Publications by authors named "Hyun-Jung Kim"

1,069 Publications

  • Page 1 of 1

Quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer (ASPIRE): A long-term prospective, multicentre, cohort study.

Lancet Reg Health West Pac 2021 Jan 28;6:100087. Epub 2020 Dec 28.

Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.

Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery.

Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525).

Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval  [CI], -1•3 to 9•7,  = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6,  = 0•0052), micturition symptoms (-8•0 points; 95% CI, -14•1 to -1•8,  = 0•0108), male sexual problems (-19•9 points; 95% CI, -33•1 to -6•7,  = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8,  = 0•0155), and worse urinary symptoms (-5•4 points on a 35-point scale; 95% CI, -8•0 to -2•7,  < 0•0001). The 5-year overall survival was worse with abdominoperineal resection in unadjusted (92•2% vs 80•9%; difference 11•3%, hazard ratio 2•38; 95% CI, 1•27 to 4•46,  = 0•0052), but did not differ after adjustment.

Interpretation: In this long-term prospective study, abdominoperineal resection failed to meet the superiority to sphincter preservation surgery in terms of quality of life. Although the global quality of life scores did not differ between groups, this study suggests that sphincter preservation surgery can be an acceptable alternative to abdominoperineal resection for low rectal cancer, offering a better quality of life and sexual-urinary functions, with no increased oncological risk even after 3 years.

Funding: Seoul National University Bundang Hospital, Korea.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315365PMC
January 2021

Unusual Cervical Lymph Node Metastasis of Papillary Urothelial Carcinoma.

Ear Nose Throat J 2021 Jul 29:1455613211036222. Epub 2021 Jul 29.

Department of Otorhinolaryngology, Jeju National University School of Medicine, Jeju, Republic of Korea.

Papillary urothelial carcinoma is aggressive and characterized by frequent metastasis to distant sites at an early stage. Papillary urothelial carcinoma of the urinary bladder usually metastasizes to the local lymph nodes, liver, lungs, bone, and mediastinum. Urogenital tract carcinoma of the head and neck metastasis is uncommon and rarely reported to the cervical lymph nodes. We present a case of cervical lymph node metastasis of papillary urothelial carcinoma of the urinary bladder.
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http://dx.doi.org/10.1177/01455613211036222DOI Listing
July 2021

Multiplex recreation of human intestinal morphogenesis on a multi-well insert platform by basolateral convective flow.

Lab Chip 2021 Jul 29. Epub 2021 Jul 29.

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, South Korea. and Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), 77, Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea and Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50, Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Here, we report a multiplex culture system that enables simultaneous recreation of multiple replications of the three-dimensional (3D) microarchitecture of the human intestinal epithelium in vitro. The "basolateral convective flow-generating multi-well insert platform (BASIN)" contains 24 nano-porous inserts and an open basolateral chamber applying controllable convective flow in the basolateral compartment that recreates a biomimetic morphogen gradient using a conventional orbital shaker. The mechanistic approach by which the removal of morphogen inhibitors in the basolateral medium can induce intestinal morphogenesis was applied to manipulate the basolateral convective flow in space and time. In a multiplex BASIN, we successfully regenerated a 3D villi-like intestinal microstructure using the Caco-2 human intestinal epithelium that presents high barrier function with minimal insert-to-insert variations. The enhanced cytodifferentiation and proliferation of the 3D epithelial layers formed in the BASIN were visualized with markers of absorptive (villin) and proliferative cells (Ki67). The paracellular transport and efflux profiles of the microengineered 3D epithelial layers in the BASIN confirmed its reproducibility, robustness, and scalability for multiplex biochemical or pharmaceutical studies. Finally, the BASIN was used to investigate the effects of dextran sodium sulfate on the intestinal epithelial barrier and morphology to validate its practical applicability for investigating the effects of external chemicals on the intestinal epithelium and constructing a leaky-gut model. We envision that the BASIN may provide an improved multiplex, scalable, and physiological intestinal epithelial model that is readily accessible to researchers in both basic and applied sciences.
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http://dx.doi.org/10.1039/d1lc00404bDOI Listing
July 2021

Comparing audio- and video-delivered instructions in dispatcher-assisted cardiopulmonary resuscitation with drone-delivered automatic external defibrillator: a mixed methods simulation study.

PeerJ 2021 15;9:e11761. Epub 2021 Jul 15.

Department of Nursing, Semyung University, Jecheon, Chungbuk, South Korea.

This study compared first responders' cardiopulmonary resuscitation (CPR) performance when a dispatcher provides audio instructions only and when both audio and video instructions are given. In the simulation, an automatic external defibrillator (AED) was delivered via drone in response to a cardiac arrest occurring outside a hospital setting. Participants' qualitative experiences were also explored.An exploratory sequential mixed methods design was used. AEDs were delivered to college students via drone with one group receiving both audio and video instructions and the other receiving audio-only instruction, and differences in CPR performance and accuracy were compared. After completion, focus group interview data were collected and analyzed. Video-based instruction was found to be more effective in the number of chest compressions ( < 0.01), chest compression rate ( < 0.01), and chest compression interruptions ( < 0.01). The accuracy of the video group for the chest compression region was high ( = 0.05). Participants' experiences were divided into three categories: "unfamiliar but beneficial experience," "met helper during a desperate and embarrassing situation," and "diverse views on drone use." Our results lay the groundwork for a development plan for providing emergency medical services using drones, as well as the preparation of guidelines for dispatchers on the provision of video instructions.
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http://dx.doi.org/10.7717/peerj.11761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286704PMC
July 2021

A Large-Scale Metagenomic Study for Enzyme Profiles Using the Focused Identification of the NGS-Based Definitive Enzyme Research (FINDER) Strategy.

Biotechnol Bioeng 2021 Jul 26. Epub 2021 Jul 26.

Department of Biotechnology, Yonsei University, Seoul, 03722, South Korea.

Excavating the molecular details of many diverse enzymes from metagenomes remains challenging in agriculture, food, health, and environmental fields. We present a versatile method that accelerates metabolic enzyme discovery for highly selective gene capture in metagenomes using next-generation sequencing. Culture-independent enzyme mining of environmental DNA is based on a set of short identifying degenerate sequences specific for a wide range of enzyme superfamilies, followed by multiplexed DNA barcode sequencing. A strategy of 'focused identification of next-generation sequencing-based definitive enzyme research' (FINDER) enabled us to generate targeted enzyme datasets from metagenomes, resulting in minimal hands-on obtention of high-throughput biological diversity and potential function profiles, without being time-consuming. This method also provided a targeted inventory of predicted proteins and molecular features of metabolic activities from several metagenomic samples. We suggest that the efficiency and sensitivity of this method will accelerate the decryption of microbial diversity and the signature of proteins and their metabolism from environmental samples. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/bit.27904DOI Listing
July 2021

Effect of Bioactive Glass-Containing Light-Curing Varnish on Enamel Remineralization.

Materials (Basel) 2021 Jul 4;14(13). Epub 2021 Jul 4.

Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul 02447, Korea.

This study aimed to evaluate the effect of novel experimental light-curing bioactive glass (BAG)-containing varnish on enamel remineralization. An experimental light-curing, BAG-containing varnish and two commercial varnishes (Nupro White Varnish; Dentsply International, York, PA, USA and Tooth Mousse; GC Corporation, Tokyo, Japan) were used. Microhardness tests (n = 3), field emission scanning electron microscopy (FE-SEM) coupled with energy dispersive X-ray spectroscopy (EDS) (n = 5), and X-ray diffraction (XRD) analysis (n = 5) were performed to compare the remineralization effect of three varnishes with and without ultrasonication. The data of microhardness test were analyzed using one-way ANOVA and Tukey's post hoc comparison ( < 0.05). Microhardness of demineralized enamel increased after the application of three varnishes ( < 0.05). The experimental BAG-containing varnish showed the highest microhardness among the three varnishes ( 0.05). Ultrasonication decreased microhardness of Tooth Mousse and BAG-containing varnish groups ( < 0.05). FE-SEM and XRD revealed precipitates of hydroxyapatite (HAP) or fluorapatite (FAP) crystals of three varnishes. The novel experimental BAG-containing varnish may be a promising clinical strategy for the remineralization of early carious lesions or demineralized enamel surfaces.
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http://dx.doi.org/10.3390/ma14133745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269883PMC
July 2021

Reversible optical tuning of GeSbTe phase-change metasurface spectral filters for mid-wave infrared imaging.

Optica 2020 Jul 1;7(7):746-754. Epub 2020 Jul 1.

National Institute of Aerospace, Hampton, Virginia 23666, USA.

Tunable narrowband spectral filtering across arbitrary optical wavebands is highly desirable in a plethora of applications, from chemical sensing and hyperspectral imaging to infrared astronomy. Yet, the ability to reconfigure the optical properties, with full reversibility, of a solid-state large-area narrowband filter remains elusive. Existing solutions require either moving parts, have slow response times, or provide limited spectral coverage. Here, we demonstrate a 1-inch diameter continuously tunable, fully reversible, all-solid-state, narrowband phase-change metasurface filter based on a GeSbTe-225 (GST)-embedded plasmonic nanohole array. The passband of the presented device is with transmittance and operates across the 3-5 µm thermal imaging waveband. Continuous, reconfigurable tuning is achieved by exploiting intermediate GST phases via optical switching with a single nanosecond laser pulse, and material stability is verified through multiple switching cycles. We further demonstrate multispectral thermal imaging in the mid-wave infrared using our active phase-change metasurfaces. Our results pave the way for highly functional, reduced power, compact hyperspectral imaging systems and customizable optical filters for real-world system integration.
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http://dx.doi.org/10.1364/OPTICA.392878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262593PMC
July 2020

Morphological Features and Cold-Response Gene Expression in Mesophilic Group and Psychrotolerant Group under Low Temperature.

Microorganisms 2021 Jun 9;9(6). Epub 2021 Jun 9.

Department of Food Analysis Center, Korea Research Institute, Wanju-gun 55365, Jeollabuk-do, Korea.

At low temperatures, psychrotolerant group strains exhibit a higher growth rate than mesophilic strains do. However, the different survival responses of the psychrotolerant strain (BCG) and the mesophilic strain (BCG) at low temperatures are unclear. We investigated the morphological and genomic features of BCG and BCG to characterize their growth strategies at low temperatures. At low temperatures, morphological changes were observed only in BCG. These morphological changes included the elongation of rod-shaped cells, whereas the cell shape in BCG was unchanged at the low temperature. A transcriptomic analysis revealed that both species exhibited different growth-related traits during low-temperature growth. The BCG strain induces fatty acid biosynthesis, sulfur assimilation, and methionine and cysteine biosynthesis as a survival mechanism in cold systems. Increases in energy metabolism and fatty acid biosynthesis in the mesophilic group strain might explain its ability to grow at low temperatures. Several pathways involved in carbohydrate mechanisms were downregulated to conserve the energy required for growth. Peptidoglycan biosynthesis was upregulated, implying that a change of gene expression in both RNA-Seq and RT-qPCR contributed to sustaining its growth and rod shape at low temperatures. These results improve our understanding of the growth response of the group, including psychrotolerant group strains, at low temperatures and provide information for improving bacterial inhibition strategies in the food industry.
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http://dx.doi.org/10.3390/microorganisms9061255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229767PMC
June 2021

A Case of Bilateral Acute Renal Infarction due to Paradoxical Embolism in a Patient with Eisenmenger Syndrome and a Ventricular Septal Defect.

Intern Med 2021 Jun 19. Epub 2021 Jun 19.

Department of Internal Medicine, College of Medicine Gyeongsang National University and Gyeongsang National University Hospital, Korea.

A 52-year-old man who was diagnosed with Eisenmenger syndrome due to a muscular-type ventricular septal defect 30 years previously, visited our emergency room after experiencing six hours of severe left flank pain and vomiting. On laboratory examination, azotemia and microscopic haematuria were identified. Contrast-enhanced computed tomography also revealed pulmonary embolism (PE) and bilateral acute renal infarction. The flank pain resolved after heparin was administered for anti-coagulation and aspiration thrombectomy was performed. The patient was discharged on warfarin as anticoagulant therapy. In this case, a paradoxical embolism was considered to have been the cause of PE and bilateral acute renal infarction in a patient with Eisenmenger syndrome.
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http://dx.doi.org/10.2169/internalmedicine.7549-21DOI Listing
June 2021

Strain variation in Bacillus cereus biofilms and their susceptibility to extracellular matrix-degrading enzymes.

PLoS One 2021 16;16(6):e0245708. Epub 2021 Jun 16.

Department of Food Biotechnology, Korea University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.

Bacillus cereus is a foodborne pathogen and can form biofilms on food contact surfaces, which causes food hygiene problems. While it is necessary to understand strain-dependent variation to effectively control these biofilms, strain-to-strain variation in the structure of B. cereus biofilms is poorly understood. In this study, B. cereus strains from tatsoi (BC4, BC10, and BC72) and the ATCC 10987 reference strain were incubated at 30°C to form biofilms in the presence of the extracellular matrix-degrading enzymes DNase I, proteinase K, dispase II, cellulase, amyloglucosidase, and α-amylase to assess the susceptibility to these enzymes. The four strains exhibited four different patterns in terms of biofilm susceptibility to the enzymes as well as morphology of surface-attached biofilms or suspended cell aggregates. DNase I inhibited the biofilm formation of strains ATCC 10987 and BC4 but not of strains BC10 and BC72. This result suggests that some strains may not have extracellular DNA, or their extracellular DNA may be protected in their biofilms. In addition, the strains exhibited different patterns of susceptibility to protein- and carbohydrate-degrading enzymes. While other strains were resistant, strains ATCC 10987 and BC4 were susceptible to cellulase, suggesting that cellulose or its similar polysaccharides may exist and play an essential role in their biofilm formation. Our compositional and imaging analyses of strains ATCC 10987 and BC4 suggested that the physicochemical properties of their biofilms are distinct, as calculated by the carbohydrate to protein ratio. Taken together, our study suggests that the extracellular matrix of B. cereus biofilms may be highly diverse and provides insight into the diverse mechanisms of biofilm formation among B. cereus strains.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245708PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208538PMC
June 2021

Spontaneous rupture of a renal artery pseudoaneurysm in a hemodialysis patient: A case report.

Medicine (Baltimore) 2021 May;100(20):e25970

Department of Internal Medicine-Nephrology, College of Medicine, Gyeongsang National University.

Rationale: Renal artery pseudoaneurysm is a rare vascular lesion usually caused by trauma or percutaneous urological procedures. Spontaneous rupture of pseudoaneurysms without predisposing events, especially in hemodialysis patients, has rarely been reported.

Patient Concerns: A 25-year-old man receiving maintenance hemodialysis visited the emergency room because of sudden severe right flank pain. He had no history of trauma or urological procedures except for a left renal biopsy to diagnose Alport syndrome 10 years prior.

Diagnosis: Contrast-enhanced computed tomography revealed a right perirenal hematoma with pseudoaneurysms.

Interventions: On renal angiography, multiple pseudoaneurysms were observed in the right renal artery branches and embolization was performed.

Outcomes: Post-angiography showed no pseudoaneurysms. His abdominal pain improved, and he was discharged 2 weeks after embolization.

Lessons: When maintenance dialysis patients complain of severe abdominal pain, spontaneous rupture of a renal pseudoaneurysm should be considered as a differential diagnosis, even if the patient has no history of trauma or previous urological procedures.
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http://dx.doi.org/10.1097/MD.0000000000025970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136987PMC
May 2021

Investigation of characteristics as endodontic sealer of novel experimental elastin-like polypeptide-based mineral trioxide aggregate.

Sci Rep 2021 May 18;11(1):10537. Epub 2021 May 18.

Department of Conservative Dentistry and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.

Although mineral trioxide aggregates (MTA) have been adopted as an endodontic sealer because of excellent sealing effect and bioactive property and been modified with improvement of its characteristics, the developed MTA sealers have not yet satisfied all the ideal requirements of endodontic sealers. The aim of this study was to assess the characteristics of elastin-like polypeptide (ELP)-incorporated MTA for use as an endodontic sealer and compare them with those of commercial MTA sealers. Two commercial MTA sealers and three experimental ELP-incorporated MTA sealers with 0.3, 0.4, and 0.5 liquid/powder (L/P) ratio for 10 wt% ELP liquid were evaluated. The push-out bond strength, flow rate, sealer penetrability and wash-out resistance were tested and the sealer-dentin interface was observed using a scanning electron microscope (SEM). Our study revealed the ELP-incorporated MTA sealer, especially in 0.4 L/P ratio, exhibited the higher push-out bond strength and flow rate (P < 0.05), and equal or superior sealer penetration and remarkable wash-out resistance compared to commercial MTA sealers. The groups of ELP-based experimental sealers also exhibited more intimate contact with dentin compared to the commercial MTA sealers. Our research will suggest the possible adoption of the ELP-incorporated MTA as endodontic sealer for clinical use.
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http://dx.doi.org/10.1038/s41598-021-90033-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131355PMC
May 2021

Erratum to: Description of Kinetic Behavior of Pathogenic in Cooked Pig Trotters under Dynamic Storage Conditions Using Mathematical Equations.

Food Sci Anim Resour 2021 Mar 1;41(2):353. Epub 2021 Mar 1.

Risk Analysis Research Center, Sookmyung Women's University, Seoul 04310, Korea.

[This corrects the article DOI: 10.5851/kosfa.2020.e64.].
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http://dx.doi.org/10.5851/kosfa.2021.e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115005PMC
March 2021

Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer.

Transl Lung Cancer Res 2021 Mar;10(3):1221-1230

Department of Internal Medicine, Inha University Hospital, Incheon, South Korea.

Background: The programmed cell death pathway necroptosis may synergize with the DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of the necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancers.

Methods: We included 394 patients with stage I non-small-cell lung cancer (NSCLC) who underwent surgical tumor resection between 1 January 1997 and 31 December 2011 and measured expression levels of nine proteins involved in necroptosis and the DDR in primary samples from 394 patients using tissue microarray. Protein expression evaluated by using an H-score method was dichotomized by the median value. The overall survival as the endpoint was calculated from the time of diagnosis to the time of the last follow-up or death.

Results: We find that low-level expression of the necroptosis markers RIPK3 and PELI1 is associated with high risk of patient death. High-level expression of the key DDR factor p53 in combination with low-level expression of either RIPK3 or PELI1 increases the risk further. These gene expression effects appear to occur specifically in the squamous cell carcinoma (SCC) subtype of stage I NSCLC, while not observed in the non-SCC subtypes.

Conclusions: Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype.
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http://dx.doi.org/10.21037/tlcr-20-1027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044481PMC
March 2021

Septal chondrocyte hypertrophy contributes to midface deformity in a mouse model of Apert syndrome.

Sci Rep 2021 Apr 12;11(1):7979. Epub 2021 Apr 12.

Department of Molecular Genetics and Dental Pharmacology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, South Korea.

Midface hypoplasia is a major manifestation of Apert syndrome. However, the tissue component responsible for midface hypoplasia has not been elucidated. We studied mice with a chondrocyte-specific Fgfr2 mutation (Col2a1-cre; Fgfr2) to investigate the effect of cartilaginous components in midface hypoplasia of Apert syndrome. In Col2a1-cre; Fgfr2 mice, skull shape was normal at birth, but hypoplastic phenotypes became evident with age. General dimensional changes of mutant mice were comparable with those of mice with mutations in EIIa-cre; Fgfr2, a classic model of Apert syndrome in mice. Col2a1-cre; Fgfr2 mice showed some unique facial phenotypes, such as elevated nasion, abnormal fusion of the suture between the premaxilla and the vomer, and decreased perpendicular plate of the ethmoid bone volume, which are related to the development of the nasal septal cartilage. Morphological and histological examination revealed that the presence of increased septal chondrocyte hypertrophy and abnormal thickening of nasal septum is causally related to midface deformities in nasal septum-associated structures. Our results suggest that careful examination and surgical correction of the nasal septal cartilage may improve the prognosis in the surgical treatment of midface hypoplasia and respiratory problems in patients with Apert syndrome.
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http://dx.doi.org/10.1038/s41598-021-87260-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041873PMC
April 2021

Natural variation in rice ascorbate peroxidase gene APX9 is associated with a yield-enhancing QTL cluster.

J Exp Bot 2021 05;72(12):4254-4268

Department of Agronomy, College of Agriculture and Life Sciences, Chungnam National University, Daejeon 34134, Republic of Korea.

We previously identified a cluster of yield-related quantitative trait loci (QTLs) including plant height in CR4379, a near-isogenic line from a cross between Oryza sativa spp. japonica cultivar 'Hwaseong' and the wild relative Oryza rufipogon. Map-based cloning and transgenic approaches revealed that APX9, which encodes an l-ascorbate peroxidase 4, is associated with this cluster. A 3 bp InDel was observed leading to the addition of a valine in Hwaseong compared with O. rufipogon. APX9-overexpressing transgenic plants in the Hwaseong background were taller than Hwaseong. Consistent with these results, APX9 T-DNA insertion mutants in the japonica cultivar Dongjin were shorter. These results confirm that APX9 is the causal gene for the QTL cluster. Sequence analysis of APX9 from 303 rice accessions revealed that the 3 bp InDel clearly differentiates japonica (APX9HS) and O. rufipogon (APX9OR) alleles. indica accessions shared both alleles, suggesting that APX9HS was introgressed into indica followed by crossing. The finding that O. rufipogon accessions with different origins carry APX9OR suggests that the 3 bp insertion was specifically selected in japonica during its domestication. Our findings demonstrate that APX9 acts as a major regulator of plant development by controlling a valuable suite of agronomically important traits in rice.
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http://dx.doi.org/10.1093/jxb/erab155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163052PMC
May 2021

Effect of combined pulmonary fibrosis and emphysema on patients with connective tissue diseases and systemic sclerosis: a systematic review and meta-analysis.

Arthritis Res Ther 2021 04 6;23(1):100. Epub 2021 Apr 6.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.

Background: This study aimed to analyze the literature systematically to determine the clinical characteristics and prognosis of patients with connective tissue disease (CTD) with combined pulmonary fibrosis and emphysema (CPFE) compared to those of patients with CTD-interstitial lung disease (CTD-ILD) without emphysema.

Methods: We searched MEDLINE, EMBASE, Cochrane Library, and KoreaMed for relevant articles published before July 2019. Studies meeting all the following criteria were included: (1) original research studies evaluating the effect of CPFE on CTD, (2) studies that compared patients with CTD-CPFE to those with CTD-ILD without emphysema, and (3) studies providing data on physical capacity, pulmonary function, or death in patients with CTD. Clinical characteristics of patients with CTD-CPFE were compared with those of patients with CTD-ILD without emphysema, and the influence of CPFE on physical capacity, pulmonary function, and death was analyzed.

Results: Six studies between 2013 and 2019 were included. Two hundred ninety-nine (29.5%) and 715 (70.5%) patients had CTD-CPFE and CTD-ILD without emphysema, respectively. Regarding the type of CTD, 711 (68.3%) patients had systemic sclerosis, 263 (25.3%) rheumatoid arthritis, and 67 (6.4%) other CTDs. Patients with CTD-CPFE had a higher frequency of pulmonary hypertension and pulmonary fibrosis > 20% of the total lung volume, higher ratio of the forced vital capacity to the diffusion capacity of the lung for carbon monoxide (DLCO), lower arterial oxygen pressure at rest, and lower DLCO compared to those in patients with CTD-ILD without emphysema. In addition, more deaths occurred among those with CTD-CPFE (odds ratio, 2.95; 95% confidence interval, 1.75-4.96).

Conclusion: CTD-CPFE is associated with worse physical and pulmonary function and more deaths compared to those in CTD-ILD without emphysema. These findings indicate the need for increased awareness and close monitoring of patients with CTD-CPFE.
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http://dx.doi.org/10.1186/s13075-021-02494-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022385PMC
April 2021

Sensitive label-free imaging of brain samples using FxClear-based tissue clearing technique.

iScience 2021 Apr 5;24(4):102267. Epub 2021 Mar 5.

Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine, Seoul 02841, Republic of Korea.

Optical clearing has emerged as a powerful tool for volume imaging. Although volume imaging with immunostaining have been successful in many protocols, yet obtaining homogeneously stained thick samples remains challenging. Here, we propose a method for label-free imaging of brain slices by enhancing the regional heterogeneity of the optical properties using the tissue clearing principle. We used FxClear, a method for delipidation of brain tissue, to retain a larger proportion of lipids at the white matter (WM). Furthermore, the embedding media affected the contrasts for the lipid-rich or extracellular matrix-rich areas, depending on their chemical properties. Thus, we tailored clearing conditions for the enhancement of the refractive indices (RIs) differences between gray and WM, or several pathological features. RI differences can be imaged using conventional light microscopy or optical coherence tomography. We propose that our protocol is simple, reliable, and flexible for label-free imaging, easily implementable to routine histology laboratory.
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http://dx.doi.org/10.1016/j.isci.2021.102267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005756PMC
April 2021

Effects of bioactive glass incorporation into glass ionomer cement on demineralized dentin.

Sci Rep 2021 Mar 29;11(1):7016. Epub 2021 Mar 29.

Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea.

The effects of the incorporation of sodium-free bioactive glass into glass ionomer cement (GIC) on the demineralized dentin are studied. Four experimental groups with various amounts of BAG in GIC were considered: BG0 group: 0 wt% (control); BG5 group: 5 wt%; BG10 group: 10 wt%; BG20 group: 20 wt%. The GIC surface and GIC-approximated demineralized dentin surfaces were evaluated using field emission scanning electron microscopy (FE-SEM). X-ray diffraction (XRD) analysis was performed to evaluate the chemical changes in the GIC-approximated dentin surface. In addition, a shear bond strength test was performed to evaluate the effects of BAG incorporation on the bond strength of GIC. FE-SEM analysis indicated that BAG-incorporated GICs formed distinct precipitates on their surface. Precipitates were also formed on the GIC-approximated demineralized dentin surface. It was more obvious when the amount of BAG increased. In the XRD analysis, fluorapatitie (FAP) peaks were detected in the BG5, BG10, and BG20 groups. There was no significant difference in the shear bond strength among all experimental groups. BAG-incorporated GIC precipitated FAP crystals underlying demineralized dentin surface without affecting bond strength. This study suggests the possibility of BAG as a beneficial additive in GIC.
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http://dx.doi.org/10.1038/s41598-021-86481-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007704PMC
March 2021

Dynamic bacterial community response to Akashiwo sanguinea (Dinophyceae) bloom in indoor marine microcosms.

Sci Rep 2021 Mar 26;11(1):6983. Epub 2021 Mar 26.

Library of Marine Samples, Korea Institute of Ocean Science and Technology, Geoje, 53201, Republic of Korea.

We investigated the dynamics of the bacterial composition and metabolic function within Akashiwo sanguinea bloom using a 100-L indoor microcosm and metagenomic next-generation sequencing. We found that the bacterial community was classified into three groups at 54% similarity. Group I was associated with "during the A. sanguinea bloom stage" and mainly consisted of Alphaproteobacteria, Flavobacteriia and Gammaproteobacteria. Meanwhile, groups II and III were associated with the "late bloom/decline stage to post-bloom stage" with decreased Flavobacteriia and Gammaproteobacteria in these stages. Upon the termination of the A. sanguinea bloom, the concentrations of inorganic nutrients (particularly PO, NH and dissolved organic carbon) increased rapidly and then decreased. From the network analysis, we found that the A. sanguinea node is associated with certain bacteria. After the bloom, the specific increases in NH and PO nodes are associated with other bacterial taxa. The changes in the functional groups of the bacterial community from chemoheterotrophy to nitrogen association metabolisms were consistent with the environmental impacts during and after A. sanguinea bloom. Consequently, certain bacterial communities and the environments dynamically changed during and after harmful algal blooms and a rapid turnover within the bacterial community and their function can respond to ecological interactions.
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http://dx.doi.org/10.1038/s41598-021-86590-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997919PMC
March 2021

Verapamil-containing silicone gel reduces scar hypertrophy.

Int Wound J 2021 Mar 17. Epub 2021 Mar 17.

Department of Plastic and Reconstructive Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

A hypertrophic scar is a common dermal fibroproliferative lesion usually treated with topical silicone. Verapamil, a type of calcium channel blocker, is considered a candidate drug for the treatment of hypertrophic scars. Here, we report that the addition of verapamil to topical silicone gel enhances treatment outcomes of hypertrophic scars. Upon creation of hypertrophic scars with the rabbit ear model, varying concentrations of verapamil-added silicone gel (0.1, 1, and 10 mg/g) were applied daily for 28 days. After the animals were euthanised, microscopic measurement was performed for (a) scar elevation index (SEI), (b) fibroblast count, and (c) capillary count. On gross analysis, features of hypertrophic scars were significantly alleviated in the verapamil-added groups. On histologic examination, verapamil-added groups showed (a) reduced SEI (1.93 (1.79-2.67) for control vs 1.34 (1.21-1.51) for silicone only and 1.13 (1.01-1.65) for verapamil-added silicone), (b) fibroblast count 700.5 (599.5-838.5) for control, 613.25 (461-762.5) for silicone only, and 347.33 (182.5-527) for verapamil-added silicone), and (c) capillary formation (52 (35.5-96.5) for control, 46 (28-64.5) for silicone only, and 39.83(24-70) for verapamil-added silicone) (Kruskal-Wallis test, P < .05). On western blot, expression levels of collagen I protein was lower in the 1 mg/g and 10 mg/g verapamil-added silicone compared with control. Therefore, we suggest a therapeutic concentration of verapamil-added silicone gel of at least over 1 mg/g. Further study regarding maximally effective concentration and deeper insight into the mechanism of action should follow.
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http://dx.doi.org/10.1111/iwj.13566DOI Listing
March 2021

Predictive Modeling for the Growth of spp. in Liquid Egg White and Application of Scenario-Based Risk Estimation.

Microorganisms 2021 Feb 25;9(3). Epub 2021 Feb 25.

Korea Food Research Institute, Wanju, Jeollabuk-do 55365, Korea.

The objective of the study was to develop a predictive model of spp. growth in pasteurized liquid egg white (LEW) and to estimate the salmonellosis risk using the baseline model and scenario analysis. Samples were inoculated with six strains of , and bacterial growth was observed during storage at 10-37 °C. The primary models were developed using the Baranyi model for LEW. For the secondary models, the obtained specific growth rate (μ) and lag phase duration were fitted to a square root model and Davey model, respectively, as functions of temperature (R ≥ 0.98). For μ, the values were satisfied within an acceptable range (A, B: 0.70-1.15). The probability of infection (P) due to the consumption of LEW was zero in the baseline model. However, scenario analysis suggested possible salmonellosis for the consumption of LEW. Because spp. proliferated much faster in LEW than in egg white (EW) during storage at 20 and 30 °C ( < 0.01), greater P may be obtained for LEW when these products are stored at the same conditions. The developed predictive model can be applied to the risk management of spp. along the food chain, including during product storage and distribution.
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http://dx.doi.org/10.3390/microorganisms9030486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996612PMC
February 2021

Label-free multimodal microscopy using a single light source and detector for biological imaging.

Opt Lett 2021 Feb;46(4):892-895

Multimodal nonlinear microscopy has been widely applied in biology and medicine due to its relatively deep penetration into tissue and its label-free manner. However, current multimodal systems require the use of multiple sources and detectors, leading to bulky, complex, and expensive systems. In this Letter, we present a novel method of using a single light source and detector for nonlinear multimodal imaging of biological samples. Using a photonic crystal fiber, a pulse picker, and multimode fibers, our developed system successfully acquired multimodal images of swine coronary arteries, including two-photon excitation fluorescence, second-harmonic generation, coherent anti-Stokes Raman scattering, and backreflection. The developed system could be a valuable tool for various biomedical applications.
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http://dx.doi.org/10.1364/OL.415938DOI Listing
February 2021

Genetic Architectures and Cell-of-Origin in Glioblastoma.

Front Oncol 2020 21;10:615400. Epub 2021 Jan 21.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.

An aggressive primary brain cancer, glioblastoma (GBM) is the most common cancer of the central nervous system in adults. However, an inability to identify its cell-of-origin has been a fundamental issue hindering further understanding of the nature and pathogenesis of GBM, as well as the development of novel therapeutic targets. Researchers have hypothesized that GBM arises from an accumulation of somatic mutations in neural stem cells (NSCs) and glial precursor cells that confer selective growth advantages, resulting in uncontrolled proliferation. In this review, we outline genomic perspectives on IDH-wildtype and IDH-mutant GBMs pathogenesis and the cell-of-origin harboring GBM driver mutations proposed by various GBM animal models. Additionally, we discuss the distinct neurodevelopmental programs observed in either IDH-wildtype or IDH-mutant GBMs. Further research into the cellular origin and lineage hierarchy of GBM will help with understanding the evolution of GBMs and with developing effective targets for treating GBM cancer cells.
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http://dx.doi.org/10.3389/fonc.2020.615400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859479PMC
January 2021

Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.

Front Med Technol 2020 Aug 7;2. Epub 2020 Aug 7.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States.

Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.
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http://dx.doi.org/10.3389/fmedt.2020.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849371PMC
August 2020

YYB-101, a Humanized Antihepatocyte Growth Factor Monoclonal Antibody, Inhibits Ovarian Cancer Cell Motility and Proliferation.

Anticancer Res 2021 Feb;41(2):671-678

Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea

Background/aim: Hepatocyte growth factor (HGF) acts as a key regulator in promoting ovarian cancer metastasis. Previously, we observed that YYB-101, a humanized anti-HGF antibody, effectively inhibits ovarian cancer cell migration, invasion, and progression. Here, we evaluated the signaling mechanisms affected by YYB-101 that are important in ovarian cancer cell progression.

Materials And Methods: Using cell migration, invasion and proliferation assays, we evaluated the effects of YYB-101 on A2780/luc and SKOV3 cells. The effects of YYB-101 on signaling molecules were determined by immunocytochemistry and immunoblot analysis.

Results: YYB-101 inhibited HGF-induced ovarian cancer cell motility by down-regulating paxillin phosphorylation and actin-cytoskeleton rearrangement. Also, YYB-101 inhibited ovarian cancer cell proliferation by reducing c-MET phosphorylation and activating apoptosis in vitro and in vivo. These effects were significantly enhanced by combining YYB-101 treatment with paclitaxel, a standard chemotherapy drug.

Conclusion: YYB-101 can be examined as a new therapeutic agent for the treatment of patients with ovarian cancer.
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http://dx.doi.org/10.21873/anticanres.14818DOI Listing
February 2021

Familial Risk of Hashimoto's Thyroiditis Among First-Degree Relatives: A Population-Based Study in Korea.

Thyroid 2021 07 19;31(7):1096-1104. Epub 2021 Mar 19.

Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea.

Few small-scale studies have reported a genetic and familial predisposition in Hashimoto's thyroiditis (HT), however, quantified familial risk estimates from population-level data are unavailable. We aimed to estimate the incidence and familial risk of HT among first-degree relatives (FDR) according to age, sex, and family relationships. We conducted a population-based study in the general population of Korea from 2002 to 2017. Using the nationwide health insurance database, which has full population coverage and family relationship information, a cohort of 22 million individuals with blood-related FDR comprising 12 million families were followed up for a familial occurrence of HT. Age- and sex-adjusted incidence risk ratios (IRRs) were calculated in individuals with an affected FDR compared with those without an affected FDR. Among 21,940,795 individuals, 234,912 had an HT-affected FDR, of whom 2425 familial cases developed HT with an incidence of 7.12/10,000 person-years. The familial risk for HT was 6.5-fold (95% confidence interval [CI]: 6.24-6.78) higher in individuals with versus without affected FDR. According to relationship, familial risks were IRR 102.71, IRR 7.80, IRR 5.54, and IRR 5.52 with an affected twin, sibling, mother, and father, respectively, and the corresponding incidence (/10,000 person-years) was 115.57, 10.66, 5.73, and 5.91. Same-sex twins had three times higher risk of developing HT than opposite-sex twins (IRR 121.01 vs. 21.46). The sex-specific familial risk was higher in males than females. The risks demonstrated age dependence, being higher in younger age groups. This study represents the largest population-based study of familial HT risk in Asia. We demonstrated elevated familial risk of incident HT among FDR, but with lower magnitude as those observed in previous studies. Familial risk increased with the degree of genetic relatedness among FDR indicating a prominent role of genetic factors in the familial aggregation of HT. Elevated risks in the younger age groups should motivate clinicians to screen people with a family history, especially those <30 years.
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http://dx.doi.org/10.1089/thy.2020.0213DOI Listing
July 2021

Bending resistance and cyclic fatigue resistance of WaveOne Gold, Reciproc Blue, and HyFlex EDM instruments.

J Dent Sci 2020 Dec 30;15(4):472-478. Epub 2019 Dec 30.

Department of Conservative Dentistry, KyungHee University Dental Hospital, 23 Kyungheedaero, Dongdaemun-gu, Seoul 02447, Republic of Korea.

Background/purpose: Several single-file systems manufactured using different heat treatment and operated by different kinematics have been released. This study compared the bending resistance and cyclic fatigue resistance of three NiTi files, and examined their phase-transformation behavior.

Materials And Methods: WaveOne Gold Primary (WOG), Reciproc Blue R25 (RPB), and HyFlex EDM OneFile (HDM) were tested (N = 40/instrument). A vertical load was applied to a point 3 mm from the tip, and the stress was measured until a displacement of 3 mm. Tests were conducted at either room temperature (RT: 22 °C) or body temperature (BT: 37 °C) (n = 10). Cyclic fatigue resistance tests were performed in an artificial canal, which had a curvature angle of 40° and a 5-mm radius. Tests were conducted at either RT or BT (n = 10). Instruments were operated according to the manufacturers' instructions. Test results were analyzed using the Kruskal-Wallis and the Mann-Whitney tests. Additional three instruments of each brand were subjected to differential scanning calorimetry (DSC).

Results: At RT the bending resistance of three files were not significantly different. However, at BT the bending resistance of RPB was highest, followed by WOG, and HDM ( < 0.05). At RT, RPB demonstrated the longest fracture time, followed by HDM, and WOG ( < 0.05). At BT, HDM had the longest fracture time, followed by RPB, and WOG ( < 0.05). The WOG, RPB consisted of austenite in a considerable proportion, whereas HDM was mainly martensite state at BT.

Conclusion: HDM presented superior flexibility and cyclic fatigue resistance at BT.
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http://dx.doi.org/10.1016/j.jds.2019.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816021PMC
December 2020

The KDM5 Inhibitor KDM5-C70 Induces Astrocyte Differentiation in Rat Neural Stem Cells.

ACS Chem Neurosci 2021 02 22;12(3):441-446. Epub 2021 Jan 22.

College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.

Members of the lysine-specific histone demethylase 5 (KDM5/JARID1) family are known to play important roles in stem cell fate determination. Here, using the KDM5 inhibitor C70 (KDM5-C70), we demonstrated that the histone demethylase activity of the KDM5 enzyme is essential for the repression of astrocytic differentiation of neural stem cells (NSCs). KDM5-C70 treatment activated the ( gene by increasing the trimethylation of histone H3 lysine 4 in the promoter regions and subsequently induced astrocytogenesis in NSCs. In addition, treatment of NSCs with KDM5-C70 activated Janus kinase-signal transducer and activator of transcription (JAK-STAT3) signaling and increased the mRNA expression of (). Our data provide evidence that KDM5 is a promising target for NSC fate modulation and suggest that epigenetic regulation is important for NSC fate determination.
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http://dx.doi.org/10.1021/acschemneuro.0c00613DOI Listing
February 2021

Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study.

Cancers (Basel) 2021 Jan 18;13(2). Epub 2021 Jan 18.

Division of Medical Oncology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea.

Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4-47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3-5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.
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http://dx.doi.org/10.3390/cancers13020331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829741PMC
January 2021
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