Publications by authors named "Jinhee Lee"

142 Publications

Genetic deficiency of nuclear factor of activated T cells 5 attenuates the development of osteoarthritis in mice.

Joint Bone Spine 2021 Sep 16:105273. Epub 2021 Sep 16.

Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 06591, Korea. Electronic address:

Objectives: This study is aimed to investigate the role of nuclear factor of activated T cells 5 (NFAT5), originally known as the osmosensitive mammalian transcription factor, in the pathogenesis of osteoarthritis (OA) in mice.

Methods: OA was induced in male C57BL/6 (wild-type) and NFAT5 haplo-insufficient (NFAT5+/-) mice via destabilization of the medial meniscus (DMM) surgery. OA severity and synovial inflammation were histologically assessed. Expression of CCL2, inflammatory cytokines, cartilage degrading enzymes was determined in the knee joints and cultured chondrocytes from wild-type and NFAT5+/- mice.

Results: NFAT5 expression was significantly upregulated in the knee joint of a mouse after DMM surgery. NFAT5 deficiency decreased the severity of synovial inflammation and osteoarthritic changes in cartilage and subchondral bone. Moreover, NFAT5 deficiency also decreased the expression of CCL2, IL-1β, MMP-13, ADMATS-5, and macrophage infiltration in the joint. In cultured chondrocytes, hyperosmolar or IL-1β stimulation significantly enhanced the expression of NFAT5, CCL2, IL-1β, IL-6, and MMP-13, and this effect was abolished in chondrocytes from NFAT5+/- mice. Hyperosmolarity or IL-1β-induced NFAT5 and CCL2 downregulated by inhibiting p38 MAPK, JNK, and ERK pathways.

Conclusions: Our results indicate that NFAT5 is a crucial regulator of OA pathogenesis by upregulating CCL2 expression and macrophage recruitment. In chondrocyte, NFAT5 plays an important role in the response to hyperosmolar or IL-1β stimulation. Thus, NFAT5 could be an attractive therapeutic target for OA treatment.
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http://dx.doi.org/10.1016/j.jbspin.2021.105273DOI Listing
September 2021

Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice.

Sci Rep 2021 Aug 11;11(1):16348. Epub 2021 Aug 11.

School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Korea.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were generated, and induced lupus-like symptoms. Eight months later, the TG mice spontaneously developed typical SLE symptoms regardless of the inducement. Furthermore, we observed increased toll-like receptor 7 (TLR7) expression with increased monocyte and neutrophil populations in the TG mice. In conclusion, overexpression of CTSS in mice influences TLR7 expression, autoantibodies and IFN-α, which leads to an autoimmune reaction and exacerbates lupus-like symptoms.
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http://dx.doi.org/10.1038/s41598-021-94855-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357804PMC
August 2021

Age factor in the fluoroquinolone susceptibility of gram-positive cocci isolates from bacterial keratitis cases between 2008 and 2016.

Graefes Arch Clin Exp Ophthalmol 2021 Aug 11. Epub 2021 Aug 11.

Miyata Eye Hospital, Kurahara 6-3, Miyakonojo, Miyazaki, 885-0051, Japan.

Purpose: To determine the relationship between fluoroquinolone susceptibility of gram-positive cocci (GPC) isolated from patients with bacterial keratitis and the age of the patients or the date of onset.

Methods: Bacterial isolates were obtained from corneal lesions of patients with infectious keratitis treated between January 2008 and December 2016. The fluoroquinolone susceptibility of GPC was assessed, and a retrospective review of microbiological records was performed. Fluoroquinolone susceptibility was measured through broth microdilution in accordance with protocols of the Clinical and Laboratory Standards Institute. Statistical analysis was performed using a generalized estimating equation and cubic spline to determine the association between fluoroquinolone susceptibility of GPC isolated from corneal lesions and patient age.

Results: Of the 1200 bacterial isolates, 471 GPC were identified. They included Staphylococcus epidermidis (45.6%), other coagulase-negative Staphylococcus sp. (17.8%), and Staphylococcus aureus (18.3%). Levofloxacin susceptibility of GPC exhibited a negative relationship with age and had an odds ratio of 0.893 (95% confidence interval, 0.825-0.967) for every 10 years of age. A non-adjusted cubic spline curve was well correlated with year-adjusted data in a generalized additive model, and the levofloxacin susceptibility of GPC was initially stable but gradually declined after 40 years of age, before re-stabilizing again after 70 years of age.

Conclusion: The fluoroquinolone susceptibility of GPC isolated from corneal lesions of infectious keratitis is high in children under 15 years of age and declines with an increase in age of patients using a generalized estimating equation and cubic spline.
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http://dx.doi.org/10.1007/s00417-021-05351-5DOI Listing
August 2021

Digital Biomarkers for Neuromuscular Disorders: A Systematic Scoping Review.

Diagnostics (Basel) 2021 Jul 15;11(7). Epub 2021 Jul 15.

Department of Neurology, Cheongna Best Rehabilitation Hospital, Incheon 22883, Korea.

Biomarkers play a vital role in clinical care. They enable early diagnosis and treatment by identifying a patient's condition and disease course and act as an outcome measure that accurately evaluates the efficacy of a new treatment or drug. Due to the rapid development of digital technologies, digital biomarkers are expected to grow tremendously. In the era of change, this scoping review was conducted to see which digital biomarkers are progressing in neuromuscular disorders, a diverse and broad-range disease group among the neurological diseases, to discover available evidence for their feasibility and reliability. Thus, a total of 10 studies were examined: 9 observational studies and 1 animal study. Of the observational studies, studies were conducted with amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), and spinal muscular atrophy (SMA) patients. Non-peer reviewed poster presentations were not considered, as the articles may lead to erroneous results. The only animal study included in the present review investigated the mice model of ALS for detecting rest disturbances using a non-invasive digital biomarker.
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http://dx.doi.org/10.3390/diagnostics11071275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307187PMC
July 2021

Association between urine cotinine and depressive symptoms in non-smokers: National representative sample in Korea.

J Affect Disord 2021 Nov 16;294:527-532. Epub 2021 Jul 16.

Department of psychiatry, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address:

Background: Secondhand smoke (SHS) exposure is known to have negative effects on mental as well as physical health. However, the association between SHS and mental health problems has not been assessed in non-smokers. To evaluate the association of exposure to tobacco smoke and depressive symptoms, and that of the prevalence of having depressive symptoms and urinary cotinine (UCo) concentrations in non-exposed subjects.

Methods: Data was extracted from the Korea National Health and Nutrition Examination Survey (KNHANES). Depressive symptoms were determined based on a patient's overall score on the Patient Health Questionnaire (PHQ)-9, and SHS exposure was evaluated using self-reported data and UCo concentration. Overall, 13,219 non-smokers, ≥ 19 years were included in the study. Multinomial logistic regression analysis was conducted to identify factors related to depressive symptoms; independent t-test was conducted to confirm the differences in UCo concentration according to the prevalence of depression.

Results: Among the non-exposure groups, 2.0% of the males and 5.6% of the females showed depressive symptoms. Lower social-economic status, higher UCo concentration, and SHS exposure increased the prevalence of depressive symptoms. The UCo concentration of females with depressive symptoms was significantly higher than those of females without depressive symptoms.

Limitations: This study only demonstrated an association between SHS exposure and depression, not the causal effects, because of the cross-sectional study design.

Conclusion: SHS exposure and depressive symptoms are correlated. The association was also confirmed by evaluating the UCo concentration of those who were not exposed to SHS based on self-reported data.
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http://dx.doi.org/10.1016/j.jad.2021.07.039DOI Listing
November 2021

Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study.

Br J Sports Med 2021 Jul 22. Epub 2021 Jul 22.

Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Purpose: To determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea.

Methods: Data regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020.

Results: Out of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500-1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses.

Conclusion: Adults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.
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http://dx.doi.org/10.1136/bjsports-2021-104203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300550PMC
July 2021

Effect of the Period From COVID-19 Symptom Onset to Confirmation on Disease Duration: Quantitative Analysis of Publicly Available Patient Data.

J Med Internet Res 2021 09 1;23(9):e29576. Epub 2021 Sep 1.

Department of Psychiatry, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.

Background: In general, early intervention in disease based on early diagnosis is considered to be very important for improving health outcomes. However, there is still insufficient evidence regarding how medical care that is based on the early diagnosis of confirmed cases can affect the outcome of COVID-19 treatment.

Objective: We aimed to investigate the effect of the duration from the onset of clinical symptoms to confirmation of COVID-19 on the duration from the onset of symptoms to the resolution of COVID-19 (release from quarantine).

Methods: For preliminary data collection, we performed data crawling to extract data from social networks, blogs, and official websites operated by local governments. We collected data from the 4002 confirmed cases in 33 cities reported up to May 31, 2020, for whom sex and age information could be verified. Subsequently, 2494 patients with unclear symptom onset dates and 1349 patients who had not been released or had no data about their release dates were excluded. Thus, 159 patients were finally included in this study. To investigate whether rapid confirmation reduces the prevalence period, we divided the duration from symptom onset to confirmation into quartiles of ≤1, ≤3, ≤6, and ≥7 days, respectively. We investigated the duration from symptom onset to release and that from confirmation to release according to these quartiles. Furthermore, we performed multiple regression analysis to investigate the effects of rapid confirmation after symptom onset on the treatment period, duration of prevalence, and duration until release from isolation.

Results: We performed multiple regression analysis to investigate the association between rapid confirmation after symptom onset and the total prevalence period (faster release from isolation). The time from symptom onset to confirmation showed a negative association with the time from confirmation to release (t=-3.58; P<.001) and a positive association with the time from symptom onset to release (t=5.86; P<.001); these associations were statistically significant.

Conclusions: The duration from COVID-19 symptom onset to confirmation date is an important variable for predicting disease prevalence, and these results support the hypothesis that a short duration of symptom onset to confirmation can reduce the time from symptom onset to release.
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http://dx.doi.org/10.2196/29576DOI Listing
September 2021

RNA-dependent assembly of chimeric antigen nanoparticles as an efficient H5N1 pre-pandemic vaccine platform.

Nanomedicine 2021 Jul 10;37:102438. Epub 2021 Jul 10.

Department of Biotechnology, College of Life Sciences and Biotechnology, Yonsei University, Seoul, Republic of Korea; Department of Microbiology, College of Medicine, Yonsei University, Seoul, Republic of Korea; Vaccine Innovative Technology Alliance-Korea, Yonsei University, Seoul, Republic of Korea. Electronic address:

Highly pathogenic avian influenza viruses (HPAIVs) pose a significant threat to human health, with high mortality rates, and require effective vaccines. We showed that, harnessed with novel RNA-mediated chaperone function, hemagglutinin (HA) of H5N1 HPAIV could be displayed as an immunologically relevant conformation on self-assembled chimeric nanoparticles (cNP). A tri-partite monomeric antigen was designed including: i) an RNA-interaction domain (RID) as a docking tag for RNA to enable chaperna function (chaperna: chaperone + RNA), ii) globular head domain (gd) of HA as a target antigen, and iii) ferritin as a scaffold for 24 mer-assembly. The immunization of mice with the nanoparticles (~46 nm) induced a 25-30 fold higher neutralizing capacity of the antibody and provided cross-protection from homologous and heterologous lethal challenges. This study suggests that cNP assembly is conducive to eliciting antibodies against the conserved region in HA, providing potent and broad protective efficacy.
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http://dx.doi.org/10.1016/j.nano.2021.102438DOI Listing
July 2021

Use of Antiplatelet Agents Decreases the Positive Predictive Value of Fecal Immunochemical Tests for Colorectal Cancer but Does Not Affect Their Sensitivity.

J Pers Med 2021 Jun 1;11(6). Epub 2021 Jun 1.

Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Korea.

Previous studies have evaluated the effects of antithrombotic agents on the performance of fecal immunochemical tests (FITs) for the detection of colorectal cancer (CRC), but the results were inconsistent and based on small sample sizes. We studied this topic using a large-scale population-based database. Using the Korean National Cancer Screening Program Database, we compared the performance of FITs for CRC detection between users and non-users of antiplatelet agents and warfarin. Non-users were matched according to age and sex. Among 5,426,469 eligible participants, 768,733 used antiplatelet agents (mono/dual/triple therapy, n = 701,683/63,211/3839), and 19,569 used warfarin, while 4,638,167 were non-users. Among antiplatelet agents, aspirin, clopidogrel, and cilostazol ranked first, second, and third, respectively, in terms of prescription rates. Users of antiplatelet agents (3.62% vs. 4.45%; relative risk (RR): 0.83; 95% confidence interval (CI): 0.78-0.88), aspirin (3.66% vs. 4.13%; RR: 0.90; 95% CI: 0.83-0.97), and clopidogrel (3.48% vs. 4.88%; RR: 0.72; 95% CI: 0.61-0.86) had lower positive predictive values (PPVs) for CRC detection than non-users. However, there were no significant differences in PPV between cilostazol vs. non-users and warfarin users vs. non-users. For PPV, the RR (users vs. non-users) for antiplatelet monotherapy was 0.86, while the RRs for dual and triple antiplatelet therapies (excluding cilostazol) were 0.67 and 0.22, respectively. For all antithrombotic agents, the sensitivity for CRC detection was not different between users and non-users. Use of antiplatelet agents, except cilostazol, may increase the false positives without improving the sensitivity of FITs for CRC detection.
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http://dx.doi.org/10.3390/jpm11060497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227279PMC
June 2021

Risk of colorectal cancer in patients with positive results of fecal immunochemical test performed within 5 years since the last colonoscopy.

Korean J Intern Med 2021 Sep 18;36(5):1083-1091. Epub 2021 Jun 18.

Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.

Background/aims: Annual fecal immunochemical tests (FITs) are often repeated within the recommended colonoscopy surveillance intervals. However, it remains unclear whether interval FITs are useful. To answer this question, we assessed the risk of colorectal cancer (CRC) according to the interval from the last colonoscopy to an FIT.

Methods: Using the Korean National Cancer Screening Program database, we collected data on patients who underwent FITs in 2011. Patients with positive FIT results were classified into three groups according to their previous colonoscopy interval: 0.5 to 5 years (group 1), 5 to 10 years (group 2), and ≥ 10 years or no colonoscopy (group 3). CRC incidence was defined as CRC diagnosed within 1 year after an FIT.

Results: Among 177,660 patients with positive FIT results, the incidence of CRC in groups 1, 2, and 3 was 0.72% (n = 214/29,575), 1.28% (n = 116/9,083), and 3.88% (n = 5,387/139,002), respectively. The age- and sex-adjusted risk for CRC was higher in groups 2 (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.43 to 2.25) and 3 (OR, 5.56; 95% CI, 4.85 to 6.38) than in group 1. Among patients who did and did not undergo a polypectomy during the previous colonoscopy, those in group 2 had a higher rate of CRC than those in group 1 (without polypectomy: 1.15% vs. 0.63%; OR, 1.79; 95% CI, 1.37 to 2.34) (with polypectomy: 2.37% vs. 0.93 %; OR, 2.30; 95% CI, 1.44 to 3.69).

Conclusion: In patients with positive FIT results who had undergone a colonoscopy within the past 5 years, the risk of CRC is very low, regardless of whether a polypectomy was performed, suggesting that interval FITs are not useful.
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http://dx.doi.org/10.3904/kjim.2020.525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435487PMC
September 2021

G-quadruplex-forming aptamer enhances the peroxidase activity of myoglobin against luminol.

Nucleic Acids Res 2021 06;49(11):6069-6081

Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.

Aptamers can control the biological functions of enzymes, thereby facilitating the development of novel biosensors. While aptamers that inhibit catalytic reactions of enzymes were found and used as signal transducers to sense target molecules in biosensors, no aptamers that amplify enzymatic activity have been identified. In this study, we report G-quadruplex (G4)-forming DNA aptamers that upregulate the peroxidase activity in myoglobin specifically for luminol. Using in vitro selection, one G4-forming aptamer that enhanced chemiluminescence from luminol by myoglobin's peroxidase activity was discovered. Through our strategy-in silico maturation, which is a genetic algorithm-aided sequence manipulation method, the enhancing activity of the aptamer was improved by introducing mutations to the aptamer sequences. The best aptamer conserved the parallel G4 property with over 300-times higher luminol chemiluminescence from peroxidase activity more than myoglobin alone at an optimal pH of 5.0. Furthermore, using hemin and hemin-binding aptamers, we demonstrated that the binding property of the G4 aptamers to heme in myoglobin might be necessary to exert the enhancing effect. Structure determination for one of the aptamers revealed a parallel-type G4 structure with propeller-like loops, which might be useful for a rational design of aptasensors utilizing the G4 aptamer-myoglobin pair.
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http://dx.doi.org/10.1093/nar/gkab388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216272PMC
June 2021

Public Interest in Immunity and the Justification for Intervention in the Early Stages of the COVID-19 Pandemic: Analysis of Google Trends Data.

J Med Internet Res 2021 06 18;23(6):e26368. Epub 2021 Jun 18.

Department of Gerontology Health and Welfare, Pai Chai University, Daejeon, Republic of Korea.

Background: The use of social big data is an important emerging concern in public health. Internet search volumes are useful data that can sensitively detect trends of the public's attention during a pandemic outbreak situation.

Objective: Our study aimed to analyze the public's interest in COVID-19 proliferation, identify the correlation between the proliferation of COVID-19 and interest in immunity and products that have been reported to confer an enhancement of immunity, and suggest measures for interventions that should be implemented from a health and medical point of view.

Methods: To assess the level of public interest in infectious diseases during the initial days of the COVID-19 outbreak, we extracted Google search data from January 20, 2020, onward and compared them to data from March 15, 2020, which was approximately 2 months after the COVID-19 outbreak began. In order to determine whether the public became interested in the immune system, we selected coronavirus, immune, and vitamin as our final search terms.

Results: The increase in the cumulative number of confirmed COVID-19 cases that occurred after January 20, 2020, had a strong positive correlation with the search volumes for the terms coronavirus (R=0.786; P<.001), immune (R=0.745; P<.001), and vitamin (R=0.778; P<.001), and the correlations between variables were all mutually statistically significant. Moreover, these correlations were confirmed on a country basis when we restricted our analyses to the United States, the United Kingdom, Italy, and Korea. Our findings revealed that increases in search volumes for the terms coronavirus and immune preceded the actual occurrences of confirmed cases.

Conclusions: Our study shows that during the initial phase of the COVID-19 crisis, the public's desire and actions of strengthening their own immune systems were enhanced. Further, in the early stage of a pandemic, social media platforms have a high potential for informing the public about potentially helpful measures to prevent the spread of an infectious disease and provide relevant information about immunity, thereby increasing the public's knowledge.
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http://dx.doi.org/10.2196/26368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216330PMC
June 2021

Deep learning for large scale MRI-based morphological phenotyping of osteoarthritis.

Sci Rep 2021 May 25;11(1):10915. Epub 2021 May 25.

Department of Radiology and Biomedical Imaging and Center for Intelligent Imaging, University of California, San Francisco, 1700 Fourth St, Suite 201, QB3 Building, San Francisco, CA, 94107, USA.

Osteoarthritis (OA) develops through heterogenous pathophysiologic pathways. As a result, no regulatory agency approved disease modifying OA drugs are available to date. Stratifying knees into MRI-based morphological phenotypes may provide insight into predicting future OA incidence, leading to improved inclusion criteria and efficacy of therapeutics. We trained convolutional neural networks to classify bone, meniscus/cartilage, inflammatory, and hypertrophy phenotypes in knee MRIs from participants in the Osteoarthritis Initiative (n = 4791). We investigated cross-sectional association between baseline morphological phenotypes and baseline structural OA (Kellgren Lawrence grade > 1) and symptomatic OA. Among participants without baseline OA, we evaluated association of baseline phenotypes with 48-month incidence of structural OA and symptomatic OA. The area under the curve of bone, meniscus/cartilage, inflammatory, and hypertrophy phenotype neural network classifiers was 0.89 ± 0.01, 0.93 ± 0.03, 0.96 ± 0.02, and 0.93 ± 0.02, respectively (mean ± standard deviation). Among those with no baseline OA, bone phenotype (OR: 2.99 (95%CI: 1.59-5.62)) and hypertrophy phenotype (OR: 5.80 (95%CI: 1.82-18.5)) each respectively increased odds of developing incident structural OA and symptomatic OA at 48 months. All phenotypes except meniscus/cartilage increased odds of undergoing total knee replacement within 96 months. Artificial intelligence can rapidly stratify knees into structural phenotypes associated with incident OA and total knee replacement, which may aid in stratifying patients for clinical trials of targeted therapeutics.
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http://dx.doi.org/10.1038/s41598-021-90292-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149826PMC
May 2021

Data on G-quadruplex topology, and binding ability of G-quadruplex forming sequences found in the promoter region of biomarker proteins and those relations to the presence of nuclear localization signal in the proteins.

Data Brief 2021 Jun 1;36:107028. Epub 2021 Apr 1.

Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.

Aptamer is a nucleic acid ligand which specifically binds to its target molecule. Previously, we have designed an identification method of aptamer called "G-quadruplex (G4) promoter-derived aptamer selection (G4PAS)" [1]. In G4PAS procedure, putative G4 forming sequences (PQS) were explored in a promoter region of a target protein in human gene through computational analysis, and evaluated binding ability towards the gene product encoded in the downstream of the promoter. We investigated the topology of the obtained PQSs by circular dichroism measurement, as well as their binding ability against its target protein by surface plasmon resonance measurement and gel-shift assay. Additionally, the presence of nuclear localization signal in the target protein was predicted . This data set summarized all the PQS sequences, their biochemical characteristics, and the presence of nuclear localization signal to address the possibility of binding of these PQS region to the target proteins . Those data should contribute to increase the success rate of G4PAS. Moreover, considering the G4 motifs in genomic DNA are suggested to be involved gene regulation [2], [3], this data set is also potentially beneficial for the cell biology field.
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http://dx.doi.org/10.1016/j.dib.2021.107028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080463PMC
June 2021

Impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course: a systematic review.

BMJ Open 2021 05 3;11(5):e047152. Epub 2021 May 3.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada

Background: Disasters are events that disrupt the daily functioning of a community or society, and may increase long-term risk of adverse cardiometabolic outcomes, including cardiovascular disease, obesity and diabetes. The objective of this study was to conduct a systematic review to determine the impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course.

Design: A systematic search was conducted in May 2020 using two electronic databases, EMBASE and Medline. All studies were screened in duplicate at title and abstract, and full-text level. Studies were eligible for inclusion if they assessed the association between a population-level or community disaster and cardiometabolic outcomes ≥1 month following the disaster. There were no restrictions on age, year of publication, country or population. Data were extracted on study characteristics, exposure (eg, type of disaster, region, year), cardiometabolic outcomes and measures of effect. Study quality was evaluated using the Joanna Briggs Institute critical appraisal tools.

Results: A total of 58 studies were included, with 24 studies reporting the effects of exposure to disaster during pregnancy/childhood and 34 studies reporting the effects of exposure during adulthood. Studies included exposure to natural (n=35; 60%) and human-made (n=23; 40%) disasters, with only three (5%) of these studies evaluating previous pandemics. Most studies reported increased cardiometabolic risk, including increased cardiovascular disease incidence or mortality, diabetes and obesity, but not all. Few studies evaluated the biological mechanisms or high-risk subgroups that may be at a greater risk of negative health outcomes following disasters.

Conclusions: The findings from this study suggest that the burden of disasters extend beyond the known direct harm, and attention is needed on the detrimental indirect long-term effects on cardiometabolic health. Given the current COVID-19 pandemic, these findings may inform public health prevention strategies to mitigate the impact of future cardiometabolic risk.

Prospero Registration Number: CRD42020186074.
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http://dx.doi.org/10.1136/bmjopen-2020-047152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098961PMC
May 2021

Molecular dynamics simulation study on the effect of perfluorosulfonic acid side chains on oxygen permeation in hydrated ionomers of PEMFCs.

Sci Rep 2021 Apr 22;11(1):8702. Epub 2021 Apr 22.

School of Chemical Engineering, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea.

We prepared two types of perfluorosulfonic acid (PFSA) ionomers with Aquivion (short side chain) and Nafion (long side chain) on a Pt surface and varied their water contents (2.92 ≤ λ ≤ 13.83) to calculate the solubility and permeability of O in hydrated PFSA ionomers on a Pt surface using full atomistic molecular dynamics (MD) simulations. The solubility and permeability of O molecules in hydrated Nafion ionomers were greater than those of O molecules in hydrated Aquivion ionomers at the same water content, indicating that the permeation of O molecules in the ionomers is affected not only by the diffusion coefficient of O but also by the solubility of O. Notably, O molecules are more densely distributed in regions where water and hydronium ions have a lower density in hydrated Pt/PFSA ionomers. Radial distribution function (RDF) analysis was performed to investigate where O molecules preferentially dissolve in PFSA ionomers on a Pt surface. The results showed that O molecules preferentially dissolved between hydrophilic and hydrophobic regions in a hydrated ionomer. The RDF analysis was performed to provide details of the O location in hydrated PFSA ionomers on a Pt surface to evaluate the influence of O solubility in ionomers with side chains of different lengths. The coordination number of C(center)-O(O) and O(side chain)-O(O) pairs in hydrated Nafion ionomers was higher than that of the same pairs in hydrated Aquivion ionomers with the same water content. Our investigation provides detailed information about the properties of O molecules in different PFSA ionomers on a Pt surface and with various water contents, potentially enabling the design of better-performing PFSA ionomers for use in polymer electrolyte membrane fuel cells.
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http://dx.doi.org/10.1038/s41598-021-87570-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062474PMC
April 2021

Evaluation of the skin sensitization potential of metal oxide nanoparticles using the ARE-Nrf2 Luciferase KeratinoSens assay.

Toxicol Res 2021 Apr 1;37(2):277-284. Epub 2021 Jan 1.

Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong, Korea.

Numerous studies have reported the potential of chemicals for inducing skin sensitization; however, few studies have examined skin sensitization induced by nanomaterials. This study aimed to evaluate skin sensitization induced by metal oxide nanoparticles (NPs) using the ARE-Nrf2 Luciferase KeratinoSens™ assay. Seven different metal oxide NPs, including copper oxide, cobalt oxide, nickel oxide, titanium oxide, cerium oxide, iron oxide, and zinc oxide, were assessed on KeratinoSens™ cells. We selected an appropriate vehicle among three vehicles (DMSO, DW, and culture medium) by assessing the hydrodynamic size at vehicle selection process. Seven metal oxide NPs were analyzed, and their physicochemical properties, including hydrodynamic size, polydispersity, and zeta potential, were determined in the selected vehicle. Thereafter, we assessed the sensitization potential of the NPs using the ARE-Nrf2 Luciferase KeratinoSens™ assay. Copper oxide NPs induced a positive response, whereas cobalt oxide, nickel oxide, titanium oxide, cerium oxide, iron oxide, and zinc oxide NPs induced no response. These results suggest that the ARE-Nrf2 Luciferase KeratinoSens™ assay may be useful for evaluating the potential for skin sensitization induced by metal oxide NPs.
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http://dx.doi.org/10.1007/s43188-020-00071-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007649PMC
April 2021

Multivariate functional principal component analysis identifies waveform features of gait biomechanics related to early-to-moderate hip osteoarthritis.

J Orthop Res 2021 Aug 7;39(8):1722-1731. Epub 2020 Dec 7.

Department of Radiology and Biomedical Imaging, Musculoskeletal Quantitative Imaging Research, University of California, San Francisco, California, USA.

Clinicians often examine movement patterns to design hip osteoarthritis (OA) interventions, yet traditional biomechanical analyses only report a single timepoint. Multivariate principal component analysis (MFPCA) analyzes the entire waveform (i.e., movement pattern), which clinicians observe to direct treatment. This study investigated hip OA indicators, by (1) employing MFPCA to characterize variance across the hip, knee, and ankle angles in healthy and early-to-moderate hip OA participants; and (2) investigating relationships between these waveform features and hip cartilage health. Bilateral hip magnetic resonance images from 72 participants with Kellgren-Lawrence grades ranging from 0 to 3 were used to calculate mean T and T relaxation times in the femoral and acetabular cartilage. MFPCA was performed on lower-limb gait biomechanics and used to identify primary modes of variation, which were related to T and T relaxation times. Here, a MFPC = mode of variation = waveform feature. In the femoral cartilage, transverse plane MFPCs 3 and 5 and body mass index (BMI) was related to T , while MFPC 2 and BMI were related to T relaxation times. In the acetabular cartilage, sagittal plane MFPC 1 and BMI were related to T , while BMI was related to T relaxation times. Greater internal rotation was related to increased T and T relaxation times in the femoral cartilage, while the greater extension was related to increased T relaxation times in the acetabular cartilage. This study established a data-driven framework to assess relationships between multi-joint biomechanics and quantitative assessments of cartilage health and identified waveform features that could be evaluated in future hip OA intervention studies.
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http://dx.doi.org/10.1002/jor.24901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180534PMC
August 2021

The longitudinal effect of leisure time physical activity on reduced depressive symptoms: The ARIRANG Study.

J Affect Disord 2021 03 17;282:1220-1225. Epub 2021 Jan 17.

Department of Preventive Medicine, Wonju College of Medicine, Yonsei University; Institute of Occupational & Environmental Medicine, Wonju College of Medicine, Yonsei University. Electronic address:

Background: Depression is a serious mental condition and physical activity is known to be effective in alleviating it. This study for rural residents of South Korea investigated whether meeting the recommended amount of physical activity during leisure time (LTPA) can reduce the depressive symptoms.

Methods: A prospective study was conducted with 5,178 participants aged 20 years and over, and we analyzed 1,888 participants excluding those diagnosed with depression at baseline and those with insufficient data after an average of 5.3 years of follow-up. LTPA was quantified by the MET (metabolic equivalent of task) and categorized according to whether the recommended physical activity was met (0, 0.1 to < 7.5, ≥ 7.5 MET h/wk). The relationship with depressive symptoms (CES-D ≥ 41) was generated by adjusted relative risks (RRs) and 95% CIs through multivariate logistic regression.

Results: During the followed-up, 100 (5.3%) participants developed depressive symptoms. Compared to the incidence of depressive symptoms in those who did not perform any LTPA (6.8%), it was significantly lower when the recommended physical activity criteria were met by combining moderate intensity (MET 3 to 6) and vigorous intensity (MET ≥ 6) exercise (3.3%). We observed a 43.7% lower risk of depressive symptoms among those performing more than the recommended minimum (RR, 0.563 [95% CI, 0.341-0.930]) than those who had no LTPA.

Limitations: This study did not address psychosocial factors, and physical activities in daily life and the occupational environment were not considered.

Conclusions: Performing adequate LTPA might be advisable to alleviate depressive symptoms.
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http://dx.doi.org/10.1016/j.jad.2021.01.014DOI Listing
March 2021

Spatio-Chemical Heterogeneity of Defect-Engineered Metal-Organic Framework Crystals Revealed by Full-Field Tomographic X-ray Absorption Spectroscopy.

Angew Chem Int Ed Engl 2021 Apr 18;60(18):10032-10039. Epub 2021 Mar 18.

Laboratory for Catalysis and Sustainable Chemistry, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.

The introduction of structural defects in metal-organic frameworks (MOFs), often achieved through the fractional use of defective linkers, is emerging as a means to refine the properties of existing MOFs. These linkers, missing coordination fragments, create unsaturated framework nodes that may alter the properties of the MOF. A property-targeted utilization of this approach demands an understanding of the structure of the defect-engineered MOF. We demonstrate that full-field X-ray absorption near-edge structure computed tomography can help to improve our understanding. This was demonstrated by visualizing the chemical heterogeneity found in defect-engineered HKUST-1 MOF crystals. A non-uniform incorporation and zonation of the defective linker was discovered, leading to the presence of clusters of a second coordination polymer within HKUST-1. The former is suggested to be responsible, in part, for altered MOF properties; thereby, advocating for a spatio-chemically resolved characterization of MOFs.
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http://dx.doi.org/10.1002/anie.202013422DOI Listing
April 2021

Spatio-Chemical Heterogeneity of Defect-Engineered Metal-Organic Framework Crystals Revealed by Full-Field Tomographic X-ray Absorption Spectroscopy.

Angew Chem Int Ed Engl 2021 Apr 18;60(18):10032-10039. Epub 2021 Mar 18.

Laboratory for Catalysis and Sustainable Chemistry, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.

The introduction of structural defects in metal-organic frameworks (MOFs), often achieved through the fractional use of defective linkers, is emerging as a means to refine the properties of existing MOFs. These linkers, missing coordination fragments, create unsaturated framework nodes that may alter the properties of the MOF. A property-targeted utilization of this approach demands an understanding of the structure of the defect-engineered MOF. We demonstrate that full-field X-ray absorption near-edge structure computed tomography can help to improve our understanding. This was demonstrated by visualizing the chemical heterogeneity found in defect-engineered HKUST-1 MOF crystals. A non-uniform incorporation and zonation of the defective linker was discovered, leading to the presence of clusters of a second coordination polymer within HKUST-1. The former is suggested to be responsible, in part, for altered MOF properties; thereby, advocating for a spatio-chemically resolved characterization of MOFs.
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http://dx.doi.org/10.1002/anie.202013422DOI Listing
April 2021

Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of , , and clinical trials.

Theranostics 2021 1;11(3):1207-1231. Epub 2021 Jan 1.

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.

Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of , , and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.
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http://dx.doi.org/10.7150/thno.48342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738873PMC
January 2021

Association of Metabolically Healthy Obesity and Future Depression: Using National Health Insurance System Data in Korea from 2009-2017.

Int J Environ Res Public Health 2020 12 23;18(1). Epub 2020 Dec 23.

Department of Psychiatry, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea.

(1) Background: The health implications associated with the metabolically healthy obese (MHO) phenotype, in particular related to symptoms of depression, are still not clear. the purpose of this study is to check whether depression and metabolic status are relevant by classifying them into four groups in accordance with the MHO diagnostic standard. Other impressions seen were the differences between sexes and the effects of the MHO on the occurrence of depression. (2) Methods: A sample of 3,586,492 adult individuals from the National Health Insurance Database of Korea was classified into four categories by their metabolic status and body mass index: (1) metabolically healthy non-obese (MHN); (2) metabolically healthy obese (MHO); (3) metabolically unhealthy non-obese (MUN); and (4) metabolically unhealthy obese (MUO). Participants were followed for six to eight years for new incidences of depression. The statistical significance of the general characteristics of the four groups, as well as the mean differences in metabolic syndrome risk factors, was assessed with the use of a one-way analysis of variance (ANOVA). (3) Results: The MHN ratio in women was higher than in men (men 39.3%, women 55.2%). In both men and women, depression incidence was the highest among MUO participants (odds ratio (OR) = 1.01 in men; OR = 1.09 in women). It was concluded as well that, among the risk factors of metabolic syndrome, waist circumference was the most related to depression. Among the four groups, the MUO phenotype was the most related to depression. Furthermore, in women participants, MHO is also related to a higher risk of depressive symptoms. These findings indicate that MHO is not a totally benign condition in relation to depression in women. (4) Conclusion: Therefore, reducing metabolic syndrome and obesity patients in Korea will likely reduce the incidence of depression.
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http://dx.doi.org/10.3390/ijerph18010063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795335PMC
December 2020

Automatic hip abductor muscle fat fraction estimation and association with early OA cartilage degeneration biomarkers.

J Orthop Res 2020 Dec 25. Epub 2020 Dec 25.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.

The aim of this study was to develop an automatic segmentation method for hip abductor muscles and find their fat fraction associations with early stage hip osteoarthritis (OA) cartilage degeneration biomarkers. This Institutional Review Board approved, Health Insurance Portability and Accountability Act compliant prospective study recruited 61 patients with evidence of hip OA or Femoroacetabular Impingement (FAI). Magnetic resonance (MR) images were acquired for cartilage segmentation, T and T relaxation times computation and grading of cartilage lesion scores. A 3D V-Net (Dice loss, Adam optimizer, learning rate = 1e , batch size = 3) was trained to segment the three muscles (gluteus medius, gluteus minimus, and tensor fascia latae). The V-Net performance was measured using Dice, distance maps between manual and automatic masks, and Bland-Altman plots of the fat fractions and volumes. Associations between muscle fat fraction and T , T relaxation times values were found using voxel based relaxometry (VBR). A p < 0.05 was considered significant. The V-Net had a Dice of 0.90, 0.88, and 0.91 (GMed, GMin, and TFL). The VBR results found associations of fat fraction of all three muscles in early stage OA and FAI patients with T , T relaxation times. Using an automatic, validated segmentation model, the associations derived between OA biomarkers and muscle fat fractions provide insight into early changes that occur in OA, and show that hip abductor muscle fat is associated with markers of cartilage degeneration.
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http://dx.doi.org/10.1002/jor.24974DOI Listing
December 2020

Influence of implantations of extended depth-of-focus on standard automated perimetry.

Sci Rep 2020 11 19;10(1):20153. Epub 2020 Nov 19.

Miyata Eye Hospital, 6-3, Kurahara-cho, Miyakonojo, Miyazaki, 885-0051, Japan.

This prospective study aimed to investigate the influence of an extended depth-of-focus intraocular lens (EDOF IOL) on standard automated perimetry. Ninety eyes of 90 patients who had undergone cataract surgery from February 2018 to December 2018 were included. No patients had any diseases that might affect the visual field. ZMB00 (+ 4.00 D add), ZXR00V (+ 1.75 D add), and ZCB00V (Johnson & Johnson Surgical Vision, Santa Ana, CA, USA) were used as multifocal, EDOF, and monofocal IOLs, respectively. Humphrey Visual Field 10-2 testing was performed 2-3 months after cataract surgery, acceptable reliability indices were measured, and mean deviation (MD), pattern standard deviation (PSD), foveal sensitivity and mean sensitivity (MS) were compared. Seventy-one eyes (ZXR00V: 24 eyes, ZMB00: 25 eyes, ZCB00V: 22 eyes) were used for the analyses. The MD and MS of the EDOF and monofocal groups were significantly higher than those of the multifocal group (P < 0.0051). However, the MD and MS of the EDOF and monofocal groups were not different (P > 0.23). The PSD and foveal sensitivity were not different among the groups. In non-glaucomatous patients, the MD and MS of the EDOF IOL were comparable to those of the monofocal IOL and better than those of the multifocal IOL.
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http://dx.doi.org/10.1038/s41598-020-77214-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678857PMC
November 2020

Effective Control of COVID-19 in South Korea: Cross-Sectional Study of Epidemiological Data.

J Med Internet Res 2020 12 10;22(12):e22103. Epub 2020 Dec 10.

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: South Korea is one of the few countries that has succeeded in flattening the curve of new COVID-19 cases and avoiding a second outbreak by implementing multiple strategies, ranging from an individual level to the population level.

Objective: We aim to discuss the unique strategies and epidemiological characteristics of COVID-19 in South Korea and present a summary of policies implemented by the Korean government during the COVID-19 pandemic.

Methods: We designed a cross-sectional study of epidemiological data published by the Korea Centers for Disease Control and Prevention on October 1, 2020. We analyzed detailed epidemiological information of COVID-19 cases, including the number of confirmed cases and resulting deaths.

Results: As of October 1, 2020, a total of 23,889 confirmed COVID-19 cases and 415 deaths were reported in South Korea. In this paper, we present data on the epidemiological characteristics and transmission of the disease and discuss how the South Korean government, health care providers, and society responded to the COVID-19 outbreak.

Conclusions: Understanding the epidemiological characteristics of COVID-19 in South Korea and the government's successful efforts in managing the spread of the disease can provide important insights to other countries dealing with the ongoing pandemic.
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http://dx.doi.org/10.2196/22103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732355PMC
December 2020

Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review.

Lancet Psychiatry 2020 11;7(11):955-970

Early Psychosis: Interventions and Clinical-Detection Lab, Department of Psychosis Studies, King's College London, London, UK; Outreach and Support in South London (OASIS) Service, South London and Maudsley NHS Foundation Trust, London, UK; National Institute of Health Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.

Background: Many potential environmental risk factors, environmental protective factors, and peripheral biomarkers for ADHD have been investigated, but the consistency and magnitude of their effects are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD.

Methods: In this umbrella review of meta-analyses, we searched PubMed including MEDLINE, Embase, and the Cochrane Database of Systematic Reviews, from database inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses that used categorical ADHD diagnosis criteria according to DSM, hyperkinetic disorder according to ICD, or criteria that were less rigorous than DSM or ICD, such as self-report. We excluded articles that did not examine environmental risk factors, environmental protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated summary effect estimates (odds ratio [OR], relative risk [RR], weighted mean difference [WMD], Cohen's d, and Hedges' g), 95% CI, heterogeneity I statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032.

Findings: We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and environmental protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median controls 187). Evidence of association was convincing (class I) for maternal pre-pregnancy obesity (OR 1·63, 95% CI 1·49 to 1·77), childhood eczema (1·31, 1·20 to 1·44), hypertensive disorders during pregnancy (1·29, 1·22 to 1·36), pre-eclampsia (1·28, 1·21 to 1·35), and maternal acetaminophen exposure during pregnancy (RR 1·25, 95% CI 1·17 to 1·34). Evidence of association was highly suggestive (class II) for maternal smoking during pregnancy (OR 1·6, 95% CI 1·45 to 1·76), childhood asthma (1·51, 1·4 to 1·63), maternal pre-pregnancy overweight (1·28, 1·21 to 1·35), and serum vitamin D (WMD -6·93, 95% CI -9·34 to -4·51).

Interpretation: Maternal pre-pregnancy obesity and overweight; pre-eclampsia, hypertension, acetaminophen exposure, and smoking during pregnancy; and childhood atopic diseases were strongly associated with ADHD. Previous familial studies suggest that maternal pre-pregnancy obesity, overweight, and smoking during pregnancy are confounded by familial or genetic factors, and further high-quality studies are therefore required to establish causality.

Funding: None.
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http://dx.doi.org/10.1016/S2215-0366(20)30312-6DOI Listing
November 2020

Interval Cancer Rate and Diagnostic Performance of Fecal Immunochemical Test According to Family History of Colorectal Cancer.

J Clin Med 2020 Oct 14;9(10). Epub 2020 Oct 14.

Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Korea.

Background: The potential role of the fecal immunochemical test (FIT) in individuals with a family history of colorectal cancer (CRC) remains unclear. We assessed interval cancer rate (ICR) after the FIT and FIT diagnostic performance according to family history of CRC.

Methods: Using the Korean National Cancer Screening Program Database, we collected data on subjects who underwent the FIT between 2009 and 2011. The interval cancer rate (ICR) was defined as the number of subjects diagnosed with CRC within 1 year after the FIT per 1000 subjects with negative FIT results.

Results: Of 5,643,438 subjects, 224,178 (3.97%) had a family history of CRC. FIT positivity rate (6.4% vs. 5.9%; adjusted relative risk (aRR) 1.11; 95% confidence interval (CI) 1.09-1.13) and ICR (1.4 vs. 1.1; aRR 1.43 (95% CI 1.27-1.60)) were higher in these subjects than in those with no such history. These results were the same regardless of whether subjects had undergone colonoscopy within the last 5 years before the FIT. However, the diagnostic performance of the FIT for CRC, as measured using the area under the operating characteristic curve, was similar between subjects without a family history and those with one (85.5% and 84.6%, respectively; = 0.259).

Conclusion: the FIT was 1.4 times more likely to miss CRC in subjects with a family history than in those without (aRR 1.43 for ICR), although its diagnostic performance was similar between the two groups. Our results suggest that for individuals with a family history of CRC, colonoscopy should be preferred over FIT for both screening and surveillance.
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http://dx.doi.org/10.3390/jcm9103302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602405PMC
October 2020

Genetic Variation and Autism: A Field Synopsis and Systematic Meta-Analysis.

Brain Sci 2020 Sep 30;10(10). Epub 2020 Sep 30.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AB, UK.

This study aimed to verify noteworthy findings between genetic risk factors and autism spectrum disorder (ASD) by employing the false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP). PubMed and the Genome-Wide Association Studies (GWAS) catalog were searched from inception to 1 August, 2019. We included meta-analyses on genetic factors of ASD of any study design. Overall, twenty-seven meta-analyses articles from literature searches, and four manually added articles from the GWAS catalog were re-analyzed. This showed that five of 31 comparisons for meta-analyses of observational studies, 40 out of 203 comparisons for the GWAS meta-analyses, and 18 out of 20 comparisons for the GWAS catalog, respectively, had noteworthy estimations under both Bayesian approaches. In this study, we found noteworthy genetic comparisons highly related to an increased risk of ASD. Multiple genetic comparisons were shown to be associated with ASD risk; however, genuine associations should be carefully verified and understood.
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http://dx.doi.org/10.3390/brainsci10100692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600188PMC
September 2020

Estimation of global case fatality rate of coronavirus disease 2019 (COVID-19) using meta-analyses: Comparison between calendar date and days since the outbreak of the first confirmed case.

Int J Infect Dis 2020 Nov 1;100:302-308. Epub 2020 Sep 1.

The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, CB1 1PT, UK.

Objective: Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, estimating the pandemic's case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time.

Methods: A proportion meta-analysis was carried out on the CFR in every country reporting COVID-19 cases. Based on these results, we performed a meta-analysis for a global COVID-19 CFR. Each analysis was performed using two different calculations of CFR: according to the calendar date and according to the days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR, concurrently based on the date of the first confirmed case as well as on a daily basis.

Results: For the first time, we showed that using meta-analyses according to the calendar date and days since the outbreak of the first confirmed case, were different.

Conclusion: We propose that a CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics.
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http://dx.doi.org/10.1016/j.ijid.2020.08.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462556PMC
November 2020
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