Publications by authors named "Han Fang"

486 Publications

FGF21 prevents low protein diet-induced renal inflammation in aged mice.

Am J Physiol Renal Physiol 2021 06 21. Epub 2021 Jun 21.

Oxidative Stress and Disease Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States.

Low protein diets extend lifespan through a comprehensive improvement in metabolic health across multiple tissues and organs. Many of these metabolic responses to protein restriction are secondary to transcriptional activation and release of FGF21 from the liver. However, the effects of a low protein (LP) diet on the kidney in the context of aging has not been examined. Therefore, the goal of the current study was to investigate the impact of chronic consumption of a LP diet on the kidney in aging mice lacking FGF21. Wild type (WT, C57BL/6J) and FGF21 KO mice were fed a normal protein (NP, 20% casein) or a LP (5% casein) diet ad libitum from 3 to19 months of age. The LP diet led to a decrease in kidney weight and urinary albumin/creatinine ratio in both WT and FGF21 KO mice. Although the LP diet produced only mild fibrosis and infiltration of leukocytes in WT kidneys, the effects were significantly exacerbated by the absence of FGF21. Accordingly, transcriptomic analysis showed that inflammation-related pathways were significantly enriched and upregulated in response to LP diet in FGF21 KO but not WT mice. Collectively, these data demonstrate that the LP diet negatively affected the kidney during aging, but in the absence of FGF21, the LP diet-induced renal damage and inflammation were significantly worse, indicating a protective role of FGF21 in the kidney.
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http://dx.doi.org/10.1152/ajprenal.00107.2021DOI Listing
June 2021

Computational design and synthesis of molecular imprinted polymers for selective solid phase extraction of sulfonylurea herbicides.

J Chromatogr A 2021 Jun 3;1651:462321. Epub 2021 Jun 3.

Technical Center for Animal Plant and Food Inspection and Quarantine of Shanghai Customs, Shanghai 200135, China.

A high-efficiency approach for the synthesis of molecularly imprinted polymers has been developed and further for the solid-phase extraction of sulfonylurea herbicides in food samples. Molecular simulation approach combined chemometric selected metsulfuron-methyl (MSM) and 2-trifluoromethyl acrylic acid (TFMAA) as the template and the monomer to synthesize the molecularly imprinted polymers (MIPs). Experimental validation confirmed that the MSM-imprinted polymers showed a higher selectivity and affinity to sulfonylurea herbicides. The optimized molecularly imprinted solid-phase extraction (MISPE) conditions, including loading, washing, and eluting conditions, were established. The developed MISPE technology combined HPLC-MSMS was successfully used for the determination of sulfonylurea herbicides in foods. Compared with commercial SPE columns, MISPE showed high affinity, excellent selectivity and low matrix effect. The recoveries of sulfonylurea herbicides spiked in four matrices were between 86.4% and 100.2%, with the relative standard deviations (RSD) in the range of 0.9%-10.5%.
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http://dx.doi.org/10.1016/j.chroma.2021.462321DOI Listing
June 2021

The Role Of Rs12901499 Polymorphism In Association With Smad3 Gene And Osteoarthritis Susceptibility: Systematic Review And Meta-Analysis.

J Ayub Med Coll Abbottabad 2021 Apr-Jun;33(2):322-327

Department of Radiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi,China.

Background: Osteoarthritis is regarded as one of the most frequent disorders of musculoskeletal, which is characterized by the degeneration of articular cartilage and loss of cartilage of the joints. However, the relationship of OA susceptibility with rs12901499 polymorphism in SMAD3 is controversial. Although multiple studies have investigated the correlation of rs12901499A/G polymorphism in SMAD family member 3 (SMAD3) andosteoarthritis (OA) susceptibility, the results from previous studies remain controversial and unsolved. A meta-analysis utilizing fixed and random effects model was performed to clarify the association.

Methods: Eligible studies were systematically searched from PubMed, Web of Science, Cochrane Library and EMBASE on April 17, 2019 for reporting the correlation of rs12901499 polymorphism and osteoarthritis susceptibility. Pooled Odds ratio of 95% confidence interval was performed to estimate the strength of relationship of rs12901499 polymorphism and osteoarthritis susceptibility. Publication bias was detected by Begg's test and STATA 11.0 software was used to evaluate statistical analysis.

Results: Seven case-control papers involving eight studies from Caucasian and Asian populations were included. A significant increase in osteoarthritis susceptibility was found in recessive, homozygous and allele models. Stratified analysis on ethnicity suggested that the polymorphism with increased risk of OA only in Asians under allele model. Stratified analysis related to population-based studies indicated the increased risk of OA with polymorphism in recessive, homozygous, allele and dominant models.

Conclusions: This meta-analysis demonstrated that there may be a weak association of rs12901499 polymorphism and OA susceptibility. Due to the limited size of sample and given ethnic groups, more studies need to validate the result in future.
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June 2021

Propofol improves brain injury induced by chronic cerebral hypoperfusion in rats.

Food Sci Nutr 2021 Jun 5;9(6):2801-2809. Epub 2021 May 5.

Department of Anesthesiology Peking University Hospital of Stomatology Beijing China.

To study effect of propofol on cognitive dysfunction and brain injury in a rat model of chronic cerebral hypoperfusion. The bilateral carotid artery ligation (bilateral common carotid artery occlusion and BCCAO) to establish rat model of chronic cerebral hypoperfusion and randomly assigned to 4 groups ( = 10): sham-operation group treated with saline model group, propofol treatment model group, normal saline treatment, propofol treatment in the sham-operation group; continuous intraperitoneal injection of propofol and saline for 12 weeks. Morris water maze was used to evaluate the learning and memory ability of rats. Determination of central cholinergic and oxidative stress in brain tissue by spectrophotometry. Detection of inflammatory response in brain tissue by immunohistochemistry and ELISA method. Detection of neuronal loss in brain tissue by Nissl and TUNEL staining. Compared with the saline-treated model group, propofol in model group significantly increased the rat brain tissue SOD activity ( < .01) and GPX activity ( < .01), decreased the MDA levels ( < .01) and protein carbonyl compound levels ( < .01). The propofol treatment of model group rats hippocampal GFAP-immunoreactive satellite glial cells ( < .01) and immune Iba1-positive microglia cells ( < .01) area percent compared to saline-treated model group decreased significantly. The number of normal propofol treatment of model group rats hippocampus neuron than in physiological saline treatment model group rats was significantly increased ( < .01). Propofol can improve chronic cerebral hypoperfusion in rats induced by cognitive dysfunction and brain damage.
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http://dx.doi.org/10.1002/fsn3.1915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194753PMC
June 2021

Implementation of dietary methionine restriction using casein after selective, oxidative deletion of methionine.

iScience 2021 May 24;24(5):102470. Epub 2021 Apr 24.

Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.

Dietary methionine restriction (MR) is normally implemented using diets formulated from elemental amino acids (AA) that reduce methionine content to ∼0.17%. However, translational implementation of MR with elemental AA-based diets is intractable due to poor palatability. To solve this problem and restrict methionine using intact proteins, casein was subjected to mild oxidation to selectively reduce methionine. Diets were then formulated using oxidized casein, adding back methionine to produce a final concentration of 0.17%. The biological efficacy of dietary MR using the oxidized casein (Ox Cas) diet was compared with the standard elemental MR diet in terms of the behavioral, metabolic, endocrine, and transcriptional responses to the four diets. The Ox Cas MR diet faithfully reproduced the expected physiological, biochemical, and transcriptional responses in liver and inguinal white adipose tissue. Collectively, these findings demonstrate that dietary MR can be effectively implemented using casein after selective oxidative reduction of methionine.
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http://dx.doi.org/10.1016/j.isci.2021.102470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169944PMC
May 2021

Identification and comparison of triterpene saponins in Aralia elata leaves and buds by the energy-resolved MS technique on a liquid chromatography/quadrupole time-of-flight mass spectrometry.

J Pharm Biomed Anal 2021 May 27;203:114176. Epub 2021 May 27.

Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin, 150040, China. Electronic address:

In this study, we identify the triterpene saponins (TSs) extracted from the leaves and buds of Aralia elata (Miq.) Seems using ultra-performance liquid chromatography and positive ionization electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF). The energy-resolved MS (erMS) technique is applied in order to simultaneously collect the diverse precursors attributed to [M+H], [M + NH] and [M + Na] ions. A practical and effective erMS workflow is established to rapidly identify and compare the saponins in the analyzed samples. In total, 111 TSs of structure are estimated, including 44 new compounds that had not been identified previously in A. elata. Of the five aglycones detected in the samples, a sapogenin 3β, 16α, 23-trihydroxyoleana-11,13-dien-28-oic acid (A5) that is identified for the first time in A. elata leaves. Compared to the buds, the leaves number twice as many hederagenin-type (A2) compounds. Although the number of other aglycones does not vary significantly between the buds and the leaves, A5 compounds are exclusively detected in the latter. Moreover, the C-3 sugar chains of TSs in A. elata leaves are mainly neutral (e.g., Hex+Hex, Hex+Hex+Hex and Hex+Hex+Hex+Hex), whereas those of bud TS compounds are primarily acidic (e.g., Pen+HexA, Hex+HexA and Hex+Pen+HexA). Some of the identified TS compounds, e.g., 27, 28, 32, 46, 54, 57, 71 and 105 can be used as indices to evaluate the quality of the plant leaves and buds. Overall, this study is of great significance for the comparative study of triterpenoid saponins in the leaves and buds of Aralia elata.
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http://dx.doi.org/10.1016/j.jpba.2021.114176DOI Listing
May 2021

Spatial variation, water quality, and health risk assessment of trace elements in groundwater in Beijing and Shijiazhuang, North China Plain.

Environ Sci Pollut Res Int 2021 Jun 3. Epub 2021 Jun 3.

Department of Hydraulic Engineering, Tongji University, 1239 Siping Road, Shanghai, 200092, China.

Metal(loid)s pollution of groundwater in northern China is of great concern due to the increasing shortage of fresh water resources. In the present study, total 159 of groundwater samples were collected from the Miyun-Huairou-Shunyi (MHS) districts in Beijing city and the Hutuo River Plain (HRP) in Shijiazhuang city. Nineteen trace elements dissolved in groundwater were measured. Results showed that Al (12.3 %), Mn (5.3%), Zn (1.8%), As (1.8%), and Pb (1.8%) in the MHS samples, and Mn (2.2%) in the HRP samples exceeded their standard threshold of WHO and China. Exceedance of trace elements was attributed to both geochemical background and local human activities. Human health risk assessment showed that local consumers were exposed at a low level of health risk, except in specific area with a high level of arsenic. Elements of arsenic and chromium were important risk contributors in the two regions. The risk of oral exposure was greater than that of skin uptake. Children were more susceptible to non-carcinogenic risk and less to carcinogenic risk than adults. A Nemerow index and CRITIC-weighted WQI were applied to classify groundwater quality. The results from the two methods were comparable to a large extend. More population living in plain rather than mountain resulted in a gradual deterioration trend of groundwater quality from mountain to plain. The samples with poor water quality were almost collected in the area with heavy industrial and agricultural activities. The CRITIC-weighted WQI was recommended for groundwater quality assessment. A simple classification criterion was reformulated based on the MHS hazard index analysis. The groundwaters in the two research fields were not seriously polluted, but potential risks should not be ignored.
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http://dx.doi.org/10.1007/s11356-021-14557-3DOI Listing
June 2021

Hepatic Is Not an Essential Mediator of the Metabolic Phenotype Produced by Dietary Methionine Restriction.

Nutrients 2021 May 24;13(6). Epub 2021 May 24.

Laboratory of Nutrient Sensing & Adipocyte Signaling, 6400 Perkins Road, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.

The principal sensing of dietary methionine restriction (MR) occurs in the liver, where it activates multiple transcriptional programs that mediate various biological components of the response. Hepatic is a key target and essential endocrine mediator of the metabolic phenotype produced by dietary MR. The transcription factor, , is also activated by MR and functions in tandem with hepatic to transactivate multiple, antioxidative components of the integrated stress response. However, it is unclear whether the transcriptional responses linked to activation by dietary MR are essential to the biological efficacy of the diet. Using mice with liver-specific deletion of () and their floxed littermates () fed either Control or MR diets, the absence of hepatic had no effect on the ability of the MR diet to increase FGF21, reduce body weight and adiposity, and increase energy expenditure. Moreover, the primary elements of the hepatic transcriptome were similarly affected by MR in both genotypes, with the only major differences occurring in induction of the P450-associated drug metabolism pathway and the pentose glucuronate interconversion pathway. The biological significance of these pathways is uncertain but we conclude that hepatic is not essential in mediating the metabolic effects of dietary MR.
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http://dx.doi.org/10.3390/nu13061788DOI Listing
May 2021

Small universal mechanical module driven by a liquid metal droplet.

Lab Chip 2021 May 28. Epub 2021 May 28.

State Key Laboratory of Robotics and System, Harbin Institute of Technology, West Da-zhi Street 92, Harbin, Heilongjiang 150001, People's Republic of China.

Gallium-based liquid metal droplets (LMDs) from micro-electromechanical systems (MEMS) have gained much attention due to their precise and sensitive controllability under an electric field. Considerable research progress has been made in the field of actuators by taking advantage of the continuous electrowetting (CEW) present within the solution. However, the motion generated is confined within the specific liquid environment and is lacking a way to transmit its motion outwardly, which undoubtedly serves as the greatest obstacle restricting any further development. Therefore, a driving module is proposed to generate rotational motion outside the solution for universality. Its performance can be easily tuned by adjusting the applied voltage. As an example of further application, the module is designed in the form of a pump that realizes the continuous/intermittent propulsion to mimic the veins/arteries of the human body without the problem in the previous LMD-based pumps. The feasibility of this pump in the on-chip in vitro analysis is proved by preparing a dynamic cell culture to simulate the movement of biofluids within human bodies. This study proposes an optional solution with an LMD-based motor for generating rotational motion and to expand current research on soft materials in actuators.
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http://dx.doi.org/10.1039/d1lc00206fDOI Listing
May 2021

Dependency analysis of frequency and strength of gamma oscillations on input difference between excitatory and inhibitory neurons.

Cogn Neurodyn 2021 Jun 28;15(3):501-515. Epub 2020 Jul 28.

College of Information Science and Technology, Donghua University, Shanghai, 201620 China.

It has been found that gamma oscillations and the oscillation frequencies are regulated by the properties of external stimuli in many biology experimental researches. To unveil the underlying mechanism, firstly, we reproduced the experimental observations in an excitatory/inhibitory (E/I) neuronal network that the oscillation became stronger and moved to a higher frequency band (gamma band) with the increasing of the input difference between E/I neurons. Secondly, we found that gamma oscillation was induced by the unbalance between positive and negative synaptic currents, which was caused by the input difference between E/I neurons. When this input difference became greater, there would be a stronger gamma oscillation (i.e., a higher peak power in the power spectrum of the population activity of neurons). Further investigation revealed that the frequency dependency of gamma oscillation on the input difference between E/I neurons could be explained by the well-known mechanisms of inter-neuron-gamma (ING) and pyramidal-interneuron-gamma (PING). Finally, we derived mathematical analysis to verify the mechanism of frequency regulations and the results were consistent with the simulation results. The results of this paper provide a possible mechanism for the external stimuli-regulated gamma oscillations.
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http://dx.doi.org/10.1007/s11571-020-09622-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131436PMC
June 2021

Ligand-Conformer-Induced Formation of  Zirconium-Organic Framework  for Methane Storage and MTO Product Separation.

Angew Chem Int Ed Engl 2021 May 21. Epub 2021 May 21.

Shaanxi Normal University, School of Chemistry and Chemical Engineering, CHINA.

In pursuit of novel adsorbents with efficient adsorptive gas storage and separation capabilities remains highly desired and challenging. Although the documented zirconium-tricarboxylate-based metal-organic frameworks (MOFs) have displayed a variety of topologies encompassing underlying and geometry mismatch ones, the employed organic linkers are exclusively rigid and poorly presenting one type of conformation in the resultant structures. Herein, a used and semirigid tricarboxylate ligand of H3TATAB was judiciously selected to isolate a zirconium-based spe-MOF after the preliminary discovery of srl-MOF. Single-crystal X-ray diffraction reveals that the fully deprotonated TATAB linker in spe-MOF exhibits two distinct conformers, concomitant with popular Oh and rare S6 symmetrical Zr6 molecular building blocks, generating an unprecedented (3,3,12,12)-c nondefault topology. Specifically, the spe-MOF exhibits structurally higher complexity, hierarchical micropores, open metal sites free and rich electronegative groups on the pore surfaces, leading to relatively high methane storage capacity without considering the missing-linker defects and efficient MTO product separation performance.
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http://dx.doi.org/10.1002/anie.202103525DOI Listing
May 2021

Efficacy and Safety of (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and Design.

Front Pharmacol 2021 22;12:648921. Epub 2021 Apr 22.

Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China.

Although revascularization treatment is recommended as the first-line therapy for patients with non-minor acute ischemic stroke (AIS), it only benefits a minority of patients. Previous studies have reported the positive effects of (PNS) (Xueshuantong lyophilized powder) on AIS, however, there have been no rigorous trials. This study aims to assess the efficacy and safety of PNS therapy for patients with AIS. The Evaluation of Xueshuantong in Patients with acutE ischemiC sTroke (EXPECT) trial is a multicenter, randomized, placebo-controlled, double-blind study aiming to enroll 480 patients in China. Eligible patients with AIS within 72 h of symptom onset will randomly receive either PNS or PNS placebo for 10 days and subsequently be followed up to 90 days. The primary outcome will be a change in the National Institute of Health Stroke Scale (NIHSS) score from baseline to 10 post-randomization days. The secondary outcomes include early neurological improvement (proportion of patients with NIHSS score 0-1), and Patient-Reported Outcomes Scale for Stroke score at 10 post-randomization days, the proportion of patients with life independence (modified Rankin Scale score of 0-1), the proportion of patients with a favorable outcome (Barthel Index ≥90), and Stroke-Specific Quality of Life score at 90 days. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of PNS. To our knowledge, this study is the first double-blind trial to assess the efficacy and safety of PNS in patients with AIS. Findings of the EXPECT trial will be valuable in improving evidence regarding the clinical application of PNS therapy in patients with AIS ineligible for revascularization treatment in the reperfusion era.
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http://dx.doi.org/10.3389/fphar.2021.648921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101545PMC
April 2021

The association between high risk of sleep apnea, comorbidities, and risk of COVID-19: a population-based international harmonized study.

Sleep Breath 2021 06 28;25(2):849-860. Epub 2021 Apr 28.

Helsinki Sleep Clinic, Vitalmed Research Center, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland.

Purpose: Obstructive sleep apnea (OSA) may increase the risk of severe COVID-19; however, the level of potential modulation has not yet been established. The objective of the study was to determine the association between high risk of OSA, comorbidities, and increased risk for COVID-19, hospitalization, and intensive care unit (ICU) treatment.

Methods: We conducted a cross-sectional population-based web survey in adults in 14 countries/regions. The survey included sociodemographic variables and comorbidities. Participants were asked questions about COVID-19, hospitalization, and ICU treatment. Standardized questionnaire (STOP questionnaire for high risk of OSA) was included. Multivariable logistic regression was conducted adjusting for various factors.

Results: Out of 26,539 respondents, 20,598 (35.4% male) completed the survey. Mean age and BMI of participants were 41.5 ± 16.0 years and 24.0 ± 5.0 kg/m, respectively. The prevalence of physician-diagnosed OSA was 4.1% and high risk of OSA was 9.5%. We found that high risk of OSA (adjusted odds ratio (aOR) 1.72, 95% confidence interval (CI): 1.20, 2.47) and diabetes (aOR 2.07, 95% CI: 1.23, 3.48) were associated with reporting of a COVID-19 diagnosis. High risk for OSA (aOR 2.11, 95% CI: 1.10-4.01), being male (aOR: 2.82, 95% CI: 1.55-5.12), having diabetes (aOR: 3.93, 95% CI: 1.70-9.12), and having depression (aOR: 2.33, 95% CI: 1.15-4.77) were associated with increased risk of hospitalization or ICU treatment.

Conclusions: Participants at high risk of OSA had increased odds of having COVID-19 and were two times more likely to be hospitalized or treated in ICU.
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http://dx.doi.org/10.1007/s11325-021-02373-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079162PMC
June 2021

Strategy for Designing a Cell Scaffold to Enable Wireless Electrical Stimulation for Enhanced Neuronal Differentiation of Stem Cells.

Adv Healthc Mater 2021 06 22;10(11):e2100027. Epub 2021 Apr 22.

School of Nano-Tech and Nano Bionics, University of Science and Technology of China, Hefei, Anhui, 230026, China.

Electrical stimulation (ES) offers significant advantages in modulating the behavior of stem cells on conductive scaffolds for neural tissue engineering. However, it is necessary to realize wireless ES to avoid the use of external wires in tissues. Thus, herein, a strategy is reported to develop a stem cell scaffold that allows wireless ES. A conductive annular graphene substrate is designed and grown by chemical vapor deposition; this substrate is used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The substrate shows excellent biocompatibility for the culture of neural stem cells (NSCs). The results indicate that the applied wireless ES enhances neuronal differentiation, facilitates the formation of neurites, and does not substantially affect the viability and stemness maintenance of NSCs. Collectively, this system provides a strategy for achieving synergy between wireless ES and conductive scaffolds for neural regenerative medicine, which can be further utilized for the regeneration of other tissues.
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http://dx.doi.org/10.1002/adhm.202100027DOI Listing
June 2021

Growth differentiation factor 11: a "rejuvenation factor" involved in regulation of age-related diseases?

Aging (Albany NY) 2021 04 22;13(8):12258-12272. Epub 2021 Apr 22.

Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β superfamily of cytokines, is a critical rejuvenation factor in aging cells. GDF11 improves neurodegenerative and neurovascular disease outcomes, increases skeletal muscle volume, and enhances muscle strength. Its wide-ranging biological effects may include the reversal of senescence in clinical applications, as well as the ability to reverse age-related pathological changes and regulate organ regeneration after injury. Nevertheless, recent data have led to controversy regarding the functional roles of GDF11, because the underlying mechanisms were not clearly established in previous studies. In this review, we examine the literature regarding GDF11 in age-related diseases and discuss potential mechanisms underlying the effects of GDF11 in regulation of age-related diseases.
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http://dx.doi.org/10.18632/aging.202881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109099PMC
April 2021

2018 worldwide survey of health-care providers caring for patients with narcolepsy: WSS narcolepsy task force.

Sleep Med 2021 Jun 15;82:23-28. Epub 2021 Mar 15.

National Reference Network for Narcolepsy, Sleep-Wake Disorders Unit, Department of Neurology, Gui-de- Chauliac Hospital, CHU Montpellier, Univ Montpellier, Institute of Neuroscience INM INSERM, Montpellier, France.

Background: There are limited data available on regional differences in the diagnosis and management of narcolepsy. In order to better understand worldwide trends in clinical assessment and management of narcolepsy, a survey of health-care providers was conducted by the World Sleep Society Narcolepsy task force.

Methods: A total of 146 surveys that included items on the diagnosis and management of narcolepsy were completed by practitioners representing 37 countries.

Results: Most of the participants were from Europe, North America, Oceania, Asia and Latin America. A consistent approach to applying the diagnostic criteria of Narcolepsy was documented with the exception of measurement of CSF hypocretin-1, which has limited availability. While the majority of practitioners (58%) reported not using the test, 1% indicated always evaluating CSF hypocretin-1 levels. There was much variability in the availability of currently recommended medications such as sodium oxybate and pitolisant; modafinil and antidepressants were the most commonly used medications. Amphetamines were unavailable in some countries.

Conclusion: The results of the study highlight clinical and therapeutic realities confronted by worldwide physicians in the management of narcolepsy. While the diagnostic criteria of narcolepsy rely in part on the quantification of CSF hypocretin-1, few physicians reported having incorporated this test into their routine assessment of the condition. Regional differences in the management of narcolepsy appeared to be related to geographic availability and expense of the therapeutic agents.
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http://dx.doi.org/10.1016/j.sleep.2021.03.014DOI Listing
June 2021

Mandibular advancement device as treatment trial for catathrenia (nocturnal groaning).

J Clin Sleep Med 2021 Apr 12. Epub 2021 Apr 12.

Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China.

Study Objectives: Catathrenia is a rare disease, classified as isolated symptoms and normal variants under sleep-related breathing disorders in the International Classification of Sleep Disorders, third edition. Because of its rarity, the research on its pathogenesis and treatment is insufficient. This study aimed to evaluate whether the mandibular advancement device (MAD) could be considered an alternative treatment trial and if so, to explore factors predicting its effectiveness.

Methods: Thirty patients (12 males and 18 females, aged 16 to 67 years) with catathrenia participated in the study. They underwent standard clinical evaluation, questionnaires, physical examinations, craniofacial evaluations, video-polysomnography, and imaging of the upper airway before and after the insertion of the MAD. Groaning index (GI, groaning episodes per hour of sleep) and apnea-hypopnea index (AHI) were evaluated and anatomic factors predicting effectiveness were explored.

Results: The sleep efficiency of most patients was higher than 80% and groaning was present throughout all stages of sleep. With the insertion of MAD, GI decreased significantly from 5.8 (2.7, 14.3) to 2.8 (1.3, 12.2) events/h (P = 0.014). Age had a negative effect on efficacy. Mandibular repositioning of MAD, especially the amount of vertical opening and changes of cross-sectional area of hypopharynx, was positively related with efficacy.

Conclusions: The MAD could be considered a possible treatment trial for those seeking treatment for groaning.

Clinical Trial Registration: Registry: Chinese Clinical Trial Registry; Identifier: ChiCTR-COC-17013239; URL: http://www.chictr.org.cn/showproj.aspx?proj=22286.
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http://dx.doi.org/10.5664/jcsm.9290DOI Listing
April 2021

Distribution and analysis of intraocular pressure and its possible association with glaucoma in children.

Int Ophthalmol 2021 Apr 11. Epub 2021 Apr 11.

Clinical College of Ophthalmology, Tianjin Medical University, No. 4 Gansu Road, Heping District, Tianjin, 300020, China.

Purpose: To analyze intraocular pressure (IOP) and glaucoma-associated factors in children.

Methods: A total of 4438 children aged 7-16 years (2321 boys and 2117 girls) were included in this study. Various ophthalmologic [IOP, central corneal thickness (CCT), etc.] and demographic (body mass index, etc.) parameters were evaluated.

Results: IOP increased between the ages of 7 and 9 years, peaking at 9 years. IOP increased after reaching a trough at 11 years and subsequently stabilized after 14 years. Girls exhibited thinner CCT (534.28 ± 30.84 µm vs. 537.04 ± 31.33 µm, P = 0.003), thicker lens thickness (3.56 ± 0.21 mm vs. 3.54 ± 0.20 mm, P = 0.001), shorter axial length (22.91 ± 0.93 mm vs. 23.32 ± 0.89 mm, P < 0.001), shallower anterior chamber depth (2.92 ± 0.27 mm vs. 3.00 ± 0.26 mm, P < 0.001), higher refraction (- 0.57 ± 1.48 D vs. 0.16 ± 1.35 D, P < 0.001), and higher mean corneal curvature (43.77 ± 1.39 vs. 43.03 ± 1.35, P < 0.001). Multivariable analysis assessed the following IOP-associated factors: thicker CCT [standardized correlation coefficient (SRC) = 0.201, P < 0.001), deeper anterior chamber depth (SRC = 0.059, P = 0.009), shorter axial length (SRC =  - 0.086, P = 0.036), lower mean corneal curvature (SRC =  - 0.123, P < 0.001), higher refraction (SRC =  - 0.090, P < 0.001).

Conclusion: IOP fluctuated in children, and a trend toward a higher mean IOP between the ages of 9 and 11 years, which stabilized after 14 years, was observed. IOP was associated with CCT, anterior chamber depth, axial length, lens thickness, mean corneal curvature, spherical equivalent, and systolic blood pressure.
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http://dx.doi.org/10.1007/s10792-021-01838-6DOI Listing
April 2021

Ferroptosis-related genes for predicting prognosis of patients with laryngeal squamous cell carcinoma.

Eur Arch Otorhinolaryngol 2021 Apr 5. Epub 2021 Apr 5.

Department of Radiology, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China.

Background: Previous studies reported that ferroptosis-related genes can regulate the process of tumor cell changes by regulating iron metabolism. However, the prognostic value of ferroptosis-related genes in LC remains to be further elucidated.

Methods: Ferroptosis-related gene expression profiles of coexisting ferroptosis-related genes were extracted from both cohorts (TCGA and GSE27020) for eligible analysis. LASSO Cox regression was utilized to build an optimum ferroptosis-related prognostic model. Kaplan-Meier curve was performed by log-rank test, and time-dependent ROC curve was constructed to evaluate the predictive power of this signature in both cohorts. GO and KEGG enrichment analysis was used to investigate the potential mechanism of differential enrichment signal pathways.

Results: 112 LC patients from the TCGA cohort and 108 LC patients with clinical information from the GEO cohorts were eventually included in the study. Three ferroptosis-related genes were identified as an independent risk factor to establish the prognostic risk score. Kaplan-Meier curve represented that patients with high-risk group favors with worse OS than their low-risk group (P = 0.04). The good performance of the gene signature for predicting OS was evaluated by area under the curve (AUC) of time-dependent ROC curves achieved 0.74 at 3 years, and 0.70 at 5 years. Similar performance has been proved in the external validation cohort. GO and KEGG enrichment analysis have been performed to explore the signaling pathways and underlying mechanisms were significantly active in LC patients.

Conclusion: In summary, our study developed a ferroptosis-related model that could be an effective biomarker to predict the prognosis of laryngeal cancer.
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http://dx.doi.org/10.1007/s00405-021-06789-3DOI Listing
April 2021

Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the gene loci.

Proc Natl Acad Sci U S A 2021 Mar;118(12)

Histocompatibility Department, Blood Center of the Community of Madrid, 28032 Madrid, Spain.

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, = 8.6 × 10) within the 3'region of gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo = 0.15; < 2.0 × 10 at = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the polymorphisms in conjunction with reported birth difficulties may predispose to KLS.
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http://dx.doi.org/10.1073/pnas.2005753118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999876PMC
March 2021

Using arthroscopy combined with fluoroscopic technique for accurate location of the bone tunnel entrance in chronic ankle instability treatment.

BMC Musculoskelet Disord 2021 Mar 18;22(1):289. Epub 2021 Mar 18.

Department of Orthopaedics, General Hospital of Central Theater Command (Wuhan General Hospital of Guangzhou Command, previously), NO. 627, Wuluo Road, Wuhan, 430030, Hubei Province, People's Republic of China.

Background: Minimally invasive reconstruction techniques are used for anatomical ligament construction of the lateral collateral ligament complex of the ankle, but the two key elements, the bone tunnel and the appropriate graft tension, for the identification of the anatomic location during the surgery are not clearly stated.

Methods: The patients with chronic ankle instability who received arthroscopic anatomic lateral ligament complex reconstruction were retrospectively analyzed. The anatomical location of the bone tunnel was performed under arthroscopy combined with fluoroscopy for accurate location of the bone tunnel entrance. The graft tension and routing were controlled under arthroscopic visualization. The clinical outcomes were assessed using the Karlsson-Peterson score, Sefton articular stability scale, and Visual Analogue Scale (VAS). The complications were recorded during the follow-up.

Results: A total of 18 patients were enrolled in this study. The mean follow-up was 33.33 ± 3.69 (range from 24 to 36) months. No patient had recurrence of ankle instability after the operation. According to the Sefton articular stability scale, 94.5% of the patients had excellent/good function. The mean value of the anterior drawer tests and the talar tilt angle examination were decreased. The mean of the Karlsson-Peterson score and the Visual Analogue Scale(VAS) score were both improved significantly.

Conclusions: The anatomic reconstruction of the ankle lateral ligament complex to treat chronic ankle instability using the arthroscopy combined with the fluoroscopic technique could improve the clinical functions, satisfaction, and reduced pain of patients.
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http://dx.doi.org/10.1186/s12891-021-04165-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977304PMC
March 2021

Asian accreditation of sleep medicine physicians and technologists: practice guidelines by the Asian Society of Sleep Medicine.

Sleep Med 2021 May 25;81:246-252. Epub 2021 Feb 25.

Department of Neurology, Samsung Medical Center, Samsung Biomedical Research Institute (SBRI), Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Neuroscience Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

Due to the rapid growth in sleep medicine's professional content, several countries have recognized sleep medicine as an independent specialty. The practice of sleep medicine and the demand for this service in Asian countries are expanding. At this point of growth, the accreditation of sleep medicine specialists is paramount to patient care and the training of physicians and technologists. The Asian Society of Sleep Medicine (ASSM) mandated a taskforce committee for the accreditation of sleep medicine practice. This taskforce developed Asian accreditation practice guidelines for sleep medicine physicians and technologists. This paper presents the newly approved Asian accreditation practice guidelines for sleep medicine physicians and technologists by the ASSM.
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http://dx.doi.org/10.1016/j.sleep.2021.02.041DOI Listing
May 2021

Genotype-Phenotype Analysis and Mutation Spectrum in a Cohort of Chinese Patients With Congenital Nystagmus.

Front Cell Dev Biol 2021 19;9:627295. Epub 2021 Feb 19.

School of Ophthalmology and Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.

Congenital nystagmus (CN) is a genetically and clinically heterogeneous ocular disorder that manifests as involuntary, periodic oscillations of the eyes. To date, only and have been reported to be responsible for causing CN. Here, we aimed to identify the disease-causing mutations and describe the clinical features in the affected members in our study. All the subjects underwent a detailed ophthalmic examination. Direct sequencing of all coding exons and splice site regions in and and a mutation assessment were performed in each patient. We found 14 mutations in 14/37 (37.8%) probands, including nine mutations in the gene and five mutations in the gene, seven of which are novel, including c.284G>A(R95K), c.964C>T(P322S), c.284+10T>G, c.901T>C (Y301H), and c.2014_2023delTCACCCATGG(S672Pfs12) in , and c.250+1G>C, and c.485G>A (W162) in . The mutation detection rate was 87.5% (7/8) of familial vs. 24.1% (7/29) of sporadic cases. Ten mutations in 24 (41.7%) non-syndromic subjects and 4 mutations in 13(30.8%) syndromic subjects were detected. A total of 77.8% (7/9) of mutations in were concentrated within the FERM and FA domains, while all mutations in were located in exons 1, 2, 4 and 6. We observed that visual acuity tended to be worse in the group than in the group, and no obvious difference in other clinical manifestations was found through comparisons in different groups of patients. This study identified 14 mutations (seven novel and seven known) in eight familial and 29 sporadic patients with congenital nystagmus, expanding the mutational spectrum and validating and as mutation hotspots. These findings also revealed a significant difference in the screening rate between different groups of participants, providing new insights for the strategy of genetic screening and early clinical diagnosis of CN.
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http://dx.doi.org/10.3389/fcell.2021.627295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958879PMC
February 2021

Sleep and circadian rhythm disturbances in intensive care unit (ICU)-acquired delirium: a case-control study.

J Int Med Res 2021 Mar;49(3):300060521990502

Department of Pulmonary and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou, China.

Objective: The relationships among sleep, circadian rhythm, and intensive care unit (ICU)-acquired delirium are complex and remain unclear. This study aimed to examine the pathophysiological mechanisms of sleep and circadian rhythm disturbances in patients with ICU-acquired delirium.

Methods: This study included critical adult patients aged 18 to 75 years who were treated in the ICU. Twenty-four-hour polysomnography was performed and serum melatonin and cortisol levels were measured six times during polysomnography. Receiver operating characteristic curves and binomial logistic regression were used to evaluate the potential of sleep, melatonin, and cortisol as indicators of delirium in the ICU.

Results: Patients with delirium (n = 24) showed less rapid eye movement (REM) sleep compared with patients without delirium (n = 24, controls). Melatonin levels were lower and cortisol levels were higher in the delirium group than in the control group. REM sleep, melatonin, and cortisol were significantly associated with delirium. The optimal cutoff values of REM sleep and mean melatonin and cortisol levels that predicted delirium were ≤1.05%, ≤422.09 pg/mL, and ≥212.14 ng/mL, respectively.

Conclusions: REM sleep, and melatonin and cortisol levels are significantly associated with the risk of ICU-acquired delirium. Improved sleep and readjustment of circadian rhythmicity may be therapeutic targets of ICU-acquired delirium.
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http://dx.doi.org/10.1177/0300060521990502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983249PMC
March 2021

Home sleep apnea testing of adults with chronic heart failure.

J Clin Sleep Med 2021 Mar 10. Epub 2021 Mar 10.

Department of Medicine and Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania.

Study Objectives: To evaluate home sleep apnea testing (HSAT) using a type 3 portable monitor (PM) to help diagnose sleep disordered breathing (SDB) and identify respiratory events including obstructive sleep apnea (OSA), central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) in adults with stable CHF.

Methods: Eighty-four adults with CHF (86.9% males, age [mean±SD] 58.7±16.3 years, body mass index 29.4±13.0 kg/m², left ventricular ejection fraction 40.3±11.5%) performed unattended HSAT followed by an in-laboratory PSG with simultaneous portable monitor (PM) recording.

Results: The apnea-hypopnea index (AHI) was 22.0±17.0 events/hour on HSAT, 26.8±20.5 events/hour on in-laboratory PM, and 23.8±21.3 events/hour on PSG (p=0.373). Bland-Altman analysis of AHI on HSAT versus PSG showed a mean difference (95% confidence interval) of -2.4 (-4.9, 0.1) events/hour and limits of agreement (±2 SDs) of -24.1 to 19.2 events/hour. HSAT underestimated AHI to a greater extent at higher AHI (rho=-0.358, P<0.001). Similar levels of agreement on HSAT versus PSG were observed when comparing obstructive apnea index (OAI), central apnea index (CAI) and percentage of time in CSR pattern. Using an AHI ≥5 events/hour to diagnose SDB, HSAT had 86.7% sensitivity, 76.5% specificity, 92.9% positive predictive value and 61.9% negative predictive value compared to PSG. Detection of CSR on HSAT had 94.6% sensitivity, 91.1% specificity, 88.6% positive predictive value and 97.6% negative predictive value compared to PSG.

Conclusions: HSAT with a type 3 portable monitor can help to diagnose SDB and identify OSA, CSA and CSR events in adults with CHF.
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http://dx.doi.org/10.5664/jcsm.9224DOI Listing
March 2021

Development of hydrophilic PES membranes using F127 and HKUST-1 based on the RTIPS method: Mitigate the permeability-selectivity trade-off.

Environ Res 2021 05 4;196:110964. Epub 2021 Mar 4.

College of Marine Ecology and Environment, Shanghai Ocean University, Shanghai, 201306, China.

In this study, to mitigate the permeability-selectivity trade-off effect, Pluronic F127 (F127) and HKUST-1 were employed to construct high-performance membranes based on the reverse thermally induced phase separation (RTIPS) method. F127, as a hydrophilic modifier, was applied to increase permeability and resist polyethersulfone (PES) membrane fouling, while the collapse of HKSUT-1 caused by its instability in pure water improved the permeability and selectivity of the membrane. Characterizations demonstrated the successful synthesis of HKUST-1, together with the successful introduction of HKSUT-1 and F127 in PES membranes. It was observed that the membrane prepared by the RTIPS process possessed a uniformly porous surface and sponge-like cross-section with excellent mechanical properties, higher permeability, and selectivity compared to the dense skin and finger-like cross-section of the membrane prepared by the nonsolvent induced phase separation (NIPS) method. Moreover, the permeation and bovine serum albumin (BSA) rejection rate of the optimal membrane reached 2378 L/m h and 89.3%, respectively, which were far higher than those of the pure membrane. Hydrophilic F127 and many microvoids formed by the collapse of HKUST-1, played an important role in excellent antifouling properties, high permeability, and selectivity by pure water flux (PWF), flux recovery rate (FRR), BSA flux, and COD removal rate tests. Overall, the membrane with F127 and HKSUT-1 prepared via the RTIPS method not only obtained excellent antifouling properties but also mitigated the permeability-selectivity trade-off.
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http://dx.doi.org/10.1016/j.envres.2021.110964DOI Listing
May 2021

The complete chloroplast genome sequence of (Moraceae), an endemic and endangered plant in China.

Mitochondrial DNA B Resour 2021 Feb 19;6(2):604-605. Epub 2021 Feb 19.

College of Horticulture and Landscape Architecture, Southwest University, Chongqing, China.

S.S.Chang is an evergreen plant of from the family Moraceae. This is an endangered species endemic to China. In terms of economic value, are used as a native plant resource of urban landscaping in Chongqing, China. Here, we sequenced, assembled and annotated the chloroplast (cp) genome of , and aim to provide genetic resources for this endangered species. The length of cp genome was 160,595 bp, with a large single-copy region (LSC) of 88,683 bp and a small single-copy region (SSC) of 20,160 bp separated by a pair of inverted repeats (IRs) of 25,876 bp. It encodes 110 unique genes, including 76 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. Besides, we reconstructed the phylogeny of Moraceae based on the whole cp genome sequences data set. Phylogenetic analysis shows that all analyzed species are clustered and form a monophyletic group. is a sister group to . In our maximum likelihood (ML) tree, is closely related to .
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http://dx.doi.org/10.1080/23802359.2020.1861556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899700PMC
February 2021

Hypercapnia and Hypoxemia in a Young Woman.

Ann Am Thorac Soc 2021 03;18(3):527-533

Department of Respiratory and Critical Care Medicine, Sleep Medicine Center, and.

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http://dx.doi.org/10.1513/AnnalsATS.202006-699CCDOI Listing
March 2021

Reliability and validity of the Chinese version of Narcolepsy Severity Scale in adult patients with narcolepsy type 1.

Sleep Med 2021 May 12;81:86-92. Epub 2021 Feb 12.

Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China. Electronic address:

Objective: To evaluate reliability and validity of the Chinese version of Narcolepsy Severity Scale (NSS) in adult patients with narcolepsy type 1 (NT1).

Methods: One hundred and fifty-one adult patients (≥18 years) with NT1 were recruited. All filled out the 15-item Chinese version of NSS. Item analysis included critical ratio and correlation analysis. The validity of NSS was assessed by exploratory factor analysis, discriminant validity and convergent validity. Reliability of NSS was assessed by Cronbach's α coefficient, spilt-half reliability and test-retest reliability.

Results: Critical value of all 15 items ranged from 3.01 to 13.36. Each item was significantly correlated with the total score by a correlation coefficient (r) ranging from 0.219 to 0.700. Three common domains were extracted and 15 items explained 54.86% of the total variance. There was a shift in domains compared to the English version likely due to cultural differences. Cronbach's α coefficient for the total scale of 15 items was 0.821 and for three factors was 0.726, 0.748 and 0.760 respectively. The NSS had good correlation with Epworth sleepiness scale scores, Insomnia severity index scores and moderate correlation with mean the sleep latency of polysomnographic recording, and European Quality of Life-5 Dimensions Questionnaire. The Chinese version of NSS showed good spilt-half reliability and test-retest reliability.

Conclusion: The Chinese version of NSS shows satisfactory psychometric properties with good validity and reliability. It is applicable to evaluate the severity and consequences of symptoms in Chinese adult patients with NT1.
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http://dx.doi.org/10.1016/j.sleep.2021.02.008DOI Listing
May 2021

Hybrid manifold-deep convolutional neural network for sleep staging.

Methods 2021 Feb 24. Epub 2021 Feb 24.

Chongqing Key Laboratory of Nonlinear Circuits and Intelligent Information Processing, College of Electronic and Information Engineering, Southwest University, Chongqing, China. Electronic address:

Analysis of electroencephalogram (EEG) is a crucial diagnostic criterion for many sleep disorders, of which sleep staging is an important component. Manual stage classification is a labor-intensive process and usually suffered from many subjective factors. Recently, more and more computer-aided techniques have been applied to this task, among which deep convolutional neural network has been performing well as an effective automatic classification model. Despite some comprehensive models have been developed to improve classification results, the accuracy for clinical applications has not been reached due to the lack of sufficient labeled data and the limitation of extracting latent discriminative EEG features. Therefore, we propose a novel hybrid manifold-deep convolutional neural network with hyperbolic attention. To overcome the shortage of labeled data, we update the semi-supervised training scheme as an optimal solution. In order to extract the latent feature representation, we introduce the manifold learning module and the hyperbolic module to extract more discriminative information. Eight subjects from the public dataset are utilized to evaluate our pipeline, and the model achieved 89% accuracy, 70% precision, 80% sensitivity, 72% f1-score and kappa coefficient of 78%, respectively. The proposed model demonstrates powerful ability in extracting feature representation and achieves promising results by using semi-supervised training scheme. Therefore, our approach shows strong potential for future clinical development.
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http://dx.doi.org/10.1016/j.ymeth.2021.02.014DOI Listing
February 2021