Publications by authors named "Atsuho Morita"

Direct reprogramming is a breakthrough technology that can alter the fate of cells without the passage of stem cells. However, direct reprogramming of somatic cells into pulmonary alveolar epithelial cells has not yet been achieved. Here, we report the direct reprogramming of mouse tail tips and embryonic fibroblasts into induced pulmonary alveolar epithelial-like cells (iPULs) using four transcription factor-coding genes (Nkx2-1, Foxa1, Foxa2, and Gata6) and three-dimensional culture.

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Objectives: We examined shifts in labor productivity and their economic ramifications among adult patients with long COVID in Japan.

Methods: A total of 396 patients were categorized into three groups based on symptom progression: non-long COVID, long COVID recovered, and long COVID persistent. Patient-reported outcomes were assessed at three time intervals: 3, 6, and 12 months after COVID-19 diagnosis.

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Airway epithelial cells (AECs) play an essential role in the immune response during bacterial pneumonia. Secreted and transmembrane 1a (Sectm1a) is specifically expressed in AECs during early (SP) infection. However, its function remains largely unexplored.

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  • * A study of 1656 Japanese patients identified rapid worsening of CXR findings—as indicated by increased lung infiltrates within 48 hours of hospital admission—as a significant risk factor for severe complications.
  • * Factors contributing to this rapid deterioration include existing health conditions, elevated body temperature, and specific genetic variants, highlighting the importance of early detection and monitoring.
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  • * Data from 1200 enrolled patients showed a decline in symptoms over time, from 93.9% during hospitalization to 33.0% at 12 months, with those experience long COVID symptoms reporting lower quality of life and higher anxiety and depression.
  • * Identified risk factors for long COVID included being female, middle-aged, requiring oxygen, and being in critical condition during hospitalization, providing valuable insights for future research in Japan.
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  • * After vaccination, 13.5% of patients experienced symptom improvement, 3.6% had worsening symptoms, while 82.9% saw no change in their long COVID symptoms.
  • * The most common symptoms that improved post-vaccination were dyspnea and alopecia, but many symptoms like sleep disturbance and myalgia persisted, indicating that vaccination did not significantly impact long COVID for most patients.
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Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available.

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  • The study investigates the relationship between COVID-19 and ABO blood group/genotype in a large Japanese population, including 1,790 patients and 611 healthy controls.
  • Blood group A was found to be more common and blood group O less common among COVID-19 patients, while genotype OO was also less frequent in this group.
  • Blood group AB was identified as a significant risk factor for severe disease, while blood group O appeared to provide some protective effect against infection.
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Background: The long-term exercise tolerance changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are of great interest because of its chronic course. This study aimed to characterize the associations between changes over time in six-minute walking test (6MWT) parameters and clinical parameters in patients with NTM-PD.

Methods: Overall, 188 patients with NTM-PD, visiting outpatient clinics at Keio University Hospital from April 2012 to March 2020 were included in the study.

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  • * Diagnostic procedures, including laryngeal endoscopy and PET/CT scans, confirmed the infection despite non-indicative initial findings, and the patient underwent a comprehensive antibiotic treatment plan, leading to a complete recovery.
  • * The study emphasizes the need for evaluating patients with positive sputum cultures for non-tuberculous mycobacterium (NTM) infections in the ears, nose, and throat, particularly noting that immunosuppressant use increases the risk of these infections
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  • A study analyzed the rates and impact of respiratory bacterial infections in Japanese patients hospitalized with COVID-19, finding that 7.5% of patients experienced such infections.
  • The most common causes of these infections included Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae, with more severe outcomes linked to hospital-acquired infections and pre-existing health conditions.
  • The research highlights the importance of monitoring and assessing bacterial complications in COVID-19 patients, as these infections can significantly increase mortality rates.
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  • The study examined the impact of non-respiratory bacterial and fungal infections on hospitalized COVID-19 patients, focusing on the types of infections, their causative organisms, and their effects on mortality rates.
  • Out of 1914 patients, 4.2% developed non-respiratory bacterial infections, predominantly bacteremia, which was linked to a higher risk of death, particularly in patients with certain predisposing factors.
  • The findings highlight the need for effective medical strategies to manage secondary infections in COVID-19 patients, especially those at a greater risk, such as older individuals and those admitted to intensive care.
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  • The study analyzed 3,261 hospitalized COVID-19 patients in Japan across five waves of the pandemic to understand differences in their characteristics.
  • Patients admitted during the second and fifth waves were younger, while those in the first wave had longer hospital stays and more post-hospitalization complications, including bacterial infections.
  • The fifth wave showed higher disease severity at admission and more patients needing oxygen, whereas the first wave had the highest mechanical ventilation rates and the third wave had the highest mortality.
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Background: Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients.

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  • The study explored different clinical profiles (or phenotypes) of COVID-19 patients in Japan, focusing on how these profiles could predict disease severity and outcomes.
  • Researchers analyzed data from 1,322 hospitalized patients, categorizing them into four clusters based on factors like age and health conditions.
  • Results showed distinct characteristics in each cluster, with younger and healthier patients having better outcomes, while older and obese patients faced more severe symptoms, highlighting the importance of phenotyping in understanding COVID-19.
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  • * 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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Background: Obesity is reported to be a risk factor for severe disease in patients with coronavirus disease 2019 (COVID-19). However, there are no specific reports on the risk of severe disease according to body mass index (BMI) in Japan. Thus, this study aimed to investigate the effect of obesity stratified by BMI on the severity of COVID-19 in the general Japanese population.

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  • 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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Purpose: Amikacin liposome inhalation suspension (ALIS), which efficiently allows amikacin to reach the pulmonary periphery for effect while minimising systemic adverse effects, was recently approved for treating complex (MAC) infections. The international Phase 3 open-label clinical trials showed promising results, contributing to sputum culture conversion, but few studies have examined the efficacy and adverse effects of ALIS using real-world data. We identified the clinical outcome and adverse effects of ALIS in the early phase of treatment, for more effective and safe use in clinical practice.

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Objectives: This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population.

Methods: We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia.

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Background: Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is common in middle-aged/elderly slender women at risk of osteoporosis, we hypothesized that NTM-PD could be associated with osteoporosis. The study aimed to evaluate the prevalence of osteoporosis in patients with NTM-PD compared with that in the general population and determine the factors associated with osteoporosis in the subjects, including the serum estradiol (E) and 25-hydroxyvitamin D (25OHD) levels.

Methods: We have recruited 228 consecutive adult patients with NTM-PD from a prospective cohort study at the Keio University Hospital, who had no history of osteoporosis or osteoporosis-associated bone fracture but underwent dual-energy X-ray absorptiometry-based bone mineral density (BMD) evaluation from August 2017-September 2019.

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A 56-year-old woman with pulmonary complex disease was started on inhalation liposomal amikacin. One month later, she developed hoarseness and was diagnosed with laryngitis. The laryngitis healed immediately after treatment discontinuation, and no recurrence occurred even after resuming intermittent inhalation.

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Background And Design: The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan.

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The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. To investigate the clinical features and prognosis of NTM pleuritis. This retrospective observational study included patients with NTM pleuritis from January 2001 to June 2018 across eight hospitals in Japan.

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We investigated the effects of bendamustine on B cell functions and explored potential clinical applications of the drugs to autoimmune diseases. Proliferation of Ramos cells, a human B cell line, was significantly inhibited by 25-100μM of bendamustine in a dose-dependent manner. Concordantly, IgM secretion from Ramos cells was significantly inhibited at these concentrations by up to 70%.

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