Retinal sensitivity above macular neovascularization under anti-VEGF therapy in exudative neovascular age-related macular degeneration.

Purpose: Growth of macular neovascularization (MNV) associated with development of complete retinal pigment epithelial and outer retina atrophy (cRORA) been observed in eyes neovascular age-related macular degeneration (nAMD) under effective anti-vascular endothelial growth factor (VEGF) therapy. We aimed to evaluate the influence of the presence of MNV on the sensitivity of the overlaying retina both in patients with or without cRORA and to generate hypotheses about their association.

Methods: Pilot study on nAMD patients undergoing long-term anti-VEGF therapy that had also undergone microperimetry testing.

Increased phenotypic diversity as a consequence of ecological opportunity in the island radiation of Sulawesi ricefishes (Teleostei: Adrianichthyidae).

Ecological opportunity is considered a main driver of adaptive diversification. Colonization of new areas and habitats provides novel opportunities, which may lead to phenotypic change and rapid diversification. The geographically isolated island Sulawesi in Indonesia hosts numerous endemic radiations.

Orbital fistula tract - a case report of a rare cause of impossible facemask ventilation.

Background: Adequate facemask ventilation during induction of anaesthesia is a key aspect of patient safety. Difficulties can therefore be life-threatening for the patient.

Case Presentation: The case presented here illustrates a rare cause of an orbital fistula that led to a serious problem during facemask ventilation and demonstrates why team communication is so important.

Personalized predictions to identify individuals most likely to achieve 10% weight loss with a lifestyle intervention.

Objective: The objective of this study is to generate an algorithm for making predictions about individual treatment responses to a lifestyle intervention for weight loss to maximize treatment effectiveness and public health impact.

Methods: Using data from Action for Health in Diabetes (Look AHEAD), a national, multisite clinical trial that ran from 2001 to 2012, and machine-learning techniques, we generated predicted individual treatment effects for each participant. We tested for heterogeneity in treatment response and computed the degree to which treatment effects could be improved by targeting individuals most likely to benefit.

Artificial Intelligence in Healthcare: Balancing Technological Innovation With Health and Care Workforce Priorities.

Artificial Intelligence (AI) has emerged as a transformative force in healthcare, offering significant potential to address workforce challenges and improve patient outcomes. This perspective article presents a framework for responsible AI innovation, emphasising ethical governance, responsible leadership and a commitment to human-centred AI. It provides guidance for healthcare organisations to position AI as a strategic enabler, augmenting the health and care workforce and fostering sustainable, patient-centred advancements in healthcare.

A translatable IR-chemometrics model for the rapid prediction of structural and material properties of technical lignins.

Technical lignins are an industrial byproduct of plant biomass processing, for example, paper production or biorefinery operations. They are highly functional and aromatic, making them potentially suitable for a diverse range of applications; however, their exact structural composition depends on the plant species and the industrial process involved. A major bottleneck to lignin valorization and to biorefining in general is the equipment and time investment required for the full characterization of each sample.

Magnetically and optically active edges in phosphorene nanoribbons.

Nanoribbons, nanometre-wide strips of a two-dimensional material, are a unique system in condensed matter. They combine the exotic electronic structures of low-dimensional materials with an enhanced number of exposed edges, where phenomena including ultralong spin coherence times, quantum confinement and topologically protected states can emerge. An exciting prospect for this material concept is the potential for both a tunable semiconducting electronic structure and magnetism along the nanoribbon edge, a key property for spin-based electronics such as (low-energy) non-volatile transistors.

The Synthesis of Hydroquinolines from Nitroaldehydes and Ketones by Hydrogenation Sequences and Condensations.

Catalytic reaction discovery or methodology development is preferably performed with homogeneous catalysts, but heterogeneous catalysts allow the design of complex multistep syntheses based on their reusability. We introduce here the catalytic synthesis of hydroquinolines starting from nitroaldehydes, ketones and hydrogen. The reaction is complex and proceeds via multiple selective hydrogenation and condensation steps.

Continuous spectroscopic monitoring of urinary catheter output: advancements and clinical implications.

Urine diagnostics are crucial for identifying urological disorders and systemic diseases. Monitoring bladder catheters for urine output and early signs of urinary tract infections (UTIs) is essential but labor-intensive and prone to documentation errors. Recent advances in electronic monitoring and spectroscopy offer potential improvement in this process.

Characterization of the two-dimensional length and diameter distributions of gold nanorods by size exclusion chromatography.

Access to complex multidimensional property distributions of nanoparticle systems is indispensable for the understanding of their synthesis, processing and application in modern production technologies. Plasmonic gold nanorods are a system of particular interest due to their shape-dependent localized surface plasmon resonance. In this study, we show how the optical back coupling technique, previously developed for the analysis of sedimentation coefficient-resolved extinction spectra derived from analytical ultracentrifugation experiments, can be transferred to standard laboratory equipment, namely size exclusion chromatography.

TBK1 is involved in programmed cell death and ALS-related pathways in novel zebrafish models.

Pathogenic mutations within the TBK1 gene leading to haploinsufficiency are causative of amyotrophic lateral sclerosis (ALS). This gene is linked to autophagy and inflammation, two cellular mechanisms reported to be dysregulated in ALS patients, although its functional role in the pathogenesis could involve other players. We targeted the TBK1 ortholog in zebrafish, an optimal vertebrate model for investigating genetic defects in neurological disorders.

Structure and function of the geldanamycin amide synthase from Streptomyces hygroscopicus.

Amide synthases catalyze the formation of macrolactam rings from aniline-containing polyketide-derived seco-acids as found in the important class of ansamycin antibiotics. One of these amide synthases is the geldanamycin amide synthase GdmF, which we recombinantly expressed, purified and studied in detail both functionally as well as structurally. Here we show that purified GdmF catalyzes the amide formation using synthetically derived substrates.

β-catenin-driven endomesoderm specification is a Bilateria-specific novelty.

Endomesoderm specification by a maternal β-catenin signal and body axis patterning by interpreting a gradient of zygotic Wnt/β-catenin signalling was suggested to predate the split between Bilateria and their sister clade Cnidaria. However, in Cnidaria, the roles of β-catenin signalling in these processes have not been demonstrated directly. Here, by tagging the endogenous β-catenin in the cnidarian Nematostella vectensis, we confirm that its oral-aboral axis is indeed patterned by a gradient of β-catenin signalling.

Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration.

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.

The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation.

During bacterial translation initiation, the 30S ribosomal subunit, initiation factors, and initiator tRNA define the reading frame of the mRNA. This process is inhibited by kasugamycin, edeine and GE81112, however, their mechanisms of action have not been fully elucidated. Here we present cryo-electron microscopy structures of 30S initiation intermediate complexes formed in the presence of kasugamycin, edeine and GE81112 at resolutions of 2.

Chromosome-level genome assembly of a specialist walnut pest Atrijuglans aristata.

Gelechioidea represents the most diverse superfamily of tiny boring pests in Lepidoptera that pose a serious threat to agricultural and forestry economic crops. However, the lack of high-quality genome of highly specialized species makes it difficult to draw general conclusions about the mechanism of the close binding relationship between pests and crops. In this study, based on second- and third-generation sequencing reads, we constructed a chromosome-level genome for the Atrijuglans aristata, a specialized boring pest, that specifically harms the green husk of cultivated walnuts.

New recommendations for reversal of high-dose methotrexate cytotoxicity with folinic acid.

Purpose: Folinic acid (FA) rescue protocols to counter the adverse effects of high-dose methotrexate (HDMTX) vary widely, and the risk of over-rescue and potential adverse effects of excessive FA (e.g., hypercalcemia) are under-recognized issues when providing augmented rescue in cases of delayed methotrexate elimination (DME).

First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-305.

Introduction: Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.

Geographic Atrophy Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Progression of the Disease at 2-Year Follow-Up.

Introduction: The purpose of the study is to characterize the rate of progression of geographic atrophy (GA) areas in patients with age-related macular degeneration (AMD) with subclinical angioid streaks (AS), compared to patients with AMD without subclinical AS.

Methods: This is a retrospective, longitudinal, case-control study. Among a cohort of patients with AMD, we selected patients with GA with subclinical AS and followed them for a 2-year follow-up.

CAG Repeat Instability and Region-Specific Gene Expression Changes in the SCA12 Brain.

Spinocerebellar ataxia type 12 (SCA12), an autosomal dominant cerebellar ataxia, caused by an expansion of (CAG) in the 5' of the PPP2R2B gene on chr5q32, is common in India. The illness often manifests late in life, with diverse neurological and psychiatric symptoms, suggesting involvement of different brain regions. Prominent neuronal loss and atrophy of the cerebellum have been noted earlier.

Update on the Treatment of Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a mast cell-mediated skin disease that presents with wheals, angioedema, or both for more than 6 weeks. Less than 10% of patients have complete control of their CSU (the main goal of CSU treatment) with second generation H1-antihistamines, the first-line treatment. About 70% of patients with antihistamine-refractory CSU do not reach complete control with omalizumab, the second-line treatment.

Safety and complications of antimicrobial coated compared to conventional intramedullary femoral nails in proximal femoral fractures.

Purpose: The aim of this study was to compare one-year mortality and the incidence of complications, particularly fracture-related infections, between patients with proximal femur fractures treated with novel noble metal-coated implants and those treated with uncoated implants, to detect possible effects of the coating on these endpoints.

Methods: Design: Retrospective cohort observational study.

Setting: Level 1 trauma centre.