CORRECTION to: “Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients” (ERJ Open Res 2024; 10: 00838-2023)
In the originally published version of this article there was an error in the follow-up time and total number of readmissions in two datasets of the hospital readmission data subset. This concerned the datasets of QUINTANA et al. [1] and LOPEZ-CAMPOS et al. [2]. Instead of a follow-up time of 365 days, the correct follow-up times were 60 and 90 days, respectively. In addition, instead of total readmission rates of 19.5% and 26.6%, the correct readmission rates were 26.0% and 35.1%, respectively. As a result, the median follow-up time in the hospital readmission data subset changed from 365 days to 90 days, whereas the overall readmission rate changed from 15 195 (32.8%, 95% CI 32.4–33.3%) to 16 646 (36.0%, 95% CI 35.5–36.4%). Corrections have been made accordingly to the Results, including table S7 and figure S8, and to the Discussion. In addition, there was an error in the coding for the 30-, 90- and 365-day categories related to post-discharge mortality and hospital readmission. The initial coding failed to capture all possible conditional statements needed to accurately capture outcome statuses based on follow-up times. This was particularly relevant in studies where the exact time until the event was not known, and was instead represented by the predetermined, or set, study follow-up period. These corrections altered the pooled 30-, 90- and 365-day post-discharge mortality and hospital readmission rates from 1.8% to 2.0%, from 5.5% to 6.4%, from 10.9% to 12.2%, and from 7.1% to 11.8%, from 12.6% to 26.5% and from 32.1% to 38.2%, respectively. Corrections have been made accordingly to the Abstract, Results (including figures 5 and 7), and to the Discussion. Figures S3 and S7 have been aligned to display only the percentages of patients with a known time of event, categorised by time intervals during follow-up after hospital discharge from the index event. Importantly, the corrections do not change the scientific conclusions drawn in the article.
P62 accumulates through neuroanatomical circuits in response to tauopathy propagation
AbstractIn Alzheimer’s disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.
TomoCPT: a generalizable model for 3D particle detection and localization in cryo-electron tomograms
Cryo-electron tomography is a rapidly developing field for studying macromolecular complexes in their native environments and has the potential to revolutionize our understanding of protein function. However, fast and accurate identification of particles in cryo-tomograms is challenging and represents a significant bottleneck in downstream processes such as subtomogram averaging. Here, we present tomoCPT (Tomogram Centroid Prediction Tool), a transformer-based solution that reformulates particle detection as a centroid-prediction task using Gaussian labels. Our approach, which is built upon the SwinUNETR architecture, demonstrates superior performance compared with both conventional binary labelling strategies and template matching. We show that tomoCPT effectively generalizes to novel particle types through zero-shot inference and can be significantly enhanced through fine-tuning with limited data. The efficacy of tomoCPT is validated using three case studies: apoferritin, achieving a resolution of 3.0 Å compared with 3.3 Å using template matching, SARS-CoV-2 spike proteins on cell surfaces, yielding an 18.3 Å resolution map where template matching proved unsuccessful, and rubisco molecules within carboxysomes, reaching 8.0 Å resolution. These results demonstrate the ability of tomoCPT to handle varied scenarios, including densely packed environments and membrane-bound proteins. The implementation of the tool as a command-line program, coupled with its minimal data requirements for fine-tuning, makes it a practical solution for high-throughput cryo-ET data-processing workflows.
The importance of microbiology reference laboratories and adequate funding for infectious disease surveillance.
Microbiology reference laboratories perform a crucial role within public health systems. This role was especially evident during the COVID-19 pandemic. In this Viewpoint, we emphasise the importance of microbiology reference laboratories and highlight the types of digital data and expertise they provide, which benefit national and international public health. We also highlight the value of surveillance initiatives among collaborative international partners, who work together to share, analyse, and interpret data, and then disseminate their findings in a timely manner. Microbiology reference laboratories have substantial impact at regional, national, and international levels, and sustained support for these laboratories is essential for public health in both pandemic and non-pandemic times.
The Clinical Utility of Next Generation Sequencing Results in a Community‐Based Hereditary Cancer Risk Program
AbstractSince the 2013 Supreme Court ruling on BRCA1/BRCA2 patenting, hereditary cancer gene panels now include BRCA1 and BRCA2, making these panels an option for first‐tier testing. However, questions remain about the clinical utility and implications of these panels for medical management with inclusion of genes of unknown to moderate penetrance. To better understand how use of these panels affected our practice, we reviewed patients who underwent testing in our clinic from July 1, 2013 through May 23, 2014. Indications for testing included personal and/or family history of breast and/or ovarian cancer. A total of 136 patients underwent panel testing via a single commercial laboratory; 12 (8.8 %) patients were positive for a pathogenic or likely pathogenic mutation (four BRCA2 mutations, two TP53 mutations, one CDH1 mutation, two ATM mutations, and one patient each with a CHEK2, NBN, or PALB2 mutation). Of these positive patients, 100 % met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer genetic testing (2.2014). Mutations in seven of twelve (58 %) patients led to changes in medical management; three of seven (43 %) had a non‐BRCA1 or BRCA2 gene mutation. Our findings suggest that there is clinical utility of panels that include genes of unknown to moderate penetrance.