Current immunodetection methods using antibody-DNA conjugates enable multiplexed target detection through orthogonal DNA barcodes, but existing conjugation approaches are labor-intensive and often compromise antibody function. Here, we present a modular, site-specific, and cost-efficient DNA tagging strategy - multiplexed and modular barcoding of antibodies (MaMBA). Utilizing nanobodies as modular adaptors, MaMBA enables direct site-specific labeling of off-the-shelf IgG antibodies with a one-component design. We first applied MaMBA to develop the MaMBA-assisted immunosignal hybridization chain reaction (misHCR) method for highly multiplexed in situ protein imaging via orthogonal HCR. Its cleavable variant, misHCRⁿ, achieves simultaneous visualization of 12 different targets within the same mouse brain sections through iterative probe use. We further extended the cleavable MaMBA to develop the barcode-linked immunosorbent assay (BLISA) for multiplexed and high-throughput biomolecule detections. By combining BLISA with next-generation sequencing, we successfully measured SARS-CoV-2 IgG and hepatitis B virus (HBV)-associated antigens in a large number of human serum samples. Additionally, we demonstrated a small-scale drug screen by using BLISA to simultaneously detect eight protein targets. In conclusion, MaMBA offers a highly modular and easily adaptable approach for antibody DNA barcoding, which can be broadly applied in basic research and clinical diagnostics.

Residual lung abnormalities on CT scans after COVID-19 respiratory infection may be associated with persistent or progressive respiratory symptoms and frequently correlate with abnormal pulmonary function testing results. These abnormalities have been described using varying terms in numerous publications. Chest CT lung abnormalities after COVID-19 infection tend to stabilize or regress over time, indicating that they are nonprogressive and postinfectious in nature. This multisociety consensus statement, developed by 21 thoracic radiologists from the European Society of Thoracic Imaging, the Society of Thoracic Radiology, and the Asian Society of Thoracic Radiology with a two-round survey process, aims to standardize the indication, acquisition, and reporting of post-COVID-19 residual lung abnormalities on CT scans. Key recommendations include performing chest CT in patients with persistent or progressive respiratory symptoms 3 months after infection, using low-dose CT protocols (range, 1-3 mSv) for follow-up chest CT examinations, using Fleischner Society glossary of terms for radiologic descriptors, and avoiding the term interstitial lung abnormality to describe post-COVID-19 abnormalities. Instead, to prevent misinterpreting post-COVID-19 abnormalities as an early manifestation of interstitial lung disease, use the term post-COVID-19 residual lung abnormality. This consensus statement will help harmonize radiology practice and research for the substantial number of affected patients.

The widespread uptake of COVID-19 vaccines by women provided a unique opportunity to study the effects of pregnancy and lactation on immune responses to vaccination. Leveraging a cohort with well-defined SARS-CoV-2 exposure history, we found that the magnitude of humoral and cellular immune responses to vaccine-delivered SARS-CoV-2 spike was not affected by pregnancy or lactation status. However, vaccination during pregnancy elicited more stem-like SARS-CoV-2-specific CD4+ T cells. Moreover, breakthrough infection promoted spike-specific IgG in pregnant individuals in contrast with IgA in those lactating, suggesting that the pregnancy-to-lactation transition favors mucosal antibody responses. Breakthrough infection also reduced peripheral cytolytic SARS-CoV-2-specific CD8+ T cell frequencies during lactation but not pregnancy, which may reflect trafficking of the cells to mammary glands. Our study also uncovered an impact of pregnancy and lactation on global T cell phenotypes. In particular, lactating individuals preferentially exhibited a state of diminished T cell activation. Furthermore, breakthrough infection during pregnancy, but not lactation, diminished frequencies of activated CD8+ T cells, tissue-homing CD8+ T cells, and γδ T cells. Our findings support the notion that immunity during pregnancy and lactation adapts to benefit the fetus or breastfed infant, with implications for eliciting effective long-term immunity for these uniquely vulnerable groups.

BackgroundCognitive Impairment (CI) represents an important extra-pulmonary feature of Chronic Obstructive Pulmonary Disease (COPD), in which its prevalence remains under-recognised. The Montreal Cognitive Assessment (MoCA) is a validated screening test for detecting CI.ObjectivesThe use of the MoCA in clinically stable COPD in routine practice. Secondary aim: CI prevalence in COPD.DesignFeasibility study.MethodsQuantitative and qualitative data were collected in 30 COPD patients, aged ≥65 years, at the Outpatient Department in Modena (Italy).ResultsThe MoCA administration was on average 11 min. Patient feedback was positive. The COPD participants (mean age 75 years) viewed the test favourably and felt that understanding more about cognitive function would help improve their care. The median MoCA score was 23 with 10% of patients had moderate CI. The prevalence of CI was 84%.ConclusionThe MoCA is not time-consuming and should be incorporated in daily routine to identify CI in COPD, in which the prevalence of mild CI remains high. Results warrant further studies in larger populations to confirm feasibility in clinical practice.

Driven by environmental pollution and the rise in infectious diseases, the increasing prevalence of lung conditions demands advancements in diagnostic techniques.

This study explores the use of various features, such as spectrograms, chromograms, and Mel Frequency Cepstral Coefficients (MFCC), to extract crucial information from auscultation recordings. It addresses challenges through filter-based audio enhancement methods. The primary goal is to improve disease detection accuracy by leveraging convolutional neural networks (CNNs) for feature extraction and dense neural networks for classification.

While deep learning models like CNNs and Recurrent Neural Network (RNN) outperform traditional machine learning models such as Sequence Vector Machine, K-Nearest Neighbours (KNN) and random forest with accuracies ranging from 70% to 85%. The combination of CNN, RNN, and long short-term memory achieved an accuracy of 88%. By integrating MFCC, Chroma Short-Term Fourier Transform (STFT), and spectrogram features with a CNN-based classifier, the proposed multi-feature deep learning model achieved the highest accuracy of 92%, surpassing all other methods.

The study effectively addresses key issues, including the overrepresentation of Chronic Obstructive Pulmonary Disease (COPD) samples over Lower Respiratory Tract Infections (LRTI) and Upper Respiratory Tract Infections (URTI) which hampers generalization across test audio samples.

The proposed methodology caters common challenges like background noise in recordings, and the limited and imbalanced nature of datasets. These findings pave the way for enhanced clinical applications, showcasing the transformative potential of multi-feature deep learning methods in the classification of pulmonary diseases.

Heat shock proteins (HSPs), particularly those in the HSP70 family, play essential roles in maintaining cellular homeostasis and orchestrating stress responses, including those triggered by viral infections. Based on data mining of published datasets and experimental characterization, this study identified HSPA9 phosphorylation at serine 627 (S627) as a potential regulatory site associated with SARS-CoV-2 infection. Our findings demonstrate that phospho-S627 HSPA9 enhances mitochondrial function and mass, potentially meeting the elevated energy demands of viral replication. Concurrently, phosphorylation at S627 suppresses host cell proliferation, potentially delaying immune activation and facilitating viral spread. Moreover, phosphorylation at both the S627 and S378 sites markedly reduces the expression of the proinflammatory cytokines IL-6 and IL-8, which may further weaken the immune response during SARS-CoV-2 infection. These data suggest that SARS-CoV-2 may exploit HSPA9 phosphorylation to bolster its replication and evade host defenses. Notably, MAPKAPK2 has emerged as a latent kinase that regulates this phosphorylation, making it a promising therapeutic target for the treatment of these conditions. Overall, our results shed light on a novel mechanism of SARS-CoV-2 pathogenesis, suggesting that HSPA9 phosphorylation may be a potential therapeutic target.

To evaluate the efficacy and safety of the S.M.A.R.T. Flex stents for treating femoropopliteal (FP) occlusive lesions, including complex Trans-Atlantic Inter-Society Consensus (TASC) II C/D and severely calcified lesions.

This retrospective study utilized the TALENT registry database (a prospective study), enrolling patients who underwent S.M.A.R.T. Flex implantation from January 2021 to July 2022. The primary effectiveness endpoint was the rate of freedom from clinically driven target lesion revascularization (CD-TLR) at 18 months, and the primary safety endpoint was the 18-month rate of freedom from major adverse events (all-cause death, above-the-ankle target limb amputation, or CD-TLR).

A total of 122 patients with 124 limbs were included, with an average follow-up of 617 days. The average lesion length was 24.9 ± 20.4 cm, and 73.8 and 54.1% of the lesions had chronic total occlusions and chronic limb-threatening ischemia, respectively. A total of 127 stents were placed in 107 limbs, with 1 stent placed in 88 limbs (82.2%), 2 stents placed in 18 limbs (16.8%), and 3 stents implanted in 1 limb (0.9%). In this study, 50.5% of the limbs were treated with DCBs, and 83.3% of the TASC C/D lesions were treated primarily with DCBs. The 12- month rate of primary patency was 73.1%. The 18-month rate of freedom from CD-TLR was 93.9% (95% CI: 89.2-98.8%), and the major adverse event-free rate was 75.7% (95% CI: 68.0-84.3%). A total of 92.5% of patients showed primary sustained clinical improvement, and the Vascular Quality of Life Questionnaire scores were significantly improved at 18 months compared with baseline.

The S.M.A.R.T. Flex stents demonstrate promising efficacy and safety as a treatment option for long-segment complex femoropopliteal artery lesions.

The American Heart Association (AHA) developed the notion of cardiovascular-kidney-metabolic (CKM) syndrome, which emphasizes the interconnection of heart, kidney, and metabolic illnesses. The C-reactive protein-triglyceride-glucose (CTI) represents a potential indicator to assess the resistance to insulin and an inflammatory response. However, the connection among CTI, cardiovascular disease (CVD) incidence, and overall mortality rates remains uncertain, particularly among individuals at CKM stages 0-3.

The China Health and Retirement Longitudinal Study (CHARLS) enrolled 17,705 middle-aged and elderly people. The primary outcome was the occurrence of CVD and overall mortality rates. The CTI was obtained by 0.412 * Ln (CRP [mg/L]) + Ln (TG [mg/dL] × FPG [mg/dL])/2. The correlation among CTI and CVD incidence and overall mortality was assessed via Cox proportional hazard models, Kaplan-Meier curves and restricted cubic spline (RCS) analysis. To improve the study results, a stratified analysis evaluated the influence of varying socio-demographic characteristics.

This study involved 5723 participants for CVD and 5847 participants for all-cause mortality in the CKM syndrome stages 0-3. RCS analysis revealed a notable non-linear association between CTI and CVD occurrence, as well as a linear association between CTI and all-cause death. After comprehensive multivariate adjustment, the data showed a striking 111% increase in overall mortality risk for every 1-unit rise in continuous CTI measurements.

Findings show that higher CTI level significantly associated with CVD and death risk, highlighting its potential as a biomarker for individuals with CKM stages 0-3.

Understanding the role of genetic risk and lifestyles on life expectancy (LE) without cardiovascular disease (CVD) and total LE may help optimize healthy aging strategies after taking genetic background into account.

The China Kadoorie Biobank recruited participants from five urban and five rural areas across China during 2004-2008 and followed them up till December 31, 2018. A polygenic risk score (PRS) comprising 3.5 million genetic variants for overall CVD was constructed by combining multiple PRSs for CVD and CVD-related risk factors in 96,400 participants. Genetic risk was categorized into low, intermediate, and high according to the PRS, and lifestyles were categorized as favorable, intermediate, and unfavorable according to the number of unfavorable lifestyles. Using multistate life tables, we estimated CVD-free and total LE at age 40 for different genetic and lifestyle risk groups.

Genetic risk was more strongly associated with CVD onset than post-CVD mortality. As a result, the increase in LE without CVD associated with low genetic risk (4.9 years (95% CI 4.3-5.5) for women and 4.4 years (3.6-5.1) for men) was greater than the increase in total LE (2.9 years (1.8-3.8) for women and 2.6 years (1.5-3.5) for men) when compared to high genetic risk. In contrast, the association strengths of lifestyles with CVD onset and mortality after CVD were similar. Correspondingly, compared to those with unfavorable lifestyles, participants with favorable lifestyles had longer total LE and LE without CVD of 3.0 (1.5-4.3) and 4.0 (3.0-4.9) years in women and 5.7 (4.1-7.1) and 5.8 (4.7-6.9) years in men, respectively. Participants with high genetic risk benefited more from favorable lifestyles than those with low and intermediate genetic risk, gaining 5.9 (2.3-9.3) and 5.3 (3.0-7.6) years in women and 6.1 (0.8-10.6) and 6.2 (2.3-9.8) years in men for total and CVD-free LE, respectively.

Improving lifestyles is critical for reducing CVD-related healthcare burden and promoting healthy aging, especially for individuals with high genetic risk.