Corticosteroid insensitivity in asthma associated with obstructive sleep apnoea: Role of oxidative stress and histone acetylation.

Background And Purpose: Obstructive sleep apnoea (OSA) worsens asthma control. Oxygen desaturation increases oxidative stress, contributing to corticosteroid insensitivity, a hallmark of severe asthma. This study investigated the impact of hypoxaemia and reactive oxygen species on corticosteroid responsiveness in asthma with OSA.

Use of multimedia shared decision-making aids (EATING program) for improving advance care planning engagement among community-dwelling older adults with chronic diseases: A cluster randomized controlled trial.

Background: Discussing advance care planning (ACP) preferences for nasogastric tube (NG) insertion remains challenging among older adults. Multimedia decision-making aids have demonstrated potential to enhance understanding and support informed decision-making.

Aim: To evaluate the effectiveness of the EATING program (multimedia decision-making aids + traditional educational module) compared to usual care (traditional educational module alone) in improving ACP readiness on NG insertion for community older adults with chronic illness.

Poly (ADP-Ribose) Polymerase Inhibitor Olaparib-Resistant -Mutant Ovarian Cancer Cells Demonstrate Differential Sensitivity to PARP Inhibitor Rechallenge.

Poly (ADP-ribose) polymerase inhibitors (PARPis) show cytotoxicity in homologous recombination deficiency (HRD) seen in -mutant ovarian cancer (OvCa). Despite initial responses, resistance often develops. The reintroduction of different PARPis, such as niraparib or rucaparib, has shown some clinical activity in mutation-associated OvCa patients with prior olaparib treatment, yet the underlying mechanisms remain unclear.

Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.

The PI3K signaling pathway plays an essential role in cancer cell proliferation and survival. PI3K pathway inhibitors are now FDA-approved as a single agent treatment or in combination for solid tumors such as renal cell carcinoma or breast cancer. However, despite the high prevalence of PI3K pathway alterations in gynecological cancers and promising preclinical activity in endometrial and ovarian cancer models, PI3K pathway inhibitors showed limited clinical activity in gynecological cancers.

Translation, cross-cultural adaptation, and measurement properties of the Traditional Chinese version of the Fear of Falling Avoidance Behavior Questionnaire in Taiwanese community-dwelling adults.

Purpose: This study aimed to translate the Fear of Falling Avoidance Behavior Questionnaire (FFABQ) into Traditional Chinese (FFABQ-TC) and to evaluate the psychometric properties of FFABQ-TC in Taiwanese adults.

Methods: We translated and culturally adapted the FFABQ into Traditional Chinese, ensuring linguistic accuracy and cultural relevance. A total of 230 Taiwanese community-dwelling adults participated in the study.

Analyses of Neural Circuits Governing Behavioral Plasticity in the Nematode Caenorhabditis elegans.

Behavioral plasticity is subjected to various sensory stimuli, experiences, and physiological states, representing the temporal and spatial patterns of neural circuit dynamics. Elucidation of how genes and neural circuits in our brain actuate behavioral plasticity requires functional imaging during behavioral assays to manifest temporal and spatial neural regulation in behaviors. The exploration of the nervous systems of Caenorhabditis elegans has catalyzed substantial scientific advancements in elucidating the mechanistic link between circuit dynamics and behavioral plasticity.

Analyses of Genetic Regulation of the Nervous System in the Nematode Caenorhabditis elegans.

This chapter aims to provide a comprehensive overview of the methodologies available to dissect genetic regulation of the nervous systems in the nematode Caenorhabditis elegans. These techniques encompass genetic screens and genetic tools to unravel the spatial-temporal contribution of genes on neural structure and function. Unbiased genetic screens on random mutations induced by ethyl methanesulfonate (EMS) or target gene silencing by genome-wide RNA interference (RNAi) help progress our understanding of the genetic control of neural development and functions.

The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial.

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR).

AKT1 interacts with DHX9 to Mitigate R Loop-Induced Replication Stress in Ovarian Cancer.

Unlabelled: PARP inhibitor (PARPi)-resistant BRCA-mutant (BRCAm) high-grade serous ovarian cancer (HGSOC) represents a new clinical challenge with unmet therapeutic needs. Here, we performed a quantitative high-throughput drug combination screen that identified the combination of an ATR inhibitor (ATRi) and an AKT inhibitor (AKTi) as an effective treatment strategy for both PARPi-sensitive and PARPi-resistant BRCAm HGSOC. The ATRi and AKTi combination induced DNA damage and R loop-mediated replication stress (RS).

Quantitative Assessment of Lipiodol-Related Artifact Reduction for Dual-Energy Computed Tomography After Transcatheter Arterial Chemoembolization: A Phantom Study Evaluating the Use of Metal Artifact Reduction Algorithms.

Objective: This study used metal artifact reduction (MAR) software to examine the computed tomography (CT) number of dual-energy CT (DECT) of hepatocellular carcinoma after transcatheter arterial chemoembolization.

Methods: Hollow columnar acrylic phantoms were filled with lipiodol and inserts of 2 sizes (large and small) were used to simulate liver tumors on a Revolution GSI CT scanner. The CT numbers of a single test object were collected twice: once with and once without the MAR algorithm.

Prediction of extranodal extension in head and neck squamous cell carcinoma by CT images using an evolutionary learning model.

Background: Extranodal extension (ENE) in head and neck squamous cell carcinoma (HNSCC) correlates to poor prognoses and influences treatment strategies. Deep learning may yield promising performance of predicting ENE in HNSCC but lack of transparency and interpretability. This work proposes an evolutionary learning method, called EL-ENE, to establish a more interpretable ENE prediction model for aiding clinical diagnosis.

Regorafenib induces damage-associated molecular patterns, cancer cell death and immune modulatory effects in a murine triple negative breast cancer model.

Damage associated molecular patterns (DAMPs), including calreticulin (CRT) exposure, high-mobility group box 1 protein (HMGB1) elevation, and ATP release, characterize immunogenic cell death (ICD) and may play a role in cancer immunotherapy. Triple negative breast cancer (TNBC) is an immunogenic subtype of breast cancer with higher lymphocyte infiltration. Here, we found that regorafenib, a multi-target angiokinase inhibitor previously known to suppress STAT3 signaling, induced DAMPs and cell death in TNBC cells.

Nicotine activates HIF-1α and regulates acid extruders through the nicotinic acetylcholine receptor to promote the Warburg effect in non-small cell lung cancer cells.

Cigarette smoking is the greatest risk factor for lung cancer, accounting for approximately 90% of all lung cancer-related deaths. Moreover, nicotine is associated with lung cancer onset and progression. Hypoxia-inducible factor 1α (HIF-1α) is involved in the metabolic reprogramming of cancer cells and accelerates cancer progression via regulation of pH and acid-base homeostasis.

Differential impacts of initial treatment status on long-term survival in patients with sarcomas treated in a referral center according to histologic type and anatomic site.

Objective: The aim of this work was to estimate the magnitude of the differential impacts of initial treatment status relative to the impact of classic clinicopathologic factors on the long-term overall survival (OS) of sarcoma patients in a referral cancer center.

Methods: From the institutional database, we identified 2185 patients who presented to the institutional multidisciplinary team (MDT) prior to (N = 717, 32.8%) or after (N = 1468, 67.

The optimal intervention for preventing physical restraints among older adults living in the nursing home: A systematic review.

Aim: This study aimed to evaluate the effectiveness of restraint reduction programs for nursing home care providers in enforcing physical restraint on residents and identify the best strategies for such programs.

Design: Systematic Review.

Methods: We searched for randomized controlled trials published until February 2021 for systematic review.

Distinct roles of treatment schemes and BRCA2 on the restoration of homologous recombination DNA repair and PARP inhibitor resistance in ovarian cancer.

Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a major advance in ovarian cancer, now as a treatment and as a maintenance therapy in the upfront and recurrent settings. However, patients often develop resistance to PARPis, underlining the importance of dissecting resistance mechanisms. Here, we report different dosing/timing schemes of PARPi treatment in BRCA2-mutant PEO1 cells, resulting in the simultaneous development of distinct resistance mechanisms.

Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive and molecularly heterogeneous non-Hodgkin's lymphoma. The B cell receptor (BCR) signaling pathway in DLBCL emerges as a new drug target. Protein phosphatase SHP-1 negatively regulates several oncogenic tyrosine kinases and plays a tumor suppressive role.

The Impact of Weight Loss during Chemoradiotherapy for Unresectable Esophageal Cancer: Real-World Results.

Weight loss is a common phenomenon presented in unresectable esophageal cancer (EC) patients during their definitive chemoradiotherapy (dCRT) treatment course. This study explored the prognostic value of weight changes during dCRT in unresectable EC patients. From 2009 to 2017, 69 cT4b thoracic EC patients undergoing complete curative dCRT without baseline malnutrition were included.

The Radiation Dose to the Left Supraclavicular Fossa is Critical for Anastomotic Leak Following Esophagectomy - A Dosimetric Outcome Analysis.

Purpose: For locally advanced esophageal cancer, definitive concurrent chemoradiotherapy (CCRT) with a radiation dose of 50-50.4 Gy/25-28 Fx is prescribed, followed by adjuvant esophagectomy for better local control or salvage treatment if locoregional recurrence occurs. However, radiation injury before surgery may delay wound healing.

Vacuum ultraviolet nonlinear metalens.

Vacuum ultraviolet (VUV) light plays an essential role across science and technology, from molecular spectroscopy to nanolithography and biomedical procedures. Realizing nanoscale devices for VUV light generation and control is critical for next-generation VUV sources and systems, but the scarcity of low-loss VUV materials creates a substantial challenge. We demonstrate a metalens that both generates-by second-harmonic generation-and simultaneously focuses the generated VUV light.

Overexpression of multiple epidermal growth factor like domains 11 rescues anoikis survival through tumor cells-platelet interaction in triple negative breast Cancer cells.

Aims: The aim of this study was to test the hypothesis that overexpression of the Multiple Epidermal Growth Factor Like Domains 11 (MEGF11) gene in TNBC cells increases tumor cell survival against anoikis via interaction with platelets.

Main Methods: The role of MEGF11 was studied in human TNBC MDA-MB-231 and MDA-MB-468 cells by overexpressing MEGF11 (o/e MEGF11) using non-attached culture. Mouse wild type 4 T1 and Δmegf11-4 T1 cells were implanted into the mammary fat pad of BALB/c mice.

Cell cycle checkpoints and beyond: Exploiting the ATR/CHK1/WEE1 pathway for the treatment of PARP inhibitor-resistant cancer.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) have become a mainstay of therapy in ovarian cancer and other malignancies, including BRCA-mutant breast, prostate, and pancreatic cancers. However, a growing number of patients develop resistance to PARPis, highlighting the need to further understand the mechanisms of PARPi resistance and develop effective treatment strategies. Targeting cell cycle checkpoint protein kinases, e.

Meta-lens light-sheet fluorescence microscopy for imaging.

Light-sheet fluorescent microscopy has become the leading technique for imaging in the fields of disease, medicine, and cell biology research. However, designing proper illumination for high image resolution and optical sectioning is challenging. Another issue is geometric constraints arising from the multiple bulky components for illumination and detection.