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Conventional magnetic biosensing technologies have reduced analytical capacity for magnetic field dimensionality and require extensive sample processing. To address these challenges, we spatially engineer 3D magnetic response gradients for direct and programmable molecular detection in native biofluids. Named magnetic augmentation through triple-gradient coupling for high-performance detection (MATCH), the technology comprises gradient-distributed magnetic nanoparticles encapsulated within responsive hydrogel pillars and suspended above a magnetic sensor array. This configuration enables multi-gradient matching to achieve optimal magnetic activation, response and transduction, respectively. Through focused activation by target biomarkers, the platform preferentially releases sensor-proximal nanoparticles, generating response gradients that complement the sensor's intrinsic detection capability. By implementing an upstream module that recognizes different biomarkers and releases universal activation molecules, the technology achieves programmable detection of various circulating biomarkers in native plasma. It bypasses conventional magnetic labeling, completes in <60 minutes and achieves sensitive detection (down to 10 RNA and 1000 protein copies). We apply the MATCH to measure RNAs and proteins directly in patient plasma, achieving accurate cancer classification., (© 2024. The Author(s).)

This study investigates CD151, a protein linked to cancer progression, in non-small cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations. These patients often have limited treatment options. The study used retrospective analysis to examine 157 adenocarcinoma biopsy specimens and 199 patient cases from The Cancer Genome Atlas, correlating CD151 expression with patient survival. Cellular studies revealed that CD151 interacts with EGFR, influencing epidermal growth factor (EGF)-induced cell proliferation and the effectiveness of the EGFR inhibitor, erlotinib. A strong association was found between CD151 expression and EGFR mutation status. High CD151 expression in the absence of EGFR mutations is correlated with poorer survival outcomes. Biological assays showed that CD151 colocalizes and associates with EGFR, playing a crucial role in regulating EGF-induced cell proliferation via the AKT and ERK1/2 pathways. Importantly, CD151 expression was found to influence the anti-proliferative effects of the EGFR tyrosine kinase inhibitor, erlotinib. High CD151 expression, in the absence of EGFR mutations, was associated with poorer survival outcomes. It could serve as a potential prognostic marker and influence cellular responses to EGFR-targeted treatments. This study highlights CD151 as a potential novel target for therapeutic intervention in NSCLC, especially in populations lacking EGFR mutations., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Background: Climate change is the greatest threat to human health. Cardiothoracic patients suffer direct consequences from poor environmental health and we have a vested interest to address this in our practice. As leaders of complex high-end surgery, we are uniquely positioned to effect practical and immediate changes to significantly pare down emissions within the operating theatre, outside the operating theatre and beyond the confines of the hospital., Methods: We aim to spotlight this pressing issue, take stock of our current efforts, and encourage fellow specialists to drive this agenda., Results: Sustainability in healthcare needs to be formalized as part of the core curriculum in surgical training and awareness generated via carbon audits and life cycle analyses. Practical actions such as reducing unnecessary equipment usage, choosing reusable equipment over single use disposables, judicious use of investigations rooted in clinical reasoning and sharing of resources across services and health systems help reduce the carbon output of our specialty., Conclusion: The 'Triple Bottom Line' serves as a good template to calibrate efforts that balance quality against environmental costs. More can be done to advocate for and find solutions for sustainable healthcare with cardiothoracic surgery., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: Minimally invasive repair of pectus excavatum (MIRPE) is a popular method for surgical correction of PE, and its impact on quality of life is a growing area of interest. We performed a systematic review and meta-analysis to evaluate the impact of MIRPE on the quality of life of patients., Methods: This study was registered with PROSPERO under reference number CRD42020222061. A literature search of PubMed, Cochrane Library, EMBASE and Scopus was conducted from the date of inception till November 23, 2020. We included studies which administered one or more questionnaires on patients up to 60 years old, parents or both, to assess the quality of life before and after MIRPE. Studies not written in English, abstracts, articles without primary data, reviews and studies which combined data on PE and other deformities were excluded. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions and the Cochrane risk of bias tool. A random-effects meta-analysis was performed to obtain mean differences for key themes of quality of life before and after MIRPE. Responses from the same questionnaires, as well as common themes across different questionnaires, were compared., Results: Of the 20 studies identified for systematic review, 7 studies that reported the responses of 478 patients were included in the meta-analysis. Patients who underwent MIRPE experienced an increased self-esteem [standardized mean difference (SMD): 1.38, 95% confidence interval (CI): 0.95 to 1.81, P<0.00001] and a smaller degree of chest interference with their social activities (SMD: 0.84, 95% CI: 0.60 to 1.08, P<0.00001). These findings were consistent even after the implanted bar was removed., Conclusions: MIRPE may be associated with a better quality of life for patients with PE as self-esteem and extent of chest interference with social activities are improved after the procedure. The key limitations of this study are the lack of high-quality evidence due to paucity of randomized trials, and the significant heterogeneity in reported outcomes due to variations in the questionnaires and timepoints of administration., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-1647/coif). J.K.C.T. serves as an unpaid editorial board member of Annals of Translational Medicine from November 2022 to October 2024. The other authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: Pembrolizumab as immunotherapy is increasingly used in adjuvant, neoadjuvant, and standalone therapy and has been described as safe. We share an experience of lung erosion post-thoracic surgery with the use of adjuvant pembrolizumab., Case Presentation: A 65-year-old Chinese gentleman with metastatic renal cell carcinoma underwent lung metastasis resection and presented with delayed onset pneumothorax while on adjuvant pembrolizumab. Failure of conservative management warranted repeat surgical intervention, and intraoperative findings showed erosion of staple lines possibly caused by poor healing associated with pembrolizumab., Conclusion: Adjuvant pembrolizumab may impair wound healing, including stapler line healing. Presentation of delayed pneumothorax in a post-surgical patient undergoing immunotherapy should warrant early surgical intervention., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Bar displacement is one of the most serious complications following the Nuss procedure for pectus excavatum repair. This paper reports a novel method of bar fixation using ZipFix, a biocompatible cable-tie implant, and shares a series of patients and outcomes., Methods: This paper describes the ZipFix stabilisation method and presents a case series of 20 patients with pectus excavatum who underwent the Nuss procedure and ZipFix stabilisation between July 2015 and September 2020., Results: A total of 34 ZipFixes were implanted in 20 patients. Six (6) patients had one ZipFix placed and 14 patients had two ZipFixes implanted: 13 were bilateral and one patient had two ZipFixes placed on the right. There was one incidence of asymptomatic posterior superior displacement of the right bar. Two (2) patients had wound infections and one patient had a previously placed bar adjusted and secured with a ZipFix. All patients had full correction of their chest wall deformity with no recurrence., Conclusions: This case series shows that the use of ZipFix for Nuss bar fixation is feasible using this technique., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: The optimal extent of surgical resection for non-myasthenic patients with thymoma is controversial. The objective of this meta-analysis was to compare complete to partial thymectomy in non-myasthenic patients for oncological and postoperative clinical outcomes., Methods: We performed a PubMed and EMBASE search (from inception to January 2020) for English-language studies directly comparing partial thymectomy (thymomectomy) to complete thymectomy for thymoma resection. Clinical endpoints studied included overall and disease-free survival, Masaoka and World Health Organization staging, adjuvant therapy, postoperative complications, postoperative drainage, length of hospital stay, thymoma-related deaths, postresection development of myasthenia gravis, incomplete resection, and recurrence. Random effects meta-analyses across all clinical endpoints was done., Results: There was no statistically significant difference between the two approaches with regard to recurrence (odds ratio [OR], 1.22; 95% confidence interval [CI], 0.78-1.92), completeness of resection (OR, 1.17; 95% CI, 0.66-2.10), adjuvant therapy (OR, 0.71; 95% CI, 0.40-1.26), or thymoma-related deaths (OR, 0.76; 95% CI, 0.12-4.66). There was a statistically significant decrease in postoperative complications (OR, 0.61; 95% CI, 0.39-0.97), drainage (mean difference [MD], -0.99; 95% CI, -1.98 to -0.01), and length of hospital length (MD, -1.88; 95% CI, -3.39 to -0.36) with partial thymectomy., Conclusions: The evidence appeared to suggest that partial thymectomy is oncologically equivalent to complete thymectomy for non-myasthenic patients with early-stage thymoma. There is an additional advantage of reduced postoperative complications and decreased length of hospital stay with partial thymectomy., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Covid-19 has touched all corners of the globe and impacted our lives in more ways than one. Thoracic surgeons are frontliners impacted in both our professional and personal capacities. In this commentary we discuss the impact that Covid-19 has had on thoracic surgery as a practice highlighting the discrepant impact upon developed and developing countries, the state of affairs of the "new normal" that we live in and the challenges ahead as we transition from pandemic living to endemic living alongside Covid-19. We need to evolve as the virus does and keep abreast of the latest developments to continue providing excellent care to our patients. While the challenges brought about by the Covid-19 pandemic are unprecedented in this generation, it can bring forth tremendous opportunities for us to redefine excellence in thoracic surgery service delivery in this endemic times., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Leow and Tam.)

The management of massive anterior mediastinal masses (AMM) is challenging. With the burgeoning role of extracorporeal membrane oxygenation support (ECMO) beyond the confines of salvage therapy, more trained clinicians are adopting it as a bridge for high-risk procedures or situations where temporary respiratory or cardiac support is required. We report our experience with using ECMO in the management of massive AMM in this case series of three patients sharing their clinical details and the lessons learned from them., (© 2021. The Japanese Society for Artificial Organs.)

Background: Lung separation may be achieved through the use of double lumen tubes or endobronchial blockers. The use of lung separation techniques carries the risk of airway injuries which range from minor complications like postoperative hoarseness and sore throat to rare and potentially devastating tracheobronchial mucosal injuries like bronchus perforation or rupture. With few case reports to date, bronchial rupture with the use of endobronchial blockers is indeed an overlooked complication., Case Presentation: A 78-year-old male patient with a left upper lobe lung adenocarcinoma underwent a left upper lobectomy with a Fuji Uniblocker® as the lung separation device. Despite an atraumatic insertion and endobronchial blocker balloon volume within manufacturer specifications, an intraoperative air leak developed, and the patient was found to have sustained a left mainstem bronchus rupture which was successfully repaired and the patient extubated uneventfully. Unfortunately, the patient passed on in-hospital from sepsis and other complications., Conclusion: Bronchial rupture is a serious complication of endobronchial blocker use that can carry significant morbidity, and due care should be exercised in its use and placement. Bronchoscopy should be used during insertion, and the volume and pressure of the balloon kept to the minimum required to prevent air leak. Bronchial injury should be considered as a differential in the presence of an unexplained air leak., (© 2021. The Author(s).)

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1 + CD274(PD-L1) + IDO1 + macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1&#95;Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Well-controlled postoperative pain is essential for early recovery after uniportal video-assisted thoracoscopic surgery (UVATS). Conventional analgesia like opioids and thoracic epidural anaesthesia have been associated with hypotension and urinary retention. Intercostal catheters are a regional analgesic alternative that can be inserted during UVATS to avoid these adverse effects. This feasibility study aims to evaluate the postoperative pain scores and analgesic requirements with incorporation of an intercostal catheter into a multimodal analgesic strategy for UVATS., Methods: In this observational study, 26 consecutive patients who underwent UVATS were administered a multilevel intercostal block and oral paracetamol. All of these patients received 0.2% ropivacaine continuously at 4 ml/h via an intercostal catheter at the level of the incision. Rescue analgesia including etoricoxib, gabapentin and opioids were prescribed using a pain ladder approach. Postoperative pain scores and analgesic usage were assessed. The secondary outcomes were postoperative complications, days to ambulation and length of stay., Results: No technical difficulties were encountered during placement of the intercostal catheter. There was only one case of peri-catheter leakage. Mean pain score was 0.31 (range 0-2) on post-operative day 1 and was 0.00 by post-operative day 5. 16 patients (61.6%) required only oral rescue analgesia. The number of patients who required rescue non-opioids only increased from 1 in the first 7 months to 8 in the next 7 months. There were no cases of hypotension or urinary retention. Median time to ambulation was 1 day (range 1-2). Mean post-operative length of stay was 4.17 ± 2.50 days., Conclusions: Incorporation of an intercostal catheter into a multimodal analgesia strategy for UVATS is feasible and may provide adequate pain control with decreased opioid usage., (© 2021. The Author(s).)

Background: The purpose of this systematic review is to evaluate the efficacy of antifibrinolytics in non-cardiac thoracic surgery., Methods: We searched for all randomized controlled trials on this topic. A set of strict inclusion and exclusion criteria was developed. Six studies were meta-analysed together then in subgroups of topical tranexamic acid and intravenous aprotinin. We compared postoperative chest drain output, transfusions requirements and duration of hospital stay where available to determine the efficacy of topical tranexamic acid or intravenous aprotinin in reducing blood loss., Results: The use of antifibrinolytics reduces 24-h chest drain output (-290.21 mL [-524.75, -55.66], P = 0.02, I 2  = 98%), red blood cell transfusion requirements (-1.27 units [-2.24, -0.30], P = 0.01, I 2  = 100%) and shortened duration of hospital stay (-1.81 days [-3.25, -0.36], P = 0.01, I 2  = 96%). The subgroup analysis also supported this trend., Conclusion: We conclude that the use of antifibrinolytics appears to reduce postoperative blood loss by reducing chest drain output, transfusion requirements and length of stay after thoracic surgery., (© 2021 Royal Australasian College of Surgeons.)

Current technologies to measure drug-target interactions require complex processing and invasive tissue biopsies, limiting their clinical utility for cancer treatment monitoring. Here we develop an analytical platform that leverages circulating extracellular vesicles (EVs) for activity-based assessment of tumour-specific drug-target interactions in patient blood samples. The technology, termed extracellular vesicle monitoring of small-molecule chemical occupancy and protein expression (ExoSCOPE), utilizes bio-orthogonal probe amplification and spatial patterning of molecular reactions within matched plasmonic nanoring resonators to achieve in situ analysis of EV drug dynamics. It measures changes in drug occupancy and protein composition in molecular subpopulations of EVs. When used to monitor various targeted therapies, the ExoSCOPE revealed EV signatures that closely reflected cellular treatment efficacy. We further applied the technology for clinical cancer diagnostics and treatment monitoring. Using a small volume of blood, the ExoSCOPE accurately classified disease status and rapidly distinguished between targeted treatment outcomes, within 24 h after treatment initiation.

Introduction: COVID-19 presented an unprecedented challenge for healthcare workers and systems around the world. Healthcare systems have adapted differently in terms of pandemic planning of regular services, adopting infection control measures and prioritising essential hospital services in the context of a burgeoning COVID-19 patient load and inevitable surge., Methods: We performed a review on current evidence and share our practices at a teaching hospital in Singapore., Results: We outline principles and make recommendations for continuity of delivering essential thoracic surgical services during this current outbreak., Conclusions: The maintenance and provision of thoracic surgery services in this context requires good preplanning and vigilance to infection control measures across all levels., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity., Competing Interests: Competing interest statement: R.Z. is the chairman and chief executive officer (CEO) of MIRXES (Hangzhou) Biotechnology Co., Ltd and has ownership interest (including patents) in the same. L.Z. is co-CEO of MIRXES (Hangzhou) Biotechnology Co., Ltd and has ownership interest (including patents) in the same.

Objective: This meta-analysis evaluates the pooled prevalence of depression, anxiety, adjustment disorder, and posttraumatic stress disorder (PTSD) among heart transplant recipients globally and determines underlying moderators., Methods: The authors searched PubMed, Embase, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL databases from inception to March 1, 2019, and 1321 records and 42 full-text articles were selected and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We calculated the pooled prevalence proportion of depression, anxiety, adjustment disorder, and PTSD using random-effects models. Meta-regression was performed to identify important moderators that contribute to heterogeneity., Results: Twenty studies met the inclusion criteria and comprised 2169 patients. The pooled prevalence of depression was 21.6% (95% confidence interval [CI] = 16.8%-27.3%), anxiety 11.1% (95% CI = 3.8%-28.5%), adjustment disorder 11.0% (95% CI = 3.1%-32.1%), and PTSD 13.5% (95% CI = 8%-21.8%). There was significant heterogeneity. Meta-regression was conducted to account for the heterogeneity of the prevalence proportion. Predisposing factors, for example, New York Heart Association classes II and III/IV, steroid treatment, and acute rejection of transplant (<3 months), were associated with high prevalence of depression. Protective factors, for example, age and higher ejection fraction after transplant of patients, were associated with low prevalence of depression. Female sex, single status, and number of months since transplant were associated with high prevalence of anxiety. Single status was associated with high prevalence of both adjustment disorder and transplant-related PTSD., Conclusions: The prevalence of psychiatric conditions, particularly depression, is high in heart transplant recipients. The identified protective and risk factors may guide psychological interventions in heart transplant recipients.

Recent studies have attempted to uncover the role of Group 1 Innate lymphoid cells (ILCs) in multiple physiological contexts, including cancer. However, the definition and precise contribution of Group 1 ILCs (constituting ILC1 and NK subsets) to metastasis is unclear due to the lack of well-defined cell markers. Here, we first identified ILC1 and NK cells in NSCLC patient blood and differentiated them based on the expression of transcription factors, T-bet and Eomes. Interestingly, Eomes downregulation in the peripheral blood NK cells of NSCLC patients positively correlated with disease progression. Additionally, we noted higher Eomes expression in NK cells (T-bet + Eomes hi ) compared to ILC1s (T-bet + Eomes lo ). We asked whether the decrease in Eomes was associated with the conversion of NK cells into ILC1 using Eomes as a reliable marker to differentiate ILC1s from NK cells. Utilizing a murine model of experimental metastasis, we observed an association between increase in metastasis and Eomes downregulation in NKp46 + NK1.1 + Group 1 ILCs, which was consistent to that of human NSCLC samples. Further confirmation of this trend was achieved by flow cytometry, which identified tissue-specific Eomes lo ILC1-like and Eomes hi NK-like subsets in the murine metastatic lung based on cell surface markers and adoptive transfer experiments. Next, functional characterization of these cell subsets showed reduced cytotoxicity and IFNγ production in Eomes lo ILC1s compared to Eomes hi cells, suggesting that lower Eomes levels are associated with poor cancer immunosurveillance by Group 1 ILCs. These findings provide novel insights into the regulation of Group 1 ILC subsets during metastasis, through the use of Eomes as a reliable marker to differentiate between NK and ILC1s., (Copyright © 2020 Verma, Er, Pu, Sheik Mohamed, Soo, Muthiah, Tam and Ding.)

Even under normoxia, cancer cells exhibit increased glucose uptake and glycolysis, an occurrence known as the Warburg effect. This altered metabolism results in increased lactic acid production, leading to extracellular acidosis and contributing to metastasis and chemoresistance. Current pH imaging methods are invasive, costly, or require long acquisition times, and may not be suitable for high-throughput pre-clinical small animal studies. Here, we present a ratiometric pH-sensitive bioluminescence reporter called pHLuc for in vivo monitoring of tumor acidosis. pHLuc consists of a pH-sensitive GFP ( superecliptic pHluorin or SEP), a pH-stable OFP (Antares), and Nanoluc luciferase. The resulting reporter produces a pH-responsive green 510nm emission (from SEP) and a pH-insensitive red-orange 580nm emission (from Antares). The ratiometric readout (R 580 / 510 ) is indicative of changes in extracellular pH (pH e ). In vivo proof-of-concept experiments with NSG mice model bearing human synovial sarcoma SW982 xenografts that stably express the pHLuc reporter suggest that the level of acidosis varies across the tumor. Altogether, we demonstrate the diagnostic value of pHLuc as a bioluminescent reporter for pH variations across the tumor microenvironment. The pHLuc reporter plasmids constructed in this work are available from Addgene., (Copyright © 2020 Ong, Ang, Verma, Koean, Tam and Ding.)

Background: Primary spontaneous pneumothorax (PSP) is a relatively common clinical entity with high incidence in the young population. Video-Assisted Thoracic Surgery (VATS) bullectomy and chemical or mechanical pleurodesis are two primary modalities of treatment. There has been much debate on the ideal mode of pleurodesis, but the literature on surgical outcomes comparing VATS pleurectomy with talc pleurodesis has been inconclusive., Methods: We performed a single-centre 5-year observational retrospective study of 202 patients who underwent VATS bullectomy with talc pleurodesis or parietal pleurectomy., Results: There were no significant differences in the demographics, pre-operative and intra-operative characteristics in both groups. Recurrence of pneumothorax, chest tube duration and hospital stay were similar in both groups. However, talc pleurodesis had a shorter operative time compared to pleurectomy., Conclusion: Our study demonstrated comparable outcomes between talc pleurodesis and pleurectomy following VATS bullectomy for patients with PSP.

Airway smooth muscle (ASM) cells exhibit plastic phenotypic behavior marked by reversible modulation and maturation between contractile and proliferative phenotypic states. Integrins are a class of transmembrane proteins that have been implicated as novel therapeutic targets for asthma treatment. We previously showed that integrin α7 is a novel marker of the contractile ASM phenotype suggesting that targeting this protein may offer new avenues to counter the increase in ASM cell mass that underlies airways hyperresponsiveness (AHR) in asthma. We now determine whether inhibition of integrin α7 expression would revert ASM cells back to a proliferative phenotype to cause an increase in ASM cell mass. This would be detrimental to asthmatic patients who already exhibit increased ASM mass in their airways. Using immunohistochemical analysis of the Melbourne Epidemiological Study of Childhood Asthma (MESCA) cohort, we show for the first time that integrin α7 expression in patients with severe asthma is increased, supporting a clinically relevant role for this protein in asthma pathophysiology. Moreover, inhibition of the laminin-integrin α7 signaling axis results in a reduction in smooth muscle-alpha actin abundance and does not revert ASM cells back to a proliferative phenotype. We determined that integrin α7-induced Kras isoform of p21 Ras acts as a point of convergence between contractile and proliferative ASM phenotypic states. Our study provides further support for targeting integrin α7 for the development of novel anti-asthma therapies.

The role of ribosomal protein S6 (rpS6) phosphorylation in mRNA translation remains poorly understood. Here, we reveal a potential role in modulating the translation rate of chemokine (C-X-C motif) ligand 8 (CXCL8 or Interleukin 8, IL8). We observed that more CXCL8 protein was being secreted from less CXCL8 mRNA in primary macrophages and macrophage-like HL-60 cells relative to other cell types. This correlated with an increase in CXCL8 polyribosome association, suggesting an increase in the rate of CXCL8 translation in macrophages. The cell type-specific expression levels were replicated by a CXCL8- UTR-reporter (Nanoluc reporter flanked by the 5' and 3' UTR of CXCL8). Mutations of the CXCL8-UTR-reporter revealed that cell type-specific expression required: 1) a 3' UTR of at least three hundred bases; and 2) an AU base content that exceeds fifty percent in the first hundred bases of the 3' UTR immediately after the stop codon, which we dub AU-rich proximal UTR sequences (APS). The 5' UTR of CXCL8 enhanced expression at the protein level and conferred cell type-specific expression when paired with a 3' UTR. A search for other APS-positive mRNAs uncovered TNF alpha induced protein 6 (TNFAIP6), another mRNA that was translationally upregulated in macrophages. The elevated translation of APS-positive mRNAs in macrophages coincided with elevated rpS6 S235/236 phosphorylation. Both were attenuated by the ERK1/2 signaling inhibitors, U0126 and AZD6244. In A549 cells, rpS6 S235/236 phosphorylation was induced by TAK1, Akt or PKA signaling. This enhanced the translation of the CXCL8-UTR-reporters. Thus, we propose that the induction of rpS6 S235/236 phosphorylation enhances the translation of mRNAs that contain APS motifs, such as CXCL8 and TNFAIP6. This may contribute to the role of macrophages as the primary producer of CXCL8, a cytokine that is essential for immune cell recruitment and activation., Competing Interests: The authors have declared that no competing interests exist.

Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs from murine lung, fat, heart, and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1 lo MHCII hi CX3CR1 hi (Lyve1 lo MHCII hi ) and Lyve1 hi MHCII lo CX3CR1 lo (Lyve1 hi MHCII lo ) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion ( Slco2b1 flox/DTR ), we found that the absence of Lyve1 hi MHCII lo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

Background: Airway smooth muscle (ASM) contraction underpins airway constriction; however, underlying mechanisms for airway hyperresponsiveness (AHR) remain incompletely defined. CD151, a 4-transmembrane glycoprotein that associates with laminin-binding integrins, is highly expressed in the human lung. The role of CD151 in ASM function and its relationship to asthma have yet to be elucidated., Objective: We sought to ascertain whether CD151 expression is clinically relevant to asthma and whether CD151 expression affects AHR., Methods: Using immunohistochemical analysis, we determined the expression of CD151 in human bronchial biopsy specimens from patients with varying asthma severities and studied the mechanism of action of CD151 in the regulation of ASM contraction and bronchial caliber in vitro, ex vivo, and in vivo., Results: The number of CD151 + ASM cells is significantly greater in patients with moderate asthma compared with those in healthy nonasthmatic subjects. From loss- and gain-of-function studies, we reveal that CD151 is required for and enhances G protein-coupled receptor (GPCR)-induced peak intracellular calcium release, the primary determinant of excitation-contraction coupling. We show that the localization of CD151 can also be perinuclear/cytoplasmic and offer an explanation for a novel functional role for CD151 in supporting protein kinase C (PKC) translocation to the cell membrane in GPCR-mediated ASM contraction at this site. Importantly, CD151 -/- mice are refractory to airway hyperreactivity in response to allergen challenge., Conclusions: We identify a role for CD151 in human ASM contraction. We implicate CD151 as a determinant of AHR in vivo, likely through regulation of GPCR-induced calcium and PKC signaling. These observations have significant implications in understanding the mechanism for AHR and the efficacy of new and emerging therapeutics., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)