The potential of lazertinib and amivantamab combination therapy as a treatment strategy for uncommon EGFR-mutated NSCLC.

Uncommon epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) pose therapeutic challenge due to limited response to EGFR tyrosine kinase inhibitors (TKIs). This study presents preclinical evidence and mechanistic insights into the combination of lazertinib, a third-generation EGFR-TKI; and amivantamab, an EGFR-MET bispecific antibody, for treating NSCLC with uncommon EGFR mutations. The lazertinib-amivantamab combination demonstrates significant antitumor activity in patient-derived models with uncommon EGFR mutations either before treatment or after progressing on EGFR-TKIs.

Preserved brain youthfulness: longitudinal evidence of slower brain aging in superagers.

Background: Superagers, older adults with exceptional cognitive abilities, show preserved brain structure compared to typical older adults. We investigated whether superagers have biologically younger brains based on their structural integrity.

Methods: A cohort of 153 older adults (aged 61-93) was recruited, with 63 classified as superagers based on superior episodic memory and 90 as typical older adults, of whom 64 were followed up after two years.

Functional analysis of AtTX11/12 TIR-domain proteins identifies key residues for basal and temperature-insensitive growth inhibition.

Plant Toll/interleukin-1 receptor (TIR) domains function as NADases and ribosyl-transferases generating second messengers that trigger hypersensitive responses. TIR-X (TX) proteins contain a TIR domain with or without various C-terminal domains and lack the canonical nucleotide-binding site and leucine-rich repeat domain. In a previous study, we identified an Arabidopsis thaliana activation-tagging line with severe growth defects caused by the overexpression of the AtTX12 gene.

Neoadjuvant and Adjuvant Osimertinib in Stage IA to IIIA, EGFR-Mutant NSCLC (NORA).

Introduction: Treatment with adjuvant osimertinib for three years is the standard-of-care for resected stage IB to IIIA NSCLC harboring EGFR mutations. The role of neoadjuvant osimertinib in the perioperative setting is yet to be elucidated in the NeoADAURA study (NCT04351555).

Methods: This is a single-center, pilot study of patients with clinical stage IA to IIIA NSCLC (American Joint Committee on Cancer eighth edition) harboring an activating EGFR mutation (Exon 19 deletion, L858R) (NCT04816838).

PARP1 promotes tumor proliferation in lenalidomide-resistant multiple myeloma via the downregulation of microRNA-192-5p-AKT signaling.

Background: Lenalidomide-based therapies are recommended as first-line treatment for multiple myeloma (MM) patients, regardless of the transplant eligibility. Resistance to lenalidomide is a clinical problem that urgently needs to be addressed. The expression of poly(ADP-ribose) polymerase 1 (PARP1) is abnormally high in a variety of tumor tissues including MM.

Improving the detection of congenital syphilis: reviewing test utility and adherence to recommendations.

Western Australia (WA) has experienced a resurgence of congenital syphilis. Appropriate microbiology testing of the neonate is recommended to confirm infection, including syphilis immunoglobulin M (IgM), rapid plasma reagin (RPR) paired with a maternal sample, and polymerase chain reaction (PCR) on placenta and nasal swabs. We examined the performance of microbiology tests in confirmed congenital syphilis cases and the adherence to testing recommendations in those assessed as high risk.

Differential proteomic profiles between cognitive frail and robust older adults from the MELoR cohort.

The present study explored for the first time the blood-based proteomic signature that could potentially distinguish older adults with and without cognitive frailty (CF). The participants were recruited under the Malaysian Elders Longitudinal Research (MELoR) study. Cognition and physical frailty were determined using the Montreal Cognitive Assessment (MoCA) and Fried's criteria, respectively.

Denfivontinib activates effector T-cells through NLRP3-inflammasome, yielding potent anticancer effects by combination with pembrolizumab.

Various combination therapies have been investigated to overcome the limitations of using immune checkpoint inhibitors. However, determining the optimal combination therapy remains challenging. To overcome the therapeutical limitation, we conducted a translational research to elucidate the mechanisms by which AXL inhibition enhances the anti-tumor effects when combined with anti-PD-1 antibody therapy.

Re-designing the experience of transition into nursing homes: A Singapore study.

Introduction: Transition of senior adults from community into nursing homes (NH) is a challenging event for both the senior adults and their family. Even with the introduction of new service models, studies continued to advocate that the navigation of services should remain simple and streamlined. In relation to the 'wicked problem' that persist, design thinking methodology and tools can be adopted to address the unacceptably huge gap between the services that NH operators aim to deliver and the actual service that is delivered.

Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced sinonasal squamous cell carcinoma.

Background: Sinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC.

Real-World Outcomes with Lurbinectedin in Second Line and Beyond for Extensive Stage Small Cell Lung Cancer in Korea.

Purpose: Small-cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers and is characterized by a high recurrence rate, early metastasis, and poor prognosis. Before the FDA approved lurbinectedin for SCLC that progressed on or after platinum-based chemotherapy in 2020, topotecan was the sole second-line option associated with hematological toxicities and modest efficacy. Lurbinectedin received conditional approval in Korea in September 2022 for metastatic SCLC progression, with the same indications.

Transforming care: Optimizing ERAS pathway in breast cancer surgery with latissimus dorsi flap.

Introduction: This study aims to establish, execute, and assess the effectiveness of a perioperative enhanced recovery after surgery (ERAS) clinical care pathway in breast reconstruction patients with LD flap breast cancer treatment. The goal is to improve early recovery outcomes, reduce hospitalization time, and enhance patient satisfaction by implementing a standardized approach to postoperative care.

Methods: This study was conducted at the University of Malaya Medical Center.

Spatial Similarity of MRI-Visible Perivascular Spaces in Healthy Young Adult Twins.

Purpose: This study aimed to determine whether genetic factors affect the location of dilated perivascular spaces (dPVS) by comparing healthy young twins and non-twin (NT) siblings.

Materials And Methods: A total of 700 healthy young adult twins and NT siblings [138 monozygotic (MZ) twin pairs, 79 dizygotic (DZ) twin pairs, and 133 NT sibling pairs] were collected from the Human Connectome Project dataset. dPVS was automatically segmented and normalized to standard space.

The Effectiveness of a Digital Mental Fitness Program (Positive Intelligence) on Perceived Stress, Self-Compassion, and Ruminative Thinking of Occupational Therapy Undergraduate Students: Longitudinal Study.

Background: Health care students often endure numerous stressors throughout their undergraduate education that can have lasting negative effects on their mental well-being. Positive Intelligence (PQ) is a digital mental fitness program designed to enhance self-mastery and help individuals reach their potential by strengthening various "mental muscles."

Objective: This study aims to evaluate the effectiveness of a 6-week app-delivered PQ program in reducing perceived stress, increasing self-compassion, and decreasing rumination tendencies among health care undergraduates.

Early Radiological Outcome of Hallux Valgus Corrective Surgery With an Intramedullary Plate: A Single-Center Case Series.

Introduction: Hallux valgus is a common foot deformity that can lead to significant pain and functional limitations. Minimally invasive corrective surgery is becoming increasingly popular. The aim of this study is to evaluate the radiological outcome of mini-open hallux valgus surgery using an intramedullary plate in Asian patients.

Faecal intestinal permeability and intestinal inflammatory markers in older adults with age-related disorders: A systematic review and meta-analysis.

This systematic review and meta-analysis appraised previous findings to uncover potential faecal intestinal permeability and intestinal inflammatory markers in older adults. A comprehensive literature search led to the identification of ten eligible studies with findings of potential faecal intestinal permeability (zonulin and alpha-1-antitrypsin) and intestinal inflammatory markers [calprotectin, lactoferrin and neutrophil gelatinase-associated lipocalin (NGAL)]. Most of the cases (n > 2) [Parkinson's disease (PD) and Alzheimer's disease (AD)] exhibited higher faecal alpha-1-antitrypsin, zonulin and calprotectin levels.

Effects of non-pharmacological interventions on gut microbiota and intestinal permeability in older adults: A systematic review: Non-pharmacological interventions on gut microbiota/barrier.

This systematic review appraised previous findings of non-pharmacological interventions on gut microbiota and/ or intestinal permeability in older adults. A literature search was performed using PubMed, Scopus, ScienceDirect and the Cochrane Library. Relevant studies were shortlisted based on the inclusion and exclusion criteria, and evaluated for risks of bias using the "Cochrane Collaboration's Risk of Bias 2" and the "NIH Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group".

The usage of anticholinergic medications in a low- and middle-income country: a longitudinal comparison of 2013-15 and 2020-22 datasets.

Background: While the effects of anticholinergic drug use have been increasingly highlighted, trends in anticholinergic use remain poorly understood.

Aim: To determine the changes in frequency and pattern of anticholinergic drug use within a low- and middle-income country.

Method: Comparisons were made between population-based datasets collected from Malaysian residents aged 55 years and older in 2013-15 and 2020-22.

A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17).

Background: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification.

Patients And Methods: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR).

A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12).

Unlabelled: Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity.