Publications by authors named "Reina Hara"

Background: Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are often misdiagnosed or undiagnosed, highlighting the need for more noninvasive and accessible diagnostic tools. Although exhaled breath condensate (EBC) is recognized as a biomarker resource for respiratory diseases, nontargeted proteomics of extracellular vesicles (EVs) in EBC has not been explored.

Objective: Our aim was to identify protein signatures in EBC-derived EVs (EBC-EVs) and potential biomarkers for BA and COPD.

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Nontuberculous mycobacterial pulmonary disease (NTM-PD), mainly caused by complex (MAC), and pulmonary tuberculosis (TB) are emerging health problems worldwide. However, because their clinical features are often similar, it remains difficult to differentiate NTM-PD from TB when the diagnosis cannot be made by sputum culture. To investigate potential serum biomarkers, we conducted non-targeted proteome analysis on serum extracellular vesicles (EVs) collected from 10 patients with MAC pulmonary disease (MAC-PD), 7 patients with TB, and 10 healthy controls.

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While research has identified several inhibitors of the main protease (Mpro) of SARS-CoV-2, a significant portion of these compounds exhibit reduced activity in the presence of reducing agents, raising concerns about their effectiveness in vivo. Furthermore, the conventional biosafety level 3 (BSL-3) for cellular assays using viral particles poses a limitation for the widespread evaluation of Mpro inhibitor efficacy in a cell-based assay. Here, we established a BSL-1 compatible cellular assay to evaluate the in vivo potential of Mpro inhibitors.

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Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways.

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Background: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes.

Objective: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs).

Methods: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA.

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Background: The coronavirus disease 2019 (COVID-19) pandemic is widespread; however, accurate predictors of refractory cases have not yet been established. Circulating extracellular vesicles, involved in many pathological processes, are ideal resources for biomarker exploration.

Methods: To identify potential serum biomarkers and examine the proteins associated with the pathogenesis of refractory COVID-19, we conducted high-coverage proteomics on serum extracellular vesicles collected from 12 patients with COVID-19 at different disease severity levels and 4 healthy controls.

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Article Synopsis
  • * Researchers analyzed RNA-seq data from 465 blood samples, uncovering 1169 expression quantitative trait loci (eQTLs) and 1549 splice QTLs (sQTLs) linked to COVID-19 severity, including immune-related expressions.
  • * The study highlights the impact of disease severity on gene expression, identifying specific eQTLs that interact with COVID-19 phenotypes, and provides an extensive resource for understanding gene regulation in response to the virus.
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Article Synopsis
  • Researchers conducted a genome-wide association study (GWAS) with 2,393 COVID-19 patients and 3,289 controls in Japan, identifying a specific genetic variant (rs60200309-A) on chromosome 5 linked to severe cases in individuals under 65.
  • The variant is more common in East Asians and associated with reduced expression of the DOCK2 gene, which was found to be lower in severe COVID-19 cases, particularly in non-classical monocytes.
  • Additionally, inhibiting DOCK2 in hamsters worsened pneumonia symptoms, indicating its potential as a biomarker and therapeutic target for severe COVID-19.
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Background: The impact of SARS-CoV-2 infection on the gut fungal (mycobiota) and bacterial (microbiota) communities has been elucidated individually. This study analyzed both gut mycobiota and microbiota and their correlation in the COVID-19 patients with severe and mild conditions and follow-up to monitor their alterations after recovery.

Methods: We analyzed the gut mycobiota and microbiota by bacterial 16S and fungal ITS1 metagenomic sequencing of 40 severe patients, 38 mild patients, and 30 healthy individuals and reanalyzed those of 10 patients with severe COVID-19 approximately 6 months after discharge.

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The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC) might depend on the presence of emphysema, but this association is not established. We aimed to investigate if quantitively and automatically measuring emphysema can predict the effect of ICIs. We retrospectively analyzed 56 patients with NSCLC who underwent immunotherapy at our hospital.

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This is the first report of COVID-19 in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. HTLV-1 infection can cause immune dysfunction even in asymptomatic carriers. This case highlights the need for guidance on management of COVID-19-HTLV-1 coinfection, specifically on the appropriate use of corticosteroid treatment while considering secondary infection.

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Coronavirus disease 2019 (COVID-19) is an emerging viral disease with a mortality that depends on the individual's condition. Underlying comorbidities are major risk factors for COVID-19-related morbidity and mortality. However, information regarding the clinical course of COVID-19 in patients with rare respiratory system diseases is lacking.

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Coronavirus disease 2019 (COVID-19) can cause severe lymphopenia and respiratory failure requiring prolonged invasive mechanical ventilation (MV). COVID-19 patients with severe lymphopenia or respiratory failure are at risk of developing secondary infections. Here, we present the needle autopsy findings of a critically ill patient with COVID-19 who required reintubation and prolonged MV, and eventually died of secondary cytomegalovirus (CMV) pneumonia.

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Here, we report a rare case involving a 66-year-old man with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and antisynthetase syndrome (ASS) treated with osimertinib. The patient presented with respiratory failure and bilateral pulmonary opacities; he was diagnosed with ASS accompanied by interstitial lung disease (ILD), consistent with paraneoplastic syndrome. After steroid pulse therapy, osimertinib was administered for lung adenocarcinoma without ILD exacerbation.

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Bronchial thermoplasty (BT) had been reported to improve the symptoms of severe asthma. However, the exertional responses of BT based on the mechanisms have not been elucidated. A 57-year-old man and a 60-year-old woman underwent BT due to intractable severe asthma.

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Combined small cell lung cancer (c-SCLC) is a relatively rare subtype of SCLC and is defined by the combination of SCLC and any elements of non-small cell carcinoma (NSCLC). Standard chemotherapy for patients with c-SCLC has not yet been established. Gene mutations such as epidermal growth factor receptor (EGFR) mutations may be detected in patients with c-SCLC.

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Although gastric aspirate culture is used for diagnosing pulmonary tuberculosis, its usefulness in diagnosing pulmonary infections of nontuberculous mycobacteria (NTM) is unknown. To investigate the diagnostic validity of gastric aspirate culture for acid-fast bacilli in NTM pulmonary disease (NTM-PD). Gastric aspirates were collected from patients with suspected NTM-PD at the Osaka Toneyama Medical Center between December 2006 and February 2018.

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Asbestos-related pulmonary conditions such as benign asbestos pleural effusion (BAPE) and diffuse pleural thickening (DPT) can develop after many years of asbestos exposure. These conditions cause progressing constrictive deficit in pulmonary function which may lead to respiratory failure and death. We report the case of a 72-year-old man with asbestos-related BAPE and DPT which developed approximately 40 years after occupational asbestos exposure, leading to chronic respiratory failure and death.

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A terminal alkyne is one of the most useful reactants for the synthesis of alkyne and alkene derivatives. Because an alkyne undergoes addition reaction at a C-C triple bond or cross-coupling at a terminal C-H bond. Combining those reaction patterns could realize a new reaction methodology to synthesize complex molecules including C-C multiple bonds.

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Article Synopsis
  • - The text reports a rare case of severe thrombocytopenia (low platelet count) that developed within one day of an influenza vaccination, which led to serious complications like diffuse alveolar hemorrhage (DAH) and acute respiratory failure.
  • - Although thrombocytopenia can be mild and asymptomatic, severe cases can result in significant bleeding and health issues, highlighting the risks associated with vaccination in some individuals.
  • - The patient received treatments including glucocorticoid pulse therapy, intravenous immunoglobulin, and temporary mechanical ventilation, ultimately recovering fully; the case emphasizes the importance of monitoring for vaccine-related adverse effects.
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The presence of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is closely associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis. Despite intensive immunosuppressive therapies, some of these patients still have a poor prognosis with few treatment options. Although removal of pathogenic autoantibodies and cytokines by plasma exchange (PE) could be a treatment option, its safety and efficacy have never been determined.

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