Machine Learning and Computed Tomography Radiomics to Predict Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer: A Pilot Study.

Background/objectives: Pembrolizumab monotherapy is approved in Canada for first-line treatment of advanced NSCLC with PD-L1 ≥ 50% and no EGFR/ALK aberrations. However, approximately 55% of these patients do not respond to pembrolizumab, underscoring the need for the early intervention of non-responders to optimize treatment strategies. Distinguishing the 55% sub-cohort prior to treatment is a real-world dilemma.

DNA targeting by compact Cas9d and its resurrected ancestor.

Type II CRISPR endonucleases are widely used programmable genome editing tools. Recently, CRISPR-Cas systems with highly compact nucleases have been discovered, including Cas9d (a type II-D nuclease). Here, we report the cryo-EM structures of a Cas9d nuclease (747 amino acids in length) in multiple functional states, revealing a stepwise process of DNA targeting involving a conformational switch in a REC2 domain insertion.

How to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology.

It is well understood that cancer therapies including chemotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiation can increase the risk of cardiovascular disease in patients with cancer. This can manifest as a multitude of pathologies including left ventricular dysfunction, myocarditis, cardiomyopathy, accelerated atherosclerosis, and coronary vasospasm. Multimodal cardiac imaging plays a critical role in diagnosing such pathologies by relying on noninvasive tools including echocardiograms, cardiac magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and coronary computed tomography angiography.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Automated Detection of Normal Pressure Hydrocephalus Using CT Imaging for Calculating the Ventricle-to-Subarachnoid Volume Ratio.

Background And Purpose: Normal pressure hydrocephalus (NPH) is a diagnostic challenge because its clinical symptoms and imaging appearance resemble normal aging and other forms of dementia. Identifying NPH is essential so that patients can receive timely treatment to improve gait distortion and quality of life. An automated marker of NPH was developed and evaluated on clinical CT images, and its utility was assessed in a large patient cohort.

Early Lung Adenocarcinoma Manifesting as Irregular Subsolid Nodules: Clinical and CT Characteristics.

Rationale And Objectives: To explore the clinical and computed tomography (CT) characteristics of early-stage lung adenocarcinoma (LADC) that presents with an irregular shape.

Materials And Methods: The CT data of 575 patients with stage IA LADC and 295 with persistent inflammatory lesion (PIL) manifesting as subsolid nodules (SSNs) were analyzed retrospectively. Among these patients, we selected 233 patients with LADC and 140 patients with PIL, who showed irregular SSNs, hereinafter referred to as irregular LADC (I-LADC) and irregular PIL (I-PIL), respectively.

Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy.

Objective: To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations.

Methods: Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT.

Periodic ER-plasma membrane junctions support long-range Ca signal integration in dendrites.

Neuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca channels and ER Ca-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca homeostasis, and local activation of the Ca/calmodulin-dependent protein kinase II.

High-Risk Embolic Sources on Cardiac Computed Tomography in Patients With Acute Ischemic Stroke: A Case-Control Study.

Background: Cardiac computed tomography (CT) is increasingly used to search for cardioembolic sources of acute ischemic stroke (AIS). We assessed the association between high-risk cardioembolic sources on cardiac CT and AIS.

Methods: We performed a case-control study using data from a prospective cohort including consecutive adult patients with suspected stroke who underwent cardiac CT acquired during the initial stroke imaging protocol between 2018 and 2020.

Diagnostic Efficacy of Ventilation-Perfusion Single Photo Emission Computed Tomography/Computed Tomography for Pulmonary Hypertension due to Fibrinous Mediastinitis.

Rationale And Objectives: Comprehensive data on the use of ventilation-perfusion single-photo emission computed tomography/computed tomography (V/Q SPECT/CT), an established diagnostic tool for chronic thromboembolic pulmonary hypertension, in identifying pulmonary hypertension secondary to fibrinous mediastinitis (PH-FM) is scarce. This study aimed to assess its diagnostic efficacy for PH-FM.

Materials And Methods: Patients with PH due to pulmonary artery stenosis were assessed using V/Q SPECT/CT, computed tomography pulmonary angiography (CTPA), and digital subtraction pulmonary angiography (PAG).

Suite of Biochemical and Cell-Based Assays for the Characterization of Kirsten Rat Sarcoma (KRAS) Inhibitors and Degraders.

KRAS is an important oncogenic driver which is mutated in numerous cancers. Recent advances in the selective targeting of KRAS mutants via small molecule inhibitors and targeted protein degraders have generated an increase in research activity in this area in recent years. As such, there is a need for new assay platforms to profile next generation inhibitors which improve on the potency and selectivity of existing drug candidates, while evading the emergence of resistance.

Comparative Efficacy of Non-contrast vs. Contrast-enhanced CT Radiomics in Predicting Coronary Artery Plaques Among Patients with Low Agatston Scores.

Rationale And Objectives: Patients with a low Agatston score often present with clinical signs and symptoms suggestive of coronary artery disease, despite having minimal calcium deposits. This study aimed to compare the efficacy of low-dose non-contrast cardiac CT with coronary computed tomography angiography (CCTA) in pericoronary adipose tissue (PCAT) radiomics for predicting coronary artery plaques, using CCTA as the reference standard.

Materials And Methods: This retrospective study analyzed 459 patients with suspected coronary artery disease and a coronary artery calcium score < 100 Agatston units, who were treated between June 2021 and December 2023 at a tertiary hospital.

Inherited Retinal Degenerations and Non-Neovascular Age-Related Macular Degeneration: Progress and Unmet Needs.

Inherited retinal degeneration (IRD) disease and age-related macular degeneration (AMD) are leading causes of irreversible vision loss and blindness. Although significant progress has advanced the field in the past 5 years, significant challenges remain. The current article reviews the accomplishments and research advances that have fueled the development of treatments for patients with IRD and AMD, including the first approved gene-augmentation treatment for RPE65-related retinal degeneration and complement inhibition therapies to slow progression of geographic atrophy (GA) in AMD.

Clinical Trial: Safety and Efficacy of a Novel Oesophageal Delivery System for Topical Corticosteroids Versus Placebo in the Treatment of Eosinophilic Oesophagitis.

Background: EsoCap is a thin mucoadhesive film designed to target the oesophageal mucosa. The device loaded with mometasone furoate (ESO-101) is under investigation for the treatment of eosinophilic oesophagitis (EoE).

Aims: To evaluate the efficacy, safety and tolerability of ESO-101 in patients with active EoE.

Feasibility of Sub-milliSievert Low-dose Computed Tomography with Deep Learning Image Reconstruction in Evaluating Pulmonary Subsolid Nodules: A Prospective Intra-individual Comparison Study.

Rationale And Objectives: To comprehensively assess the feasibility of low-dose computed tomography (LDCT) using deep learning image reconstruction (DLIR) for evaluating pulmonary subsolid nodules, which are challenging due to their susceptibility to noise.

Materials And Methods: Patients undergoing both standard-dose CT (SDCT) and LDCT between March and June 2023 were prospectively enrolled. LDCT images were reconstructed with high-strength DLIR (DLIR-H), medium-strength DLIR (DLIR-M), adaptive statistical iterative reconstruction-V level 50% (ASIR-V-50%), and filtered back projection (FBP); SDCT with FBP as the reference standard.

Predicting High-risk Lung Adenocarcinoma in Solid and Part-solid Nodules on Low-dose CT: A Multicenter Study.

Rationale And Objectives: High-grade patterns, visceral pleural invasion, lymphovascular invasion, spread through air spaces, and lymph node metastasis are high-risk factors and associated with poor prognosis in lung adenocarcinomas (LUADs). This study aimed to construct and validate a radiomic model and a radiographic model derived from low-dose CT (LDCT) for predicting high-risk LUADs in solid and part-solid nodules.

Materials And Methods: This study retrospectively enrolled 658 pathologically confirmed LUADs from July 2018 to December 2022 from four centers, which were divided into training set (n=411), internal validation set (n=139), and external validation set (n=108).

F-FLT PET and Blood-based Biomarkers for Identifying Gastrointestinal Graft versus Host Disease after Allogeneic Cell Transplantation.

Purpose To determine whether fluorine 18 (F) fluorothymidine (FLT) PET imaging alone or combined with Mount Sinai Acute GVHD International Consortium (MAGIC) biomarkers could help identify subclinical gastrointestinal graft versus host disease (GI-GVHD) by day 100 following hematopoietic stem cell transplantation (HSCT). Materials and Methods F-FLT PET imaging was analyzed in a prospective pilot study (ClinicalTrials.gov identifier no.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Computed tomography enterography-based deep learning radiomics to predict stratified healing in patients with Crohn's disease: a multicenter study.

Objectives: This study developed a deep learning radiomics (DLR) model utilizing baseline computed tomography enterography (CTE) to non-invasively predict stratified healing in Crohn's disease (CD) patients following infliximab (IFX) treatment.

Methods: The study included 246 CD patients diagnosed at three hospitals. From the first two hospitals, 202 patients were randomly divided into a training cohort (n = 141) and a testing cohort (n = 61) in a 7:3 ratio.

Feasibility of Ultra-low Radiation and Contrast Medium Dosage in Aortic CTA Using Deep Learning Reconstruction at 60 kVp: An Image Quality Assessment.

Objective: To assess the viability of using ultra-low radiation and contrast medium (CM) dosage in aortic computed tomography angiography (CTA) through the application of low tube voltage (60kVp) and a novel deep learning image reconstruction algorithm (ClearInfinity, DLIR-CI).

Methods: Iodine attenuation curves obtained from a phantom study informed the administration of CM protocols. Non-obese participants undergoing aortic CTA were prospectively allocated into two groups and then obtained three reconstruction groups.