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1.
Clin Lab ; 70(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38747932

ABSTRACT

BACKGROUND: Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. METHODS: In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. RESULTS: At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. CONCLUSIONS: HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.


Subject(s)
Respiratory Tract Infections , Humans , Female , Male , Infant , Child, Preschool , Prevalence , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Respiratory Tract Infections/diagnosis , Child , Republic of Korea/epidemiology , Paramyxoviridae Infections/epidemiology , Paramyxoviridae Infections/virology , Paramyxoviridae Infections/diagnosis , Adolescent
2.
Micromachines (Basel) ; 15(4)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38675354

ABSTRACT

This paper presents a direct 3D numerical simulation of biaxial surface wrinkling of thin metal film on a compliant substrate. The selected compliant substrate is a commercial Scotch tape on which a gold metal thin film has been transferred by using low adhesion between the thin metal film and polyimide substrate. Compared with the previous fabrication of a cylindrical thin-film wrinkling pattern, an undulated wrinkling pattern has been implemented by increasing the width of the thin metal film in order to create biaxial straining in the thin film. To understand the wrinkling behavior due to biaxial loading, a simple direct numerical simulation based on material imperfections defined in the compliant substrate has been conducted. Through modeling and simulation, it was found that the wrinkling mode is determined by the biaxiality ratio (BR), the ratio between transversal strain and longitudinal strain. Depending on the BR, the wrinkling mode belongs to one of the cylindrical, undulated (or herringbone), checkerboard, or labyrinth modes as a function of applied strain. The cylindrical wrinkling is dominant at the input of BR less than 0.5, while the undulated (or herringbone) ones become dominant just after the onset of the wrinkling pattern at BR greater than 0.9. Through the comparison of the wrinkling patterns between simulation and experiment, the applied BR of the fabricated thin film has been successfully estimated.

3.
Mol Biol Evol ; 41(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38427787

ABSTRACT

Advancements in next-generation sequencing (NGS) technologies have led to a substantial increase in the availability of population genetic variant data, thus prompting the development of various population analysis tools to enhance our understanding of population structure and evolution. The tools that are currently used to analyze population genetic variant data generally require different environments, parameters, and formats of the input data, which can act as a barrier preventing the wide-spread usage of such tools by general researchers who may not be familiar with bioinformatics. To address this problem, we have developed an automated and comprehensive pipeline called PAPipe to perform nine widely used population genetic analyses using population NGS data. PAPipe seamlessly interconnects and serializes multiple steps, such as read trimming and mapping, genetic variant calling, data filtering, and format converting, along with nine population genetic analyses such as principal component analysis, phylogenetic analysis, population tree analysis, population structure analysis, linkage disequilibrium decay analysis, selective sweep analysis, population admixture analysis, sequentially Markovian coalescent analysis, and fixation index analysis. PAPipe also provides an easy-to-use web interface that allows for the parameters to be set and the analysis results to be browsed in intuitive manner. PAPipe can be used to generate extensive results that provide insights that can help enhance user convenience and data usability. PAPipe is freely available at https://github.com/jkimlab/PAPipe.


Subject(s)
Computational Biology , Software , Phylogeny , Computational Biology/methods , High-Throughput Nucleotide Sequencing/methods , Genetics, Population
4.
Sci Rep ; 14(1): 3372, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38336989

ABSTRACT

This study aimed to create Greenhouse Gas - Air Pollution Interactions and Synergies (GAINS)-Korea, an integrated model for evaluating climate and air quality policies in Korea, modeled after the international GAINS model. GAINS-Korea incorporates specific Korean data and enhances granularity for enabling local government-level analysis. The model includes source-receptor matrices used to simulate pollutant dispersion in Korea, generated through CAMx air quality modeling. GAINS-Korea's performance was evaluated by examining different scenarios for South Korea. The business as usual scenario projected emissions from 2010 to 2030, while the air quality scenario included policies to reduce air pollutants in line with air quality and greenhouse gas control plans. The maximum feasible reduction scenario incorporated more aggressive reduction technologies along with air quality measures. The developed model enabled the assessment of emission reduction effects by both greenhouse gas and air pollutant emission reduction policies across 17 local governments in Korea, including changes in PM2.5 (particulate matter less than 2.5 µm) concentration and associated benefits, such as reduced premature deaths. The model also provides a range of visualization tools for comparative analysis among different scenarios, making it a valuable resource for policy planning and evaluation, and supporting decision-making processes.

5.
J Neural Eng ; 21(2)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38408386

ABSTRACT

Objective.This study aims to develop and validate a sophisticated fork-shaped neural interface (FNI) designed for peripheral nerves, focusing on achieving high spatial resolution, functional selectivity, and improved charge storage capacities. The objective is to create a neurointerface capable of precise neuroanatomical analysis, neural signal recording, and stimulation.Approach.Our approach involves the design and implementation of the FNI, which integrates 32 multichannel working electrodes featuring enhanced charge storage capacities and low impedance. An insertion guide holder is incorporated to refine neuronal selectivity. The study employs meticulous electrode placement, bipolar electrical stimulation, and comprehensive analysis of induced neural responses to verify the FNI's capabilities. Stability over an eight-week period is a crucial aspect, ensuring the reliability and durability of the neural interface.Main results.The FNI demonstrated remarkable efficacy in neuroanatomical analysis, exhibiting accurate positioning of motor nerves and successfully inducing various movements. Stable impedance values were maintained over the eight-week period, affirming the durability of the FNI. Additionally, the neural interface proved effective in recording sensory signals from different hind limb areas. The advanced charge storage capacities and low impedance contribute to the FNI's robust performance, establishing its potential for prolonged use.Significance.This research represents a significant advancement in neural interface technology, offering a versatile tool with broad applications in neuroscience and neuroengineering. The FNI's ability to capture both motor and sensory neural activity positions it as a comprehensive solution for neuroanatomical studies. Moreover, the precise neuromodulation potential of the FNI holds promise for applications in advanced bionic prosthetic control and therapeutic interventions. The study's findings contribute to the evolving field of neuroengineering, paving the way for enhanced understanding and manipulation of peripheral neural functions.


Subject(s)
Peripheral Nerves , Rats , Animals , Reproducibility of Results , Electrodes, Implanted , Peripheral Nerves/physiology , Electric Stimulation
6.
J Am Chem Soc ; 146(7): 4532-4541, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38326951

ABSTRACT

Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.

8.
J Am Chem Soc ; 146(1): 543-551, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38147538

ABSTRACT

A nanographene-fused expanded carbaporphyrin (5) and its BF2 complex (6) were synthesized. Single-crystal X-ray structures revealed that 5 and 6 are connected by two hexa-peri-hexabenzocoronene (HBC) units and two dipyrromethene or BODIPY units, respectively. As prepared, 5 and 6 both show nonaromatic character with figure-of-eight carbaoctaphyrin (1.1.1.0.1.1.1.0) cores and adopt tweezers-like conformations characterized by a partially confined space between the two constituent HBC units. The distance between the HBC centers is >10 Å, while the dihedral angles between the two HBC planes are 30.5 and 35.2° for 5 and 6, respectively. The interactions between 5 and 6 and fullerene C60 were studied both in organic media and in the solid state. Proton NMR spectral titrations of 5 and 6 with C60 revealed a 1:1 binding mode for both macrocycles. In toluene-d8, the corresponding binding constants were determined to be 1141 ± 17 and 994 ± 10 M-1 for 5 and 6, respectively. Single-crystal X-ray diffraction structural analyses confirmed the formation of 1:1 fullerene inclusion complexes in the solid state. The C60 guests in both complexes are found within triangular pockets composed of two HBC units from the tweezers-like receptor most closely associated with the bound fullerene, as well as an HBC unit from an adjacent host. Femtosecond transient absorption measurements revealed subpicosecond ultrafast charge separation between 5 (and 6) and C60 in the complexes. To the best of our knowledge, the present report provides the first example wherein a nanographene building block is incorporated into the core of a porphyrinic framework.

9.
Org Lett ; 25(45): 8121-8126, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37930089

ABSTRACT

5,10,23-Trimesityl-substituted [24]hexaphyrin(1.1.0.0.1.0) was synthesized as a stable antiaromatic molecule by base-catalyzed twofold SNAr reaction and was reduced to the corresponding [26]hexaphyrin, which was an unstable aromatic molecule because it easily oxidized to the [24]hexaphyrin. The [24]hexaphyrin served as a ligand to give the bis-PdII complex and tris-RhI complex with unique structures. The former complex has two square-planar-coordinated PdII ions bridged by an acetate anion and shows a strong paratropic ring current, while the latter complex has three RhI ions coordinated with two pyrrolic nitrogen atoms and two carbonyl groups, but one carbonyl group is shared with two RhI ions in a unique manner.

10.
Article in English | MEDLINE | ID: mdl-37708012

ABSTRACT

Spinal cord stimulation (SCS) is an emerging therapeutic option for patients with neuropathic pain due to spinal cord injury (SCI). Numerous studies on pain relief effects with SCS have been conducted and demonstrated promising results while the mechanisms of analgesic effect during SCS remain unclear. However, an experimental system that enables large-scale long-term animal studies is still an unmet need for those mechanistic studies. This study proposed a fully wireless neurostimulation system that can efficiently support a long-term animal study for neuropathic pain relief. The developed system consists of an implantable stimulator, an animal cage with an external charging coil, and a wireless communication interface. The proposed device has the feature of remotely controlling stimulation parameters via radio-frequency (RF) communication and wirelessly charging via magnetic induction in freely moving rats. Users can program stimulation parameters such as pulse width, intensity, and duration through an interface on a computer. The stimulator was packaged with biocompatible epoxy to ensure long-term durability under in vivo conditions. Animal experiments using SCI rats were conducted to demonstrate the functionality of the device, including long-term usability and therapeutic effects. The developed system can be tailored to individual user needs with commercially available components, thus providing a cost-effective solution for large-scale long-term animal studies on neuropathic pain relief.


Subject(s)
Neuralgia , Spinal Cord Injuries , Humans , Animals , Rats , Prostheses and Implants , Communication , Heart Rate , Longitudinal Studies , Neuralgia/therapy
11.
Micromachines (Basel) ; 14(4)2023 Mar 28.
Article in English | MEDLINE | ID: mdl-37420980

ABSTRACT

This paper presents a direct numerical simulation for the extraction of material properties based on thin-film wrinkling on scotch tape. Conventional FEM-based buckling simulation sometimes requires complex modeling techniques concerning mesh element manipulation or boundary conditions. The direct numerical simulation differs from FEM (finite element method)-based conventional two-step linear-nonlinear buckling simulation in that mechanical imperfections are directly applied into the elements of the simulation model. Hence, it can be performed in one step to find the wrinkling wavelength and amplitude, which are key parameters to extract the material mechanical properties. Moreover, the direct simulation can reduce simulation time and modeling complexity. Using the direct model, the effect of the number of imperfections on wrinkling characteristics was first studied, and then wrinkling wavelengths depending on the elastic moduli of the associated materials were prepared for the extraction of material properties. Thin-film wrinkling test patterns on scotch tape were fabricated using the transfer technique with low adhesion between metal films and the polyimide substrate. The material properties of the thin metal films were determined by comparing the measured wrinkling wavelengths and the proposed direct simulation results. By consequence, the elastic moduli of 300 nm thick gold film and 300 nm thick aluminum were determined as 250 GPa and 300 GPa, respectively.

12.
J Control Release ; 360: 796-809, 2023 08.
Article in English | MEDLINE | ID: mdl-37437850

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death and has a poor 5-year overall survival. The superior therapeutic benefits of combination or co-administration of drugs as intraperitoneal chemotherapy have increased interest in developing strategies to deliver chemotherapeutic agents to patients safely. In this study, we prepared a gel comprising the thermosensitive poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) polymer and gemcitabine (GEM), which is currently used as the primary chemotherapy for PDAC and rapamycin (RAPA), a mammalian TOR (mTOR) inhibitor, to deliver the drug through intraperitoneal injection. We performed in vitro cytotoxicity experiments to verify the synergistic effects of the two drugs at different molar ratios and characterized the physicochemical properties of the GEM, RAPA, and GEM/RAPA-loaded thermosensitive PLGA-PEG-PLGA gels, hereafter referred to as (g(G), g(R), and g(GR)), respectively. The g(GR) comprising PLGA-PEG-PLGA polymer (25% w/v) and GEM and RAPA at a molar ratio of 11:1 showed synergism and was optimized. An in vitro cytotoxicity assay was performed by treating Panc-1-luc2 tumor spheroids with g(G), g(R), or g(GR). The g(GR) treatment group showed a 2.75-fold higher inhibition rate than the non-treated (NT) and vehicle-treated groups. Furthermore, in vivo drug release assay in mice by intraperitoneal injection of g(G), g(R), or g(GR) showed a more rapid release rate of GEM than RAPA, similar to the in vitro release pattern. The drugs in the gel were released faster in vivo than in vitro and degraded in 48 h. In addition, g(GR) showed the highest anti-tumor efficacy with no toxicity to mice. These results provide evidence for the safety and efficacy of g(GR) for intraperitoneal drug delivery. This study will assist in developing and clinically administering topical anti-cancer formulations.


Subject(s)
Gemcitabine , Pancreatic Neoplasms , Mice , Animals , Sirolimus , Polyglactin 910 , Polyethylene Glycols/chemistry , Pancreatic Neoplasms/drug therapy , Hydrogels/chemistry , Cell Line, Tumor , Mammals , Pancreatic Neoplasms
13.
J Rheum Dis ; 30(3): 185-197, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37476678

ABSTRACT

Objective: The extent of regional variations in cardiovascular risk and associated risk factors in patients with gout in South Korea remains unclear. Therefore, we aimed to investigate the risk of major cardiovascular events in gout patients in different regions. Methods: This was a nationwide cohort study based on the claims database of the Korean National Health Insurance and the National Health Screening Program. Patients aged 20 to 90 years newly diagnosed with gout after January 2012 were included. After cardiovascular risk profiles before gout diagnosis were adjusted, the relative risks of incident cardiovascular events (myocardial infarction, cerebral infarction, and cerebral hemorrhage) in gout patients in different regions were assessed. Results: In total, 231,668 patients with gout were studied. Regional differences in cardiovascular risk profiles before the diagnosis were observed. Multivariable analysis showed that patients with gout in Jeolla/Gwangju had a significantly high risk of myocardial infarction (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.02~1.56; p=0.03). In addition, patients with gout in Gangwon (aHR, 1.38; 95% CI, 1.09~1.74; p<0.01), Jeolla/Gwangju (aHR, 1.41; 95% CI, 1.19~1.67; p<0.01), and Gyeongsang/Busan/Daegu/Ulsan (aHR, 1.37; 95% CI, 1.19~1.59; p<0.01) had a significantly high risk of cerebral infarction. Conclusion: We found there were regional differences in cardiovascular risk and associated risk factors in gout patients. Physicians should screen gout patients for cardiovascular risk profiles in order to facilitate prompt diagnosis and treatment.

14.
Ann Occup Environ Med ; 35: e8, 2023.
Article in English | MEDLINE | ID: mdl-37342825

ABSTRACT

Background: Prolonged use of visual display terminal (VDT) can cause eyestrain, dry eyes, blurred vision, double vision, headache and musculoskeletal symptoms (neck, shoulder, and wrist pain). VDT working hours among workers have greatly increased during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, this study aimed to investigate the relationship between VDT working hours and headache/eyestrain in wage workers using data from the sixth Korean Working Conditions Survey (KWCS) (2020-2021) conducted during the COVID-19 pandemic. Methods: We analyzed the sixth KWCS data of 28,442 wage workers aged 15 years or older. The headache/eyestrain that occurred in the last year was assessed. The VDT work group included workers who use VDT always, almost always, and three-fourth of the working hours, while the non-VDT work group included workers who use VDT half of the working hours, one-fourth of the working hours, almost never, and never. To analyze the relationship between VDT working hours and headache/eyestrain, the odds ratios (ORs) and 95% confidence interval (CI) were calculated using logistic regression analysis. Results: Among the non-VDT work group, 14.4% workers experienced headache/eyestrain, whereas 27.5% workers of the VDT work group experienced these symptoms. For headache/eyestrain, the VDT work group showed adjusted OR of 1.94 (95% CI: 1.80-2.09), compared with the non-VDT work group, and the group that always used VDT showed adjusted OR of 2.54 (95% CI: 2.26-2.86), compared with the group that never used VDT. Conclusions: This study suggests that during the COVID-19 pandemic, as VDT working hours increased, the risk of headache/eyestrain increased for Korean wage workers.

15.
Front Public Health ; 11: 1151452, 2023.
Article in English | MEDLINE | ID: mdl-37213618

ABSTRACT

Objectives: Despite the epidemiological importance of social vulnerabilities in compliance with preventive measures, little is known about the disproportional nature of preventive behaviors in crisis-affected populations. We examined adherence to COVID-19 preventive behaviors, focusing on social distancing measures in the conflict-affected regions in eastern Ukraine. Methods: From a multisectoral needs assessment conducted in 2020 using a household interview of a stratified simple random sample, we included 1,617 rural and urban households located in the government-controlled area. We performed multivariable binary logistic regression analysis with latent class analysis (LCA) to identify unmeasured patterns of classification of preventive measures using data from a cross-sectional survey. Results: The conflict-affected populations showed difficulty in complying with COVID-19 preventive measures due to losses of housing, partners, and access to food resources due to conflicts. Among the various preventive measures, wearing a face mask (88.1%) and washing hands more regularly (71.4%) were the most frequently reported. Compliance with social distancing was significantly lower in those who experienced the direct impacts of conflicts indicated by damaged accommodation or being widowed. Three different groups who showed distinctive patterns of employing COVID-19 preventive measures were identified via the LCA model, which were "highly complying group", "moderately complying group", and "face masks only group". The group membership was associated with a respondent's poverty status. Conclusion: The findings show the difficulty in compliance with COVID-19 preventive measures among conflict-affected populations indicating secondary impacts of the conflicts on preventive health behaviors. To mitigate the health impacts of conflicts, immediate attention is needed to address barriers to COVID-19 preventive measures among conflict-affected populations in Ukraine. This study suggests the need for public health strategies to improve preventive health behaviors in conflict-affected populations under pandemics or large-scale outbreaks.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Ukraine , Cross-Sectional Studies , Pandemics/prevention & control
16.
Materials (Basel) ; 16(9)2023 May 02.
Article in English | MEDLINE | ID: mdl-37176387

ABSTRACT

A nonlinear finite element model for axisymmetric bending of micro circular/annular plates under thermal and mechanical loading was developed using quasi-3D Reddy third-order shear deformation theory. The developed finite element model accounts for a variation of material constituents utilizing a power-law distribution of a two-constituent material, three different porosity distributions through plate thickness, and geometrical nonlinearity. The modified couple stress theory was utilized to account for the strain gradient effects using a single material length scale parameter. Three different types of porosity distributions that have the same overall volume fraction but different enhanced areas were considered as a form of cosine functions. The effects of the material and porosity distribution, microstructure-dependency, the geometric nonlinearity, and various boundary conditions on the bending response of functionally-graded porous axisymmetric microplates under thermomechanical loads were studied using the developed nonlinear finite element model.

17.
J Clin Med ; 12(7)2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37048759

ABSTRACT

Drug-eluting stent (DES) recipients require 6-12 months of dual antiplatelet treatment (DAPT) and long-term aspirin mono-antiplatelet treatment (MAPT). Given the diversity of contemporary antiplatelet agents, antiplatelet treatment (APT) selection is becoming more complicated. We evaluated 15-year APT trends based on nationwide prescription data of 79,654 patients who underwent percutaneous coronary intervention (PCI) using DESs from 2002 to 2018 in Korea. DAPT (80.7%) was the most preferred initial APT post-PCI. Many DES recipients received prolonged DAPT (post-PCI 3 years: 41.0%; 10 years: 27.7%). There was a noticeable delay in DAPT-to-MAPT conversion from the mid to late 2000s (after the late-stent thrombosis concerns of first-generation DESs raised); the conversion after that was similar during the 2010s, occurring most robustly at 12-18 months post-PCI. Clopidogrel had long and increasingly been used for MAPT, surpassing aspirin. The recent increase in newer P2Y12 inhibitor prescriptions was noted. The patients treated with newer P2Y12 inhibitors were more likely younger men and presented with acute myocardial infarction. Real-world APT is evolving, and guideline-practice gaps exist. Further studies exploring the impact of diverse APT strategies on patient outcomes are expected to provide insights into optimal APT that can sophisticatedly balance the ischemic and bleeding risks.

18.
Nature ; 617(7959): 170-175, 2023 05.
Article in English | MEDLINE | ID: mdl-37076618

ABSTRACT

Nucleotide excision repair removes DNA lesions caused by ultraviolet light, cisplatin-like compounds and bulky adducts1. After initial recognition by XPC in global genome repair or a stalled RNA polymerase in transcription-coupled repair, damaged DNA is transferred to the seven-subunit TFIIH core complex (Core7) for verification and dual incisions by the XPF and XPG nucleases2. Structures capturing lesion recognition by the yeast XPC homologue Rad4 and TFIIH in transcription initiation or DNA repair have been separately reported3-7. How two different lesion recognition pathways converge and how the XPB and XPD helicases of Core7 move the DNA lesion for verification are unclear. Here we report on structures revealing DNA lesion recognition by human XPC and DNA lesion hand-off from XPC to Core7 and XPA. XPA, which binds between XPB and XPD, kinks the DNA duplex and shifts XPC and the DNA lesion by nearly a helical turn relative to Core7. The DNA lesion is thus positioned outside of Core7, as would occur with RNA polymerase. XPB and XPD, which track the lesion-containing strand but translocate DNA in opposite directions, push and pull the lesion-containing strand into XPD for verification.


Subject(s)
DNA Damage , DNA Repair , DNA-Binding Proteins , DNA , Transcription Factor TFIIH , Xeroderma Pigmentosum Group A Protein , Humans , DNA/chemistry , DNA/metabolism , DNA Helicases/metabolism , DNA-Binding Proteins/metabolism , Transcription Factor TFIIH/metabolism , Xeroderma Pigmentosum Group A Protein/metabolism , Substrate Specificity , DNA-Directed RNA Polymerases/metabolism
19.
Pharmaceutics ; 15(4)2023 Apr 10.
Article in English | MEDLINE | ID: mdl-37111691

ABSTRACT

Ovarian cancer has a high mortality rate due to difficult detection at an early stage. It is necessary to develop a novel anticancer treatment that demonstrates improved efficacy while reducing toxicity. Here, using the freeze-drying method, micelles encapsulating paclitaxel (PTX) and sorafenib (SRF) with various polymers were prepared, and the optimal polymer (mPEG-b-PCL) was selected by measuring drug loading (%), encapsulation efficiency (%), particle size, polydispersity index, and zeta potential. The final formulation was selected based on a molar ratio (PTX:SRF = 1:2.3) with synergistic effects on two ovarian cancer cell lines (SKOV3-red-fluc, HeyA8). In the in vitro release assay, PTX/SRF micelles showed a slower release than PTX and SRF single micelles. In pharmacokinetic evaluation, PTX/SRF micelles showed improved bioavailability compared to PTX/SRF solution. In in vivo toxicity assays, no significant differences were observed in body weight between the micellar formulation and the control group. The anticancer effect of PTX/SRF combination therapy was improved compared to the use of a single drug. In the xenografted BALB/c mouse model, the tumor growth inhibition rate of PTX/SRF micelles was 90.44%. Accordingly, PTX/SRF micelles showed improved anticancer effects compared to single-drug therapy in ovarian cancer (SKOV3-red-fluc).

20.
PLoS One ; 18(3): e0283342, 2023.
Article in English | MEDLINE | ID: mdl-36961852

ABSTRACT

Randomized controlled trials (RCTs) play a major role in aiding biomedical research and practices. To inform this research, the demand for highly accurate retrieval of scientific articles on RCT research has grown in recent decades. However, correctly identifying all published RCTs in a given domain is a non-trivial task, which has motivated computer scientists to develop methods for identifying papers involving RCTs. Although existing studies have provided invaluable insights into how RCT tags can be predicted for biomedicine research articles, they used datasets from different sources in varying sizes and timeframes and their models and findings cannot be compared across studies. In addition, as datasets and code are rarely shared, researchers who conduct RCT classification have to write code from scratch, reinventing the wheel. In this paper, we present Bat4RCT, a suite of data and an integrated method to serve as a strong baseline for RCT classification, which includes the use of BERT-based models in comparison with conventional machine learning techniques. To validate our approach, all models are applied on 500,000 paper records in MEDLINE. The BERT-based models showed consistently higher recall scores than conventional machine learning and CNN models while producing slightly better or similar precision scores. The best performance was achieved by the BioBERT model when trained on both title and abstract texts, with the F1 score of 90.85%. This infrastructure of dataset and code will provide a competitive baseline for the evaluation and comparison of new methods and the convenience of future benchmarking. To our best knowledge, our study is the first work to apply BERT-based language modeling techniques to RCT classification tasks and to share dataset and code in order to promote reproducibility and improvement in text classification in biomedicine research.


Subject(s)
Benchmarking , Machine Learning , Randomized Controlled Trials as Topic , Language , MEDLINE , Natural Language Processing
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