Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay.

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau, p-tau and p-tau) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field.

Integrated multi-omics analyses of oral squamous cell carcinoma reveal precision patient stratification and personalized treatment strategies.

Oral cavity squamous cell carcinoma (OSCC), a leading subtype of head and neck cancer, exhibits high global incidence and mortality rates. Despite advancements in surgery and radiochemotherapy, approximately one-third of patients experience relapse. To improve current targeted and immunotherapy strategies for recurrent OSCC, we conducted multi-omics analyses on pretreatment OSCC samples (cohorts 1 and 2, n=137) and identified A3A and EGFR, both at the RNA and protein levels, as inversely expressed markers for patient stratification and response prediction.

Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity.

A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature.

A network-based systems genetics framework identifies pathobiology and drug repurposing in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments only manage symptoms and lack the ability to slow or prevent disease progression. We utilized a systems genetics approach to identify potential risk genes and repurposable drugs for PD.

Structure-guided insights into TIR-mediated bacterial and eukaryotic immunity.

Within the course of evolution, TIR (Toll/interleukin-1 receptor) domains acquired a myriad of functional specificities. This has significantly added to their well-established roles in innate immune signaling. These additional functions include nicotinamide adenine dinucleotide (NAD)(P) hydrolase, RNA/DNA nuclease (in plants), CN (cyclic nucleotide) cyclase, and base exchanger activities.

SyncGenie: A programmable event synchronization device for neuroscience research.

In neuroscience, accurately correlating brain activity with stimuli and other events requires precise synchronization between neural data and event timing. To achieve this, purpose-built synchronization devices are often used to detect events. This paper introduces SyncGenie, a programmable synchronization device designed for a range of uses in neuroscience research-primarily as a "trigger box" to align neurophysiological data with physical stimulus events, among other possibilities.

Comparing quantitative imaging biomarker alliance volumetric CT classifications with RECIST response categories.

Purpose: To assess agreement between CT volumetry change classifications derived from Quantitative Imaging Biomarker Alliance Profile cut-points (ie, QIBA CTvol classifications) and the Response Evaluation Criteria in Solid Tumors (RECIST) categories.

Materials And Methods: Target lesions in lung, liver, and lymph nodes were randomly chosen from patients in 10 historical clinical trials for various cancers, ensuring a balanced representation of lesion types, diameter ranges described in the QIBA Profile, and variations in change magnitudes. Three radiologists independently segmented these lesions at baseline and follow-up scans using 2 software tools.

An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis.

Human endogenous retroviruses (HERVs) occupy a large portion of the human genome. Most HERVs are transcriptionally silent, but they can be reactivated during pathological states such as viral infection and certain cancers. The HERV-K HML-2 clade includes elements that recently integrated have in the human germ line and often contain intact open reading frames that possibly support peptide and protein expression.

SMC translocation is unaffected by an excess of nucleoid associated proteins in vivo.

Genome organization is important for DNA replication, gene expression, and chromosome segregation. In bacteria, two large families of proteins, nucleoid-associated proteins (NAPs) and SMC complexes, play important roles in organizing the genome. NAPs are highly abundant DNA-binding proteins that can bend, wrap, bridge, and compact DNA, while SMC complexes load onto the chromosome, translocate on the DNA, and extrude DNA loops.

Modeling dissolved organic carbon export from water supply catchments in the northeastern United States.

Natural organic matter (NOM) in rivers is an important energy source to sustain aquatic ecosystem health. However, in surface water supply systems where chlorination is often used for disinfection, NOM is also a precursor for the carcinogenic and mutagenic disinfection byproducts such as trihalomethanes and haloacetic acids. Effective management of NOM in rivers to maintain both aquatic ecosystem functions and high-quality water supply requires better understanding of the NOM transport patterns.

Prediction of response to anti-HER2 therapy using a multigene assay.

HER2-positive breast cancer (BC), which constitutes 13-15% of cases, shows variable response to anti-HER2 therapies. HER2-positivity, defined as protein overexpression (immunohistochemistry (IHC) score 3+) or equivocal expression (IHC 2+) with evidence of HER2 gene amplification, determines the eligibility to anti-HER2 therapy. MammaTyper® assay (Cerca Biotech GmbH) is a RT-qPCR BC subtyping platform based on the mRNA expression of ERBB2, ESR1, PGR, and MKI67.

The Impact of COVID-19 on the Division of Household Labor Among Women Physicians and Advanced Practice Providers.

Background: COVID-19 increased the burden of childcare on parents, leaving women vulnerable to increased disparities in the division of domestic labor. Women healthcare workers may be at heightened risk of worsening gender parity in the workplace as a result.

Objective: To examine the impact of the COVID-19 pandemic on gender parity in the division of household responsibilities among women healthcare workers.

Simplifying clinical use of TCGA molecular subtypes through machine learning models.

In this issue of Cancer Cell, Ellrott et al. present machine learning models to classify samples into The Cancer Genome Atlas molecular subtypes using compact sets of genomic features. These validated, ready-to-use models are publicly available, although some clinical hurdles need to be cleared before they are fully implemented.

Nucleic acid recognition during prokaryotic immunity.

Parasitic elements often spread to hosts through the delivery of their nucleic acids to the recipient. This is particularly true for the primary parasites of bacteria, bacteriophages (phages) and plasmids. Although bacterial immune systems can sense a diverse set of infection signals, such as a protein unique to the invader or the disruption of natural host processes, phage and plasmid nucleic acids represent some of the most common molecules that are recognized as foreign to initiate defense.

Adjuvant radiation therapy is not associated with a survival benefit after R0 resection in non-metastatic adrenocortical carcinoma.

The benefit of adjuvant radiation therapy (RT) in adrenocortical carcinoma (ACC) is not well characterized for those who undergo initial R0 surgical resection. Patients in the NCDB who underwent R0 resection were placed into two cohorts - those who underwent adjuvant RT and those who did not. 388 patients were identified with 51 receiving RT.

Semi-supervised learning from small annotated data and large unlabeled data for fine-grained Participants, Intervention, Comparison, and Outcomes entity recognition.

Objective: Extracting PICO elements-Participants, Intervention, Comparison, and Outcomes-from clinical trial literature is essential for clinical evidence retrieval, appraisal, and synthesis. Existing approaches do not distinguish the attributes of PICO entities. This study aims to develop a named entity recognition (NER) model to extract PICO entities with fine granularities.

Centering historically minoritized populations to design effective messages about an evidence-based policy to advance social equity.

Researchers have raised concerns that messages describing racial disparities in social outcomes can reduce or polarize support for public policies to address inequality. We questioned this assumption by testing the impact of carefully crafted messages about child tax credit (CTC) expansion. We conducted two randomized message trials, study 1 using Prolific's nonprobability panel ( = 1,402) and study 2 using SSRS's Opinion Panel, a web-based probability sample of US adults ( = 4,483).

Feasibility and acceptability of a mindfulness app-based intervention among patients with metastatic renal cell carcinoma: a multinational study.

Background: Patients with metastatic renal cell carcinoma (mRCC) experience emotional distress and limited supportive care access. This study assesses a mindfulness app's feasibility, acceptability, and preliminary efficacy in improving emotional symptoms, trait mindfulness, and overall quality of life for patients with mRCC on immunotherapy.

Methods: This multinational study recruited patients with mRCC undergoing immunotherapy from Brazil and the United States.

Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning.

Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species.

The immunology of stroke and dementia.

Ischemic stroke and vascular cognitive impairment, caused by a sudden arterial occlusion or more subtle but protracted vascular insufficiency, respectively, are leading causes of morbidity and mortality worldwide with limited therapeutic options. Innate and adaptive immunity have long been implicated in neurovascular injury, but recent advances in methodology and new experimental approaches have shed new light on their contributions. A previously unappreciated dynamic interplay of brain-resident, meningeal, and systemic immune cells with the ischemic brain and its vasculature has emerged, and new insights into the frequent overlap between vascular and Alzheimer pathology have been provided.

Randomized clinical trial of a digital integrative medicine intervention among patients undergoing active cancer treatment.

Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.

Reanalysis of Samburupithecus reveals similarities to nyanzapithecines.

Samburupithecus kiptalami is an ape found in Late Miocene deposits (ca. 9.5 Ma) of northern Kenya.