Heterogeneity in the diagnosis and prognosis of ischemic stroke subtypes: 9-year follow-up of 22,000 cases in Chinese adults.

Background: Reliable classification of ischemic stroke (IS) etiological subtypes is required in research and clinical practice, but the predictive properties of these subtypes in population studies with incomplete investigations are poorly understood.

Aims: To compare the prognosis of etiologically classified IS subtypes and use machine learning (ML) to classify incompletely investigated IS cases.

Methods: In a 9-year follow-up of a prospective study of 512,726 Chinese adults, 22,216 incident IS cases, confirmed by clinical adjudication of medical records, were assigned subtypes using a modified Causative Classification System for Ischemic Stroke (CCS) (large artery atherosclerosis (LAA), small artery occlusion (SAO), cardioaortic embolism (CE), or undetermined etiology) and classified by CCS as "evident," "probable," or "possible" IS cases.

Development, validation and comparison of multivariable risk scores for prediction of total stroke and stroke types in Chinese adults: a prospective study of 0.5 million adults.

Background And Purpose: Low-income and middle-income countries have the greatest stroke burden, yet remain understudied. This study compared the utility of Framingham versus novel risk scores for prediction of total stroke and stroke types in Chinese adults.

Methods: China Kadoorie Biobank (CKB) is a prospective study of 512 726 adults, aged 30-79 years, recruited from 10 areas in China in 2004-2008.

Utility of single versus sequential measurements of risk factors for prediction of stroke in Chinese adults.

Absolute risks of stroke are typically estimated using measurements of cardiovascular disease risk factors recorded at a single visit. However, the comparative utility of single versus sequential risk factor measurements for stroke prediction is unclear. Risk factors were recorded on three separate visits on 13,753 individuals in the prospective China Kadoorie Biobank.

Immunotherapy combinations overcome resistance to bispecific T cell engager treatment in T cell-cold solid tumors.

Therapeutic approaches are needed to promote T cell-mediated destruction of poorly immunogenic, "cold" tumors typically associated with minimal response to immune checkpoint blockade (ICB) therapy. Bispecific T cell engager (BiTE) molecules induce redirected lysis of cancer cells by polyclonal T cells and have demonstrated promising clinical activity against solid tumors in some patients. However, little is understood about the key factors that govern clinical responses to these therapies.

How Do Novice Hapticians Design? A Case Study in Creating Haptic Learning Environments.

Access to haptic technology is on the rise, in smartphones, virtual reality gear, and open-source education kits. However, engineers and interaction designers are often inexperienced in designing with haptics, and rarely have tools and guidelines for creating multisensory experiences. To examine the impact of this deficit, we supplied a haptic design kit, custom software, and technical support to nine teams (25 students) for an innovation challenge at a major haptics conference.

The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non-small cell lung cancer.

The LKB1 tumor suppressor is often mutationally inactivated in non-small cell lung cancer (NSCLC). LKB1 phosphorylates and activates members of the AMPK family of Ser/Thr kinases. Within this family, the salt-inducible kinases (SIKs) modulate gene expression in part via the inhibitory phosphorylation of the CRTCs, coactivators for CREB (cAMP response element-binding protein).

Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates.

Many tumors become addicted to autophagy for survival, suggesting inhibition of autophagy as a potential broadly applicable cancer therapy. ULK1/Atg1 is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. Despite recent advances in the understanding of ULK1 activation by nutrient deprivation, how ULK1 promotes autophagy remains poorly understood.

Genetic deletion of the desmosomal component desmoplakin promotes tumor microinvasion in a mouse model of pancreatic neuroendocrine carcinogenesis.

We used the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis to profile the transcriptome of pancreatic neuroendocrine tumors (PNET) that were either non-invasive or highly invasive, seeking to identify pro- and anti-invasive molecules. Expression of multiple components of desmosomes, structures that help maintain cellular adhesion, was significantly reduced in invasive carcinomas. Genetic deletion of one of these desmosomal components, desmoplakin, resulted in increased local tumor invasion without affecting tumor growth parameters in RT2 PNETs.

Polymorphic genetic control of tumor invasion in a mouse model of pancreatic neuroendocrine carcinogenesis.

Cancer is a disease subject to both genetic and environmental influences. In this study, we used the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis to identify a genetic locus that influences tumor progression to an invasive growth state. RT2 mice inbred into the C57BL/6 (B6) background develop both noninvasive pancreatic neuroendocrine tumors (PNET) and invasive carcinomas with varying degrees of aggressiveness.

MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer.

While altered expression of microRNAs (miRs) in tumors has been well documented, it remains unclear how the miR transcriptome intersects neoplastic progression. By profiling the miR transcriptome we identified miR expression signatures associated with steps in tumorigenesis and the acquisition of hallmark capabilities in a prototypical mouse model of cancer. Metastases and a rare subset of primary tumors shared a distinct miR signature, implicating a discrete lineage for metastatic tumors.

Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis.

Here, we describe the surprising residual capability of the Rb pathway to negatively regulate proliferation and tumorigenesis in a SV40 large T antigen (Tag)-driven mouse model of pancreatic islet carcinogenesis. Heterogeneous Tag expression during all progression stages suggested that a threshold level of the T antigen oncoprotein might be deterministic for beta-cell hyperproliferation and led us to hypothesize that Tag might not be fully inhibiting the tumor suppressor activity of Rb. Moreover, genomic profiling of these tumors by array CGH pointed to regions of loss on chromosomes 6 and 14, where the Rb pathway inhibitor p27 and Rb itself, respectively, reside.