Multimodality curative-intent treatment in NSCLC: an unprecedented era of change 2017-2025.

Curative-intent multimodality treatment-combining local treatments such as surgery or radiotherapy with systemic therapy-is the cornerstone of care in stage II-III non-small cell lung cancer (NSCLC). Since 2017, the systemic therapy backbones with multimodality treatment have undergone a dramatic transformation, driven by a series of pivotal, practice-changing clinical trials. Immunotherapy and targeted therapies, previously confined to the advanced/metastatic setting, are now firmly embedded in curative-intent regimens.

Germline Disruption of Retinal Pigment Epithelium-Expressed Zebrafish rlbp1b Results in Selective Dim Light Visual Behavior Deficits and Provides a Screening Platform for Evaluating the Pathogenicity of Human RLBP1 Variants.

Cellular retinaldehyde binding protein (CRALBP) plays a crucial role in the visual cycle by chaperoning 11-cis-retinoids. Mutations in its encoding gene RLBP1 lead to inherited retinal diseases with the common feature of poor night vision. Zebrafish possess two RLBP1 paralogs, rlbp1a and rlbp1b, with distinct retinal expression profiles, providing a bespoke opportunity to dissect cell-specific functions of CRALBP.

Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation.

Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by Candida albicans trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway.

Methotrexate-associated Peripheral Neuropathy on 18F-FDG PET/CT and MRI Masquerading as Neurolymphomatosis.

A 53-year-old woman with primary central nervous system lymphoma with vitreal involvement presented with upper extremity weakness, pain, and contractures following methotrexate infusion. Electromyography showed mononeuropathies of the upper extremities, suspicious for neurolymphomatosis versus vasculitis. An 18F-FDG PET CT indicated neurolymphomatosis, while an MRI of the bilateral forearms demonstrated intramuscular fluid collections, suspicious for abscesses or infarcts.

Association between immunotherapy timing and efficacy in non-small cell lung cancer: a comprehensive analysis at a high-volume specialist centre.

Background: The timing of immune checkpoint inhibitor (ICI) administration may influence clinical outcomes in non-small cell lung cancer (NSCLC) patients. Previous studies have shown varying effects of chronotherapy on survival rates, with some suggesting that a higher percentage of doses administered in the morning improves overall survival (OS) and progression-free survival (PFS). This study aimed to evaluate the impact of the timing of the first dose and the percentage of doses administered in the afternoon on survival outcomes in advanced NSCLC patients, as well as explore seasonal variations.

Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation.

Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway.

Update on F-Fluoroestradiol.

F-16α-Fluoroestradiol (F-FES) is a radiolabeled estrogen analogue positron emission tomography (PET) imaging agent that binds to the estrogen receptor (ER) in the nucleus of ER-expressing cells. Proof-of-concept studies of F-FES demonstrated expected correlation between tumoral F-FES-positivity on PET-imaging and ER+ status assessed on biopsy samples by radioligand binding and immunohistochemistry. After decades of study, F-FES PET/CT gained clinical approval in 2016 in France and 2020 in the United States for use in patients with ER+ metastatic or recurrent breast cancer.

Are we joining the One Health dots? A scoping review of research on the one health effects of extreme weather events in eastern Australia.

Extreme weather events such as floods, bushfires, cyclones, and drought, are projected to increase in eastern Australia. Understanding how these events influence the combined, sustainable well-being of humans, animals, and ecosystems - that is One Health - will enable development of transdisciplinary and ultimately more effective interventions. A scoping review was conducted to explore the research associated with the effects of extreme weather events in eastern Australia using a One Health lens, specifically identifying the type of extreme weather events studied, the research conducted in the context of One Health, and gaps to inform improved One Health implementation.

Botensilimab, an Fc-Enhanced Anti-CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy.

This study reveals that Fc-enhanced anti-CTLA-4 harnesses novel mechanisms to overcome the limitations of conventional anti-CTLA-4, effectively treating poorly immunogenic and treatment-refractory cancers. Our findings support the development of a new class of immuno-oncology agents, capable of extending clinical benefit to patients with cancers resistant to current immunotherapies.

Fungal melanin suppresses airway epithelial chemokine secretion through blockade of calcium fluxing.

Respiratory infections caused by the human fungal pathogen Aspergillus fumigatus are a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been fully defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of the chemokines CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction in neutrophil recruitment to the apical airway both in vitro and in vivo.

Host innate immune systems gather intel on invading microbes via pathogen-derived extracellular vesicles.

Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular milieu from various cell types including host cells and pathogens that infect them. As carriers of nucleic acids, proteins, lipids, metabolites, and virulence factors, EVs act as delivery vehicles for intercellular communication and quorum sensing. Innate immune cells have the capacity to intercept, internalize, and interpret 'messages' contained within these EVs.

'It Is Good to See the Person As a Whole Person and… Continue to Improve Our Psychologically Informed Working': A Thematic Analysis of Clinical Psychology Trainee Placements in Homelessness Settings.

Objectives: The National Framework for Inclusion Health identified the need for collaborative action between the NHS and third sector health to improve access and outcomes for Inclusion Health groups. Clinical psychology trainee placements in homelessness settings could be a valuable pathway to improving access to psychological support for people experiencing homelessness and the provision of clinical services, which is key to developing the workforce and a catalyst for the future recruitment of clinical psychologists in the third sector.

Methods: A qualitative evaluation was conducted using semistructured interviews to explore the perspectives of clinical psychology trainees, supervisors, staff in homelessness settings and a peer mentor.

BTK inhibitor-induced defects in human neutrophil effector activity against Aspergillus fumigatus are restored by TNF-α.

Inhibition of Bruton's tyrosine kinase (BTK) through covalent modifications of its active site (e.g., ibrutinib [IBT]) is a preferred treatment for multiple B cell malignancies.

The effectiveness of pharmacological and lifestyle interventions to reduce the risk of diabetes and hyperglycaemia following gestational diabetes: A systematic review and meta-analysis.

Aims: To synthesize the available evidence to better understand the effectiveness of interventions to prevent or delay hyperglycaemia and Type 2 diabetes mellitus (T2DM) postnatally in women with current or previous gestational diabetes mellitus (GDM).

Methods: We searched five databases up to December 2020 for primary peer-reviewed articles reporting postpartum glycaemic outcomes in women with (previous) GDM following pharmacological or lifestyle intervention. Outcomes were relative risk of T2DM or continuous measures of glycaemia, change or at follow-up.

Point-of-Care Ultrasound for High-Risk Pregnancy Screening in Rural Nepal.

By training nurses and midwives on the basics of obstetric ultrasound, high-risk pregnancies in remote Nepalese villages can be identified and triaged. American radiology residents traveling to Nepal can improve their real-time, hands-on ultrasound scanning skills while learning the intricacies of practicing medicine in a low- and middle-income country. Global outreach work is increasing in popularity among US radiologists, emphasizing the importance of training radiology residents in point-of-care ultrasound.

Lewy body dementia: Overcoming barriers and identifying solutions.

Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public-domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements.

Sonothrombolysis: State-of-the-Art and Potential Applications in Children.

In recent years, advances in ultrasound therapeutics have been implemented into treatment algorithms for the adult population; however, the use of therapeutic ultrasound in the pediatric population still needs to be further elucidated. In order to better characterize the utilization and practicality of sonothrombolysis in the juvenile population, the authors conducted a literature review of current pediatric research in therapeutic ultrasound. The PubMed database was used to search for all clinical and preclinical studies detailing the use and applications of sonothrombolysis, with a focus on the pediatric population.

Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING.

The host type I interferon (IFN) pathway is a major signature of inflammation induced by the human fungal pathogen, Candida albicans. However, the molecular mechanism for activating this pathway in the host defence against C. albicans remains unknown.

Correction: Spatial variation and antecedent sea surface temperature conditions influence Hawaiian intertidal community structure.

[This corrects the article DOI: 10.1371/journal.pone.

Predicting language outcomes in bilingual children with Down syndrome.

Continuous approaches to measuring bilingualism have recently emerged as a means of understanding individual variation in language abilities. To date, limited information is available to assist in understanding the language abilities of bilingual children with Down syndrome (DS), who are specifically known to have a large variation in linguistic outcomes. Group studies in this population report that children exposed to two languages do not differ from their monolingual counterparts after considering age and non-verbal cognitive abilities, although no study to date has examined the relationship between the amount of exposure to one language and the linguistic abilities in the other language within this population.