Ivacaftor, a CFTR potentiator, synergizes with osimertinib against acquired resistance to osimertinib in NSCLC by regulating CFTR-PTEN-AKT axis.

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has demonstrated significant clinical benefits in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). However, inevitable acquired resistance to osimertinib limits its clinical utility, and there is a lack of effective countermeasures. Here, we established osimertinib-resistant cell lines and performed drug library screening.

Identifying risk factors and biomarkers for severe CIP in lung cancer patients- a retrospective case series study.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but they can induce immune-related adverse events, including immune checkpoint inhibitor-associated pneumonia (CIP), a severe lung complication. CIP, particularly Grades 3-4, is associated with poor prognosis, indicating a critical need for research on this issue. Our study aimed to investigate the risk factors and biomarkers associated with severe CIP in lung cancer patients treated with ICIs, where OS represents overall survival and PFS denotes progression-free survival.

Arch dam point cloud segmentation based on deep feature learning and normal vector data optimization.

Separating the dam body, spillway, and other structures from the point cloud in the dam area is an important step in dam deformation monitoring. Manual segmentation is time consuming and inaccurate. This study proposes a point cloud segmentation neural network model based on normal vector optimization suitable for dam environment: (1) This model utilizes the voxel uniform sampling method of equal length cubes to solve the problem of uneven point cloud density caused by wide range and long-distance measurement during point cloud measurement in dam areas.

CD161CD127CD8 T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161CD127CD8 T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8 T cell subsets in NSCLC with diabetes. We recruited NSCLC patients ( = 436) treated with anti-PD-1 immunotherapy as first-line treatment.

Josephin domain containing 2 (JOSD2) promotes lung cancer by inhibiting LKB1 (Liver kinase B1) activity.

Non-small cell lung cancer (NSCLC) ranks as one of the leading causes of cancer-related deaths worldwide. Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment, these drugs are suitable for and beneficial to a mere ~30% of NSCLC patients. Consequently, the need for novel strategies addressing NSCLC remains pressing.

Efficacy and surgical safety of sequential surgical resection after pembrolizumab plus chemotherapy for initial unresectable stage IIIB non-small cell lung cancer.

Introduction: Neoadjuvant immunochemotherapy is effective in resectable NSCLC. However, its role in unresectable stage IIIB NSCLC patients remains controversial. This study aimed to demonstrate the efficacy and safety of neoadjuvant immunochemotherapy followed by surgical resection to treat initial unresectable stage IIIB NSCLC patients.

The Role of Contextual Factors in Shaping Urban Older Adults' Intention of Institutional Care in China: A Mixed-Methods Study.

Background: This mixed-methods study explores older people's intention of institutional care and its contributing contextual factors, and the meaning given to their intention by older adults in the transitioning Chinese society.

Methods: Guided by the extended Anderson model and frameworks of the ecological theory of aging, survey data collected from 1937 Chinese older adults were used. Transcripts from six focus group interviews were analyzed to incorporate the voices of the participants.

Deubiquitinating enzymes: Promising targets for drug resistance.

Drug resistance to chemotherapy and molecularly targeted therapies is a current challenge in cancer treatments. The underlying mechanisms of resistance to cytotoxic chemotherapeutics and to drugs that target a specific molecule are not understood completely. In recent years, emerging evidence has frequently suggested that the dysregulation of deubiquitinating enzymes (DUBs) plays important roles in the development of drug resistance.

Avoiding Structural Collapse to Reduce Lead Leakage in Perovskite Photovoltaics.

Perovskite solar cells (PSCs) have become a promising candidate for the next-generation photovoltaic technologies. As an essential element for high-efficiency PSCs however, the heavy metal Pb is soluble in water, causing a serious threat to the environment and human health. Due to the weak ionic bonding in three-dimensional (3D) perovskites, drastic structure decomposition occurs when immersing the perovskite film in water, which accelerates the Pb leakage.

Authenticated social capital: conceptualising power, resistance and well-being in the lives of transgender older adults.

Trans people experience social marginalisation, stigmatisation and violent oppression in US society and worldwide. Given the importance of social capital for wellbeing, this study sought to illuminate the ways in which trans people build social capital throughout their lives and to use this knowledge to promote new and helpful ways of thinking about social capital concerning the human life course in the 21st century. We conducted a secondary interpretive content analysis of 86 in-depth interviews with trans older adults generated as part of the arts project .

Neighborhood resources associated with frailty trajectories over time among community-dwelling older adults in China.

Background And Objectives: Recent research has identified neighborhoods as an important contributor to later-life frailty. However, little is known about how neighborhood resources are associated with frailty trajectories over time, especially in developing countries. This study examines the impact of neighborhood physical and social resources on the trajectories of frailty over time among older people in China.

AKR1C1 connects autophagy and oxidative stress by interacting with SQSTM1 in a catalytic-independent manner.

Targeting autophagy might be a promising anticancer strategy; however, the dual roles of autophagy in cancer development and malignancy remain unclear. NSCLC (non-small cell lung cancer) cells harbour high levels of SQSTM1 (sequestosome 1), the autophagy receptor that is critical for the dual roles of autophagy. Therefore, mechanistic insights into SQSTM1 modulation may point towards better approaches to treat NSCLC.

Within-couple dissimilarities in functional impairment as determinants of spousal care arrangement among older married couples.

Existing research on spousal care focuses on one spouse receiving care from the other, which fails to address the complexity that is created when both spouses experience some impairments. Our study included situations in which one or both spouses have functional impairments when examining the extent to which spouses from the same couple hold a (dis)similar level of functional impairment and whether such within-couple (dis)similarity has an impact on the spousal care arrangement. A subsample of 1170 older married couples was selected from the 2014 Health and Retirement Study.

Machado-Joseph Deubiquitinases: From Cellular Functions to Potential Therapy Targets.

Ubiquitination is known as important post-translational modification in cancer-related pathways. Human deubiquitinases (DUBs), with functions of modulating the ubiquitination process, are a family with about 100 proteins. They mainly function by cutting ubiquitin chains of the substrates.

Neighborhood Effects on the Health of Chinese Older Adults: Beyond the Rural and Urban Dichotomy.

Background And Objectives: The associations between physical frailty and depressive symptoms among older individuals were established in the existing literature. Taking the person-environment perspective, we argue that neighborhood environment could either buffer the stress derived from being physically vulnerable or worsen it by adding another layer of stressors in the environmental context when physical health declined. The objectives of this study were to explore to what extent the neighborhood-level characteristics moderate the relationship between physical frailty and depressive symptoms.

Initially Negative Affect Predicts Lower Satisfaction With Future Social Contact: A Time-Lagged Analysis Using Ecological Momentary Assessment.

Objectives: Prior research has linked subjective features of social situations with short-term changes in affect (e.g., across days, hours), but little is known about the directionality of such links.

Development and Validation of a Prognostic Tool for Identifying Residents at Increased Risk of Death in Long-Term Care Facilities.

Background: To promote better care at the end stage of life in long-term care facilities, a culturally appropriate tool for identifying residents at the end of life is crucial.

Objective: This study aimed to develop and validate a prognostic tool, the increased risk of death (IRD) scale, based on the minimum data set (MDS).

Design: A retrospective study using data between 2005 and 2013 from six nursing homes in Hong Kong.