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  1. Article ; Online: Developmental alcohol exposure is exhausting: Sleep and the enduring consequences of alcohol exposure during development.

    Wilson, Donald A / Sullivan, Regina M / Smiley, John F / Saito, Mariko / Raineki, Charlis

    Neuroscience and biobehavioral reviews

    2024  Volume 158, Page(s) 105567

    Abstract: Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional ... ...

    Abstract Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems. Among these diverse impacts is sleep disruption. In this review, we describe how prenatal alcohol exposure affects sleep, and potential mechanisms of those effects. Furthermore, we outline the evidence that sleep disruption across the lifespan may be a mediator of some cognitive and behavioral impacts of developmental alcohol exposure, and thus may represent a promising target for treatment.
    MeSH term(s) Female ; Humans ; Pregnancy ; Fetal Alcohol Spectrum Disorders/etiology ; Prenatal Exposure Delayed Effects ; Ethanol/adverse effects ; Sleep
    Chemical Substances Ethanol (3K9958V90M)
    Language English
    Publishing date 2024-02-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 282464-4
    ISSN 1873-7528 ; 0149-7634
    ISSN (online) 1873-7528
    ISSN 0149-7634
    DOI 10.1016/j.neubiorev.2024.105567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development of a New Methodology for Dearomative Borylation of Coumarins and Chromenes and Its Applications to Synthesize Boron-Containing Retinoids.

    Das, Bhaskar C / Yadav, Pratik / Das, Sasmita / Saito, Mariko / Evans, Todd

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 3

    Abstract: Dearomative borylation of coumarins and chromenes via conjugate addition represents a relatively unexplored and challenging task. To address this issue, herein, we report a new and general copper (I) catalyzed dearomative borylation process to synthesize ...

    Abstract Dearomative borylation of coumarins and chromenes via conjugate addition represents a relatively unexplored and challenging task. To address this issue, herein, we report a new and general copper (I) catalyzed dearomative borylation process to synthesize boron-containing oxacycles. In this report, the borylation of coumarins, chromones, and chromenes comprising functional groups, such as esters, nitriles, carbonyls, and amides, has been achieved. In addition, the method generates different classes of potential boron-based retinoids, including the ones with oxadiazole and anthocyanin motifs. The borylated oxacycles can serve as suitable intermediates to generate a library of compounds.
    MeSH term(s) Benzopyrans ; Boron ; Coumarins ; Copper ; Amides
    Chemical Substances Benzopyrans ; Boron (N9E3X5056Q) ; Coumarins ; Copper (789U1901C5) ; Amides
    Language English
    Publishing date 2023-01-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28031052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Post-exposure environment modulates long-term developmental ethanol effects on behavior, neuroanatomy, and cortical oscillations.

    Apuzzo, Justin / Saito, Mariko / Wilson, Donald A

    Brain research

    2020  Volume 1748, Page(s) 147128

    Abstract: Developmental exposure to ethanol has a wide range of anatomical, cellular, physiological and behavioral impacts that can last throughout life. In humans, this cluster of effects is termed fetal alcohol spectrum disorder and is highly prevalent in ... ...

    Abstract Developmental exposure to ethanol has a wide range of anatomical, cellular, physiological and behavioral impacts that can last throughout life. In humans, this cluster of effects is termed fetal alcohol spectrum disorder and is highly prevalent in western cultures. The ultimate expression of the effects of developmental ethanol exposure however can be influenced by post-exposure experience. Here we examined the effects of developmental binge exposure to ethanol (postnatal day 7) in C57BL/6By mice on a specific cohort of inter-related long-term outcomes including contextual memory, hippocampal parvalbumin-expressing neuron density, frontal cortex oscillations related to sleep-wake cycling including delta oscillation amplitude and sleep spindle density, and home-cage behavioral activity. When assessed in adults that were raised in standard housing, all of these factors were altered by early ethanol exposure compared to saline controls except home-cage activity. However, exposure to an enriched environment and exercise from weaning to postnatal day 90 reversed most of these ethanol-induced impairments including memory, CA1 but not dentate gyrus PV+ cell density, delta oscillations and sleep spindles, and enhanced home-cage behavioral activity in Saline- but not EtOH-treated mice. The results are discussed in terms of the inter-dependence of diverse developmental ethanol outcomes and potential mechanisms of post-exposure experiences to regulate those outcomes.
    MeSH term(s) Animals ; Behavior, Animal/drug effects ; Cerebral Cortex/drug effects ; Delta Rhythm/drug effects ; Ethanol/administration & dosage ; Female ; Hippocampus/drug effects ; Hippocampus/metabolism ; Male ; Mice ; Neurons/drug effects ; Neurons/metabolism ; Parvalbumins/metabolism
    Chemical Substances Parvalbumins ; Ethanol (3K9958V90M)
    Language English
    Publishing date 2020-09-17
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2020.147128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Detection of Respiratory Viruses during the Early Phase of the Coronavirus Disease 2019 Pandemic in Ibaraki and Gunma Prefectures, Japan.

    Shinoda, Daisuke / Tsukagoshi, Hiroyuki / Komuro, Keiko / Yoshida, Daisuke / Yanaoka, Toshikazu / Saito, Mariko / Saruki, Nobuhiro

    Japanese journal of infectious diseases

    2022  Volume 75, Issue 5, Page(s) 530–532

    Abstract: Respiratory infections are common, and the most common causative agent is a virus. Therefore, routine surveillance of respiratory viruses is useful in the case of novel viral diseases such as coronavirus disease 2019 (COVID-19). In this study, to clarify ...

    Abstract Respiratory infections are common, and the most common causative agent is a virus. Therefore, routine surveillance of respiratory viruses is useful in the case of novel viral diseases such as coronavirus disease 2019 (COVID-19). In this study, to clarify the kind of virus involved in suspected cases of COVID-19 in the early stages of the pandemic, we attempted to detect various respiratory viruses in 613 specimens that tested negative for severe acute respiratory syndrome coronavirus 2 using reverse transcription polymerase chain reaction. As a result, viruses were detected in 59 (9.6%) patients. In addition, human rhinovirus (HRV), human metapneumovirus (HMPV), human respiratory syncytial virus, and human parechovirus were detected in 29, 25, 3, and 2 patients, respectively. Although this study was conducted over a short period of time and not all specimens were tested, these results indicate that various respiratory viruses, especially HRV and HMPV, can be detected even during the early stages of the COVID-19 pandemic. Because various respiratory viruses maintain a constant effect during the outbreak of the newly emerged pandemic, systematic surveillance of respiratory viruses is needed during the normal period to make good use for clinical and public health.
    MeSH term(s) COVID-19/diagnosis ; COVID-19/epidemiology ; Humans ; Infant ; Japan/epidemiology ; Metapneumovirus/genetics ; Pandemics ; Respiratory Tract Infections/diagnosis ; Respiratory Tract Infections/epidemiology ; Viruses
    Language English
    Publishing date 2022-04-28
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1478383-6
    ISSN 1884-2836 ; 1344-6304
    ISSN (online) 1884-2836
    ISSN 1344-6304
    DOI 10.7883/yoken.JJID.2022.061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Estimates of total neuron number show that neonatal ethanol causes immediate and lasting neuron loss in cortical and subcortical areas.

    Smiley, John F / Bleiwas, Cynthia / Marino, Brandon M / Vaddi, Prerana / Canals-Baker, Stefanie / Wilson, Donald A / Saito, Mariko

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1186529

    Abstract: In neonatal brain development there is a period of normal apoptotic cell death that regulates adult neuron number. At approximately the same period, ethanol exposure can cause a dramatic spike in apoptotic cell death. While ethanol-induced apoptosis has ... ...

    Abstract In neonatal brain development there is a period of normal apoptotic cell death that regulates adult neuron number. At approximately the same period, ethanol exposure can cause a dramatic spike in apoptotic cell death. While ethanol-induced apoptosis has been shown to reduce adult neuron number, questions remain about the regional selectivity of the ethanol effect, and whether the brain might have some capacity to overcome the initial neuron loss. The present study used stereological cell counting to compare cumulative neuron loss 8 h after postnatal day 7 (P7) ethanol treatment to that of animals left to mature to adulthood (P70). Across several brain regions we found that the reduction of total neuron number after 8 h was as large as that of adult animals. Comparison between regions revealed that some areas are more vulnerable, with neuron loss in the anterior thalamic nuclei > the medial septum/vertical diagonal band, dorsal subiculum, and dorsal lateral geniculate nucleus > the mammillary bodies and cingulate cortex > whole neocortex. In contrast to estimates of total neuron number, estimates of apoptotic cell number in Nissl-stained sections at 8 h after ethanol treatment provided a less reliable predictor of adult neuron loss. The findings show that ethanol-induced neonatal apoptosis often causes immediate neuron deficits that persist in adulthood, and furthermore suggests that the brain may have limited capacity to compensate for ethanol-induced neuron loss.
    Language English
    Publishing date 2023-05-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1186529
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  6. Article: Effects of retinoic acid receptor α modulators on developmental ethanol-induced neurodegeneration and neuroinflammation.

    Saito, Mariko / Subbanna, Shivakumar / Zhang, Xiuli / Canals-Baker, Stefanie / Smiley, John F / Wilson, Donald A / Das, Bhaskar C

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1170259

    Abstract: Ethanol exposure in neonatal mice induces acute neurodegeneration followed by long-lasting glial activation and GABAergic cell deficits along with behavioral abnormalities, providing a third trimester model of fetal alcohol spectrum disorders (FASD). ... ...

    Abstract Ethanol exposure in neonatal mice induces acute neurodegeneration followed by long-lasting glial activation and GABAergic cell deficits along with behavioral abnormalities, providing a third trimester model of fetal alcohol spectrum disorders (FASD). Retinoic acid (RA), the active form of vitamin A, regulates transcription of RA-responsive genes and plays essential roles in the development of embryos and their CNS. Ethanol has been shown to disturb RA metabolism and signaling in the developing brain, which may be a cause of ethanol toxicity leading to FASD. Using an agonist and an antagonist specific to RA receptor α (RARα), we studied how RA/RARα signaling affects acute and long-lasting neurodegeneration and activation of phagocytic cells and astrocytes caused by ethanol administered to neonatal mice. We found that an RARα antagonist (BT382) administered 30 min before ethanol injection into postnatal day 7 (P7) mice partially blocked acute neurodegeneration as well as elevation of CD68-positive phagocytic cells in the same brain area. While an RARα agonist (BT75) did not affect acute neurodegeneration, BT75 given either before or after ethanol administration ameliorated long-lasting astrocyte activation and GABAergic cell deficits in certain brain regions. Our studies using Nkx2.1-Cre;Ai9 mice, in which major GABAergic neurons and their progenitors in the cortex and the hippocampus are labeled with constitutively expressed tdTomato fluorescent protein, indicate that the long-lasting GABAergic cell deficits are mainly caused by P7 ethanol-induced initial neurodegeneration. However, the partial reduction of prolonged GABAergic cell deficits and glial activation by post-ethanol BT75 treatment suggests that, in addition to the initial cell death, there may be delayed cell death or disturbed development of GABAergic cells, which is partially rescued by BT75. Since RARα agonists including BT75 have been shown to exert anti-inflammatory effects, BT75 may rescue GABAergic cell deficits by reducing glial activation/neuroinflammation.
    Language English
    Publishing date 2023-05-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1170259
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  7. Article: Somatostatin neuron contributions to cortical slow wave dysfunction in adult mice exposed to developmental ethanol.

    Wilson, Donald A / Fleming, G / Williams, C R O / Teixeira, C M / Smiley, J F / Saito, Mariko

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1127711

    Abstract: Introduction: Transitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential ... ...

    Abstract Introduction: Transitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential unique vulnerability of sleep circuits to early ethanol. In fact, developmental ethanol exposure can produce long-lasting impairments in sleep, including increased sleep fragmentation and decreased delta wave amplitude. Here, we assessed the efficacy of optogenetic manipulations of somatostatin (SST) GABAergic neurons in the neocortex of adult mice exposed to saline or ethanol on P7, to modulate cortical slow-wave physiology.
    Methods: SST-cre × Ai32 mice, which selectively express channel rhodopsin in SST neurons, were exposed to ethanol or saline on P7. This line expressed similar developmental ethanol induced loss of SST cortical neurons and sleep impairments as C57BL/6By mice. As adults, optical fibers were implanted targeting the prefrontal cortex (PFC) and telemetry electrodes were implanted in the neocortex to monitor slow-wave activity and sleep-wake states.
    Results: Optical stimulation of PFC SST neurons evoked slow-wave potentials and long-latency single-unit excitation in saline treated mice but not in ethanol mice. Closed-loop optogenetic stimulation of PFC SST neuron activation on spontaneous slow-waves enhanced cortical delta oscillations, and this manipulation was more effective in saline mice than P7 ethanol mice.
    Discussion: Together, these results suggest that SST cortical neurons may contribute to slow-wave impairment after developmental ethanol.
    Language English
    Publishing date 2023-03-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1127711
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  8. Article ; Online: Anti-inflammatory Action of BT75, a Novel RARα Agonist, in Cultured Microglia and in an Experimental Mouse Model of Alzheimer's Disease.

    Zhang, Xiuli / Subbanna, Shivakumar / Williams, Colin R O / Canals-Baker, Stefanie / Smiley, John F / Wilson, Donald A / Das, Bhaskar C / Saito, Mariko

    Neurochemical research

    2023  Volume 48, Issue 6, Page(s) 1958–1970

    Abstract: BT75, a boron-containing retinoid, is a novel retinoic acid receptor (RAR)α agonist synthesized by our group. Previous studies indicated that activation of retinoic acid (RA) signaling may attenuate progression of Alzheimer's disease (AD). Presently, we ... ...

    Abstract BT75, a boron-containing retinoid, is a novel retinoic acid receptor (RAR)α agonist synthesized by our group. Previous studies indicated that activation of retinoic acid (RA) signaling may attenuate progression of Alzheimer's disease (AD). Presently, we aimed to examine the anti-inflammatory effect of BT75 and explore the possible mechanism using cultured cells and an AD mouse model. Pretreatment with BT75 (1-25 µM) suppressed the release of nitric oxide (NO) and IL-1β in the culture medium of mouse microglial SIM-A9 cells activated by LPS. BMS195614, an RARα antagonist, partially blocked the inhibition of NO production by BT75. Moreover, BT75 attenuated phospho-Akt and phospho-NF-κB p65 expression augmented by LPS. In addition, BT75 elevated arginase 1, IL-10, and CD206, and inhibited inducible nitric oxide synthase (iNOS) and IL-6 formation in LPS-treated SIM-A9 cells, suggesting the promotion of M1-M2 microglial phenotypic polarization. C57BL/6 mice were injected intracerebroventricularly (icv) with streptozotocin (STZ) (3 mg/kg) to provide an AD-like mouse model. BT75 (5 mg/kg) or the vehicle was intraperitoneally (ip) injected to icv-STZ mice once a day for 3 weeks. Immunohistochemical analyses indicated that GFAP-positive cells and rod or amoeboid-like Iba1-positive cells, which increased in the hippocampal fimbria of icv-STZ mice, were reduced by BT75 treatment. Western blot results showed that BT75 decreased levels of neuronal nitric oxide synthase (nNOS), GFAP, and phosphorylated Tau, and increased levels of synaptophysin in the hippocampus of icv-STZ mice. BT75 may attenuate neuroinflammation by affecting the Akt/NF-κB pathway and microglial M1-M2 polarization in LPS-stimulated SIM-A9 cells. BT75 also reduced AD-like pathology including glial activation in the icv-STZ mice. Thus, BT75 may be a promising anti-inflammatory and neuroprotective agent worthy of further AD studies.
    MeSH term(s) Mice ; Animals ; Microglia/metabolism ; NF-kappa B/metabolism ; Alzheimer Disease/chemically induced ; Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Lipopolysaccharides/toxicity ; Proto-Oncogene Proteins c-akt/metabolism ; Mice, Inbred C57BL ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use
    Chemical Substances NF-kappa B ; Lipopolysaccharides ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Anti-Inflammatory Agents
    Language English
    Publishing date 2023-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 199335-5
    ISSN 1573-6903 ; 0364-3190
    ISSN (online) 1573-6903
    ISSN 0364-3190
    DOI 10.1007/s11064-023-03888-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Involvement of AMP-activated protein kinase in neuroinflammation and neurodegeneration in the adult and developing brain.

    Saito, Mariko / Saito, Mitsuo / Das, Bhaskar C

    International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience

    2019  Volume 77, Page(s) 48–59

    Abstract: Microglial activation followed by neuroinflammation is a defense mechanism of the brain to eliminate harmful endogenous and exogenous materials including pathogens and damaged tissues, while excessive or chronic neuroinflammation may cause or exacerbate ... ...

    Abstract Microglial activation followed by neuroinflammation is a defense mechanism of the brain to eliminate harmful endogenous and exogenous materials including pathogens and damaged tissues, while excessive or chronic neuroinflammation may cause or exacerbate neurodegeneration observed in brain injuries and neurodegenerative diseases. Depending on conditions/environments during activation, microglia acquire distinct phenotypes, such as pro-inflammatory, anti-inflammatory, and disease-associated phenotypes, and show their ability to phagocytose various objects and produce pro-and anti-inflammatory mediators. Prevention of excessive inflammation by regulating the microglia's pro/anti-inflammatory balance is important for alleviating progression of brain injuries and diseases. Among many factors involved in the regulation of microglial phenotypes, cellular energy status plays an important role. Adenosine monophosphate-activated protein kinase (AMPK), which serves as a master sensor and regulator of energy balance, is considered a candidate molecule. Accumulating evidence from adult rodent studies indicates that AMPK activation promotes anti-inflammatory responses in microglia exposed to danger signals or various stressors mainly through inhibition of the nuclear factor κB (NF-κB) signaling and activation of the nuclear factor erythroid-2-related factor-2 (Nrf2) pathway. However, AMPK activation in neurons exposed to stressors/insults may exacerbate neuronal damage if AMPK activation is excessive or prolonged. While AMPK affects microglial activation states and neuronal cell survival rates in both the adult and the developing brain, studies in the developing brain are still scarce, even though activated AMPK is highly expressed especially in the neonatal brain. More in depth studies in the developing brain are important, because neuroinflammation/neurodegeneration occurred during development can result in long-lasting brain damage.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Animals ; Brain/metabolism ; Brain/pathology ; Humans ; Inflammation/metabolism ; Inflammation/pathology ; Microglia/metabolism ; Microglia/pathology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Signal Transduction/physiology
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2019-01-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 605533-3
    ISSN 1873-474X ; 0736-5748
    ISSN (online) 1873-474X
    ISSN 0736-5748
    DOI 10.1016/j.ijdevneu.2019.01.007
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  10. Article ; Online: Relationships between Viral Load and the Clinical Course of COVID-19.

    Tsukagoshi, Hiroyuki / Shinoda, Daisuke / Saito, Mariko / Okayama, Kaori / Sada, Mitsuru / Kimura, Hirokazu / Saruki, Nobuhiro

    Viruses

    2021  Volume 13, Issue 2

    Abstract: To predict the clinical outcome of coronavirus disease-2019 (COVID-19), we examined relationships among epidemiological data, viral load, and disease severity. We examined viral loads of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ... ...

    Abstract To predict the clinical outcome of coronavirus disease-2019 (COVID-19), we examined relationships among epidemiological data, viral load, and disease severity. We examined viral loads of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in fatal (15 cases), symptomatic/survived (133 cases), and asymptomatic cases (138 cases) using reverse transcription quantitative real-time PCR (RT-qPCR). We examined 5768 nasopharyngeal swabs (NPS) and attempted to detect the SARS-CoV-2 genome using RT-qPCR. Among them, the viral genome was detected using the method for the 370 NPS samples with a positive rate of 6.4%. A comparison of each age showed that the fatal case was higher than the survived case and asymptomatic patients. Survived cases were older than asymptomatic patients. Notably, the viral load in the fatal cases was significantly higher than in symptomatic or asymptomatic cases (
    MeSH term(s) Adult ; Aged ; COVID-19/diagnosis ; COVID-19/virology ; Female ; Humans ; Japan ; Male ; Middle Aged ; Nasal Mucosa/virology ; RNA, Viral/analysis ; SARS-CoV-2/isolation & purification ; Severity of Illness Index ; Viral Load
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2021-02-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13020304
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