Publications by authors named "Min Kang"

1,165 Publications

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Improving trauma care in exsanguinating patients with CHOP (critical haemorrhage to operating-room patient) resuscitation protocol-A cumulative summation (CUSUM) analysis.

Injury 2021 May 29. Epub 2021 May 29.

Department of Surgery, Khoo Teck Puat Hospital, 90 Yishun Central, 768828 Singapore.

Introduction: The standard protocol for exsanguinating trauma patients involves initial evaluation and resuscitation in the emergency department which then sets the stage for subsequent definitive care and disposition. This involves major coordination and mobilisation of resources which may cause a delay in intervention especially when most of these cases present after office hours. Our centre has employed a second-tier activation system (CHOP protocol) that immediately mobilises all respective trauma specialists including interventional radiologists and allows rapid access to the operating room.

Objective: We hypothesised that exsanguinating patients managed by CHOP protocol have better overall outcome and survival.

Methods: We identified trauma patients that fulfilled CHOP criteria from 2016 to 2019 and divided them into two groups: preCHOP (standard protocol) and CHOP. Data was extracted from a prospectively maintained trauma registry. Demographics, injury pattern and in-hospital data were analysed. The key outcome studied was the impact of CHOP protocol on the mortality rate. Success and failure of the two groups were analysed using CUSUM methodology.

Results: Thirty-seven patients were managed by CHOP protocol since its introduction in March 2018 compared to 36 patients who underwent standard protocol. Majority of the cases were blunt trauma (89% CHOP vs 92% preCHOP). The mean Injury Severity Score was 37 for CHOP group and 39 for preCHOP group. We observed a significant improvement in time to intervention in CHOP patients (78 min vs 113 min), both during and after office hours. CHOP patients had lower mortality compared to preCHOP group (11% vs 31%) and the effectiveness of the protocol was seen in achieving significantly lower mortality compared to the predicted model. CHOP protocol was able to produce a consistent trend of desired outcomes leading to the CUSUM curve exhibiting a sustained downward slope.

Conclusion: The CHOP protocol, a relatively novel system in the local context, was able to achieve sustained improved outcomes compared to standard protocol. The CUSUM analysis concurred that implementation of CHOP protocol has helped to achieve consistent desired outcomes. It also suggested that the uptake and use of this protocol has integrated well into the existing workflow.
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http://dx.doi.org/10.1016/j.injury.2021.05.038DOI Listing
May 2021

Decreased Exosomal Acetylcholinesterase Activity in the Plasma of Patients With Parkinson's Disease.

Front Aging Neurosci 2021 28;13:665400. Epub 2021 May 28.

Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, South Korea.

Exosomes, which are small extracellular vesicles produced from various cell types, contain a variety of molecular constituents, such as proteins, lipids, and RNA. Recently, exosomal biomarkers have been investigated to probe the understanding and diagnosis of neurodegenerative disorders. Previous reports have demonstrated increased exosomal α-synuclein (α-syn) in patients with Parkinson's disease (PD) in comparison to healthy controls (HC). Interestingly, the cholinergic loss was revealed in the central and peripheral nervous systems in histopathology and molecular neuroimaging. Thereby, we simultaneously examined acetylcholinesterase (AChE) with α-syn as exosomal markers. Exosomes were isolated from the plasma of 34 FP-CIT PET proven patients with PD and 29 HC. Exosomal α-syn and AChE activity were quantified andthe relationship with clinical parameters was analyzed. Remarkably, exosomal AChE activity was significantly decreased in PD compared to HC ( = 0.002). Moreover, exosomal AChE activity in PD revealed a strong negative correlation with disease severity, including H&Y ( = 0.007) and UPDRS part III ( = 0.047) scores. By contrast, no significant difference in exosomal α-syn concentration was observed between groups. These results support the occurrence of cholinergic dysfunction in PD, and they could be implicated with disease progression, especially motor deficits. Exosomal AChE activity with advanced exosome isolation techniques may be a reliable biomarker for the early diagnosis and prognosis of PD.
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http://dx.doi.org/10.3389/fnagi.2021.665400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193230PMC
May 2021

Singapore: A Diverse Research Hub of Asia.

Org Lett 2021 Jun 11;23(12):4509-4510. Epub 2021 Jun 11.

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http://dx.doi.org/10.1021/acs.orglett.1c01588DOI Listing
June 2021

Singapore: A Diverse Research Hub of Asia.

J Org Chem 2021 Jun 11;86(12):7893-7894. Epub 2021 Jun 11.

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http://dx.doi.org/10.1021/acs.joc.1c01114DOI Listing
June 2021

The impacts of precipitation patterns on dengue epidemics in Guangzhou city.

Int J Biometeorol 2021 Jun 11. Epub 2021 Jun 11.

Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.

Some studies have demonstrated that precipitation is an important risk factor of dengue epidemics. However, current studies mostly focused on a single precipitation variable, and few studies focused on the impact of precipitation patterns on dengue epidemics. This study aims to explore optimal precipitation patterns for dengue epidemics. Weekly dengue case counts and meteorological data from 2006 to 2018 in Guangzhou of China were collected. A generalized additive model with Poisson distribution was used to investigate the association between precipitation patterns and dengue. Precipitation patterns were defined as the combinations of three weekly precipitation variables: accumulative precipitation (Pre_A), the number of days with light or moderate precipitation (Pre_LMD), and the coefficient of precipitation variation (Pre_CV). We explored to identify optimal precipitation patterns for dengue epidemics. With a lead time of 10 weeks, minimum temperature, relative humidity, Pre_A, and Pre_LMD were positively associated with dengue, while Pre_CV was negatively associated with dengue. A precipitation pattern with Pre_A of 20.67-55.50 mm per week, Pre_LMD of 3-4 days per week, and Pre_CV less than 1.41 per week might be an optimal precipitation pattern for dengue epidemics in Guangzhou. The finding may be used for climate-smart early warning and decision-making of dengue prevention and control.
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http://dx.doi.org/10.1007/s00484-021-02149-2DOI Listing
June 2021

Clonal dissemination of Salmonella enterica serovar albany with concurrent resistance to ampicillin, chloramphenicol, streptomycin, sulfisoxazole, tetracycline, and nalidixic acid in broiler chicken in Korea.

Poult Sci 2021 Mar 22;100(7):101141. Epub 2021 Mar 22.

Department of Veterinary Infectious Diseases and Avian Diseases, College of Veterinary Medicine and Center for Poultry Diseases Control, Jeonbuk National University, South Korea; Bio Disease Control(BIOD) Co., Ltd., Iksan, South Korea. Electronic address:

The aim of this study was to determine the prevalence, serovar distribution, antimicrobial resistance, and genotypic analyses of the dominating serovars of Salmonella in chickens from a national study in Korea. Between 2017 and 2018, a total of 550 chicken samples were collected from the top 12 integrated broiler chicken operations in Korea. Salmonella was isolated from 117 (32.5%) chicken feces and 19 (10.0%) retail chicken meat sources. Ten serovars were identified, and the most common Salmonella serovar was Salmonella ser. Albany (50 isolates, 36.8%), followed by S. Enteritidis (38 isolates, 27.9%), and S. Montevideo (23 isolates, 16.9%) isolated from 6, 10, and 6 operations, respectively. A total of 35 (25.7%) isolates were with the ACSSuTN (ampicillin, chloramphenicol, streptomycin, sulfisoxazole, tetracycline, and nalidixic acid) resistance pattern, with high prevalence of this resistance pattern in S. Albany (29 isolates, 58.0%). A total of 35 PFGE types were identified among Salmonella isolates of the serovars Albany, Enteritidis, Virchow, Montevideo, and Senftenberg, while 11 distinct types of PFGE patterns were found among S. Albany isolates, which showed an overall homology similarity of higher than 85%. Among these 35 PFGE types, 22 PFGE types corresponded to 32 isolates from samples limited to one operation, and the other 13 PFGE types corresponded to 72 isolates from samples widely distributed among different operations. These results highlighted rapid colony dissemination of multidrug-resistant S. Albany in chicken all over Korea after it first appeared in 2016; furthermore, the spread of Salmonella colonies between various integrated operations was common, and several operations played an important role in Salmonella carriage and transmission in Korea.
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http://dx.doi.org/10.1016/j.psj.2021.101141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182268PMC
March 2021

Generation of Stilbene Glycoside with Promising Cell Rejuvenation Activity through Biotransformation by the Entomopathogenic Fungus .

Biomedicines 2021 May 17;9(5). Epub 2021 May 17.

College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Korea.

A stilbene glycoside (resvebassianol A) () with a unique sugar unit, 4--methyl-D-glucopyranose, was identified through biotransformation of resveratrol (RSV) by the entomopathogenic fungus to obtain a superior RSV metabolite with enhanced safety. Its structure, including its absolute configurations, was determined using spectroscopic data, HRESIMS, and chemical reactions. Microarray analysis showed that the expression levels of filaggrin, HAS2-AS1, and CERS3 were higher, while those of IL23A, IL1A, and CXCL8 were lower in the resvebassianol A-treated group than in the RSV-treated group, as confirmed by qRT-PCR. Compound exhibited the same regenerative and anti-inflammatory effects as RSV with no cytotoxicity in skin keratinocytes and TNF-α/IFN-γ-stimulated HIEC-6 cells, suggesting that compound is a safe and stable methylglycosylated RSV. Our findings suggest that our biotransformation method can be an efficient biosynthetic platform for producing a broad range of natural glycosides with enhanced safety.
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http://dx.doi.org/10.3390/biomedicines9050555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156121PMC
May 2021

Evidence for lack of transmission by close contact and surface touch in a restaurant outbreak of COVID-19.

J Infect 2021 May 29. Epub 2021 May 29.

Guangdong Provincial Center for Disease Control and Prevention, Guangdong province, China. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease that has become a global pandemic. Close contact plays an important role in infection spread, while fomite may also be a possible transmission route. Research during the COVID-19 pandemic has identified long-range airborne transmission as one of the important transmission routes although lack solid evidence.

Methods: We examined video data related to a restaurant associated COVID-19 outbreak in Guangzhou. We observed more than 40,000 surface touches and 13,000 episodes of close contacts in the restaurant during the entire lunch duration. These data allowed us to analyse infection risk via both the fomite and close contact routes.

Results: There is no significant correlation between the infection risk via both fomite and close contact routes among those who were not family members of the index case. We can thus rule out virus transmission via fomite contact and interpersonal close contact routes in the Guangzhou restaurant outbreak. The absence of a fomite route agrees with the COVID-19 literature.

Conclusions: These results provide indirect evidence for the long-range airborne route dominating SARS-CoV-2 transmission in the restaurant. We note that the restaurant was poorly ventilated, allowing for increasing airborne SARS-CoV-2 concentration.
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http://dx.doi.org/10.1016/j.jinf.2021.05.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164346PMC
May 2021

Autophagy was activated against the damages of placentas caused by nano-copper oral exposure.

Ecotoxicol Environ Saf 2021 May 26;220:112364. Epub 2021 May 26.

College of Veterinary Medicine, Sichuan Agricultural University, 211 Huimin Road, Chengdu 611130, Sichuan, China. Electronic address:

Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and bioactivities. In our previous study, nano-Cu was found to hamper fetal development; however, the toxicity of nano-Cu and its effects in placental function have not been elucidated. Therefore, we investigated the toxic effects of nano-Cu using rat placenta. Pregnant Sprague-Dawley rats were orally exposed to different copper sources from the third day of gestation (GD 3) to GD 18. We found that nano-Cu (180 mg/kg) and CuCl.2 HO increased the accumulation of copper. Besides, nano-Cu and CuCl.2 HO disrupted the placental morphology and induced oxidative stress. Micro-copper (micro-Cu) caused similar toxicity in the placenta, but its effects were weaker than that of nano-Cu and CuCl.2 HO. In addition, exposure to nano-Cu (180 mg/kg) and CuCl.2 HO induced inflammation in the rat placenta. Furthermore, nano-Cu, micro-Cu, and CuCl.2 HO upregulated the expression of the autophagy-related proteins, Beclin-1 and LC3 II/ LC3 I, and downregulated that of p62. Moreover, nano-Cu, micro-Cu, and CuCl.2 HO downregulated the protein expression of PI3K, p-AKT/AKT, and p-mTOR/mTOR in rat placentas, whereas the protein expression of p-AMPK/AMPK was upregulated. Taken together, our data indicated that prenatal exposure to nano-Cu induced autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways, which associated with oxidative stress and inflammation in rat placenta.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112364DOI Listing
May 2021

Development of allergic conjunctivitis induced by excretory-secretory protein and the effect of resolvin D1 on treatment.

Curr Eye Res 2021 May 24. Epub 2021 May 24.

Department of Ophthalmology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea.

Purpose: To evaluate whether allergic conjunctivitis (AC) could be induced by excretory-secretory protein (ESP) and analyze the therapeutic effect of resolvin (Rv) D1 and antiallergic agents.

Methods: Human conjunctival epithelial cells (HCVCs) were treated with 10 µg/well of ESP, and Th2 cytokines were measured using real-time PCR. C57BL/6 mice were treated with 10 µg/5 µL of ESP after sensitization, and conjunctivas isolated from the mice were stained with hematoxylin and eosin (H&E) for the analysis of eosinophils and periodic acid-Schiff (PAS) for the analysis of goblet cells. Cytokine levels in the eye-draining lymph nodes (dLNs) and spleens were measured using the enzyme-linked immunosorbent assay (ELISA). Then, the treatment effects of RvD1 and the antiallergic agents (olopatadine, bepotastine, and alcaftadine) on the HCVCs, mouse conjunctivas, dLNs, and spleens were assessed.

Results: Th2 cytokines were increased in the ESP-treated conjunctival cells. Mouse conjunctivas treated with ESP showed significant infiltration of eosinophils and goblet cells, and the dLN and spleen exhibited increased IL-4, IL-5 and IL-13 levels. All findings were significantly decreased upon treatment with RvD1 and the antiallergic agents.

Conclusions: could be used to establish an animal model of AC, which could be effectively treated with RvD1 or topical antiallergic agents.
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http://dx.doi.org/10.1080/02713683.2021.1934878DOI Listing
May 2021

Outdoor-Useable, Wireless/Battery-Free Patch-Type Tissue Oximeter with Radiative Cooling.

Adv Sci (Weinh) 2021 05 9;8(10):2004885. Epub 2021 Mar 9.

School of Electrical Engineering and Computer Science (EECS) Gwangju Institute of Science and Technology (GIST) 123, Cheomdangwagi-ro, Bukgu Gwangju 61005 Republic of Korea.

For wearable electronics/optoelectronics, thermal management should be provided for accurate signal acquisition as well as thermal comfort. However, outdoor solar energy gain has restricted the efficiency of some wearable devices like oximeters. Herein, wireless/battery-free and thermally regulated patch-type tissue oximeter (PTO) with radiative cooling structures are presented, which can measure tissue oxygenation under sunlight in reliable manner and will benefit athlete training. To maximize the radiative cooling performance, a nano/microvoids polymer (NMVP) is introduced by combining two perforated polymers to both reduce sunlight absorption and maximize thermal radiation. The optimized NMVP exhibits sub-ambient cooling of 6 °C in daytime under various conditions such as scattered/overcast clouds, high humidity, and clear weather. The NMVP-integrated PTO enables maintaining temperature within ≈1 °C on the skin under sunlight relative to indoor measurement, whereas the normally used, black encapsulated PTO shows over 40 °C owing to solar absorption. The heated PTO exhibits an inaccurate tissue oxygen saturation (StO) value of ≈67% compared with StO in a normal state (i.e., ≈80%). However, the thermally protected PTO presents reliable StO of ≈80%. This successful demonstration provides a feasible strategy of thermal management in wearable devices for outdoor applications.
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http://dx.doi.org/10.1002/advs.202004885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132059PMC
May 2021

Primary pulmonary diffuse large B-cell lymphoma in a young female patient.

Clin Case Rep 2021 May 4;9(5):e04102. Epub 2021 May 4.

Department of Thoracic and Cardiovascular Surgery Haeundae Paik Hospital Inje University College of Medicine Busan Korea.

Even if the patient is young or female, a primary pulmonary diffuse large B-cell lymphoma could be considered as a differential diagnosis of multifocal consolidation in the lung.
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http://dx.doi.org/10.1002/ccr3.4102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122132PMC
May 2021

Repurposing Kinase Inhibitor Bay 11-7085 to Combat and Biofilms.

Front Pharmacol 2021 5;12:675300. Epub 2021 May 5.

Infectious Diseases Division, Department of Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, United States.

and spp. are commonly linked with topical biofilm-associated infections such as those found on chronic wounds. These biofilms are notoriously difficult to treat, highlighting the grave need to discover and study new broad-spectrum agents to combat associated infections. Here we report that the kinase inhibitor Bay 11-7085 exhibited bactericidal activity against multidrug-resistant with a minimum inhibitory concentration (MIC) of 4 μg/ml. In addition, strain MW2 did not acquire resistance to antibiotic pressure. Furthermore, Bay 11-7085 exhibited potency against and the emerging pathogen with a MIC of 0.5-1 μg/ml. Bay 11-7085 partially inhibited and eradicated biofilm formation of various pathogens, such as VRSA (vancomycin-resistant ), as well as antifungal-resistant spp. isolates. Notably, Bay 11-7085 partially inhibited initial cell attachment and formation of a VRSA- polymicrobial biofilm . In contrast to , inhibition of VRSA biofilm was linked to initial cell attachment independent of its bactericidal activity. Finally, Bay 11-7085 was effective at increasing the lifespan of during an and a infection. Our work proposes kinase inhibitor Bay 11-7085 as a potential compound capable of combating biofilms associated with primary multidrug-resistant bacteria and yeast pathogens associated with wound infections.
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http://dx.doi.org/10.3389/fphar.2021.675300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133364PMC
May 2021

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study.

Kidney Res Clin Pract 2021 Apr 20. Epub 2021 Apr 20.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Background: An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation.

Methods: The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities.

Results: Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02-1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity.

Conclusion: The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.
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http://dx.doi.org/10.23876/j.krcp.20.186DOI Listing
April 2021

Atrial fibrillation and kidney function: a bidirectional Mendelian randomization study.

Eur Heart J 2021 May 23. Epub 2021 May 23.

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.

Aims: The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function.

Methods And Results: We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta -0.003 (standard error, 0.0005), P < 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P < 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta -0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta -0.079 (0.021), P < 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta -0.005 (0.008), P = 0.530].

Conclusions: Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study.
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http://dx.doi.org/10.1093/eurheartj/ehab291DOI Listing
May 2021

Two cases of myelin oligodendrocyte glycoprotein antibody-associated disease presenting with Cauda Equina Syndrome without conus myelitis.

Mult Scler Relat Disord 2021 May 8;52:103017. Epub 2021 May 8.

Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Guro-gu, Seoul 08308, Korea. Electronic address:

Myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) is a central nervous system inflammatory disorder associated with MOG antibodies. Two patients with clinical symptoms of cauda equina syndrome had positive serum MOG antibody tests, and spinal magnetic resonance imaging showed cauda equina enhancement. They were diagnosed with incomplete cauda equina syndrome associated with MOGAD. A few cases of lumbosacral radiculomyelitis associated with MOGAD have been reported; however, this is the first report of isolated lumbosacral radiculitis associated with MOGAD without transverse myelitis. The MOG antibody test should be considered for cauda equina syndrome without compressive lesions.
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http://dx.doi.org/10.1016/j.msard.2021.103017DOI Listing
May 2021

Switchable Self-Assembly of Elastin- and Resilin-Based Block Copolypeptides with Converse Phase Transition Behaviors.

ACS Appl Mater Interfaces 2021 Jun 18;13(21):24385-24400. Epub 2021 May 18.

Department of Bionano Engineering and Department of Bionanotechnology, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan 15588, Republic of Korea.

Self-assembly of thermally responsive polypeptides into unique nanostructures offers intriguing attributes including dynamic physical dimensions, biocompatibility, and biodegradability for the smart bio-nanomaterials. As elastin-based polypeptide (EBP) fusion proteins with lower critical solution temperature (LCST) are studied as drug delivery systems, EBP block copolypeptides with the resilin-based polypeptide (RBP) displaying an upper critical solution temperature (UCST) have been of great interest. In this study, we report thermally triggered, dynamic self-assembly of EBP- and RBP-based diblock copolypeptides into switched nanostructures with reversibility under physiological conditions. Molecular DNA clones encoding for the EBP-RBP diblocks at different block length ratios were biosynthesized via recursive directional ligation and overexpressed, followed by nonchromatographic purification by inverse transition cycling. Genetically engineered diblock copolypeptides composed of the EBP with an LCST and the RBP with a UCST showed converse phase transition behaviors with both a distinct LCST and a distinct UCST (LCST < UCST). As temperature increased, three phases of these EBP-RBP diblocks were observed: (1) self-assembled micelles or vesicles below both LCST and UCST, (2) whole aggregates above LCST and below UCST, and (3) reversed micelles above both LCST and UCST. In conclusion, these stimuli-triggered, dynamic protein-based nanostructures are promising for advanced drug delivery systems, regenerative medicine, and biomedical nanotechnology.
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http://dx.doi.org/10.1021/acsami.1c00676DOI Listing
June 2021

Potential prognostic factors in progression-free survival for patients with cervical cancer.

BMC Cancer 2021 May 10;21(1):531. Epub 2021 May 10.

Zhuhai Hospital of Traditional Chinese and Western Medicine, Zhuhai City, Guangdong, People's Republic of China.

Background: Cervical cancer continues to be one of the leading causes of cancer deaths among females in low and middle-income countries. In this study, we aimed to assess the independent prognostic value of clinical and potential prognostic factors in progression-free survival (PFS) in cervical cancer.

Methods: We conducted a retrospective study on 92 cervical cancer patients treated from 2017 to 2019 at the Zhuhai Hospital of Traditional Chinese and Western Medicine. Tumor characteristics, treatment options, progression-free survival and follow-up information were collected. Kaplan-Meier method was used to assess the PFS.

Results: Results showed that the number of retrieved lymph nodes had a statistically significant effect on PFS of cervical cancer patients (P = 0.002). Kaplan-Meier survival curve analysis showed that cervical cancer patients with initial symptoms age 25-39 had worse survival prognoses (P = 0.020). And the using of uterine manipulator in laparoscopic treatment showed a better prognosis (P < 0.001). A novel discovery of our study was to verify the prognostic values of retrieved lymph nodes count combining with FIGO staging system, which had never been investigated in cervical cancer before. According to the Kaplan-Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis, significant improvements were found after the combination of retrieved lymph nodes count and FIGO stage in predicting PFS for cervical cancer patients (P < 0.001, AUC = 0.826, 95% CI: 0.689-0.962).

Conclusion: Number of retrieved lymph nodes, initial symptoms age, uterine manipulator, and retrieved lymph nodes count combining with FIGO staging system could be potential prognostic factors for cervical cancer patients.
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http://dx.doi.org/10.1186/s12885-021-08243-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112015PMC
May 2021

Computational phenotyping of brain-behavior dynamics underlying approach-avoidance conflict in major depressive disorder.

PLoS Comput Biol 2021 May 10;17(5):e1008955. Epub 2021 May 10.

Department of Cognitive, Linguistic & Psychological Sciences, Brown University, Providence, Rhode Island, United States of America.

Adaptive behavior requires balancing approach and avoidance based on the rewarding and aversive consequences of actions. Imbalances in this evaluation are thought to characterize mood disorders such as major depressive disorder (MDD). We present a novel application of the drift diffusion model (DDM) suited to quantify how offers of reward and aversiveness, and neural correlates thereof, are dynamically integrated to form decisions, and how such processes are altered in MDD. Hierarchical parameter estimation from the DDM demonstrated that the MDD group differed in three distinct reward-related parameters driving approach-based decision making. First, MDD was associated with reduced reward sensitivity, measured as the impact of offered reward on evidence accumulation. Notably, this effect was replicated in a follow-up study. Second, the MDD group showed lower starting point bias towards approaching offers. Third, this starting point was influenced in opposite directions by Pavlovian effects and by nucleus accumbens activity across the groups: greater accumbens activity was related to approach bias in controls but avoid bias in MDD. Cross-validation revealed that the combination of these computational biomarkers were diagnostic of patient status, with accumbens influences being particularly diagnostic. Finally, within the MDD group, reward sensitivity and nucleus accumbens parameters were differentially related to symptoms of perceived stress and depression. Collectively, these findings establish the promise of computational psychiatry approaches to dissecting approach-avoidance decision dynamics relevant for affective disorders.
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http://dx.doi.org/10.1371/journal.pcbi.1008955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136861PMC
May 2021

Plasma levels of phosphorylated tau 181 are associated with cerebral metabolic dysfunction in cognitively impaired and amyloid-positive individuals.

Brain Commun 2021 15;3(2):fcab073. Epub 2021 Apr 15.

Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montréal, QC, Canada.

Alzheimer's disease biomarkers are primarily evaluated through MRI, PET and CSF methods in order to diagnose and monitor disease. Recently, advances in the assessment of blood-based biomarkers have shown promise for simple, inexpensive, accessible and minimally invasive tools with diagnostic and prognostic value for Alzheimer's disease. Most recently, plasma phosphorylated tau181 has shown excellent performance. The relationship between plasma phosphorylated tau181 and cerebral metabolic dysfunction assessed by [F]fluorodeoxyglucose PET in Alzheimer's disease is still unknown. This study was performed on 892 older individuals (297 cognitively unimpaired; 595 cognitively impaired) from the Alzheimer's Disease Neuroimaging Initiative cohort. Plasma phosphorylated tau181 was assessed using single molecular array technology and metabolic dysfunction was indexed by [F]fluorodeoxyglucose PET. Cross-sectional associations between plasma and CSF phosphorylated tau181 and [F]fluorodeoxyglucose were assessed using voxelwise linear regression models, with individuals stratified by diagnostic group and by β-amyloid status. Associations between baseline plasma phosphorylated tau181 and longitudinal (24 months) rate of brain metabolic decline were also assessed in 389 individuals with available data using correlations and voxelwise regression models. Plasma phosphorylated tau181 was elevated in β-amyloid positive and cognitively impaired individuals as well as in apolipoprotein E ε4 carriers and was significantly associated with age, worse cognitive performance and CSF phosphorylated tau181. Cross-sectional analyses showed strong associations between plasma phosphorylated tau181 and [F]fluorodeoxyglucose PET in cognitively impaired and β-amyloid positive individuals. Voxelwise longitudinal analyses showed that baseline plasma phosphorylated tau181 concentrations were significantly associated with annual rates of metabolic decline in cognitively impaired individuals, bilaterally in the medial and lateral temporal lobes. The associations between plasma phosphorylated tau181 and reduced brain metabolism, primarily in cognitively impaired and in β-amyloid positive individuals, supports the use of plasma phosphorylated tau181 as a simple, low-cost, minimally invasive and accessible tool to both assess current and predict future metabolic dysfunction associated with Alzheimer's disease, comparatively to PET, MRI and CSF methods.
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http://dx.doi.org/10.1093/braincomms/fcab073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088291PMC
April 2021

Large pulmonary sclerosing pneumocytoma in a young female: A rare lung tumor.

Thorac Cancer 2021 Jun 5;12(12):1909-1911. Epub 2021 May 5.

Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea.

We report a case of a 28-year-old female who presented with a solid mass lesion in the right middle lobe (RML). A chest computed tomography (CT) scan showed a 3.5 cm sized round and solid mass between the medial and lateral segment of the RML. The patient underwent a percutaneous lung biopsy with CT scan guidance and pathological examination showed pulmonary sclerosing pneumocytoma. RML lobectomy was performed for definitive treatment. Here, we describe this rare lung disease which presented as a large homogeneous lesion. Pulmonary sclerosing pneumocytoma should be considered in the differential diagnosis of solitary lung tumor, even if the patient is young.
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http://dx.doi.org/10.1111/1759-7714.13970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201539PMC
June 2021

Distribution of waist-to-height ratio and cardiometabolic risk in children and adolescents: a population-based study.

Sci Rep 2021 May 4;11(1):9524. Epub 2021 May 4.

Department of Pediatrics, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea.

This study was performed to evaluate the waist-to-height ratio (WHtR) distribution and assess its relationship with cardiometabolic risk in children and adolescents. A total of 8091 subjects aged 10-18 years were included from a nationally representative survey. Participants were classified into three groups: (1) < 85th, (2) ≥ 85th and < 95th, and (3) ≥ 95th percentile of WHtR. The WHtR distribution varied with sex and age. Whereas WHtR decreased from age 10-15 years in boys and from age 10-12 years in girls, it slightly increased thereafter. Compared to the < 85th percentile group, the WHtR ≥ 85th and < 95th percentile group had an odds ratio (OR) of 1.2 for elevated blood pressure (BP), 1.89 for elevated triglycerides (TGs), 1.47 for reduced high-density lipoprotein cholesterol (HDL-C) and 4.82 for metabolic syndrome (MetS). The ≥ 95th percentile group had an OR of 1.4 for elevated BP, 2.54 for elevated glucose, 2.22 for elevated TGs, 1.74 for reduced HDL-C, and 9.45 for MetS compared to the < 85th percentile group. Our results suggest that sex- and age-specific WHtR percentiles can be used as a simple clinical measurement to estimate cardiometabolic risk.
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http://dx.doi.org/10.1038/s41598-021-88951-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096959PMC
May 2021

Comparative analysis of three nutrition scores in predicting mortality after acute myocardial infarction.

Nutrition 2021 Mar 17;90:111243. Epub 2021 Mar 17.

Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea. Electronic address:

Objective: We investigated the utility of nutrition scores in predicting mortality and prognostic importance of nutrition status using three different scoring systems in patients with acute myocardial infarction (AMI).

Methods: In total, 1147 patients with AMI were enrolled in this study (72.5 % men; mean age 65.6 years). Patients were divided into three groups according to the geriatric nutritional risk index (GNRI); prognostic nutritional index (PNI); and triglycerides, total cholesterol, and body weight index(TCBI) scores as tertile: low (GNRI ≤ 103.8, n = 382), intermediate (103.8 < GNRI ≤ 112.3, n = 383), and high (GNRI > 112.3, n = 382) GNRI groups; low (PNI ≤ 50.0, n = 382), intermediate (50.0 < PNI ≤ 56.1, n = 383), and high (PNI > 56.1, n = 382) PNI groups; and low (TCBI ≤ 1086.4, n = 382), intermediate (1086.3 < GNRI ≤ 2139.1, n = 383), and high (TCBI > 2139.1, n = 382) TCBI groups.

Results: In the GNRI, TCBI, and PNI groups, the cumulative incidence of all-cause death and major adverse cardiovascular events (MACEs) was significantly higher in the low score group, followed by the intermediate and high score groups. Moreover, both intermediate and low PNI groups had a similar cumulative incidence of all-cause death and MACE. The GNRI score (AUC 0.753, 95% CI 0.608~0.745, P = 0.009) had significantly higher areas under the curve (AUCs) than the TCBI (AUC 0.659, 95% CI 0.600~0.719, reference) and PNI (AUC 0.676, 95% CI 0.608~0.745, P = 0.669) scores.

Conclusions: Patients with low nutrition scores were at a higher risk of MACE and all-cause death than patients with high nutrition scores. Additionally, the GNRI had the greatest incremental value in predicting risks among the three different scoring systems used in this study.
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http://dx.doi.org/10.1016/j.nut.2021.111243DOI Listing
March 2021

Right Atrial Strain as a Surrogate Marker for Right Ventricular Function in Patients with Heart Failure.

Authors:
Min Kyung Kang

J Cardiovasc Imaging 2021 Apr;29(2):144-146

Division of Cardiology, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Seoul, Korea.

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http://dx.doi.org/10.4250/jcvi.2020.0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099581PMC
April 2021

Large infected pulmonary cyst mimicking empyema thoracis.

Clin Case Rep 2021 Apr 3;9(4):2467-2468. Epub 2021 Mar 3.

Department of Thoracic and Cardiovascular Surgery Haeundae Paik Hospital Inje University College of Medicine Busan Korea.

Infected pulmonary cyst could be misdiagnosed as empyema thoracis. Here, we report an infected pulmonary cyst in a middle-aged male patient. This report could serve as a reminder for differential diagnosis of infected pulmonary cyst, for which surgical approach would be more safe and effective method.
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http://dx.doi.org/10.1002/ccr3.3894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077240PMC
April 2021

Multiple small bowel metastasis of primary non-small cell lung cancer.

Clin Case Rep 2021 Apr 11;9(4):1896-1898. Epub 2021 Mar 11.

Department of Pathology Haeundae Paik Hospital Inje University College of Medicine Busan Korea.

Gastrointestinal metastasis could be considered in the differential diagnosis of melena in the patient with NSCLC history.
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http://dx.doi.org/10.1002/ccr3.3821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077344PMC
April 2021

Myocardial injury in a pediatric patient with diabetic ketoacidosis: A case report.

Medicine (Baltimore) 2021 Apr;100(17):e25702

Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

Rationale: Diabetic ketoacidosis (DKA) can cause several complications. Among them, cardiac complications are the most fatal and difficult to detect. Cardiac markers are prognostic factors for morbidity and mortality in adult patients with DKA. But, there have been very few discussed cases in pediatrics. We report a case of severe DKA in child with elevated cardiac enzymes and prolonged QT interval.

Patient Concerns: A 12-year-old girl admitted by nausea, vomiting, and lethargy for 1 day.

Diagnoses: Her blood sugar level was initially undetectable by the capillary blood glucose meter, and blood gas analysis showed severe DKA with elevated cardiac enzymes and prolonged QT interval.

Interventions: The patient was admitted to hospital and intensive intravenous fluid and regular insulin infusion were administered.

Outcomes: After 5 days of supportive care, the patient was fully recovered, discharged, and followed up in an outpatient clinic.

Lessons: Since the relationship between DKA and myocardial injury has not been clearly elucidated, pediatricians and emergency physicians should remain careful throughout the recovery time as it can lead to life-threatening conditions in various courses.
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http://dx.doi.org/10.1097/MD.0000000000025702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084016PMC
April 2021

Association between childhood obesity and familial salt intake: analysis of data from Korean National Health and Nutrition Examination Survey, 2014-2017.

Endocr J 2021 Apr 27. Epub 2021 Apr 27.

Department of Pediatrics, Hallym University College of Medicine, 1, Hallymdaehak-gil, Chuncheon-si, Gangwon-do 24252, Republic of Korea.

High salt intake is known as a risk factor of childhood obesity. As family members share not only genes but also their diet habit, parents' salt intake may affect to their children's obesity. In this study, we investigated correlations between childhood obesity and parents' or children's sodium intakes based on a nationwide survey data. From the Korean National Health and Nutrition Examination Survey data from 2014 to 2017, 802 boys and 657 girls aged 10-18 years, and their parents were included. BMI z-score and 24-hour urinary sodium excretion, which is estimated through Tanaka's equation, were used to examine associations between obesity and sodium intakes. The BMI status and the prevalence of obesity between children and their parents showed strong positive correlations in both sexes (all p < 0.001). The urinary sodium excretion between children and their parents showed positive correlations in both sexes (all p < 0.05). Children with higher urinary sodium excretion showed higher BMI (in both sexes, p < 0.001) and higher parental obesity compared to those with lower urinary sodium excretion, however, statistical significances of the latter relationship were varied by sex. In conclusion, our study suggests close relationship between childhood obesity and their sodium intakes, which also correlate well with parental BMIs and diet behavior. Therefore, parental education and active participation could be crucial in regulating childhood obesity.
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http://dx.doi.org/10.1507/endocrj.EJ21-0111DOI Listing
April 2021

USP48 is upregulated by Mettl14 to attenuate hepatocellular carcinoma via regulating SIRT6 stabilization.

Cancer Res 2021 Apr 26. Epub 2021 Apr 26.

Hiroshima Shudo University

Exploiting cancer metabolism for the clinical benefit of hepatocellular carcinoma (HCC) patients is a topic under active investigation. Ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family, is involved in tumor growth, inflammation, and genome stability. However, the role of USP48 in HCC tumorigenesis remains unknown. In this study, we report that expression of USP48 is downregulated in diethylnitrosamine-induced liver tumorigenesis in mice as well as in human HCC. USP48 physically bound and stabilized SIRT6 by K48-linked deubiquitination at the K33 and K128 sites of SIRT6, which impeded metabolic reprogramming to hamper HCC tumorigenesis. Moreover, methyltransferase-like 14 (Mettl14)-induced m6A modification participated in the regulation of USP48 in HCC by maintaining USP48 mRNA stability. Our work uncovers the tumor suppressive function of the Mettl14-USP48-SIRT6 axis via modulation of glycolysis, providing new insights into the critical roles of metabolic activities in HCC and identifying an attractive target for future treatment studies.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-4163DOI Listing
April 2021

Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.

Mol Neurodegener 2021 04 26;16(1):28. Epub 2021 Apr 26.

Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, 6875 Boulevard LaSalle, Montreal, H4H 1R3, Canada.

Background: Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer's disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [F]BCPP-EF.

Methods: Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [F]BCPP-EF mitochondrial function, [C]PBB3 for tau deposition, and [C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed.

Results: The [F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [F]BCPP-EF SUVR and [C]PBB3 BP (R = 0.2679, p = 0.04), but not [C] PiB SUVR.

Conclusions: Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.
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http://dx.doi.org/10.1186/s13024-021-00448-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074456PMC
April 2021