Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD. RESEARCH QUESTION: We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD. METHODS: Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses. RESULTS: Among 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density. INTERPRETATION: MRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

Genetic susceptibility to neurodevelopmental conditions associates with neonatal DNA methylation patterns in the general population: an individual participant data meta-analysis.

Background: Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) are highly heritable and linked to disruptions in foetal (neuro)development. While epigenetic processes are considered an important underlying pathway between genetic susceptibility and neurodevelopmental conditions, it is unclear (i) whether genetic susceptibility to these conditions is associated with epigenetic patterns, specifically DNA methylation (DNAm), already at birth; (ii) to what extent DNAm patterns are unique or shared across conditions, and (iii) whether these neonatal DNAm patterns can be leveraged to enhance genetic prediction of (neuro)developmental outcomes. Methods: We conducted epigenome-wide meta-analyses of genetic susceptibility to ASD, ADHD, and schizophrenia, quantified using polygenic scores (PGSs) on cord blood DNAm, using four population-based cohorts (n pooled=5,802), all North European. Heterogeneity statistics were used to estimate overlap in DNAm patterns between PGSs. Subsequently, DNAm-based measures of PGSs were built in a target sample, and used as predictors to test incremental variance explained over PGS in 130 (neuro)developmental outcomes spanning birth to 14 years. Outcomes: In probe-level analyses, SCZ-PGS associated with neonatal DNAm at 246 loci (p<9×10-8), predominantly in the major histocompatibility complex. Functional characterization of these DNAm loci confirmed strong genetic effects, significant blood-brain concordance and enrichment for immune-related pathways. 8 loci were identified for ASD-PGS (mapping to FDFT1 and MFHAS1), and none for ADHD-PGS. Regional analyses indicated a large number of differentially methylated regions for all PGSs (SCZ-PGS: 157, ASD-PGS: 130, ADHD-PGS: 166). DNAm signals showed little overlap between PGSs. We found suggestive evidence that incorporating DNAm-based measures of genetic susceptibility at birth increases explained variance for several child cognitive and motor outcomes over and above PGS. Interpretation: Genetic susceptibility for neurodevelopmental conditions, particularly schizophrenia, is detectable in cord blood DNAm at birth in a population-based sample, with largely distinct DNAm patterns between PGSs. These findings support an early-origins perspective on schizophrenia. Funding: HorizonEurope; European Research Council.

Corrigendum to 'Transplant oncology - Current indications and strategies to advance the field' [JHEP Reports 6 (2024) 100965].

[This corrects the article DOI: 10.1016/j.jhepr.2023.100965.].

Radiation Principles, Protection and Reporting for Interventional Pulmonology.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology is rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimizing radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

Causal Latent Class Analysis with Distal Outcomes: A Modified Three-Step Method Using Inverse Propensity Weighting.

Bias-adjusted three-step latent class (LC) analysis is a popular technique for estimating the relationship between LC membership and distal outcomes. Since it is impossible to randomize LC membership, causal inference techniques are needed to estimate causal effects leveraging observational data. This paper proposes two novel strategies that make use of propensity scores to estimate the causal effect of LC membership on a distal outcome variable. Both strategies modify the bias-adjusted three-step approach by using propensity scores in the last step to control for confounding. The first strategy utilizes inverse propensity weighting (IPW), whereas the second strategy includes the propensity scores as control variables. Classification errors are accounted for using the BCH or ML corrections. We evaluate the performance of these methods in a simulation study by comparing it with three existing approaches that also use propensity scores in a stepwise LC analysis. Both of our newly proposed methods return essentially unbiased parameter estimates outperforming previously proposed methods. However, for smaller sample sizes our IPW based approach shows large variability in the estimates and can be prone to non-convergence. Furthermore, the use of these newly proposed methods is illustrated using data from the LISS panel.

Percutaneous Ultrasound-Guided Medication Injection, a Potential Technique for Subglottic Stenosis.

INTRODUCTION: Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and antiinflammatory properties. Submucosal injection of glucocorticoids or mitomycin, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks. CASE PRESENTATION: We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost. CONCLUSION: POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis.

Silver/gold nanoalloy implant coatings with antibiofilm activity via pH-triggered silver ion release.

Implant infections are a major challenge for the healthcare system. Biofilm formation and increasing antibiotic resistance of common bacteria cause implant infections, leading to an urgent need for alternative antibacterial agents. In this study, the antibiofilm behaviour of a coating consisting of a silver (Ag)/gold (Au) nanoalloy is investigated. This alloy is crucial to reduce uncontrolled potentially toxic Ag+ ion release. In neutral pH environments this release is minimal, but the Ag+ ion release increases in acidic microenvironments caused by bacterial biofilms. We perform a detailed physicochemical characterization of the nanoalloys and compare their Ag+ ion release with that of pure Ag nanoparticles. Despite a lower released Ag+ ion concentration at pH 7.4, the antibiofilm activity against Escherichia coli (a bacterium known to produce acidic pH environments) is comparable to a pure nanosilver sample with a similar Ag-content. Finally, biocompatibility studies with mouse pre-osteoblasts reveal a decreased cytotoxicity for the alloy coatings and nanoparticles.

Endovascular treatment of primary M3 occlusion stroke in clinical practice: analysis of the German Stroke Registry.

BACKGROUND: Endovascular treatment (ET) options for acute stroke due to distal middle cerebral artery occlusions are rapidly evolving, but data on outcome and safety are sparse. We therefore performed an analysis of patients undergoing ET for primary M3 occlusions in routine clinical practice in a nationwide registry. METHODS: Patients enrolled between 01/20 and 12/21 in the prospective, multicenter German Stroke Registry-Endovascular Treatment (GSR-ET) were screened for mechanical thrombectomy performed for primary M3 occlusion. We analyzed neurological deficit as measured by the National Institute of Health Stroke Scale (NIHSS), symptomatic intracranial hemorrhage (sICH), thrombectomy technique, successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3) and functional outcome as measured by the modified Rankin Scale (mRS) at discharge and 90 days. RESULTS: Out of 5574 patients, 11 patients (0.2%, median age 80 years, 54.5% female) underwent ET for primary M3 occlusion. All patients had pre-admission mRS ≤ 1, median NIHSS on admission was 8, and successful reperfusion was achieved in 6/11 patients (54.5%). While no vasospasm, dissection or perforation was reported, symptomatic intracranial hemorrhage occurred in 2 patients (18.2%). Favorable outcome (mRS ≤ 2) was achieved in 6/11 patients (54.5%) at 90-day follow-up. CONCLUSIONS: ET for primary M3 occlusions is rarely performed. While technically feasible, the procedure's potential benefits must be carefully weighed against its associated risks, including clinically relevant complications. Caution and further research is needed to optimize patient selection for this intervention. TRIAL REGISTRATION: GSR-ET; ClinicalTrials.gov Identifier: NCT03356392; Trial Registration Date: 11/29/2017.

Endobronchial ultrasound-based support vector machine model for differentiating between benign and malignant mediastinal and hilar lymph nodes.

INTRODUCTION: To establish an ultrasonographic radiomics machine learning model based on endobronchial ultrasound (EBUS) to assist in diagnosing benign and malignant mediastinal and hilar lymph nodes (LNs). METHODS: The clinical and ultrasonographic image data of 197 patients were retrospectively analyzed. The radiomics features extracted by EBUS-based radiomics were analyzed by the least absolute shrinkage and selection operator (LASSO). Then, we used a support vector machine (SVM) algorithm to establish an EBUS-based radiomics model. A total of 205 lesions were randomly divided into training (n=143) and validation (n=62) groups. The diagnostic efficiency was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 13 stable radiomics features with non-zero coefficients were selected. The SVM model exhibited promising performance in both groups. In the training group, the SVM model achieved a ROC area under the curve (AUC) of 0.892 (95% CI: 0.885-0.899), with an accuracy of 85.3%, sensitivity of 93.2%, and specificity of 79.8%. In the validation group, the SVM model had an ROC AUC of 0.906 (95% CI: 0.890-0.923), an accuracy of 74.2%, a sensitivity of 70.3%, and a specificity of 74.1%. CONCLUSION: The EBUS-based radiomics model can be used to differentiate mediastinal and hilar benign and malignant LNs. The SVM model demonstrated excellent potential as a diagnostic tool in clinical practice.

Endobronchial Valves in Treatment of Persistent Air Leak: European Case-Series Study and Best Practice Recommendations - From an Expert Panel.

INTRODUCTION: Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage, and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3-5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. METHODS: We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. RESULTS: We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%) and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (interquartile range: 14.0-54.3). Air leak resolved in 40/66 patients (60.6%) within 30 days after EBV treatment. Concerning safety outcome, no procedure-related mortality was reported and complication rate was low (6.1%). Five patients (7.6%) died in the first 30 days after intervention. CONCLUSION: EBV placement is a treatment option in patients with PAL. In this multicenter case-series of high-risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients.

À la carte: how mosquitoes choose their blood meals.

Mosquitoes are important vectors for human diseases, transmitting pathogens that cause a range of parasitic and viral infections. Mosquito blood-feeding is heterogeneous, meaning that some human hosts are at higher risk of receiving bites than others, and this heterogeneity is multifactorial. Mosquitoes integrate specific cues to locate their hosts, and mosquito attraction differs considerably between individual human hosts. Heterogeneous mosquito biting results from variations in both host attractiveness and availability and can impact transmission of vector-borne diseases. However, the extent and drivers of this heterogeneity and its importance for pathogen transmission remain incompletely understood. Here, we review methods and recent data describing human characteristics that affect host-seeking behavior and host preferences of mosquito disease vectors, and the implications for vector-borne disease transmission.

The Diagnostic Efficiency and Safety of Transbronchial Lung Cryobiopsy Using 1.1-mm Cryoprobe in Diagnosing Interstitial Lung Disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed. METHODS: A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis. RESULTS: A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress. CONCLUSION: Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe. TRAIL REGISTRATION: Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

Correlation of diaphragm thickening fraction and oesophageal pressure swing in non-invasive ventilation of healthy subjects.

INTRODUCTION: The diaphragm thickening fraction (DTF) may be a valuable tool for estimating respiratory effort in non-invasive ventilation. The primary aim of this physiological study is the investigation of the correlation of DTF with oesophageal pressure swings (ΔPoes). A secondary aim is to assess the discriminatory capacity of the index tests for different exercise loads. METHODS: Healthy volunteers underwent spontaneous breathing and non-invasive ventilation with a sequence of different respirator settings. The first sequence was carried out at rest. The same sequence was repeated twice, with additional ergometry of 25 and 50 Watts, respectively. DTF and ΔPoes were measured during each ventilation configuration. RESULTS: 23 individuals agreed to participate. DTF was moderately correlated with ΔPoes (repeated measures correlation ρ = 0.410, p < 0.001). Both ΔPoes and DTF increased consistently with exercise loading in every ventilation configuration, however ΔPoes showed greater discriminatory capacity. CONCLUSION: DTF was moderately correlated with ΔPoes and could discriminate reasonably between exercise loads in a small cohort of non-invasively ventilated healthy subjects. While it may not accurately reflect the absolute respiratory effort, DTF might help titrating individual non-invasive respiratory support. Further investigations are needed to test this hypothesis. TRIAL REGISTRATION: This study was not prospectively registered.

Body Composition after Endoscopic Lung Volume Reduction with Endobronchial Valves: A Prospective Study.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and emphysema experience malnutrition and pulmonary cachexia. Endoscopic lung volume reduction (ELVR) with endobronchial valves has not only improved lung function, exercise capacity, and quality of life but also influenced body weight. Only a few data are available on body composition changes after ELVR. METHODS: This single-center prospective study of patients with advanced COPD investigates body composition before and after endoscopic valve treatment using multifrequency bioelectrical impedance analysis (BIA). The following parameters were evaluated in addition to clinical data and routine tests: body weight, body mass index (BMI), basal metabolic rate, total body water, body fat, cell percentage, phase angle, intracellular water (ICW), extracellular water (ECW), extracellular mass (ECM), body cell mass (BCM), lean body mass (ECM + BCM), and fat-free mass index. RESULTS: A total of 23 patients (mean emphysema index 37.2 ± 7.5%, BMI 23.4 ± 4.3 kg/m2) experienced improvements in lung function and exercise capacity with ELVR. Complete lobar atelectasis was achieved in 39.1% of participants. A non-statistically significant increase in body weight and BMI was observed after ELVR (p = 0.111 and p = 0.102). BIA measurement revealed a worsening of phase angle, cell percentage and ECM/BCM and thus of body composition, but without statistical significance. This is mainly due to a statistically significant increase in ECM, ECW, and ICW (all p < 0.001). CONCLUSION: ELVR demonstrated no beneficial changes in body composition, although patients tend to gain weight. A larger cohort is warranted to confirm these findings.

Heat-activated growth of metastable and length-defined DNA fibers expands traditional polymer assembly.

Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combination of dynamic, energy-driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here we show that highly charged, monodisperse DNA-oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating; when the temperature is lowered, these metastable fibers slowly disassemble. Furthermore, the specific molecular structures of oligomers that promote fiber formation contradict the typical theory of block copolymer self-assembly. Efficient curling and packing of the oligomers - or 'curlamers' - determine morphology, rather than hydrophobic to hydrophilic ratio. Addition of a small molecule stabilises the DNA fibers, enabling temporal control of polymer lifetime and underscoring their potential use in nucleic-acid delivery, stimuli-responsive biomaterials, and soft robotics.

Multiple primary lung cancer: Updates and perspectives.

Management of multiple primary lung cancer (MPLC) remains challenging, partly due to its increasing incidence, especially with the significant rise in cases of multiple lung nodules caused by low-dose computed tomography screening. Moreover, the indefinite pathogenesis, diagnostic criteria, and treatment selection add to the complexity. In recent years, there have been continuous efforts to dissect the molecular characteristics of MPLC and explore new diagnostic approaches as well as treatment modalities, which will be reviewed here, with a focus on newly emerging evidence and future perspectives, hope to provide new insights into the management of MPLC and serve as inspiration for future research related to MPLC.

Low Inter-Rater Reliability and Reproducibility of Neck Reflex/"Adler-Langer" Points in Neural Therapy Diagnostics but Increased Pressure Pain Threshold after Therapy: Results of a Randomized Controlled Observer-Blind Trial.

BACKGROUND: Neck reflex points or Adler-Langer points are commonly used in neural therapy to detect so-called interference fields. Chronic irritations or inflammations in the sinuses, teeth, tonsils, or ears are supposed to induce tension and tenderness of the soft tissues and short muscles in the upper cervical spine. The individual treatment strategy is based on the results of diagnostic Adler-Langer point palpation. This study investigated the inter- and intra-rater reliability and explored treatment effects. METHODS: We performed a randomized controlled trial with 104 inpatients (80.8% female, 51.8 ± 12.74 years) of a German department for internal and integrative medicine. Patients were randomized to individual neural therapy according to the pathological findings (n = 48) or no treatment (n = 56). In each patient, three experienced raters (20-45 years of experience in neural therapy) and two novice raters (medical students) rated Adler-Langer points rigidity on a standardized rating scale ("strong," "weak," "none"). The patients independently evaluated the tenderness on palpation of the eight points using the same scale. Pressure pain thresholds were assessed at the eight Adler-Langer points. All patients were retested after 30 min. The five raters were blinded to treatment allocation and assessments of the other raters. Video recordings were obtained to assess the consistency of the areas tested by the different raters. RESULTS: Agreement between patients and raters (Cohen's kappa = 0.161-0.400) and inter-rater reliability were low (Fleiss kappa = 0.132-0.150). Moreover, the individual agreement (pre-post comparisons in untreated patients) was similarly low even in experienced raters (Cohen's kappa = 0.099-0.173). Video documentation suggests that raters do not place their fingers in the correct segments (percentage of correct position: 42.0-60.6%). Pressure pain thresholds at five of the eight Adler-Langer points showed significant changes after treatment compared to none in the control group. CONCLUSION: Under this artificial experimental setting, this method of Adler-Langer point palpation has not proven to be a reliable diagnostic tool. But it could be shown that, as claimed by the method, the tenderness in five of eight Adler-Langer points decreased after neural therapy.

Rapid and scalable photocatalytic C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling of aryl bromides with alkyl boranes.

In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp3-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a powerful approach for the light-mediated B-alkyl Suzuki-Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes were easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring under photocatalytic conditions. This methodology eliminates the need for expensive catalytic systems and sensitive organometallic compounds, operating efficiently at room temperature within just 30 min. We further demonstrate the translation of the present protocol to continuous-flow conditions, enhancing scalability, safety, and overall efficiency of the method. This versatile approach offers significant potential for accelerating drug discovery efforts by enabling the introduction of complex aliphatic fragments in a straightforward and reliable manner.

Autophagy preferentially degrades non-fibrillar polyQ aggregates.

Aggregation of proteins containing expanded polyglutamine (polyQ) repeats is the cytopathologic hallmark of a group of dominantly inherited neurodegenerative diseases, including Huntington's disease (HD). Huntingtin (Htt), the disease protein of HD, forms amyloid-like fibrils by liquid-to-solid phase transition. Macroautophagy has been proposed to clear polyQ aggregates, but the efficiency of aggrephagy is limited. Here, we used cryo-electron tomography to visualize the interactions of autophagosomes with polyQ aggregates in cultured cells in situ. We found that an amorphous aggregate phase exists next to the radially organized polyQ fibrils. Autophagosomes preferentially engulfed this amorphous material, mediated by interactions between the autophagy receptor p62/SQSTM1 and the non-fibrillar aggregate surface. In contrast, amyloid fibrils excluded p62 and evaded clearance, resulting in trapping of autophagic structures. These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates.

Building and validating an artificial intelligence model to identify tracheobronchopathia osteochondroplastica by using bronchoscopic images.

BACKGROUND: Given the rarity of tracheobronchopathia osteochondroplastica (TO), many young doctors in primary hospitals are unable to identify TO based on bronchoscopy findings. OBJECTIVES: To build an artificial intelligence (AI) model for differentiating TO from other multinodular airway diseases by using bronchoscopic images. DESIGN: We designed the study by comparing the imaging data of patients undergoing bronchoscopy from January 2010 to October 2022 by using EfficientNet. Bronchoscopic images of 21 patients with TO at Anhui Chest Hospital from October 2019 to October 2022 were collected for external validation. METHODS: Bronchoscopic images of patients with multinodular airway lesions (including TO, amyloidosis, tumors, and inflammation) and without airway lesions in the First Affiliated Hospital of Guangzhou Medical University were collected. The images were randomized (4:1) into training and validation groups based on different diseases and utilized for deep learning by convolutional neural networks (CNNs). RESULTS: We enrolled 201 patients with multinodular airway disease (38, 15, 75, and 73 patients with TO, amyloidosis, tumors, and inflammation, respectively) and 213 without any airway lesions. To find multinodular lesion images for deep learning, we utilized 2183 bronchoscopic images of multinodular lesions (including TO, amyloidosis, tumor, and inflammation) and compared them with images without any airway lesions (1733). The accuracy of multinodular lesion identification was 98.9%. Further, the accuracy of TO detection based on the bronchoscopic images of multinodular lesions was 89.2%. Regarding external validation (using images from 21 patients with TO), all patients could be diagnosed with TO; the accuracy was 89.8%. CONCLUSION: We built an AI model that could differentiate TO from other multinodular airway diseases (mainly amyloidosis, tumors, and inflammation) by using bronchoscopic images. The model could help young physicians identify this rare airway disease.