Dissection of Progressive Disease Patterns for a Modified Classification for Immunotherapy.

Importance: Progressive disease (PD) in patients treated with immune checkpoint inhibitors (ICIs) varies widely in outcomes according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Efforts to modify RECIST for ICI treatment have not resolved the heterogeneity in PD patterns, posing a clinical challenge.

C-Reactive Protein Facilitates Premetastatic Niche Formation in the Lungs.

C-reactive protein (CRP) has long been recognized as a marker of inflammation, but its evolving role in immunomodulation and cancer has increasingly been recognized. In recent years, multiple studies have explored CRP as a biomarker for prognosis and therapy response, particularly in the context of cancer immunotherapy. In this issue of Cancer Research, Feng and colleagues investigate the role of CRP in the development of lung metastasis.

The modified Glasgow Prognostic Score (mGPS) can guide decisions for immunotherapy treatment beyond progression.

Background: Treatment beyond progression (TBP) is common in patients treated with immune-checkpoint inhibitors (ICI), however, there is no biomarker to select patients that are more likely to derive benefit from TBP. Here, we investigated the potential of the modified Glasgow Prognostic Score (mGPS) as a predictive biomarker to select patients for TBP.

Methods: We performed a post-hoc analysis of the immunotherapy arms in the randomized phase 3 trials IMmotion151 (renal cell carcinoma), OAK (non-small cell lung cancer) and IMvigor211 (urothelial cancer).

High serum sodium predicts immunotherapy response in metastatic renal cell and urothelial carcinoma.

Objectives: The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending.

Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.

Purpose: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. is located on chromosome 1q23.

Integration of on-treatment modified Glasgow prognostic score (mGPS) to improve imaging-based prediction of outcomes in patients with non-small cell lung cancer on immune checkpoint inhibition.

Introduction: A large number of patients with non-small cell lung cancer (NSCLC) on immune checkpoint inhibition (ICI) achieve stable disease (SD) as the best overall response, which is associated with heterogeneous outcomes. In this context, complementary biomarkers that improve outcome prediction are needed. We have recently demonstrated that measuring the on-treatment modified Glasgow prognostic score (mGPS), which is based on the two serum markers C-reactive protein (CRP) and albumin, can improve outcome prediction complementary to radiological staging in metastatic renal cell carcinoma.

On-treatment Modified Glasgow Prognostic Score Provides Predictive Information Complementary to Radiological Staging in Metastatic Urothelial Carcinoma on Immunotherapy.

In the immunotherapy era it is difficult to predict patient prognosis on the basis of radiological staging alone, especially for the subgroup with stable disease (SD), which encompasses a wide range of clinical outcomes. Thus, there is need for reliable and, ideally, cost-efficient biomarkers to improve the accuracy of outcome prediction. We evaluated the on-treatment modified Glasgow Prognostic Score (mGPS)-a known predictor of outcomes in several cancers that is based on serum C-reactive protein and albumin-in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibition (ICI) in the phase 2 IMvigor210 and phase 3 IMvigor211 trials.

Pretreatment albumin is a prognostic and predictive biomarker for response to atezolizumab across solid tumors.

Objectives: Reliable predictive biomarkers for response to immune checkpoint inhibition (ICI) are lacking. Pretreatment serum albumin, a known prognostic and predictive factor in ICI-treated patients, has been proposed as a potential pharmacokinetic surrogate marker for anti-PD1/PD-L1 antibodies, as it shares a homeostatic pathway with IgG. However, this hypothesis is currently based on theoretical considerations and limited evidence from retrospective data.

Development and validation of the ADHD Symptom and Side Effect Tracking - Baseline Scale (ASSET-BS): a novel short screening measure for ADHD in clinical populations.

Objective: The aim was to develop and test a novel screen of adult ADHD, with a specific focus on clinical use. We designed a series of three studies to accomplish this aim.

Method: Study One (n = 155) and Study Two (n = 591) collected data via surveys to conduct exploratory and confirmatory factor analyses, respectively.

() promoter hypomethylation predicts immunotherapy response in metastatic urothelial carcinoma.

PD-L1 status assessed by immunohistochemistry (IHC) has failed to reliably predict outcomes for patients with metastatic urothelial carcinoma (mUC) on immune checkpoint blockade (ICB). promoter methylation is an epigenetic mechanism that has been shown to regulate mRNA expression in various malignancies. The aim of our present study was to evaluate the predictive potential of promoter methylation status () in ICB-treated mUC compared to conventional IHC-based PD-L1 assessment.

Towards hippocampal navigation for brain-computer interfaces.

Automatic wheelchairs directly controlled by brain activity could provide autonomy to severely paralyzed individuals. Current approaches mostly rely on non-invasive measures of brain activity and translate individual commands into wheelchair movements. For example, an imagined movement of the right hand would steer the wheelchair to the right.

Integrating On-Treatment Modified Glasgow Prognostic Score and Imaging to Predict Response and Outcomes in Metastatic Renal Cell Carcinoma.

Importance: In the era of immuno-oncology, imaging alone seems to be insufficient to capture treatment responses, as patients with stable disease treated with immunotherapy have a wide range of clinical outcomes. There is an unmet need for complementary (ideally cost-efficient) markers that enable assessment of therapy response and outcomes in conjunction with imaging.

Objectives: To examine whether longitudinal changes in the modified Glasgow prognostic score (mGPS), which is based on C-reactive protein and albumin, can predict responses and outcomes in patients with metastatic renal cell carcinoma (mRCC).

Early C-reactive protein kinetics predicts immunotherapy response in non-small cell lung cancer in the phase III OAK trial.

Static biomarkers like programmed death-ligand 1 (PD-L1) are insufficient to accurately predict response to immune checkpoint inhibition. Therefore, on-treatment biomarkers, which measure immediate therapy-associated changes, are currently shifting into the focus of immuno-oncology. A prime example of a simple predictive on-treatment biomarker is the early C-reactive protein (CRP) kinetics with its predictive CRP flare-response phenomenon.

Two cases of EBV infection preceding lymphoma.

Infection of lymphocytes with the Epstein-Barr virus (EBV) is a well-documented risk factor for developing lymphoma. The incidence of EBV positivity in lymphoma depends on the subtype and can range from 10% in diffuse large B-cell lymphoma (DLBCL) to 100% in endemic Burkitt lymphoma (BL), (Shannon-Lowe and Rickinson, Front Oncol 9:713, 2019). However, in most cases, EBV infection remains unnoticed until diagnosis of lymphoma is made.

C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma.

Purpose: Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response.

Methods: We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders.

C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer.

Biomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain in demand. Since anti-tumor immune activation is a process, early dynamic changes of the acute-phase reactant C reactive protein (CRP) may serve as a predictive on-treatment biomarker. In a retrospective (N=105) and prospective (N=108) ICB-treated NSCLC cohort, early CRP kinetics were stratified after the start of immunotherapy until weeks 4, 6, and 12 as follows: an early doubling of baseline CRP followed by a drop below baseline (CRP flare-responder), a drop of at least 30% below baseline without prior flare (CRP responders), or those who remained as CRP non-responders.

Real-time synthesis of imagined speech processes from minimally invasive recordings of neural activity.

Speech neuroprosthetics aim to provide a natural communication channel to individuals who are unable to speak due to physical or neurological impairments. Real-time synthesis of acoustic speech directly from measured neural activity could enable natural conversations and notably improve quality of life, particularly for individuals who have severely limited means of communication. Recent advances in decoding approaches have led to high quality reconstructions of acoustic speech from invasively measured neural activity.

Embedded adaptive deep brain stimulation for cervical dystonia controlled by motor cortex theta oscillations.

Dystonia is a disabling movement disorder characterized by excessive muscle contraction for which the underlying pathophysiology is incompletely understood and treatment interventions limited in efficacy. Here we utilize a novel, sensing-enabled, deep brain stimulator device, implanted in a patient with cervical dystonia, to record local field potentials from chronically implanted electrodes in the sensorimotor cortex and subthalamic nuclei bilaterally. This rechargeable device was able to record large volumes of neural data at home, in the naturalistic environment, during unconstrained activity.

Musical Hallucinations in Chronic Pain: The Anterior Cingulate Cortex Regulates Internally Generated Percepts.

The anterior cingulate cortex (ACC) has been extensively implicated in the functional brain network underlying chronic pain. Electrical stimulation of the ACC has been proposed as a therapy for refractory chronic pain, although, mechanisms of therapeutic action are still unclear. As stimulation of the ACC has been reported to produce many different behavioral and perceptual responses, this region likely plays a varied role in sensory and emotional integration as well as modulating internally generated perceptual states.

Electrochemical metrics for corrosion resistant alloys.

Corrosion is an electrochemical phenomenon. It can occur via different modes of attack, each having its own mechanisms, and therefore there are multiple metrics for evaluating corrosion resistance. In corrosion resistant alloys (CRAs), the rate of localized corrosion can exceed that of uniform corrosion by orders of magnitude.

Expanded dataset of mechanical properties and observed phases of multi-principal element alloys.

This data article presents a compilation of mechanical properties of 630 multi-principal element alloys (MPEAs). Built upon recently published MPEA databases, this article includes updated records from previous reviews (with minor error corrections) along with new data from articles that were published since 2019. The extracted properties include reported composition, processing method, microstructure, density, hardness, yield strength, ultimate tensile strength (or maximum compression strength), elongation (or maximum compression strain), and Young's modulus.

Machine-Learning Guided Quantum Chemical and Molecular Dynamics Calculations to Design Novel Hole-Conducting Organic Materials.

Materials exhibiting higher mobilities than conventional organic semiconducting materials such as fullerenes and fused thiophenes are in high demand for applications such as printed electronics, organic solar cells, and image sensors. In order to discover new molecules that might show improved charge mobility, combined density functional theory (DFT) and molecular dynamics (MD) calculations were performed, guided by predictions from machine learning (ML). A ML model was constructed based on 32 values of theoretically calculated hole mobilities for thiophene derivatives, benzodifuran derivatives, a carbazole derivative and a perylene diimide derivative with the maximum value of 10 cm/(V s).

Analysing detection of chronic diseases with prolonged sub-clinical periods: modelling and application to hypertension in the U.S.

Background: We recently introduced a system of partial differential equations (PDEs) to model the prevalence of chronic diseases with a possibly prolonged state of asymptomatic, undiagnosed disease preceding a diagnosis. Common examples for such diseases include coronary heart disease, type 2 diabetes or cancer. Widespread application of the new method depends upon mathematical treatment of the system of PDEs.