Topography of Slowed Dark Adaptation in Pseudoxanthoma Elasticum: PROPXE Study Report 1.

Purpose: To determine the prevalence and spatial pattern of rod and cone dysfunction in patients with pseudoxanthoma elasticum (PXE) and to correlate these with Bruch's membrane (BrM) calcification. PXE is a rare genetic disorder that causes calcification of Bruch's membrane, which eventually leads to loss of central vision. Understanding the functional implications of BrM calcification is crucial for developing effective treatments.

Early Childhood Vaccination Coverage and Patterns by Rural-Urban Commuting Area.

Introduction: National surveillance efforts have reported rural-urban disparities in childhood vaccination coverage by metropolitan statistical area designations, measured at the county level. This study's objective was to quantify vaccination trends using more discrete measures of coverage and rurality than prior work.

Methods: Serial, cross-sectional analyses of National Immunization Survey-Child restricted-use data collected in 2015-2021 for U.

Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain.

Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.

Invalid Vaccine Doses Among Children Aged 0 to 35 Months: 2011 to 2020.

Background And Objectives: Vaccine doses provided outside the Advisory Committee on Immunization Practices for minimum and maximum ages of vaccination and minimum intervals between doses are considered invalid. Our objective was to quantify the prevalence of and factors associated with invalid doses among US children aged 0 to 35 months.

Methods: We analyzed provider-verified vaccination records from the nationally representative 2011-2020 National Immunization Survey-Child.

Diaci v3.0: chromosome-level assembly, de novo transcriptome, and manual annotation of Diaphorina citri, insect vector of Huanglongbing.

Background: Diaphorina citri is an insect vector of "Candidatus Liberibacter asiaticus" (CLas), the gram-negative bacterial pathogen associated with citrus greening disease. Control measures rely on pesticides with negative impacts on the environment, natural ecosystems, and human and animal health. In contrast, gene-targeting methods have the potential to specifically target the vector species and/or reduce pathogen transmission.

Aflibercept high-dose (8mg) related intraocular inflammation (IOI) - a case series.

Background: Monitoring for potential inflammatory events following intravitreal anti-vascular endothelial factor (VEGF) injection is crucial with the use of new agents such as aflibercept 8 mg. Despite a safety profile comparable to aflibercept 2 mg in pivotal and phase 3 studies, reporting such cases in clinical practice helps evaluate potential risk of these agents.

Case Presentation: In this case series, a cluster of 8 patients manifesting acute intraocular inflammation (IOI) after intravitreal aflibercept 8 mg injection at three different centers are described.

Small cell transformation in EGFR-mutated non-small cell lung cancer: DLL3 expression and efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with chemotherapy.

Introduction: Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (chemo) or in combination with EGFR inhibitors (EGFRi+chemo) or immune checkpoint inhibitors (ICI+chemo).

Next-generation lung cancer pathology: Development and validation of diagnostic and prognostic algorithms.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. In this study, we develop a clinically useful computational pathology platform for NSCLC that can be a foundation for multiple downstream applications and provide immediate value for patient care optimization and individualization. We train the primary multi-class tissue segmentation algorithm on a substantial, high-quality, manually annotated dataset of whole-slide images with lung adenocarcinoma and squamous cell carcinomas.

National trends in patterns of under-vaccination in early childhood: National Immunization Survey-Child, United States, 2011-2021.

Background: The study's objective was to examine national trends in patterns of under-vaccination in the United States.

Research Design And Methods: The National Immunization Survey-Child (NIS-Child) is an annual cross-sectional survey that collects provider-verified vaccination records from a large national probability sample of children. Records from the 2011-2021 NIS-Child were used to assess receipt of the combined 7-vaccine series by age 24 months.

Vaccination Timeliness Among US Children Aged 0-19 Months, National Immunization Survey-Child 2011-2021.

Importance: Delays in receiving vaccinations lead to greater vaccine-preventable disease risk. Timeliness of receipt of recommended vaccinations is not routinely tracked in the US, either overall or for populations that have known barriers to accessing routine health care, including lower-income families and children.

Objective: To measure vaccination timeliness among US children aged 0 to 19 months, overall and by socioeconomic indicators.

Early Metabolic Response by PET Predicts Sensitivity to Next-Line Targeted Therapy in -Mutated Lung Cancer with Unknown Mechanism of Acquired Resistance.

Targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has established the precision oncology paradigm in lung cancer. Most patients with -mutated lung cancer respond but eventually acquire resistance. Patients exhibiting the p.

Completion of multidose vaccine series in early childhood: current challenges and opportunities.

Purpose Of Review: Completion of all doses in multidose vaccine series provides optimal protection against preventable infectious diseases. In this review, we describe clinical and public health implications of multidose vaccine series noncompletion, including current challenges to ensuring children receive all recommended vaccinations. We then highlight actionable steps toward achieving early childhood immunization goals.

TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.

Purpose: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.

Design: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.

Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial.

Background: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations.

TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in ALS/FTD and related disorders.

Nuclear clearance and cytoplasmic aggregation of the RNA-binding protein TDP-43 are observed in many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and fronto- temporal dementia (FTD). Although TDP-43 dysregulation of splicing has emerged as a key event in these diseases, TDP-43 can also regulate polyadenylation; yet, this has not been adequately studied. Here, we applied the dynamic analysis of polyadenylation from RNA-seq (DaPars) tool to ALS/FTD transcriptome datasets, and report extensive alternative polyadenylation (APA) upon TDP-43 alteration in ALS/FTD cell models and postmortem ALS/FTD neuronal nuclei.

n-3 Polyunsaturated Fatty Acids Modulate LPS-Induced ARDS and the Lung-Brain Axis of Communication in Wild-Type versus Fat-1 Mice Genetically Modified for Leukotriene B4 Receptor 1 or Chemerin Receptor 23 Knockout.

Specialized pro-resolving mediators (SPMs) and especially Resolvin E1 (RvE1) can actively terminate inflammation and promote healing during lung diseases such as acute respiratory distress syndrome (ARDS). Although ARDS primarily affects the lung, many ARDS patients also develop neurocognitive impairments. To investigate the connection between the lung and brain during ARDS and the therapeutic potential of SPMs and its derivatives, mice were crossbred with RvE1 receptor knockout mice.

Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer.

The discovery of frequent 8p11-p12 amplifications in squamous cell lung cancer (SQLC) has fueled hopes that FGFR1, located inside this amplicon, might be a therapeutic target. In a clinical trial, only 11% of patients with 8p11 amplification (detected by FISH) responded to FGFR kinase inhibitor treatment. To understand the mechanism of FGFR1 dependency, we performed deep genomic characterization of 52 SQLCs with 8p11-p12 amplification, including 10 tumors obtained from patients who had been treated with FGFR inhibitors.

Clinicopathologic and molecular characteristics of small-scale ROS1-mutant non-small cell lung cancer (NSCLC) patients.

Background: ROS1 fusions are well treatable aberrations in NSCLC. Besides solvent-front mutations (SFM) in resistance to targeted therapy, small-scale ROS1 mutations are largely unknown. We exploratively analyzed the clinical and molecular characteristics of small-scale ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs.

Failure to Complete Multidose Vaccine Series in Early Childhood.

Background: Most early childhood immunizations require 3 to 4 doses to achieve optimal protection. Our objective was to identify factors associated with starting but not completing multidose vaccine series.

Methods: Using 2019 National Immunization Survey-Child data, US children ages 19 to 35 months were classified in 1 of 3 vaccination patterns: (1) completed the combined 7-vaccine series, (2) did not initiate ≥1 of the 7 vaccine series, or (3) initiated all series, but did not complete ≥1 multidose series.

MET Fusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition.

Introduction: MET fusions have been described only rarely in NSCLC. Thus, data on patient characteristics and treatment response are limited. We here report histopathologic data, patient demographics, and treatment outcome including response to MET tyrosine kinase inhibitor (TKI) therapy in MET fusion-positive NSCLC.

Association of blood lipids with onset and prognosis of amyotrophic lateral sclerosis: results from the ALS Swabia registry.

Background: To date, the role of blood lipid levels and their association with the onset and prognosis of ALS is controversial. We explored these associations in a large, population-based case-control study.

Methods: Between October 2010 and June 2014, 336 ALS patients (mean age 65.

Alternative polyadenylation transcriptome-wide association study identifies APA-linked susceptibility genes in brain disorders.

Alternative polyadenylation (APA) plays an essential role in brain development; however, current transcriptome-wide association studies (TWAS) largely overlook APA in nominating susceptibility genes. Here, we performed a 3' untranslated region (3'UTR) APA TWAS (3'aTWAS) for 11 brain disorders by combining their genome-wide association studies data with 17,300 RNA-seq samples across 2,937 individuals. We identified 354 3'aTWAS-significant genes, including known APA-linked risk genes, such as SNCA in Parkinson's disease.

Resistance to MET inhibition in MET-dependent NSCLC and therapeutic activity after switching from type I to type II MET inhibitors.

Objectives: Resistance to MET inhibition occurs inevitably in MET-dependent non-small cell lung cancer and the underlying mechanisms are insufficiently understood. We describe resistance mechanisms in patients with MET exon 14 skipping mutation (METΔ), MET amplification, and MET fusion and report treatment outcomes after switching therapy from type I to type II MET inhibitors.

Materials And Methods: Pre- and post-treatment biopsies were analysed by NGS (next generation sequencing), digital droplet PCR (polymerase chain reaction), and FISH (fluorescense in situ hybridization).