Summary
COVID‐19, caused by SARS‐CoV‐2, is a contagious life‐threatening viral disease that has killed more than three million people worldwide to date. Attempts have been made to identify ...biomarker(s) to stratify disease severity and improve treatment and resource allocation. Patients with SARS‐COV‐2 infection manifest with a higher inflammatory response and platelet hyperreactivity; this raises the question of the role of thrombopoiesis in COVID‐19 infection. Immature platelet fraction (IPF, %) and immature platelet counts (IPC, ×109/l) can be used to assess thrombopoiesis. This study investigates whether the level of thrombopoiesis correlates with COVID‐19 severity. A large cohort of 678 well‐characterized COVID‐19 patients was analyzed, including 658 (97%) hospitalized and 139 (21%) admitted to the intensive care unit (ICU). Elevated percentage IPF at presentation was predictive of length of hospitalization (P < 0·01) and ICU admission (P < 0·05). Additionally, percentage IPF at the peak was significantly higher among ICU patients than non‐ICU patients (6·9 ± 5·1 vs 5·3 ± 8·4, P < 0·01) and among deceased patients than recovered patients (7·9 ± 6·3 vs 5·4 ± 7·8, P < 0·01). Furthermore, IPC at the peak was significantly higher among ICU patients than non‐ICU patients (18·5 ± 16·2 vs. 13·2 ± 8·3, P < 0·05) and among patients on a ventilator than those not (22·1 ± 20·1 vs.13·4 ± 8·4, P < 0·05). Our study demonstrated that elevated initial and peak values of percentage IPF and IPC might serve as prognostic biomarkers for COVID‐19 progression to severe conditions.
Objectives
Persistent postural‐perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter ...study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration.
Methods
Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments.
Results
Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space‐motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD.
Conclusion
This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.
Insulin resistance (IR) affects not only the regulation of carbohydrate metabolism but all aspects of lipid and lipoprotein metabolism. IR is associated with increased secretion of VLDL and increased ...plasma triglycerides, as well as with hepatic steatosis, despite the increased VLDL secretion. Here we link IR with increased VLDL secretion and hepatic steatosis at both the physiologic and molecular levels. Increased VLDL secretion, together with the downstream effects on high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) size, is proatherogenic. Hepatic steatosis is a risk factor for steatohepatitis and cirrhosis. Understanding the complex inter-relationships between IR and these abnormalities of liver lipid homeostasis will provide insights relevant to new therapies for these increasing clinical problems.
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•Ionic and neutral PFASs were analyzed simultaneously in 9 environmental matrices.•Industrial complex and WWTP were major emission sources•The effects of emission source and their ...spatial distribution were confirmed.•Long chain PFCAs and PFOS were dominant in dust, soil, sediment and sludge.•PFBS and neutral PFASs were dominant in air, whereas PFCAs were dominant in biota.
This study investigated perfluoroalkyl substances (PFASs) in multimedia environments to confirm the effects of emission sources of PFASs and to elucidate their spatial distribution. The highest PFAS levels were detected from the samples of air (272.30 pg/m3) and surface water (36.54 ng/L) in an industrial complex area, meanwhile high PFAS levels were found from the samples of soil (8.80 ng/g) and sediment (84.98 ng/g) in urban areas and near wastewater treatment plants (WWTPs). Perfluorobutane sulfonate (PFBS) was primarily detected in water, influent and effluent, whereas long chain perfluorocarboxylic acids (PFCAs) and perfluorooctane sulfonate (PFOS) were dominant in dust, soil, sediment and sludge. While PFBS and neutral PFASs were dominant in air, PFCAs were primarily detected in plant and fish. The specific distribution patterns of PFASs in each matrix showed the influences of surrounding environments and different physicochemical characteristics of each congener. These findings suggest that the industrial complex and WWTP might be major emission sources to air and aquatic environments, respectively. This is the first study in which 6 neutral and 13 ionic PFASs were investigated simultaneously for nine different matrices in multimedia environments, and also it would be a good model study for future assessment of PFASs.
Insects are the most abundant animals on Earth, and the microbiota within their guts play important roles by engaging in beneficial and pathological interactions with these hosts. In this study, we ...comprehensively characterized insect-associated gut bacteria of 305 individuals belonging to 218 species in 21 taxonomic orders, using 454 pyrosequencing of 16S rRNA genes. In total, 174,374 sequence reads were obtained, identifying 9,301 bacterial operational taxonomic units (OTUs) at the 3% distance level from all samples, with an average of 84.3 (± 97.7) OTUs per sample. The insect gut microbiota were dominated by Proteobacteria (62.1% of the total reads, including 14.1% Wolbachia sequences) and Firmicutes (20.7%). Significant differences were found in the relative abundances of anaerobes in insects and were classified according to the criteria of host environmental habitat, diet, developmental stage, and phylogeny. Gut bacterial diversity was significantly higher in omnivorous insects than in stenophagous (carnivorous and herbivorous) insects. This insect-order-spanning investigation of the gut microbiota provides insights into the relationships between insects and their gut bacterial communities.
The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a ...cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Collectively, the pleiotropic nature of TGF-β signaling contributes to drug resistance, tumor escape and undermines clinical response to therapy. Based upon a wealth of preclinical studies, the TGF-β pathway has been pharmacologically targeted using small molecule inhibitors, TGF-β-directed chimeric monoclonal antibodies, ligand traps, antisense oligonucleotides and vaccines that have been now evaluated in clinical trials. Here, we have assessed the safety and efficacy of TGF-β pathway antagonists from multiple drug classes that have been evaluated in completed and ongoing trials. We highlight Vactosertib, a highly potent small molecule TGF-β type 1 receptor kinase inhibitor that is well-tolerated with an acceptable safety profile that has shown efficacy against multiple types of cancer. The TGF-β ligand traps Bintrafusp alfa (a bifunctional conjugate that binds TGF-β and PD-L1), AVID200 (a computationally designed trap of TGF-β receptor ectodomains fused to an Fc domain) and Luspatercept (a recombinant fusion that links the activin receptor IIb to IgG) offer new ways to fight difficult-to-treat cancers. While TGF-β pathway antagonists are rapidly emerging as highly promising, safe and effective anticancer agents, significant challenges remain. Minimizing the unintentional inhibition of tumor-suppressing activity and inflammatory effects with the desired restraint on tumor-promoting activities has impeded the clinical development of TGF-β pathway antagonists. A better understanding of the mechanistic details of the TGF-β pathway should lead to more effective TGF-β antagonists and uncover biomarkers that better stratify patient selection, improve patient responses and further the clinical development of TGF-β antagonists.
This study demonstrated the 10-year trend of 13 perfluoroalkyl substances (PFASs) serum levels among 786 adults living in Seoul, Korea. PFAS levels gradually increased from 2006 to 2013, decreasing ...thereafter. We found that PFAS levels were higher in male than in female participants and were positively correlated with age. PFASs were not significantly correlated with body mass index, although we observed positive correlations with total cholesterol, low-density lipoprotein cholesterol, and triglycerides and negative correlations with high-density lipoprotein cholesterol. Uric acid and free thyroxine (fT4) also showed positive correlations with major congeners while correlations between thyroid stimulating hormone and PFASs were inconsistent. We demonstrated significant correlations between fT4 and perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoic acid (PFDA). There were significant differences in PFHxS and perfluorododecanoic acid (PFDoDA) levels between participants with and without diabetes. Furthermore, principal component analysis suggested possible differences in disease manifestation based on the congener distribution of PFASs. This study is the first study of temporal trends of 13 PFAS congeners in serum samples obtained from the Korean general population; it is currently longest and largest scale study of this type.
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•We conducted a time-trend analysis of 13 major PFASs over 10 years for 786 adults.•This is the longest and largest scale research and the first study in Korea.•The relationships between PFAS levels and sex, age, and BMI were assessed.•We observed significant correlations between PFASs and cholesterol levels.•Uric acid and free thyroxine showed positive correlations with PFAS levels.
This study evaluated the 12-year trends in serum levels of 28 organochlorine pesticides (OCPs) in 880 adults living in Seoul, Korea. The OCP levels decreased from 2006 to 2017, and ...p,p′-dichlorodiphenyldichloroethylene was a predominant compound. OCP levels were higher in females than in males, and showed positive associations with BMI and age. The OCP concentrations had inverted U-shaped associations with low-density lipoprotein cholesterol and total cholesterol. Concentrations of β-hexachlorocyclohexane were significantly higher in patients with hypertension than in participants that were normotensive. OCP levels showed positive associations with uric acid, creatinine, and thyroid-stimulating hormone, but negative associations with free thyroxine. Participants with diabetes had significantly higher OCP levels than those without it. Principal component analysis suggested possible differences in disease manifestation depending on the composition of OCPs. These results suggest that OCPs might disturb renal transport and thyroid homeostasis. To our knowledge, the inverted U-shaped associations of heptachlor epoxide and endosulfan with cholesterol, the epidemiological associations of trans-nonachlor and endosulfan with thyroid hormones, and the association of p,p′-DDE with hyperuricemia have not been previously reported in general population. This is the first long-term study to show trends of 28 OCPs in serum and associations with various health indicators in Korea.
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●We conducted a time-trend analysis of 28 OCPs over 12 years for 880 adults.●Cholesterol levels had inverted U-shaped associations with OCP levels.●Uric acid and thyroid stimulating hormone showed positive correlations with OCPs.●Free thyroxine had negative associations with OCP levels.●Hypertension and diabetes had significant correlations with OCP exposure.
Magnetic skyrmions are topologically protected spin textures with attractive properties suitable for high-density and low-power spintronic device applications. Much effort has been dedicated to ...understanding the dynamical behaviours of the magnetic skyrmions. However, experimental observation of the ultrafast dynamics of this chiral magnetic texture in real space, which is the hallmark of its quasiparticle nature, has so far remained elusive. Here, we report nanosecond-dynamics of a 100nm-diameter magnetic skyrmion during a current pulse application, using a time-resolved pump-probe soft X-ray imaging technique. We demonstrate that distinct dynamic excitation states of magnetic skyrmions, triggered by current-induced spin-orbit torques, can be reliably tuned by changing the magnitude of spin-orbit torques. Our findings show that the dynamics of magnetic skyrmions can be controlled by the spin-orbit torque on the nanosecond time scale, which points to exciting opportunities for ultrafast and novel skyrmionic applications in the future.
Oral lichen planus (OLP) is one of the most prevalent oral mucosal diseases, but there is no cure for OLP yet. The aim of this study was to gain insights into the role of barrier dysfunction and ...infection in OLP pathogenesis through analysis of transcriptome datasets available in public databases. Two transcriptome datasets were downloaded from the Gene Expression Omnibus database and analyzed as whole and as partial sets after removing outliers. Differentially expressed genes (DEGs) upregulated in the dataset of OLP versus healthy epithelium were significantly enriched in epidermal development, keratinocyte differentiation, keratinization, responses to bacterial infection, and innate immune response. In contrast, the upregulated DEGs in the dataset of the mucosa predominantly reflected chemotaxis of immune cells and inflammatory/immune responses. Forty-three DEGs overlapping in the two datasets were identified after removing outliers from each dataset. The overlapping DEGs included genes associated with hyperkeratosis (upregulated LCE3E and TMEM45A), wound healing (upregulated KRT17, IL36G, TNC, and TGFBI), barrier defects (downregulated FRAS1 and BCL11A), and response to infection (upregulated IL36G, ADAP2, DFNA5, RFTN1, LITAF, and TMEM173). Immunohistochemical examination of IL-36γ, a protein encoded by one of the DEGs IL36G, in control (n = 7) and OLP (n = 25) tissues confirmed the increased expression of IL-36γ in OLP. Collectively, we identified gene signatures associated with hyperkeratosis, wound healing, barrier defects, and response to infection in OLP. IL-36γ, a cytokine involved in both wound repair and antimicrobial defense, may be a possible therapeutic target in OLP.
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