Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

Purpose: The prognostic value of vitamin D receptor gene (VDR) expression in breast cancer development is unclear. Here, we aimed to investigate whether VDR expression can be used as a prognostic indicator of breast cancer. Methods: We used various public bioinformatics platforms: Oncomine, GEPIA, UALCAN, Kaplan-Meier plotter, UCSC XENA, bc-GenExMiner, WebGestalt, and STRING database. Results: We found that VDR was upregulated in breast cancer in comparison to normal tissues. Overexpression of VDR was significantly associated with worse overall survival in breast cancer. The expression of VDR was related to age, TNM stages, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, basallike (PAM 50) status, triple-negative breast cancer (TNBC) status, and basal-like (PAM 50) & TNBC status (P < 0.05). Increased VDR expression in breast cancer was significantly associated with older age. The 5 hub genes for VDR were NCOA1, EP300, CREBBP, and RXRA. Conclusion Our investigation offers hints about the prognostic role of VDR in breast cancer. The findings suggest that VDR expression might be used as a marker to determine a breast cancer patient’s prognosis. Nevertheless, further validation is warranted.

Purpose: Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. Methods: Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. Results: Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). Conclusion The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.

Objective: The study investigated the effects of severe human rights abuses in North Korean on Posttraumatic-stress disorder (PTSD) in North Korean Refugees (NKRs). Methods: The study included 300 NKRs (245 females and 55 males) who completed self-report questionnaires that assessed PTSD, experiences of imprisonment, and exposure to inhumane treatment, by authorities in North Korea. A moderation analysis was conducted using a hierarchical multiple regression model to determine whether a moderation effect existed. In the next step, a post-hoc probing procedure of the moderation effect was performed using multiple regression models that included conditional moderator variables. Results: The influence of the frequency of being imprisoned on PTSD varied as a function of recurrent exposure to inhumane treatment or punishment by authorities. Experiences of imprisonment were associated with PTSD only among those who were exposed to recurrent violence, such as beating or torture, by North Korean authorities. Conclusion The present findings highlight the significant effects of human rights violations, such as the inhumane treatment of prisoners in North Korea, on the PTSD of NKRs.

Objective: The study investigated the effects of severe human rights abuses in North Korean on Posttraumatic-stress disorder (PTSD) in North Korean Refugees (NKRs). Methods: The study included 300 NKRs (245 females and 55 males) who completed self-report questionnaires that assessed PTSD, experiences of imprisonment, and exposure to inhumane treatment, by authorities in North Korea. A moderation analysis was conducted using a hierarchical multiple regression model to determine whether a moderation effect existed. In the next step, a post-hoc probing procedure of the moderation effect was performed using multiple regression models that included conditional moderator variables. Results: The influence of the frequency of being imprisoned on PTSD varied as a function of recurrent exposure to inhumane treatment or punishment by authorities. Experiences of imprisonment were associated with PTSD only among those who were exposed to recurrent violence, such as beating or torture, by North Korean authorities. Conclusion The present findings highlight the significant effects of human rights violations, such as the inhumane treatment of prisoners in North Korea, on the PTSD of NKRs.

Purpose: Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. Methods: Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. Results: Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). Conclusion The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.

Purpose: High microsatellite instability (MSI) is related to good prognosis in gastric cancer. We aimed to identify the prognostic factors of patients with recurrent gastric cancer and investigate the role of MSI as a prognostic and predictive biomarker of survival after tumor recurrence. Materials and Methods: This retrospective cohort study enrolled patients treated for stage II/III gastric cancer who developed tumor recurrence and in whom the MSI status or mismatch repair (MMR) status of the tumor was known. MSI status and the expression of MMR proteins were evaluated using polymerase chain reaction and immunohistochemical analysis, respectively. Results: Of the 790 patients included, 64 (8.1%) had high MSI status or MMR deficiency. The tumor-node-metastasis stage, type of recurrence, Lauren classification, chemotherapy after recurrence, and interval to recurrence were independently associated with survival after tumor recurrence. The MSI/MMR status and receiving adjuvant chemotherapy were not associated with survival after recurrence. In a subgroup analysis of patients with high MSI or MMR-deficient gastric cancer, those who did not receive adjuvant chemotherapy had better treatment response to chemotherapy after recurrence than those who received adjuvant chemotherapy. Conclusion Patients with high MSI/MMR-deficient gastric cancer should be spared from adjuvant chemotherapy after surgery, but aggressive chemotherapy after recurrence should be considered. Higher tumor-node-metastasis stage, Lauren classification, interval to recurrence, and type of recurrence are associated with survival after tumor recurrence and should thus be considered when establishing a treatment plan and designing clinical trials targeting recurrent gastric cancer.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.
Blood Pressure ; Diabetes Mellitus, Type 2 ; Diagnosis ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Korea ; Obesity ; Overweight

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.
Aphasia, Primary Progressive ; Cognition ; Comprehension ; Humans ; Magnetic Resonance Imaging ; Neurofibrillary Tangles ; Neuropsychological Tests ; Parietal Lobe ; Positron-Emission Tomography ; Prefrontal Cortex ; Rabeprazole ; Semantics ; Temporal Lobe

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10−6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10−6) and rs9390170 (OR=0.6778, p=7.67×10−6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10−18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.
Epidemiology ; Genetic Markers ; Genome ; Genome-Wide Association Study* ; Haplotypes ; Korea ; Restless Legs Syndrome* ; Synapses ; Utrophin