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"Kim, Hyun A"
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Time-varying stimuli that prolong IKK activation promote nuclear remodeling and mechanistic switching of NF-κB dynamics
Temporal properties of molecules within signaling networks, such as sub-cellular changes in protein abundance, encode information that mediate cellular responses to stimuli. How dynamic signals relay and process information is a critical gap in understanding cellular behaviors. In this work, we investigate transmission of information about changing extracellular cytokine concentrations from receptor-level supramolecular assemblies of IKK kinases downstream to the NF-κB transcription factor. In a custom robot-controlled microfluidic cell culture, we simultaneously measure input-output encoding of IKK-NF-κB in dual fluorescent-reporter cells. When compared with single cytokine pulses, dose-conserving pulse trains prolong IKK assemblies and lead to disproportionately enhanced retention of nuclear NF-κB. Using particle swarm optimization, we demonstrate that a mechanistic model does not recapitulate this emergent property. By contrast, invoking mechanisms for NF-κB-dependent chromatin remodeling to the model recapitulates experiments, showing how temporal dosing that prolongs IKK assemblies facilitates switching to permissive chromatin that sequesters nuclear NF-κB. Remarkably, using simulations to resolve single-cell receptor data accurately predicts same-cell NF-κB time courses for more than 80% of our single cell trajectories. Our data and simulations therefore suggest that cell-to-cell heterogeneity in cytokine responses are predominantly due to mechanisms at the level receptor-associated protein complexes.
Cells rely on limited numbers of transmembrane receptors to process signals from dynamic microenvironments. Using microfluidics and endogenous reporters, the authors track single cells to reveal how temporal dosing rewires chromatin, leading to a model of signalling with near single-cell accuracy.
Journal Article
The Effects of Group Sandplay Therapy (GST) on Child Victims of Cyberbullying: Focusing on Internalizing and Externalizing Problems
Objective: Cyberbullying among children and adolescents is a serious and increasingly prevalent issue worldwide. Victims often experience various emotional issues such as depression, anxiety, and suicidal thoughts, as well as disruptive and impulsive behavioral problems. Therefore, effective therapeutic interventions and social support are essential. This study investigated the effects of group sandplay therapy (GST) on children who have been victims of cyberbullying. Method: This study was designed as a non-randomized controlled trial with an intervention group and a control group. The participants included 127 children aged 11 to 12 years old who had experienced cyberbullying, with 64 participants in the GST intervention group and 63 participants in a matched control group based on gender and age. The intervention group participated in 10 GST sessions, each lasting 40 min, held once a week in groups of three or four. The control group received no treatment. The Korean Youth Self Report (K-YSR) was employed to evaluate the effectiveness of the intervention. Results: The results indicated that the GST intervention group experienced significant reductions in anxiety/depression (F = 7.09, p = 0.009, d = 0.49), somatic symptoms (F = 10.02, p = 0.002, d = 0.58), and aggressive behavior (F = 3.94, p = 0.049, d = 0.36) on the K-YSR scale compared to the control group. Conclusions: Thus, GST was found to be effective in alleviating negative emotions and aggressive behavior in children affected by cyberbullying.
Journal Article
Radiographic Knee Osteoarthritis and Knee Pain: Cross-sectional study from Five Different Racial/Ethnic Populations
The weak correlation between pain and structural changes in knee osteoarthritis is widely reported. In a previous within-person, knee-matched case-control study among Caucasians, the severity of radiographic osteoarthritis (ROA) was strongly associated with both the presence of frequent knee pain and pain severity. We studied the association between ROA and knee pain in five racial/ethnic populations by using the same method. Subjects were selected from China; Japan; Korea and the United States. Among subjects with knees discordant for either frequent knee pain or pain severity, we examined the relationship between ROA and the presence of frequent knee pain using conditional logistic regression, and between ROA and pain severity using a stratified proportional odds model with an amalgamating conditional likelihood. In total, 252 urban Chinese, 221 rural Chinese, 297 Japanese, 122 Korean, 1,735 Caucasian, and 394 African-American patients were included. There was a strong dose-response relationship between the severity of ROA and the prevalence of frequent knee pain in all five racial/ethnic populations. Even mild ROA was significantly associated with frequent knee pain. In addition, ROA was also strongly associated with the severity of knee pain. These results show that structural pathology is associated with knee pain in different ethnic populations.
Journal Article
Triple-negative breast cancer: correlation between imaging and pathological findings
Objective
This study was designed to investigate the mammography and ultrasound findings of triple-negative breast cancer and to compare the results with characteristics of ER-positive/PR-negative/HER2-negative breast cancer and ER-negative/PR-negative/HER2-positive breast cancer.
Methods
From January 2007 to October 2008, mammography and ultrasound findings of 245 patients with pathologically confirmed triple-negative (
n
= 87), ER-positive/PR-negative/HER2-negative (
n
= 93) or ER-negative/PR-negative/HER2-positive breast cancers (
n
= 65) were retrospectively reviewed. We also reviewed pathological reports for information on the histological type, histological grade and the status of the biological markers.
Results
Triple-negative breast cancers showed a high histological grade. On mammography, triple-negative breast cancers usually presented with a mass (43/87, 49%) or with focal asymmetry (19/87, 22%), and were less associated with calcifications. On ultrasound, the cancers were less frequently seen as non-mass lesions (12/87, 14%), more likely to have circumscribed margins (43/75, 57%), were markedly hypoechoic (36/75, 57%) and less likely to show posterior shadowing (4/75, 5%). Among the three types of breast cancers, ER-negative/PR-negative/HER2-positive breast cancers most commonly had associated calcifications (52/65, 79%) on mammography and were depicted as non-mass lesions (21/65, 32%) on ultrasound.
Conclusion
Our results suggest that the imaging findings might be useful in diagnosing triple-negative breast cancer.
Journal Article
Comparison of MRI cross-sectional area and functions of core muscles among asymptomatic individuals with and without lumbar intervertebral disc degeneration
Background
Previous studies suggested that patients with symptomatic intervertebral disc degeneration (IDD) of lumbar spine have reduced cross-sectional area (CSA) and functions of core muscles. However, reduced CSA and functions of core muscles have been observed not only in patients with symptomatic IDD but also in patients with other subgroups of low back pain (LBP). Thus, it is uncertain whether reduced CSA and functions of core muscles lead to IDD and LBP, or pain leads to reduced CSA and functions of core muscles in patients with symptomatic IDD. Therefore, this study aimed to compare the CSA and functions of core muscles between asymptomatic participants with and without IDD in magnetic resonance imaging (MRI).
Methods
Twenty asymptomatic participants (12 men and 8 women) participated in this study. Ten participants had asymptomatic IDD at L4–5. The others were healthy controls (without IDD at all levels of lumbar spine). The CSA of core muscles was measured using MRI. Maximal isometric trunk flexor strength and side bridge strength were measured by a Smart KEMA strength sensor. Trunk flexor endurance test, side bridge endurance test and plank endurance test were used to measure core endurance. Double legs loading test was used to measure core stability. Mann-Whitney U test was used to compare the differences between two groups.
Results
There were no significant differences in core muscle functions between the two groups (
p
> 0.05). Moreover, there was no significant difference in CSA between the two groups (p > 0.05).
Conclusions
There was no significant difference in CSA and core muscle functions between asymptomatic participants with and without IDD. These findings indicate that a degenerative or bulging disc in asymptomatic individuals has little effect on CSA and functions of core muscles, especially in young age. Therefore, the general core endurance test or strength test could not differentiate asymptomatic people with and without IDD of lumbar spine.
Trial registration number
Clinical Research information Service.
KCT0004061
. Registered 13 June 2019. retrospectively registered.
Journal Article
Comparison of biannual ultrasonography and annual non-contrast liver magnetic resonance imaging as surveillance tools for hepatocellular carcinoma in patients with liver cirrhosis (MAGNUS-HCC): a study protocol
Background
Ultrasonography (US) is recommended as a standard surveillance tool for patients with a high risk of developing hepatocellular carcinoma (HCC). However, the low sensitivity of US for small HCC can lead to surveillance failure, resulting in advanced stage tumor presentations. For the early detection of HCC in high-risk patients and to improve survival and prognosis, a new efficient imaging tool with a high sensitivity for HCC detection is needed. The purpose of this study is to evaluate and compare the feasibility and efficacy of non-contrast magnetic resonance imaging (MRI) with US as a surveillance tool for HCC in patients with liver cirrhosis.
Methods
MAGNUS-HCC is a prospective, multicenter clinical trial with a crossover design for a single arm of patients. This study was approved by six Institutional Review Boards, and informed consent was obtained from all participants. All patients will undergo liver US every 6 months and non-contrast liver MRI every 12 months during a follow-up period of 3 years. If a focal liver lesion suspected of harboring HCC is detected, dynamic liver computed tomography (CT) will be performed to confirm the diagnosis. After the last surveillance round, patients without suspicion of HCC or who are not diagnosed with HCC will be evaluated with a dynamic liver CT to exclude false-negative findings. The primary endpoint is to compare the rate of detection of HCC by US examinations performed at 6-month intervals with that of yearly non-contrast liver MRI studies during a 3-year follow-up. The secondary endpoint is the survival of the patients who developed HCC within the 3-year follow-up period.
Discussion
MAGNUS-HCC is the first study to compare the feasibility of non-contrast MRI with US as a surveillance tool for the detection of HCC in high-risk patients. We anticipate that the evidence presented in this study will establish the efficacy of non-contrast MRI as a surveillance tool for HCC in high-risk patients.
Trial registration
The date of trial registration (
NCT02551250
) in this study was September 15, 2015, and follow-up is still ongoing.
Journal Article
Altered muscle recruitment patterns during isometric shoulder abduction in individuals with chronic upper trapezius pain: a cross sectional study
Background
Upper trapezius (UT) pain with myofascial trigger points (MTrPs) can affect movement at the glenohumeral joint as well as at the scapulothoracic joint. The investigation of muscle recruitment patterns can discern motor control strategies. The purpose of this study was to compare shoulder muscle recruitment patterns and muscle activity according to various loads between individuals with and without chronic UT pain.
Methods
In this cross-sectional study, twenty-four participants that had UT pain with MTrPs and sex, age, body weight matched 24 controls with no UT pain were recruited. Surface EMG electrodes were attached to the UT, the serratus anterior (SA), the lower trapezius (LT) and the middle deltoid (MD). All participants performed isometric shoulder abduction with a load of 25%, 50%, or 75% of the maximum strength at 60° of shoulder abduction. The EMG activity, the activity ratio (SA/UT, LT/UT, MD/UT), and the relative contribution of each muscle activity were calculated.
Results
MD activity was significantly decreased in the UT pain group compared to that in the control group (
p
< 0.05). The EMG activity ratio of SA/UT (
p
< 0.025) and the relative contribution of SA activity to shoulder abduction (
p
< 0.05) were significantly greater in the UT pain group than in the control group in the 25% loading condition.
Conclusion
The results of present study showed that UT pain with MTrPs may increase the relative contribution of SA activity and decrease MD activity at low loads. Altered recruitment patterns of scapular upward rotators can be altered in the proper scapular position, which results in decreased MD activity. Clinicians should consider altered recruitment patterns when managing UT pain.
Trial registration
Clinical Research Information Service: Clinical Research Information Service (KCT0007370; 08/06/2022).
Journal Article
Efficiency of Non-Contrast-Enhanced Liver Imaging Sequences Added to Initial Rectal MRI in Rectal Cancer Patients
The purpose of this study was to estimate the value of addition of liver imaging to initial rectal magnetic resonance imaging (MRI) for detection of liver metastasis and evaluate imaging predictors of a high risk of liver metastasis on rectal MRI.
We enrolled 144 patients who from October 2010 to May 2013 underwent rectal MRI with T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) (b values = 50, 500, and 900 s/mm2) of the liver and abdominopelvic computed tomography (APCT) for the initial staging of rectal cancer. Two reviewers scored the possibility of liver metastasis on different sets of liver images (T2WI, DWI, and combined T2WI and DWI) and APCT and reached a conclusion by consensus for different analytic results. Imaging features from rectal MRI were also analyzed. The diagnostic performances of CT and an additional liver scan to detect liver metastasis were compared. Multivariate logistic regression to determine independent predictors of liver metastasis among rectal MRI features and tumor markers was performed. This retrospective study was approved by the Institutional Review Board, and the requirement for informed consent was waived.
All sets of liver images were more effective than APCT for detecting liver metastasis, and DWI was the most effective. Perivascular stranding and anal sphincter invasion were statistically significant for liver metastasis (p = 0.0077 and p = 0.0471), while extramural vascular invasion based on MRI (mrEMVI) was marginally significant (p = 0.0534).
The addition of non-contrast-enhanced liver imaging, particularly DWI, to initial rectal MRI in rectal cancer patients could facilitate detection of liver metastasis without APCT. Perivascular stranding, anal sphincter invasion, and mrEMVI detected on rectal MRI were important imaging predictors of liver metastasis.
Journal Article
Comparison of ultrasound-detected and undetected hepatocellular carcinomas: a post-hoc, subgroup analysis from the MAGNUS-HCC surveillance trial
Purpose: This study aimed to compare the clinical and imaging features of hepatocellular carcinomas (HCCs) detected versus undetected on surveillance ultrasound (US), based on a prospective cohort.Methods: This post-hoc subgroup study analyzed data from MAGNUS-HCC trial, a prospective multicenter study evaluating both biannual US and annual non-contrast abbreviated magnetic resonance imaging (NC-AMRI) for HCC surveillance in high-risk patients. Among 34 HCCs, 16 tumors were detected and 18 tumors were undetected on US. We compared clinical features such as sex, age, body mass index (BMI), liver disease etiology, α-fetoprotein (AFP) level, and Child-Pugh class between participants who were diagnosed on US and those who were not. Imaging features including size, hemiliver distribution, anatomical section, subcapsular location, blind spot location, the presence of hepatic steatosis, and the presence of poor sonic window were also compared. NC-AMRI features were also assessed.Results: No significant differences were observed between US-detected and US-undetected groups in terms of sex, age, liver disease etiology, AFP level, or Child-Pugh class. Patients with US-undetected HCCs had higher BMI (25.7 vs. 23.8 kg/m 2 , P=0.049). Lesions in blind spots were significantly more common in the US-undetected group (55.6% vs. 18.8%, P=0.039), as were lesions in the left hemiliver (38.9% vs. 6.3%, P=0.043). No significant differences were found in tumor size, anatomical section, subcapsular location, presence of poor sonic window, presence of hepatic steatosis, or magnetic resonance imaging characteristics. Of the 16 US-detected tumors, 62.5% were hypoechoic and 37.5% were hyperechoic.Conclusion: US is less effective in detecting HCCs in patients with a higher BMI and tumors located in the blind spots or left hemiliver. These limitations should be considered in planning and interpreting surveillance strategies.
Journal Article