagon-like peptide-1 receptor agonists act via appetite suppression and caloric restriction. These treatments can result in significant muscle loss, likely due to evolutionary mechanisms protecting against food scarcity as muscle is a major energy utilizer. One mechanism that reduces muscle mass involves activation of type II activin receptors, ActRIIA/B, which yield profound muscle growth in humans when blocked.

Prevalence and Development of Cachexia Before and After Diagnosis of Non-small Cell Lung Cancer.

Objective: Cachexia is commonly defined based on weight loss at the time of cancer diagnosis. However, regular weight measurements before cancer diagnosis are often lacking and may be subject to recall bias if retrospectively self-reported by patients. To analyze the development and progression of cachexia, we employ body weight trajectories from 1 year before and after diagnosis of non-small cell lung cancer (NSCLC).

Hybrid Approaches to Local Management of Pulmonary Metastatic Disease.

With increasingly effective systemic therapies for stage IV disease, the addition of local control strategies for a subset of patients with limited metastatic disease has contributed to improved disease control and life prolongation. While surgery has been the mainstay strategy for local control, stereotactic ablative body radiation and percutaneous ablation techniques are alternate methods that have been demonstrated to be safe and effective and offer options to those patients who are unresectable, inoperable, or who do not desire surgery. A hybrid approach combining surgery and radiotherapy can maximize the ability to treat more lesions.

Modeling dynamic inflow effects in fMRI to quantify cerebrospinal fluid flow.

Cerebrospinal fluid (CSF) flow in the brain is tightly regulated and essential for brain health, and imaging techniques are needed to quantitatively establish the properties of this flow system. Flow-sensitive fMRI has recently emerged as a tool to measure large scale CSF flow dynamics with high sensitivity and temporal resolution; however, the measured signal is not quantitative. Here, we developed a dynamic model to simulate fMRI inflow signals based on time-varying flow velocities.

Cell-Free Circulating Tumor DNA for NonInvasive Molecular Profiling Among Patients Undergoing Definitive Chemoradiation for Locally Advanced Lung Cancer.

Purpose: We prospectively explored the utility of liquid biopsy for cell-free circulating tumor DNA (ctDNA) as a prognostic and predictive biomarker in patients with non-small cell lung cancer (NSCLC) treated with definitive chemoradiation therapy.

Methods And Materials: This prospective clinical cohort consisted of patients with unresectable, locally advanced NSCLC who had liquid biopsy testing before initiation of cancer therapy. Liquid biopsy testing was performed using an institutional assay that included 129 genes and paired white blood cell sequencing.

Tungsten oxide nanocrystals doped with interstitial methylammonium cations.

Doping of semiconductor nanocrystals is a well-established process to impart new or enhanced functionalities to the host material. In this work we present the synthesis of colloidal WO nanocrystals doped with interstitial methylammonium cations. The organic cations are located within the voids of the WO cage and increase the charge carrier concentration.

CADD-based discovery of novel oligomeric modulators of PKM2 with antitumor activity in aggressive human glioblastoma models.

Pyruvate kinase isoform M2 (PKM2) is a multifunctional enzyme capable of transitioning between monomeric, dimeric, and tetrameric states, with its oligomeric equilibrium playing a pivotal role in tumour progression and survival. The unique exon ten at the dimer-dimer interface represents an attractive target for isoform-specific modulation, offering opportunities for disrupting this equilibrium and altering tumour cell dynamics. This study identifies a novel druggable pocket at the PKM2 dimer interface through conformational analysis.

Probiotic supplementation mitigates sex-dependent nociceptive changes and gut dysbiosis induced by prenatal opioid exposure.

The gut microbiome has emerged as a promising target for modulating adverse effects of opioid exposure due to its significant role in health and disease. Opioid use disorder (OUD) has become increasingly prevalent, specifically in women of reproductive age, contributing to an increased incidence of offspring exposed to opioids in utero. Recent studies have shown that prenatal opioid exposure (POE) is associated with notable changes to the maternal gut microbiome, with subsequent implications for the offspring's microbiome and other adverse outcomes.

Intracranial Disease Control and Survival among Patients with KRAS-mutant Lung Adenocarcinoma and Brain Metastases Treated with Stereotactic Radiosurgery.

Purpose: Precision medicine according to molecularly defined subgroups offers great potential to improve outcomes for patients with metastatic lung adenocarcinoma. This study describes clinical outcomes and the impact of co-occurring genetic alterations on outcomes following stereotactic radiosurgery (SRS) among patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung adenocarcinoma.

Methods And Materials: A total of 195 patients with KRAS-mutant lung adenocarcinoma were treated with SRS for brain metastases (BMs) between 2014 and 2018 with follow-up until 2022 or death.

Management of oligoprogressive and oligopersistent disease in advanced NSCLC.

The oligometastatic disease state is defined as an intermediate state between localized cancer and widespread systemic metastases. Oligoprogression is defined as a subgroup in which limited metastatic areas are progressing in the background of oligometastatic or polymetastatic disease, whereas oligopersistent disease refers to an induced state in which formerly polymetastatic disease responds to treatment and decreases to fewer than 5 sites of active disease. With modern improvements in systemic therapy for patients with non-small cell lung cancer, including immunotherapies and targeted therapies, there may be a role for local therapy in selected patients with limited metastases-a subset of patients with potentially curable metastatic disease.

Clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma.

Objective: To identify clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma (LUAD) and to evaluate survival after brain metastasis.

Methods: Patients who underwent complete resection of stage I-IIIA LUAD between 2011 and 2020 were included. A subset of patients had broad-based panel next-generation sequencing performed on their tumors.

Association of the time of day of chemoradiotherapy and durvalumab with tumor control in lung cancer.

Background/purpose: The circadian clock governs the expression of genes related to immunity and DNA repair. We investigated whether the time of day of radiotherapy and/or systemic therapy infusions (chemotherapy or anti-PD-L1) are associated with disease control and survival in locally advanced non-small cell lung cancer (LA-NSCLC).

Materials/methods: 178 consecutive patients with inoperable LA-NSCLC who received definitive chemoradiotherapy followed by durvalumab between 5/2017-8/2022 were reviewed.

Retina and optic nerve diffusion restriction in acute central retinal artery occlusion: A case-control study.

ObjectiveTo determine the frequency and accuracy of diffusion restriction (DR) of the retina and/or optic nerve (ON) detection on standard brain magnetic resonance diffusion-weighted imaging (DWI-MRI) in patients presenting with acute non-arteritic central retinal artery occlusion (CRAO).MethodsThis is a retrospective case-control study that includes all consecutive patients presenting to our tertiary academic center from 2013-2021 with acute non-arteritic CRAO (cases) or acute ischemic stroke syndrome (controls, age and gender-matched) that had brain MRI performed within 14 days from symptom onset. Two neurology residents (junior and senior), a vascular neurologist, and two neuroradiologists, blinded to the site of CRAO, independently reviewed the brain MRIs to assess for the presence of retina and ON DR.