The YAP1-MAML2 fusion drives tumorigenesis and sustains tumor growth.

The Yes1-associated transcriptional regulator-mastermind-like transcriptional co-activator 2 (YAP1-MAML2 [YM]) fusion protein arises from an intrachromosomal inversion and is implicated in various cancers. However, the oncogenic role of the endogenous YM fusion protein remained undefined. In this study, we employed YM-positive ES-2 ovarian cancer cells as a model to explore the roles of the YM fusion in cancer initiation and maintenance.

Development of Novel Indole-Based Covalent Inhibitors of TEAD as Potential Antiliver Cancer Agents.

Abnormal activation of the YAP transcriptional signaling pathway drives proliferation in many hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cases. Current treatment options often face resistance and toxicity, highlighting the need for alternative therapies. This article reports the discovery of a hit compound from docking-based virtual screening targeting TEAD lipid binding pocket, which inhibited TEAD-mediated transcription.

Design and Realization of Lung Organoid Cultures for COVID-19 Applications.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading globally and threatening public health. Advanced models that recapitulate the architecture and functioning of specific tissues and organs are in high demand for COVID-19-related pathology studies and drug screening. Three-dimensional (3D) cultures such as self-assembled and engineered organoid cultures surpass conventional two-dimensional (2D) cultures and animal models with respect to the increased cellular complexity, better human-relevant environment, and reduced cost, thus presenting as promising platforms for understanding viral pathogenesis and developing new therapeutics.

Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine.

Evidence from physical sciences in oncology increasingly suggests that the interplay between the biophysical tumor microenvironment and genetic regulation has significant impact on tumor progression. Especially, tumor cells and the associated stromal cells not only alter their own cytoskeleton and physical properties but also remodel the microenvironment with anomalous physical properties. Together, these altered mechano-omics of tumor tissues and their constituents fundamentally shift the mechanotransduction paradigms in tumorous and stromal cells and activate oncogenic signaling within the neoplastic niche to facilitate tumor progression.

PROTAC therapy as a new targeted therapy for lung cancer.

Despite recent advances in molecular therapeutics, lung cancer is still a leading cause of cancer deaths. Currently, limited targeted therapy options and acquired drug resistance present significant barriers in the treatment of patients with lung cancer. New strategies in drug development, including those that take advantage of the intracellular ubiquitin-proteasome system to induce targeted protein degradation, have the potential to advance the field of personalized medicine for patients with lung cancer.

Epithelial-Mesenchymal Transition Suppresses AMPK and Sensitizes Cancer Cells to Pyroptosis under Energy Stress.

Epithelial-mesenchymal transition (EMT) is implicated in tumor metastasis and therapeutic resistance. It remains a challenge to target cancer cells that have undergone EMT. The Snail family of key EMT-inducing transcription factors directly binds to and transcriptionally represses not only epithelial genes but also a myriad of additional genomic targets that may carry out significant biological functions.

The impact of COVID-19 on older adults: Results from an annual survey.

Objectives: Assess well-being among older adults through secondary analysis measured during an annual survey in 2018, 2019, and 2020, to determine trends from before and during the COVID-19 pandemic.

Methods: Mailed surveys sent annually included measures related to various psychosocial factors.

Main Findings: Response rates were 29% in 2018, 25% in 2019, and 24% in 2020.

Dependency of human and murine LKB1-inactivated lung cancer on aberrant CRTC-CREB activation.

Lung cancer with loss-of-function of the LKB1 tumor suppressor is a common aggressive subgroup with no effective therapies. LKB1deficiency induces constitutive activation of cAMP/CREB-mediated transcription by a family of three CREB-regulated transcription coactivators (CRTC1-3). However, the significance and mechanism of CRTC activation in promoting the aggressive phenotype of LKB1-null cancer remain poorly characterized.

Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response.

Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair.

The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma.

No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown.

Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC) is the most common type of salivary gland cancers and patients with advanced, metastatic, and recurrent MECs have limited therapeutic options and poor treatment outcomes. MEC is commonly associated with a chromosomal translocation t(11;19) (q14-21;p12-13) that encodes the CRTC1-MAML2 oncogenic fusion. The CRTC1-MAML2 fusion is required for MEC growth in part through inducing autocrine AREG-EGFR signaling.

Limited Health Literacy and Hearing Loss Among Older Adults.

Background: Effective communications between health care providers and patients are critical for high-quality health care.

Objective: This study sampled adults age 65 years and older to explore (1) characteristics associated with limited health literacy (LHL) and (2) medical costs and gaps in care based on health literacy, hearing loss, and hearing aid use status.

Methods: The study included 19,223 adults age 65 years and older who completed a health survey that was linked to his or her medical claims that were generated after medical care provided in the year prior to survey completion.

Reducing loneliness and improving well-being among older adults with animatronic pets.

Background: Studies consistently demonstrate that older adults who are lonely have higher rates of depression and increased mortality risk. Pet ownership may be a solution for loneliness; however, challenges related to pet ownership exist for older adults. Therefore, researchers and practitioners are examining the use of animatronic pets to reduce loneliness.

LATS kinase-mediated CTCF phosphorylation and selective loss of genomic binding.

Chromatin topological organization is instrumental in gene transcription. Gene-enhancer interactions are accommodated in the same CTCF-mediated insulated neighborhoods. However, it remains poorly understood whether and how the 3D genome architecture is dynamically restructured by external signals.

Hepatocyte nuclear factor 4α negatively regulates connective tissue growth factor during liver regeneration.

Liver regeneration after injury requires fine-tune regulation of connective tissue growth factor (Ctgf). It also involves dynamic expression of hepatocyte nuclear factor (Hnf)4α, Yes-associated protein (Yap), and transforming growth factor (Tgf)-β. The upstream inducers of Ctgf, such as Yap, etc, are well-known.

Self-Reported Hearing Loss in Older Adults Is Associated With Higher Emergency Department Visits and Medical Costs.

Hearing loss is common among older adults. Thus, it was of interest to explore differences in health care utilization and costs associated with hearing loss and hearing aid use. Hearing loss and hearing aid use were assessed through self-reports and included 5 categories: no hearing loss, aided mild, unaided mild, aided severe, and unaided severe hearing loss.

MYB-activated models for testing therapeutic agents in adenoid cystic carcinoma.

Objective: There are no effective systemic therapies for adenoid cystic cancer (ACC) and lack of tumor lines and mouse models have hindered drug development.We aim to develop MYB-activated models for testing new therapeutic agents.

Materials And Methods: We studied new ACC patient-derived xenograft (PDX) models and generated a matched cell line from one patient.

Characteristics and Health Outcomes Associated With Hearing Loss and Hearing Aid Use Among Older Adults.

This study recruited older adults to explore physical and psychosocial conditions and other health outcomes associated with hearing loss (HL) and hearing aid use. Survey data were used to categorize 20,244 participants into five groups: no HL, unaided mild HL, aided mild HL, unaided severe HL, and aided severe HL. Individuals with unaided severe HL were more likely to report poor-fair self-rated health and were less likely to leave the home, or exercise 4 to 7 days per week, while there were no such associations for those with aided mild or severe HL.

Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer.

Background: The LKB1 tumor suppressor gene is commonly inactivated in non-small cell lung carcinomas (NSCLC), a major form of lung cancer. Targeted therapies for LKB1-inactivated lung cancer are currently unavailable. Identification of critical signaling components downstream of LKB1 inactivation has the potential to uncover rational therapeutic targets.

Notch1 activation enhances proliferation via activation of cdc2 and delays differentiation of myeloid progenitors.

Accumulating evidence indicates that the Notch signaling pathway has crucial roles in the control of fate decision and differentiation in numerous cell types. However, the role of Notch signaling in regulating proliferation and differentiation of myeloid progenitor cells remains controversial. To elucidate this issue, we modulated Notch activity through transducing a constitutively activated form of Notch1 and/or a dominant-negative form of MAML1 (DNMAML1) into myeloid progenitor 32D cells and assessed their effects on cell proliferation and differentiation.

CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells.

Mucoepidermoid carcinoma (MEC) arises in many glandular tissues and contributes to the most common malignant salivary gland cancers. MEC is specifically associated with a unique t(11;19) translocation and the resulting CRTC1-MAML2 fusion is a major oncogenic driver for MEC initiation and maintenance. However, the molecular basis underlying the CRTC1-MAML2 oncogenic functions remains elusive.

A Pilot Online Mindfulness Intervention to Decrease Caregiver Burden and Improve Psychological Well-Being.

Interventions to reduce caregiver burden are of great interest as the number of informal family caregivers continues to grow. The purpose of this study was to test the feasibility of an online mindfulness meditation intervention for community-dwelling older adult caregivers and to evaluate its impact on quality of life, caregiver burden, and psychological well-being. A total of 40 caregivers were recruited from 2 community center support groups to participate in an 8-week online mindfulness intervention.

Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells.

Carcinoma cells can acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT). However, the significance of EMT in cancer metastasis has been controversial, and the exact fates and functions of EMT cancer cells in vivo remain inadequately understood. Here, we tracked epithelial cancer cells that underwent inducible or spontaneous EMT in various tumor transplantation models.

The Impact of Deep Sternal Wound Infection on Mortality and Resource Utilization: A Population-based Study.

Background: Recent national infection control efforts have been directed at reducing postsurgical infection rates, related morbidity, and cost. We sought to evaluate population-level rates of deep sternal wound infection (DSWI) after cardiac surgery, associated mortality, and resource use compared to patients undergoing cardiac surgery without postoperative DSWI relative to historical trends.

Methods: We analyzed the MarketScan Commercial Claims Databases from 2009 to 2013 to identify adult patients who developed DSWI after open cardiac surgery.