Publications by authors named "Jihye Choi"

147 Publications

Efficacy of a phospholipid-stabilized sulfur hexafluoride microsphere contrast agent and water for hydrosonography of the upper portion of the gastrointestinal tract in dogs.

Am J Vet Res 2021 Sep;82(9):712-721

Objective: To investigate the efficacy of a phospholipid-stabilized sulfur hexafluoride microsphere (SHM) contrast agent and water for hydrosonography of the upper portion of the gastrointestinal tract of dogs.

Animals: 12 healthy adult Beagles.

Procedures: In a crossover study, each dog was anesthetized and underwent noncontrast ultrasonography then hydrosonography following administration of tap water (30 mL/kg) without (water method) or with SHM (0.1 mL; SHM method) via an orogastric tube. There were at least 3 days between hydrosonographic procedures. Wall thickness, wall layer definition, conspicuity of the mucosal-luminal interface, and image quality were evaluated separately in the near and far fields for the gastric cardia, body, and pylorus and descending duodenum and compared among the 3 scanning methods.

Results: Mean wall thickness measurements did not differ significantly between the water and SHM methods at any location except the far-field gastric cardia where the mean wall thickness for the SHM method was less than that for the water method. In general, the SHM method improved wall layer definition and conspicuity of the mucosal-luminal interface of structures in the near field, compared with noncontrast method. The water and SHM methods both resulted in superior image quality relative to the noncontrast method for the near-field gastric cardia, far-field gastric cardia, and far-field duodenum.

Conclusions And Clinical Relevance: Results indicated that, for dogs, gastrointestinal hydrosonography by use of the SHM method improved wall layer definition and mucosal conspicuity, particularly in near-field images of the upper portion of the gastrointestinal tract.
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http://dx.doi.org/10.2460/ajvr.82.9.712DOI Listing
September 2021

Susceptibility to Acaricides and the Frequencies of Point Mutations in Etoxazole- and Pyridaben-Resistant Strains and Field Populations of the Two-Spotted Spider Mite, (Acari: Tetranychidae).

Insects 2021 Jul 20;12(7). Epub 2021 Jul 20.

Department of Plant Medicine, College of Agriculture, Life and Environment Sciences, Chungbuk National University, Cheongju 28644, Korea.

The two-spotted spider mite Koch is a major agricultural pest worldwide and is known to rapidly develop resistance to pesticides. In the present study, we explored a field strain that was collected in 2000 and 2003 and has been exhibiting resistance to etoxazole and pyridaben over the last 16 years. The resistance ratios of the etoxazole- and pyridaben-resistant strains (ER and PR) to etoxazole or pyridaben were more than 5,000,000- and 4109.6-fold higher than that of the susceptible strain, respectively. All field-collected populations showed resistance to etoxazole and pyridaben. The ER and PR strains showed cross-resistance to several acaricides. Both I1017F and H92R point mutations were detected in 7 out of 8 field groups. Spirodiclofen and spiromesifen resulted in more than 77.5% mortality in the 8 field groups. In addition, the genotype frequency of the I1017F point mutation was 100.0% in the ER strain, and that of the H92R point mutation was 97.0% in the PR strain. All of the field populations were found to have a high frequency of I1017F. These results suggest that the observation of resistance patterns will help in designing a sustainable IPM program for .
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http://dx.doi.org/10.3390/insects12070660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306671PMC
July 2021

Echocardiographic features of accessory mitral valve tissue presenting left ventricular outflow tract obstruction in a dog.

J Vet Sci 2021 Jul;22(4):e57

Department of Veterinary Medical Imaging, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea.

In a 3-year-old Samoyed, aortic bulging was found on radiography during a general check-up. On echocardiography, turbulent flow was found in left ventricular outflow tract (LVOT) with high velocity (6.1 m/s). A linear structure was attached to the interventricular septum and connected to the chordae tendineae reaching the papillary muscle. A part of the structure moved during cardiac cycle, similar to mitral motion. This dog was diagnosed with LVOT obstruction caused by accessory mitral valve tissue (AMVT). This is the first report of AMVT in veterinary medicine. AMVT should be considered as a possible cause of LVOT obstruction in dogs.
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http://dx.doi.org/10.4142/jvs.2021.22.e57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318797PMC
July 2021

Renal Diffusion-Weighted Imaging in Healthy Dogs: Reproducibility, Test-Retest Repeatability, and Selection of the Optimal b-value Combination.

Front Vet Sci 2021 2;8:641971. Epub 2021 Jul 2.

College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju, South Korea.

Diffusion-weighted imaging (DWI) magnetic resonance imaging can evaluate alterations in the microstructure of the kidney. The purpose of this study was to assess the apparent diffusion coefficient (ADC) and the intravoxel incoherent motion model (IVIM) parameters of a normal kidney in healthy dogs, to evaluate the effect of b-value combinations on the ADC value, and the reproducibility and test-retest repeatability in monoexponential and IVIM analysis. In this experimental study, the ADC, pure diffusion coefficient (D), pseudodiffusion coefficient (D), and perfusion fraction ( ) were measured from both kidneys in nine healthy beagles using nine b-values (b = 0, 50, 70, 100, 150, 200, 500, 800, and 1,000 s/mm) twice with a 1-week interval between measurements. Interobserver and intraobserver reproducibility, and test-retest repeatability of the measurements were calculated. ADC values were measured using 10 different b-value combinations consisting of three b-values each, and were compared to the ADC obtained from nine b-values. All the ADC, D, D, and values measured from the renal cortex, medulla, and the entire kidney had excellent interobserver and intraobserver reproducibility, and test-retest repeatability. The ADC obtained from a b-value combination of 0, 100, and 800 s/mm had the highest intraclass correlation coefficient with the ADC from nine b-values. The results of this study indicated that DWI MRI using multiple b-values is feasible for the measurement of ADC and IVIM parameters with high reproducibility and repeatability in the kidneys of healthy dogs. A combination of b = 0, 100, and 800 s/mm can be used for ADC measurements when multiple b-values are not available in dogs.
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http://dx.doi.org/10.3389/fvets.2021.641971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282824PMC
July 2021

CT features of malignant and benign oral tumors in 28 dogs.

Vet Radiol Ultrasound 2021 Sep 8;62(5):549-556. Epub 2021 Jul 8.

College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju, South Korea.

An improved understanding of the computed tomographic (CT) features for malignant versus benign oral tumors would be helpful for guiding prognosis and treatment planning decisions in dogs. This retrospective, multi-center, observational study compared the CT features of malignant and benign tumors in 28 dogs with 31 oral masses. Malignant tumors were present in 20 dogs, including malignant melanoma (n = 14), squamous cell carcinoma (SCC, n = 4), adenocarcinoma (n = 1), and fibrosarcoma (n = 1). Eight dogs had benign tumors, including giant cell granuloma (n = 2), peripheral odontogenic fibroma (n = 2), acanthomatous ameloblastoma (n = 2), plasmacytoma (n = 1), and oncocytoma (n = 1). Common CT features of malignant tumors included heterogeneous enhancement, tumor invasion into the adjacent bone, tooth loss, and ipsilateral mandibular lymphadenopathy. Malignant tumors were significantly larger than benign tumors. Bone lysis was found in benign tumors (n = 4) such as acanthomatous ameloblastoma, giant cell granuloma, and plasmacytoma. The bone lysis was a well-defined geographic area regardless of malignancy and tumor type. In periosteal reactions, amorphous patterns were seen in both malignant (n = 2) and benign tumors (n = 2); the latter subgroup also showed solid patterns. Bone expansion (n = 2) was identified in malignant melanoma and acanthomatous ameloblastoma. Findings supported a diagnosis of possible malignancy for dogs with oral tumors having the following CT characteristics: large size, heterogeneous contrast enhancement pattern, bone lysis, tooth loss, and ipsilateral lymphadenopathy. However, there was a considerable overlap of CT findings among the different types of oral tumors and between benign and malignant tumors. Histological evaluation therefore remains necessary for definitive diagnosis.
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http://dx.doi.org/10.1111/vru.12996DOI Listing
September 2021

Review of ERCP Techniques in Roux-en-Y Gastric Bypass Patients: Highlight on the Novel EUS-Directed Transgastric ERCP (EGDE) Technique.

Curr Gastroenterol Rep 2021 Jul 1;23(7):10. Epub 2021 Jul 1.

Department of Gastroenterology, University of Rochester Medical Center, Rochester, NY, 14642, USA.

Purpose Of Review: Hepatobiliary complications are common in Roux-en-Y gastric bypass (RYGB) patients. Despite development of multiple surgical and endoscopic access techniques over the years, ERCP using standard duodenoscope remains challenging in these patients due to the altered anatomy.

Recent Findings: Limited success with enteroscope-assisted and laparoscope-assisted ERCP led to the evolution of the novel EUS-directed transgastric ERCP (EDGE) procedure, with variations of this technique termed as Gastric Access Temporary for Endoscopy (GATE), EUS-guided TransGastric ERCP (EUS-TG-ERCP), EUS-guided GastroGastrostomy-assisted ERCP (EUS-GG-ERCP), and EUS-directed transgastric intervention (EDGI). EDGE has high technical (100%) and clinical success rates (60-100%), lower adverse event rate (1.5-7.6%), and up to 20% access stent migration rate; without any significant weight changes. EDGE has significantly shorter procedure time (73vs184min), post-procedural hospital stays (0.8vs2.65 days) and is more cost effective compared to other modalities. EDGE technique addresses the challenges of RYGB anatomy as a minimally invasive, clinically successful, fully endoscopic, and cost-effective option. We present a literature review of the EDGE technique from its inception to current, in addition to reviewing other access techniques, their advantages, disadvantages and outcomes.
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http://dx.doi.org/10.1007/s11894-021-00808-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249251PMC
July 2021

Comparison of sulfur hexafluoride microbubbles and perfluorobutane for performance of contrast-enhanced ultrasonography of the pancreas in dogs.

Am J Vet Res 2021 Jul;82(7):538-545

Objective: To compare qualitative features and quantitative parameters of 2 contrast agents (sulfur hexafluoride microbubbles [SHM; SonoVue] and perfluorobutane [PFB; Sonazoid]) for performance of contrast-enhanced ultrasonography (CEUS) of the pancreas in dogs.

Animals: 8 healthy Beagles.

Procedures: In a crossover study design, CEUS of the pancreas was performed twice in each dog, once with SHM and once with PFB, in random order with at least 3 days between examinations. The recorded cine images were qualitatively assessed for homogeneity of pancreatic enhancement and conspicuity of the pancreatic signal relative to the background. For the quantitative assessment, circular regions of interest were placed over the pancreatic body, and a time-intensity curve was obtained. For each region of interest, CEUS parameters including peak intensity (PI), time to peak pancreatic enhancement, area under the curve (AUC), and wash-in rate were obtained.

Results: The homogeneity of the pancreatic parenchyma was not significantly different between contrast agents. The signal conspicuity relative to background noise was significantly higher with PFB than with SHM. Mean values of PI, wash-in rate, and AUC were significantly higher with PFB than with SHM. Time to peak enhancement was not significantly different between contrast agents.

Conclusions And Clinical Relevance: Pancreatic CEUS with SHM and PFB produced similar homogeneity scores, but only PFB provided excellent signal conspicuity. Perfluorobutane produced higher values of PI, wash-in rate, and AUC. Findings indicated that PFB can provide homogeneous and strong enhancement of the pancreas during CEUS in healthy dogs and that pancreatic CEUS parameter values differ with the contrast agent used.
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http://dx.doi.org/10.2460/ajvr.82.7.538DOI Listing
July 2021

Radiographic assessment of splenic size and correlation with splenic measurements estimated by use of computed tomography in healthy cats.

Am J Vet Res 2021 Jul;82(7):546-553

Objective: To investigate radiographic variables for correlation with splenic size as estimated with CT in cats.

Animals: 38 healthy adult cats.

Procedures: The width and height of the splenic head and total length, segmental length, and width of the spleen were measured on radiographic and CT images obtained from 10 cats in prospective, exploratory experiments. Distance between the splenic head and left kidney, anatomic locations of the head and tail of the spleen, and CT-derived splenic volume were also assessed. Correlation and agreement between radiographic and CT measurements and interobserver agreement for measurements with each method were determined. A retrospective evaluation of radiographs obtained without sedation or anesthesia for 28 cats was performed to establish preliminary guidelines for the measurement deemed the most reliable estimator of splenic size.

Results: Radiographic measurements of total and segmental splenic length were significantly correlated with the respective CT measurements and with splenic volume. Agreement between radiographic and CT measurements of segmental length was good; interobserver agreement was excellent for all variables. In retrospective evaluations, median segmental length of the spleen was 57.87 mm (range, 34.72 to 105.44 mm) on radiographs; the caudal border of the splenic head on lateral views was located from the cranial part of L1 to the caudal part of L2, and the caudal border of the splenic tail on ventrodorsal views was located from the caudal part of L2 to the caudal part of L5.

Conclusions And Clinical Relevance: Results indicated that segmental length of the spleen on radiographs is a reliable estimator of splenic size in healthy cats.
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http://dx.doi.org/10.2460/ajvr.82.7.546DOI Listing
July 2021

Caudate nucleus volume mediates the link between glutamatergic neurotransmission and problematic smartphone use in youth.

J Behav Addict 2021 Apr 26. Epub 2021 Apr 26.

Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background And Aims: Problematic smartphone use (PSU) is growing rapidly among teens. It has similar presentations as other behavioral addictions in terms of excessive use, impulse control problems, and negative consequences. However, the underlying neurobiological mechanisms remain undiscovered. We hypothesized that structural changes in the striatum might serve as an important link between alteration in glutamate signaling and development of PSU.

Methods: Among 88 participants, twenty (F:M, 12:8; age 16.2 ± 1.1) reported high scores in the smartphone addiction proneness scale (SAPS) with a cut-off score of 42; the other 68 (F:M, 19:49; age 15.3 ± 1.7) comprised the control group. Sociodemographic data and depression, anxiety, and impulsivity traits were measured. Striatal volumes (caudate, putamen, and nucleus accumbens) were estimated from T1 imaging data. Serum glutamate levels were estimated from peripheral blood samples. Group comparisons of each data were performed after controlling for age and gender. Mediation analyses were conducted to test the indirect effects of glutamate level alteration on PSU through striatal volumetric alteration.

Results: The PSU group showed a decrease in both caudate volumes than the control group. Left caudate volume was positively correlated with serum glutamate level, and negatively with impulsivity traits and SAPS scores. The mediation model revealed a significant indirect effect of serum glutamate on SAS scores through the reduced left caudate volume.

Discussion And Conclusions: This study suggests that altered glutamatergic neurotransmission may be associated with PSU among teens, possibly through reduced left caudate volume. Current findings might support neural mechanisms of smartphone addiction.
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http://dx.doi.org/10.1556/2006.2021.00024DOI Listing
April 2021

Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic.

Int J Environ Res Public Health 2021 03 23;18(6). Epub 2021 Mar 23.

Department of Child Development and Family Studies, College of Human Ecology, Seoul National University, Seoul 08826, Korea.

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey ( = 1236) and the 2019 Korean Children and Youth Well-being Index Survey ( = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic.
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http://dx.doi.org/10.3390/ijerph18063324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004811PMC
March 2021

Diet-Related Mobile Apps to Promote Healthy Eating and Proper Nutrition: A Content Analysis and Quality Assessment.

Int J Environ Res Public Health 2021 03 28;18(7). Epub 2021 Mar 28.

Department of Health Administration, Kongju National University, Chungnam 32588, Korea.

Dietary mobile applications (apps) continue to hold promise for facilitating a healthy diet and managing nutrition. However, few studies have objectively evaluated the content and quality of such apps in Korea. The present study assessed the content and quality of dietary mobile apps using the Mobile App Rating Scale (MARS). We selected 29 dietary apps based on keywords and eligibility criteria for inclusion in the analyses. We conducted regression analyses to examine the association between app content and MARS scores. Most of the apps featured a tracking tool, while few featured rewards or follow-up management. Our quality assessment revealed that the top-rated apps have distinct levels of quality in terms of MARS scores. The regression analyses showed that the ways in which the apps provide information and motivate the users are statistically significant predictors of app quality. Our findings may facilitate the selection of dietary apps in Korea and provide guidelines for app developers regarding potential improvements in terms of content and quality.
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http://dx.doi.org/10.3390/ijerph18073496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037032PMC
March 2021

The neural basis underlying impaired attentional control in problematic smartphone users.

Transl Psychiatry 2021 02 18;11(1):129. Epub 2021 Feb 18.

Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, 06591, Republic of Korea.

As a portable media device that enables ubiquitous access to friends and entertainment, smartphones are inextricably linked with our lives. Although there is growing concern about the detrimental effect of problematic smartphone use on attentional control, the underlying neural mechanisms of impaired attentional control in problematic smartphone users (PSU) has yet to be investigated. Using a modified cognitive conflict task, we examined behavioral performance in the presence of distracting words during functional magnetic resonance imaging in 33 PSU and 33 control participants (CON). Compared with the CON group, the PSU group demonstrated impaired performance that was accompanied by constantly enhanced but not differentiated activation in the frontoparietal regions across all conditions, regardless of distractor saliency. The inferior parietal lobule (IPL) activation in the PSU group, in particular, showed an association with performance deficits in the distractor conditions. Furthermore, the PSU group exhibited decreased functional connectivity of the right IPL with the right superior temporal gyrus of the ventral attention system in the attention-demanding condition relative to the easiest condition, which was associated with the severe dependence on smartphone use. Our findings suggest that greater distractibility in the PSU group during the attentional control task may be associated with inefficient recruitment of the ventral attention network involved in bottom-up attentional processing, as indicated by hyperactivation but less coherence within the network. The present study provides evidence for understanding the neural mechanisms underlying the impaired ability to keep attention from being oriented to task-irrelevant stimuli observed in PSU.
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http://dx.doi.org/10.1038/s41398-021-01246-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892559PMC
February 2021

A comparative study of sono-urethrography using saline, agitated saline, and an ultrasound contrast agent in normal beagles.

Vet Radiol Ultrasound 2021 May 21;62(3):342-349. Epub 2021 Jan 21.

College of Veterinary Medicine and BK 21 Plus Project Team, Chonnam National University, Gwangju, South Korea.

Sono-urethrography is a technique used to evaluate the integrity of the urethra utilizing fluid dilation of the urethral lumen. The purpose of this prospective, method comparison, pilot study was to investigate the feasibility of sono-urethrography in male dogs and to compare the quality of the images obtained using three different contrast solutions. The prostatic, membranous, and penile urethra was evaluated using saline, agitated saline, and ultrasound contrast agent (Sonovue) in 10 adult, male Beagles. Visibility of the urethral wall was better with sono-urethrography than with conventional ultrasonography, and the conspicuity of urethra could be assessed using all solutions. Hyperechoic lines created by agitated saline and Sonovue were more useful than anechoic saline in allowing identification of the urethra. Visibility scores for the internal margin of the urethral wall using sono-urethrography were significantly higher with saline and one-minute post agitated saline injection. However, the individual layers of the urethral wall could not be observed, regardless of the contrast solution used. Shadowing created by the pelvic bone deteriorated the window through which the urethra could be visualized, and this could not be overcome using sono-urethrography. The results of this study indicated that sono-urethrography is a feasible option for the visualization of the male urethra in dogs. The authors recommend sono-urethrography using saline or agitated saline infusion to evaluate the urethral wall and lumen. Sono-urethrography using ultrasound contrast agent can be applied to assess the integrity of the urethra by improving its conspicuity.
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http://dx.doi.org/10.1111/vru.12952DOI Listing
May 2021

Radiography and ct features of atherosclerosis in two miniature schnauzer dogs.

J Vet Sci 2020 Nov;21(6):e89

College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea.

Two miniature Schnauzer dogs with chronic pancreatitis were investigated. Both dogs showed systemic hypertension and increased concentrations of triglycerides and C-reactive protein. Abdominal radiography revealed cylindrical calcification in the retroperitoneum, and computed tomography (CT) showed extensive calcification of the abdominal and peripheral arteries in both dogs. Metastases and other dystrophic conditions that can cause arterial calcification were excluded based on the laboratory tests, and the dogs were diagnosed with atherosclerosis ante mortem. Atherosclerosis should be considered when extensive arterial calcification is observed on abdominal radiography or CT in miniature Schnauzers.
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http://dx.doi.org/10.4142/jvs.2020.21.e89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710456PMC
November 2020

Effects of kernel and window setting combinations on assessments of small and complicated vasculature in computed tomography angiographic images of dogs with and without tumors.

Am J Vet Res 2020 Dec;81(12):940-949

Objective: To evaluate the effect of kernel and window settings on the assessment of small and complicated vasculature in CT angiographic (CTA) images of kidneys, jejunum with mesentery, and tumors in dogs.

Animals: 20 healthy dogs and 20 dogs with tumors.

Procedures: Images from CTA performed previously in dogs were reconstructed with 3 different combinations of kernel and window settings (soft kernel with soft tissue window, soft kernel with bone window, and sharp kernel with bone window), and reconstructed images of the left kidney and the jejunum with the mesentery in healthy dogs and tumors in affected dogs were evaluated by reviewers blinded to the settings.

Results: For images of kidney and jejunum with mesentery, reviewers' scores for the conspicuity of vascularity in the arterial phase and the differentiation of the organs from the adjacent structures were significantly higher when viewed in bone window (vs soft tissue window) regardless of kernel setting. For images of head and gastrointestinal tumors, reviewers' scores for differentiation of intratumoral vasculature were higher when viewed in sharp kernel with bone window versus other setting combinations. However, the conspicuity of gastrointestinal, hepatic, or splenic tumoral vessels from the adjacent structures had higher reviewer scores for images in soft kernel with soft tissue window, compared with other setting combinations.

Conclusions And Clinical Relevance: Results indicated that reconstruction of CTA images with sharp kernel combined with bone window settings might have clinical utility in evaluating and planning treatments for dogs with various tumors; however, additional research is warranted to further identify effects of various kernel and window setting combinations on assessments of small and complicated vasculature in larger and more diverse populations of dogs with and without tumors.
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http://dx.doi.org/10.2460/ajvr.81.12.940DOI Listing
December 2020

Comparison of Renal Blood Flow Using Maximum Slope-Based Computed Tomography Perfusion and Ultrasound Flow Probe in Healthy Dogs.

Front Vet Sci 2020 9;7:541747. Epub 2020 Oct 9.

Veterinary Medical Imaging, College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju, South Korea.

Computed tomography (CT) perfusion can analyze tissue perfusion and quantitative parameters, including blood flow, blood volume, and transit time. CT perfusion has been used for evaluating split renal function. However, its applicability in veterinary medicine was not validated. This study aimed to evaluate the correlation of renal blood flow (RBF) derived by maximum slope-based CT perfusion and an ultrasonic flow probe and assess the effect of the presence of a pre-existing contrast medium on CT perfusion in the kidneys. In five healthy purpose-bred beagles, CT perfusion was performed at the level of the left renal hila after injection of 1 mg/kg iohexol, during measuring RBF with an ultrasonic flow probe placed on the left renal artery. After post-contrast CT scan with injection of 2 mg/kg iohexol, CT perfusion scan was repeated with the same protocol used in the first perfusion study. The CT perfusion derived RBF was analyzed based on the maximum slope and was compared with the true RBF obtained using an ultrasonic flow probe. Results indicated that CT perfusion derived RBF was significantly correlated with true RBF, although CT perfusion derived RBF did not match the absolute value of the true RBF. It was correlated with the true RBF, even in the presence of a pre-existing contrast medium in the kidney. CT perfusion can estimate the change in individual renal perfusion non-invasively, and this method can be used supplementary to the conventional CT protocol in clinic.
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http://dx.doi.org/10.3389/fvets.2020.541747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581705PMC
October 2020

A Systems Biology Approach to Identifying a Master Regulator That Can Transform the Fast Growing Cellular State to a Slowly Growing One in Early Colorectal Cancer Development Model.

Front Genet 2020 8;11:570546. Epub 2020 Oct 8.

Laboratory for Systems Biology and Bio-inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.

Colorectal cancer (CRC) has been most extensively studied for characterizing genetic mutations along its development. However, we still have a poor understanding of CRC initiation due to limited measures of its observation and analysis. If we can unveil CRC initiation events, we might identify novel prognostic markers and therapeutic targets for early cancer detection and prevention. To tackle this problem, we establish the early CRC development model and perform transcriptome analysis of its single cell RNA-sequencing data. Interestingly, we find two subtypes, fast growing vs. slowly growing populations of distinct growth rate and gene signatures, and identify CCDC85B as a master regulator that can transform the cellular state of fast growing subtype cells into that of slowly growing subtype cells. We further validate this by experiments and suggest CCDC85B as a novel potential therapeutic target that may prevent malignant CRC development by suppressing stemness and uncontrolled cell proliferation.
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http://dx.doi.org/10.3389/fgene.2020.570546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579420PMC
October 2020

Effect of slice thickness on computed tomographic perfusion analysis of the pancreas in healthy dogs.

Am J Vet Res 2020 Sep;81(9):732-738

Objective: To evaluate the effect of slice thickness on CT perfusion analysis of the pancreas in healthy dogs.

Animals: 12 healthy Beagles.

Procedures: After precontrast CT scans, CT perfusion scans of the pancreatic body were performed every second for 30 seconds by sequential CT scanning after injection of contrast medium (iohexol; 300 mg of 1/kg) at a rate of 3 mL/s. Each dog underwent CT perfusion scans twice in a crossover-design study with 2 different slice thicknesses (2.4 and 4.8 mm). Computed tomographic pancreatic perfusion variables, including blood flow, blood volume determined with the maximum slope model, times to the start of enhancement and peak enhancement, permeability, and blood volume determined by Patlak plot analysis, were measured independently by 2 reviewers. The CT perfusion variables were compared between slice thicknesses. Interoperator reproducibility was determined by ICC calculation.

Results: Interoperator reproducibility of CT perfusion variable measurements was excellent on 2.4-mm (mean ± SD ICC, 0.81 ± 0.17) and 4.8-mm (0.90 ± 0.07) slice thicknesses, except for time to peak pancreatic enhancement on 2.4-mm-thick slices, which had moderate reproducibility (intraclass correlation coefficient, 0.473). There was no significant difference in measurements of blood flow, blood volume by either method, times to the start and peak of pancreatic enhancement, or permeability between slice thicknesses.

Conclusions And Clinical Relevance: Results supported that a thin slice thickness of 2.4 mm can be used for assessment of pancreatic perfusion variables in healthy dogs.
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http://dx.doi.org/10.2460/ajvr.81.9.732DOI Listing
September 2020

Two-Dimensional Shear Wave Elastography of Normal Soft Tissue Organs in Adult Beagle Dogs; Interobserver Agreement and Sources of Variability.

Front Bioeng Biotechnol 2020 19;8:979. Epub 2020 Aug 19.

College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju, South Korea.

Shear wave elastography (SWE) induces lateral shear wave through acoustic pulses of the transducer and evaluates tissue stiffness quantitatively. This study was performed to evaluate feasibility and reproducibility of two-dimensional shear wave elastography (2D SWE) for evaluation of tissue stiffness and to examine technical factors that affect shear wave speed (SWS) measurements in adult dogs. Nine healthy, 2 year-old, adult beagles with the median weight of 9.8 kg were included. In this prospective, experimental, exploratory study, 2D SWE (Aplio 600) from the liver, spleen, kidneys, pancreas, prostate, lymph nodes (submandibular, retropharyngeal, axillary, medial iliac, and inguinal), submandibular salivary gland, and thyroid was performed in anesthetized beagles. Color map was drawn and SWS of each SWE were measured as Young's modulus (kPa) and shear wave velocity (m/s). The effect of measuring site, scan approach, depth, and anesthesia on SWE was assessed in abdominal organs by two observers independently. A total of 27 SWE examinations were performed in 12 organs by each observer. All SWS measurements were preformed successfully; however, SWE in the renal medulla could not be successfully conducted, and it was excluded from further analysis. Interobserver agreement of SWE was moderate to excellent in all organs, except for the left liver lobe at 10-15 mm depth with the intercostal scan. In the liver, there was no significant effect of the measuring site and scan approach on SWE. SWS of the liver and spleen tended to be higher with increasing the depth, but no significant difference. However, anesthesia significantly increased tissue stiffness in the spleen compared to awake dog regardless of the depth ( < 0.05). There was a significant difference in SWS according to the measuring site in the kidneys and pancreas ( < 0.001). 2D SWE was feasible and highly reproducible for the estimation of tissue stiffness in dogs. Measuring site and anesthesia are sources of variability affecting SWE in abdominal organs. Therefore, these factors should be considered during SWS measurement in 2D SWE. This study provides basic data for further studies on 2D SWE on pathological conditions that may increase tissue stiffness in dogs.
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http://dx.doi.org/10.3389/fbioe.2020.00979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466577PMC
August 2020

A phase I, randomized, single-dose pharmacokinetic study comparing sb8 (bevacizumab biosimilar) with reference bevacizumab in healthy volunteers.

Cancer Chemother Pharmacol 2020 10 19;86(4):567-575. Epub 2020 Sep 19.

Clinical Pharmacology Unit, SGS LSS, Antwerpen, Lange Beeldekensstraat 267, 2060, Antwerpen, Belgium.

Purpose: To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US).

Methods: In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUC) and to the last quantifiable concentration (AUC), and maximum observed serum concentration (C). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00-125.00%. Safety and immunogenicity were also investigated.

Results: The 90% CIs for the geometric LSMean ratios of AUC, AUC and C were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUC, 88.65%, 89.08% and 100.49% for AUC and 99.59%, 101.15% and 101.56% for C, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected.

Conclusion: This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. CLINICALTRIALS.

Gov Identifier: NCT02453672 (submitted date); EudraCT number: 2015-001,026-41.
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http://dx.doi.org/10.1007/s00280-020-04144-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515939PMC
October 2020

Target-Site Mutations and Glutathione -Transferases Are Associated with Acequinocyl and Pyridaben Resistance in the Two-Spotted Spider Mite (Acari: Tetranychidae).

Insects 2020 Aug 7;11(8). Epub 2020 Aug 7.

Department of Plant Medicine, College of Agriculture, Life and Environment Sciences, Chungbuk National University, Cheongju 28644, Korea.

The two-spotted spider mite is a difficult-to-control pest due to its short life cycle and rapid resistance development. In this study, we characterized field strains collected in 2001 and 2003 that were selected for acequinocyl resistance (AR) and pyridaben resistance (PR), respectively. These strains displayed resistance ratios of 1798.6 (susceptible vs. AR) and 5555.6 (susceptible vs. PR), respectively, and were screened for cross-resistance against several currently used acaricides. The AR strain exhibited pyridaben cross-resistance, but the PR strain showed no cross-resistance. The AR strain exhibited point mutations in (I256V, N321S) and PSST (H92R). In contrast, the PR strain exhibited the H92R but not the I256V and N321S point mutations. In some cases increased glutathione -transferase (GST) activity has previously been linked to enhanced detoxification. The AR strain exhibited approximately 2.3-, 1.8-, and 2.2-fold increased GST activity against 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), and 4-nitrobenzyl chloride (NBC), respectively. Among the five GST subclass genes (delta, omega, mu, zeta, and kappa), the relative expression of delta class GSTs in the AR strain were significantly higher than the PR and susceptible strain. These results suggest that the I256V and N321S mutations and the increased GST metabolism and GST delta overexpression might be related to acequinocyl resistance in .
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http://dx.doi.org/10.3390/insects11080511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469217PMC
August 2020

Split-bolus CT urography with synchronous nephrographic and excretory phase in dogs: comparison of image quality with three-phase CT urography and optimal allocation ratio of contrast medium.

J Vet Sci 2020 Jul;21(4):e55

College of Veterinary Medicine and BK 21 Plus Project Team, Chonnam National University, Gwangju 61186, Korea.

Background: Computed tomography urography (CTU), based on the excretion of contrast medium after its injection, allows visualization of the renal parenchyma and the renal collecting system.

Objectives: To determine the optimal contrast medium dose allocation ratio to apply in split-bolus CTU in dogs.

Methods: This prospective, experimental, exploratory study used 8 beagles. In 3-phase CTU, unenhanced-, nephrographic-, and excretory-phase images were obtained with a single injection of 600 mg iodine/kg iohexol. In split-bolus CTU, two different contrast medium allocation ratios (30% and 70% for split CTU 1; 50% and 50% for split CTU 2) were used. Unenhanced phase image and a synchronous nephrographic-excretory phase image were acquired.

Results: Although the attenuation of the renal parenchyma was significantly lower when using both split CTUs than the 3-phase CTU, based on qualitative evaluation, the visualization score of the renal parenchyma of split CTU 1 was as high as that of the 3-phase CTU, whereas the split CTU 2 score was significantly lower than those of the two others. Artifacts were not apparent, regardless of CTU protocol. The diameter and opacification of the ureter in both split CTUs were not significantly different from those using 3-phase CTU.

Conclusions: Split-bolus CTU with a contrast medium allocation ratio of 30% and 70% is feasible for evaluating the urinary system and allows sufficient enhancement of the renal parenchyma and appropriate distention and opacification of the ureter, with similar image quality to 3-phase CTU in healthy dogs. Split-bolus CTU has the advantages of reducing radiation exposure and the number of CT images needed for interpretation.
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http://dx.doi.org/10.4142/jvs.2020.21.e55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402936PMC
July 2020

Perfusion change in benign prostatic hyperplasia before and after castration in a canine model: Contrast enhanced ultrasonography and CT perfusion study.

Theriogenology 2020 Oct 1;156:97-106. Epub 2020 Jul 1.

Veterinary Medical Imaging, College of Veterinary Medicine, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address:

Hormonal and vascular changes affecting the canine prostate after castration were investigated to identify the effects of hormones and perfusion on the development of benign prostatic hyperplasia (BPH). Concentrations of serum testosterone and estrogen and intraprostatic dihydrotestosterone (DHT) were compared between 5 normal dogs, 6 dogs with mild BPH, and 6 dogs with marked BPH. In addition, prostatic perfusion using contrast-enhanced ultrasonography (CEUS) and CT perfusion (CTP), as well as CT volumes of the prostates were compared. The changes in these values following castration were assessed in 6 dogs with marked BPH. CEUS revealed significantly slower prostatic arterial inflow and relatively faster venous outflow in BPH versus normal prostate. Permeability and blood volume were not significantly different between the groups via CTP. Intraprostatic DHT level was higher in BPH than in normal prostate and decreased significantly following castration, which was accompanied by a rapid decrease in prostatic volume. On CEUS, arterial inflow to the prostate significantly decreased following castration. Blood volume within the prostate decreased significantly by day 60 following castration. Permeability increased significantly during the early phase after castration; however, by day 60 post-castration, all perfusion parameters decreased significantly. Perfusion changes including venous parameters measured by CEUS and blood volume changes measured by CTP, however, did not support the backflow theory postulating that BPH is induced by vascular changes from congested testes. The major etiology for the development of BPH is attributed to be increased levels of DHT rather than vascular changes.
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http://dx.doi.org/10.1016/j.theriogenology.2020.06.026DOI Listing
October 2020

Altered core networks of brain connectivity and personality traits in internet gaming disorder.

J Behav Addict 2020 Jun 1;9(2):298-311. Epub 2020 Apr 1.

1Department of Medical Informatics, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.

Background And Aims: Although the Internet has provided convenience and efficiency in many areas of everyday life, problems stemming from Internet use have also been identified, such as Internet gaming disorder (IGD). Internet addiction, which includes IGD, can be viewed as a behavioral addiction or impulse control disorder. This study investigated the altered functional and effective connectivity of the core brain networks in individuals with IGD compared to healthy controls (HCs).

Methods: Forty-five adults with IGD and 45 HCs were included in this study. To examine the brain networks related to personality traits that influence problematic online gaming, the left and right central executive network (CEN) and the salience network (SN) were included in the analysis. Also, to examine changes in major brain network topographies, we analyzed the default mode network (DMN).

Results: IGD participants showed lower functional connectivity between the dorsal lateral prefrontal cortex (DLPFC) and other regions in the CEN than HC participants during resting state. Also, IGD participants revealed reduced functional connectivity between the dorsal anterior cingulate cortex and other regions in the SN and lower functional connectivity in the medial prefrontal cortex of the anterior DMN. Notably, in IGD individuals but not HC individuals, there was a positive correlation between IGD severity and effective connectivity and a positive correlation between reward sensitivity and effective connectivity within the ventral striatum of the SN.

Conclusions: Problematic online gaming was associated with neurofunctional alterations, impairing the capacity of core brain networks.
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http://dx.doi.org/10.1556/2006.2020.00014DOI Listing
June 2020

A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer.

Lung Cancer 2020 08 28;146:12-18. Epub 2020 May 28.

Clinical Development, Samsung Bioepis Co., Ltd., Suwon, Republic of Korea. Electronic address:

Objectives: Efficacy, safety, pharmacokinetics (PK), and immunogenicity of the biosimilar candidate SB8 was compared to its reference product bevacizumab (BEV) in patients with metastatic or recurrent nonsquamous non-small cell lung cancer.

Methods: Patients were randomized (1:1) in a phase III, double-blind study to receive intravenous SB8 or BEV 15 mg/kg with paclitaxel/carboplatin every 3 weeks for 24 weeks, followed by SB8 or BEV maintenance monotherapy. The primary endpoint was best overall response rate (ORR) by 24 weeks. Secondary endpoints included survival outcomes, safety, PK, and immunogenicity.

Results: 763 patients (SB8, n = 379; BEV, n = 384) were randomized; baseline characteristics were well balanced. Best ORR in the FAS was 47.6% and 42.8%, and best ORR in the PPS was 50.1% and 44.8% for SB8 and BEV, respectively. The risk ratio of best ORR was 1.11 (90% CI, 0.975-1.269), and the risk difference in best ORR was 5.3% (95% CI, -2.2%-12.9%). Median survival outcomes were comparable between SB8 and BEV: progression-free survival was 8.50 vs 7.90 months, respectively (HR [95% CI], 0.99 [0.83-1.18]; p = 0.9338); overall survival was 14.90 vs 15.80 months, respectively (HR [95% CI], 1.03 [0.83-1.28]; p = 0.7713); and duration of response was 7.70 vs 7.00 months, respectively (HR [95% CI], 1.05 [0.81-1.37]; p = 0.6928). Severity and incidence of treatment-emergent adverse events, PK, and immunogenicity were comparable between SB8 and BEV.

Conclusion: This study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio, with comparable safety, PK, and immunogenicity.
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http://dx.doi.org/10.1016/j.lungcan.2020.05.027DOI Listing
August 2020

Comparison of Synthetic Neuronal Model Membrane Mimics in Amyloid Aggregation at Atomic Resolution.

ACS Chem Neurosci 2020 07 19;11(13):1965-1977. Epub 2020 Jun 19.

Department of Biophysics, Bose Institute, Kolkata 700054, India.

Alzheimer's disease (AD) is a severe neurodegenerative disorder caused by abnormal accumulation of toxic amyloid plaques of the amyloid-beta (Aβ) or the tau proteins in the brain. The plaque deposition leading to the collapse of the cellular integrity is responsible for a myriad of surface phenomena acting at the neuronal lipid interface. Recent years have witnessed dysfunction of the blood-brain barriers (BBB) associated with AD. Several studies support the idea that BBB acts as a platform for the formation of misfolded Aβ peptide, promoting oligomerization and fibrillation, compromising the overall integrity of the central nervous system. While the amyloid plaque deposition has been known to be responsible for the collapse of the BBB membrane integrity, the causal effect relationship between BBB and Aβ amyloidogenesis remains unclear. In this study, we have used physiologically relevant synthetic model membrane systems to gain atomic insight into the functional aspects of the lipid interface. Here, we have used a minimalist BBB mimic, POPC/POPG/cholesterol/GM1, to compare with the native BBB (total lipid brain extract (TLBE)), to understand the molecular events occurring in the membrane-induced Aβ amyloid aggregation. Our study showed that the two membrane models accelerated the Aβ aggregation kinetics with differential secondary structural transitions of the peptide. The observed structural transitions are defined by the lipid compositions, which in turn undermines the differences in lipid surface phenomena, leading to peptide induced cellular toxicity in the neuronal membrane.
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http://dx.doi.org/10.1021/acschemneuro.0c00166DOI Listing
July 2020

Investigation on the Stability of Random Vortices in an Ion Concentration Polarization Layer with Imposed Normal Fluid Flow.

Micromachines (Basel) 2020 May 22;11(5). Epub 2020 May 22.

Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Korea.

While nanoscale electrokinetic studies based on ion concentration polarization has been actively researched recently, random vortices naturally occur, leading to significantly destabilize in laboratory experiments or practical applications. These random vortices agitate the fluid inside microchannels and let the sample molecules seriously leak out preventing them from being controlled. Therefore, several trials have been reported to regulate those uninvited fluctuations by fluid flow tangential to a nanoporous membrane. Indeed, the influence of normal flow should be studied since the mass transport happens in the normal direction to the membrane. Thus, in this work, the nonlinear influence of normal flow to the instability near ion-selective surface was investigated by fully-coupled direct numerical simulation using COMSOL Multiphysics. The investigation on the effect of normal flow revealed that a space charge layer plays a significant role in the onset and growth of instability. The normal flow from the reservoir into the ion-selective surface pushed the space charge layer and decreased the size of vortices. However, there existed a maximum point for the growth of instability. The squeeze of the space charge layer increased the gradient of ion concentration in the layer, which resulted in escalating the velocity of vortices. On the other hand, the normal flow from the ion-selective surface into the reservoir suppressed the instability by spreading ions in the expanding space charge layer, leading to the reduction of ion concentration delayed the onset of instability. These two different mechanisms rendered asymmetric transition of stability as a function of the number and applied voltage. Therefore, this investigation would help understand the growth of instability and control the inevitable random vortices for the inhibition of fluid-agitation and leakage.
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http://dx.doi.org/10.3390/mi11050529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281587PMC
May 2020

Cellular Functions of OCT-3/4 Regulated by Ubiquitination in Proliferating Cells.

Cancers (Basel) 2020 Mar 12;12(3). Epub 2020 Mar 12.

Department of Biomedical Science, CHA University, Gyeonggi-Do 13488, Korea.

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.
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http://dx.doi.org/10.3390/cancers12030663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139964PMC
March 2020

Effect of expiratory phase for radiographic detection of left heart enlargement in dogs with mitral regurgitation.

Vet Radiol Ultrasound 2020 May 15;61(3):291-301. Epub 2020 Mar 15.

College of Veterinary Medicine and BK21 Plus project team, Chonnam National University, Gwangju, Republic of Korea.

Radiography is a standard diagnostic test for characterizing left heart enlargement in dogs however limited information is available on the effects of respiratory phases. This prospective and retrospective method comparison study investigated the respiratory effect on the size and shape of the left heart in dogs to determine the usefulness of expiratory radiographs to detect enlargements in the left atrium (LA) and left ventricle (LV). Thoracic radiographs taken at full inspiration and expiration were evaluated in 20 normal beagles and 100 dogs diagnosed with mitral regurgitation (MR). Vertebral heart score (VHS), vertebral left atrial size, elevation of the carina, and dorsal bulging of LA on lateral view and lateral bulging of the left auricular appendage and LV on ventrodorsal view were assessed. In normal dogs, there were no significant differences in the evaluative factors between inspiration and expiration. In dogs with MR, VHS did not change according to respiration. However, bulging of the LA, left auricular appendage, and LV had sharp margin during expiration compared with inspiration. The expiratory radiographic finding of LA bulging had a higher correlation with the LA to aorta ratio compared with LA bulging in the inspiratory radiography. Using a LA to aorta echocardiographic ratio greater than 1.5 as the gold standard, the radiographic sensitivity for LA enlargement was higher during expiration than inspiration. These findings of our study indicated that expiratory radiography can be helpful to support the detection of left heart enlargement, although it can overestimate LA enlargement in dogs with MR.
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http://dx.doi.org/10.1111/vru.12850DOI Listing
May 2020

Feedback analysis identifies a combination target for overcoming adaptive resistance to targeted cancer therapy.

Oncogene 2020 05 10;39(19):3803-3820. Epub 2020 Mar 10.

Laboratory for Systems Biology and Bio-inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

Targeted drugs aim to treat cancer by directly inhibiting oncogene activity or oncogenic pathways, but drug resistance frequently emerges. Due to the intricate dynamics of cancer signaling networks, which contain complex feedback regulations, cancer cells can rewire these networks to adapt to and counter the cytotoxic effects of a drug, thereby limiting the efficacy of targeted therapies. To identify a combinatorial drug target that can overcome such a limitation, we developed a Boolean network simulation and analysis framework and applied this approach to a large-scale signaling network of colorectal cancer with integrated genomic information. We discovered Src as a critical combination drug target that can overcome the adaptive resistance to the targeted inhibition of mitogen-activated protein kinase pathway by blocking the essential feedback regulation responsible for resistance. The proposed framework is generic and can be widely used to identify drug targets that can overcome adaptive resistance to targeted therapies.
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http://dx.doi.org/10.1038/s41388-020-1255-yDOI Listing
May 2020
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