Cell death in multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) characterized by inflammatory demyelination and progressive neurodegeneration. Although current disease-modifying therapies modulate peripheral autoimmune responses, they are insufficient to fully prevent tissue specific neuroinflammation and long-term neuronal and oligodendrocyte loss. Growing evidence implicates various regulated cell death (RCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, not only as downstream consequences of chronic inflammation, but also as active drivers of demyelination, axonal injury, and glial dysfunction in MS.

The molecular blueprint of targeted radionuclide therapy.

Targeted radionuclide therapy (TRT) is a cutting-edge treatment approach in oncology that combines the molecular precision of targeted agents with the effect of radiotherapy to selectively deliver cytotoxic radiation to cancer cells. Research efforts from the past few decades have led to a diverse molecular landscape of TRT and have provided lessons for further rational development of targeted radiopharmaceuticals and expansion of the clinical applications of this treatment modality. In this Review, we discuss TRT in the context of therapeutic approaches currently available in oncology, describe the broad range of established and emerging targets for TRT including innovative approaches to exploit vulnerabilities presented by the tumour microenvironment, and address the challenges for clinical translation and molecular optimization.

Economic evaluation of antibody-drug conjugates (ADCs) in patients with breast cancer: systematic review.

Introduction: Metastatic breast cancer (mBC) is a major global health challenge. Antibody-drug conjugates (ADCs), including trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG), offer clinical benefits but are associated with high costs, making cost-effectiveness assessments essential for policy decisions.

Methods: This systematic review analyzed economic evaluations comparing T-DM1, T-DXd, and SG with conventional treatments in breast cancer.

Unravelling novel microbial players in the breast tissue of TNBC patients: a meta-analytic perspective.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC), accounting for nearly 40% of BC-related deaths. Emerging evidence suggests that the breast tissue microbiome harbors distinct microbial communities; however, the microbiome specific to TNBC remains largely unexplored. This study presents the first comprehensive meta-analysis of the TNBC tissue microbiome, consolidating 16S rRNA amplicon sequencing data from 200 BC samples across four independent cohorts.

Public Health Risks Under Temporally Compounding Climate Extremes.

Climate change is causing a significant increase in the number of compound extreme events that pose significantly greater threats to public safety. Chongqing is a megacity in southwestern China that took the brunt of temporally compounding events (TCEs) in the summer of 2022. We developed an approach based on the Intergovernmental Panel on Climate Change (IPCC) risk framework to assess the public health risks posed by TCEs.

Isolated Congenital Middle Ear Malformations: Comparison of preoperative 0.1 mm Ultra-High-Resolution CT and Conventional High-Resolution CT.

Background And Purpose: Isolated congenital middle ear malformation contributes significantly to congenital hearing loss and growth problems. This study aims to compare 0.1 mm isotropic ultra-high-resolution computed tomography and conventional high-resolution computed tomography for assessing isolated congenital middle ear malformation, using surgical exploration as the gold standard.

Socioeconomic disparity and risk of irritable bowel syndrome: a cohort study with mediation analysis.

Background & Aims: To investigate association between socioeconomic status (SES) and risk of incident irritable bowel syndrome (IBS), and mediating role of lifestyle factors.

Methods: Participants free of IBS at recruitment were included in this retrospective analysis of a prospectively collected cohort (N=353,790). SES was assessed through household income, education and employment status, with different patterns identified through latent class analysis.

Associations between age of onset and domain-specific cognitive deficits in major depressive disorder.

Background: This study aimed to examine associations between age of onset and domain-specific cognitive deficits in major depressive disorder (MDD).

Methods: We assessed 582 MDD patients (389 first-episode [FED], 193 recurrent [RMD]) and 280 healthy controls (HCs) using five cognitive domains from the MATRICS Consensus Cognitive Battery. Of these patients, 289 were reassessed after 8 weeks of antidepressant treatment.

Nationwide Insights on Immunotherapy in a Low- and Middle-Income Country: Armenia's Struggle for Equitable Cancer Care in an Out-of-Pocket System.

Purpose: In Armenia, a lower-middle-income country, cancer causes 21% of all deaths, with over half of cases diagnosed at advanced stages. Without universal health insurance, patients rely on out-of-pocket payments or black-market channels for costly immunotherapies, underscoring the need for real-world data to inform equitable policy reforms.

Methods: We conducted a multicenter, retrospective cohort study of patients who received at least one dose of an immune checkpoint inhibitor (ICI) between January 2017 and December 2023 across six Armenian oncology centers.

Understanding financial hardship in families of people living with dementia: Protocol for a scoping review to identify subjective self-report measures that evaluate financial hardship.

Background: Financial hardship (including financial stress, financial strain, asset depletion, and financial toxicity) is a highly relevant construct among the 6.9 million people living with Alzheimer's disease and related dementias (ADRD) in the United States and their family networks. This scoping review will identify existing measures and approaches for capturing financial strain among these families.

Community-level social capital and postoperative outcomes following intracranial tumor surgery: an exploration of the Social Capital Atlas in neurosurgical oncology.

Background And Objectives: Explore whether community social capital measures (system of resources available to individuals through community engagement) are related to surgical outcomes among intracranial tumor patients.

Methods: Adults who underwent resection at a single medical center for intracranial tumor was identified and their zip codes were matched to three variables derived from the Social Capital Atlas: economic connectedness, volunteering rate, and civic organizations. The economic connectedness score quantifies the degree to which low-income and high-income community members are friends with each other, the volunteering rate is defined as the proportion of a given community engaged in community organizations and the civic organization score is defined as the number of local civic organizations within a given community.

Age interaction in associations between geriatric nutritional risk index and prognosis in diffuse large B-cell lymphoma.

To evaluate whether age modifies the association between the geriatric nutritional risk index (GNRI) and overall survival (OS) in patients aged ≥ 18 years with newly diagnosed diffuse large B-cell lymphoma (DLBCL), we conducted a multi-centre retrospective study of 552 patients. Multivariable Cox regression with restricted cubic spline (RCS) modelling showed that GNRI was significantly associated with OS, but the relationship was non-linear (P for non-linearity = 0.0158).

The Financial, Operational, and Clinical Advantages of Generalist Radiology AI.

Despite the rapid growth of Food and Drug Administration-cleared artificial intelligence (AI)- and machine learning-enabled medical devices for use in radiology, current tools remain limited in scope, often focusing on narrow tasks and lacking the ability to comprehensively assist radiologists. These narrow AI solutions face limitations in financial sustainability, operational efficiency, and clinical utility, hindering widespread adoption and constraining their long-term value in radiology practice. Recent advances in generative and multimodal AI have expanded the scope of image interpretation, prompting discussions on the development of generalist medical AI.

Cost-benefit analysis of screening programme for diabetic retinopathy in Bulgaria.

Aims: Late-diagnosed diabetic retinopathy (DR) is difficult and expensive to treat. Screening programmes can identify the disease early and reduce the costs of its future treatment. This study aims to analyse the cost-benefit of screening programmes for DR.

Tibia-Fibula Relative Motion During Gait Cycle by 2D-3D Registration.

Injuries to the distal tibiofibular joint are often associated with ankle fractures, sports-related injuries, or instability, whereas proximal tibiofibular joint injuries are more commonly present with lateral- or posterolateral-compartment lesions of the knee. These conditions may be related to the relative motion between the tibia and fibula; however, precise movement patterns have yet to be fully elucidated. This study analyzes the relative motion of the tibia and fibula in 16 healthy adults (32 bones; 8 males and 8 females) throughout a normal gait cycle.

Evidence of Overlapping Roles Between Clinics and Hospitals in Primary Care.

Background: Clinics and hospitals in South Korea are often perceived as competitors to each other. This study examines the overlapping roles in providing primary care provision between clinics and hospitals by analyzing the healthcare facility type where patients first receive diagnoses of hypertension (HTN) or diabetes mellitus (DM). We also explore the characteristics of patients that influence their choice of healthcare facility and compare healthcare utilization patterns in the first year post-diagnosis by facility type.

Prospective randomised controlled trial comparing PLLA and PLDLA/HA/β-TCP interference screws in anterior cruciate ligament reconstruction: CT scans, MRI and clinical outcomes.

Purpose: Modifying interference screw composition may ensure better osteoconductive properties in order to reduce tunnel enlargement after anterior cruciate ligament (ACL) reconstruction. The primary and secondary purposes were to evaluate tunnel and screw volume changes in poly-L-lactide acid (PLLA) and poly-D-lactic acid + hydroxyapatite + β-tricalcium phosphate (PLDLA+) screws. The tertiary purpose was to compare patient reported- and functional outcomes between PLLA and PLDLA+ group.

The AI and Automation in Anaesthesia (TRIPLE-A) Perioperative Database in Eastern Denmark 2017-: A Platform for Epidemiology, AI-Driven Prediction, Quality Control and Automated Data Retrieval.

Introduction: Electronic health records can be used to create high-quality databases if data are structured and well-registered, which is the case for most perioperative data in the Capital and Zealand Regions of Denmark. We present the purpose and development of the AI and Automation in Anaesthesia (TRIPLE-A) database-a platform designed for epidemiology, prediction, quality control, and automated research data collection.

Methods: Data collection from the electronic medical record (EPIC Systems Corporation, WI, USA) was approved by the Capital Region, Denmark, and ethical approval was waived.

Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B).

Purpose: WU-KONG1B (ClinicalTrials.gov identifier: NCT03974022) is a multinational phase II, dose-randomized study to assess the antitumor efficacy of sunvozertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion mutations (exon20ins).

Methods: Eligible patients with advanced-stage exon20ins NSCLC were randomly assigned by 1:1 ratio to receive sunvozertinib 200 mg or 300 mg once daily (200 and 300 mg-rand cohorts).

Outcomes of Novel Hormonal Therapies in Men With Advanced Prostate Cancer by Treating Specialist.

Introduction: In the past decade, the management of advanced prostate cancer has shifted to novel hormonal therapies. As a result, urologists have increased their involvement in the management of advanced prostate cancer. These therapies require close monitoring due to the possibility of adverse cardiometabolic events.

Exploring the Arousal Intensity in Patients with Obstructive Sleep Apnea: Based on Odds Ratio Product.

Aim: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse during sleep, resulting in frequent cortical arousals. However, currently used frequency-based arousal metrics do not sufficiently capture the heterogeneity and clinical significance of arousal responses. The odds ratio product (ORP) is a novel electroencephalographic marker that provides a continuous assessment of sleep depth and has the potential to serve as an objective measure of arousal intensity.

Vaping health perceptions and never vaping among Australian adolescents: a strength-based analysis of cross-sectional survey data.

Introduction: Curbing adolescent vaping is a public health priority and little evidence exists examining protective factors. Using a strength-based approach, this study explored the relationship between adolescent vaping health perceptions and vaping use.

Methods: Cross-sectional data from 9000 Australian adolescents aged 14-17 years recruited via multiple online panels as part of the Generation Vape Study were used.

Short- and Long-Term Outcomes of Open, Laparoscopic, and Robot-Assisted Surgery for Rectal Cancer.

Background: Robot-assisted surgery has short-term benefits in rectal cancer surgery; however, its long-term advantages remain unclear. This study compared short- and long-term outcomes of open, laparoscopic, and robot-assisted rectal cancer surgeries using large-scale, database-driven evidence.

Methods: Patients (28 711) diagnosed with clinical stages I-III rectal cancer who underwent rectal resection and were registered in the Japanese Medical Data Vision Co.

The impact of genetics and the environment on cancer risk in Indigenous Australians: a narrative review.

Aboriginal and Torres Strait Islander (hereafter respectfully named Indigenous) Australians are diagnosed with some cancers substantially more frequently than non-Indigenous Australians implying a different risk factor landscape. Additionally, poorer outcomes for certain cancers are exacerbated by lower cancer screening rates and later diagnoses compared to non-Indigenous Australians. An improved understanding of cancer causation would allow better shaping and targeting of screening programs for those at the highest risk.