Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

OBJECTIVE: Persistent infection of HPV increases the chance of carcinoma in situ of cervix through stages of cervical intraepithelial neoplasia (CIN) 1, 2, and 3, and finally progresses into cervical cancer. We aimed to explore the safety and efficacy of BLS-M07 which is orally administered agent expressing human papillomavirus (HPV) 16 E7 antigen on the surface of Lactobacillus casei in patients with CIN 3. METHODS: Patients with CIN 3 were recruited in our clinical trial. Reid Colposcopic Index (RCI) grading and serum HPV16 E7 specific antibody production were used to evaluate efficacy of BLS-M07. In phase 1, BLS-M07 was administered orally, 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1,000 mg, and 1,500 mg. In phase 2a, patients were treated with 1,000 mg. The primary endpoints were the safety and the pathologic regression on colposcopic biopsy. RESULTS: Nineteen patients were enrolled in the CIN 3 cohort. In phase 1, no patients experienced dose limiting toxicity. No grade 3 or 4 treatment-related adverse events or deaths were observed. At 16 weeks after treatment, RCI grading was improved and serum HPV16 E7 specific antibody production increased (p<0.05). Six of 8 (75%) patients with CIN 3 were cured in phase 2a. CONCLUSIONS: Oral immunization with BLS-M07 increases production of serum HPV16 E7 specific antibody which induces protective humoral immunity. The safety of this oral vaccine was proved and could be a competitive non-surgical therapeutic agent of CIN 3. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02195089
Antibody Formation ; Biopsy ; Carcinoma in Situ ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Cohort Studies ; Female ; Humans ; Immunity, Humoral ; Immunization ; Lactobacillus casei ; Papillomavirus E7 Proteins ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms

OBJECTIVE: To investigate the relationships of T2 *-corrected 6-echo Dixon volumetric interpolated breath-hold examination (VIBE) imaging-based fat fraction (FF) and R2 * values with bone mineral density (BMD); determine their associations with sex, age, and menopause; and evaluate the diagnostic performance of the FF and R2 * for predicting osteopenia and osteoporosis. MATERIALS AND METHODS: This study included 153 subjects who had undergone magnetic resonance (MR) imaging, including MR spectroscopy (MRS) and T2 *-corrected 6-echo Dixon VIBE imaging. The FF and R2 * were measured at the L4 vertebra. The male and female groups were divided into two subgroups according to age or menopause. Lin's concordance and Pearson's correlation coefficients, Bland-Altman 95% limits of agreement, and the area under the curve (AUC) were calculated. RESULTS: The correlation between the spectroscopic and 6-echo Dixon VIBE imaging-based FF values was statistically significant for both readers (pc = 0.940 [reader 1], 0.908 [reader 2]; both p < 0.001). A small measurement bias was observed for the MRS-based FF for both readers (mean difference = −0.3% [reader 1], 0.1% [reader 2]). We found a moderate negative correlation between BMD and the FF (r = −0.411 [reader 1], −0.436 [reader 2]; both p <0.001) with younger men and premenopausal women showing higher correlations. R2 * and BMD were more significantly correlated in women than in men, and the highest correlation was observed in postmenopausal women (r = 0.626 [reader 1], 0.644 [reader 2]; both p < 0.001). For predicting osteopenia and osteoporosis, the FF had a higher AUC in men and R2 * had a higher AUC in women. The AUC for predicting osteoporosis was highest with a combination of the FF and R2 * in postmenopausal women (AUC = 0.872 [reader 1], 0.867 [reader 2]; both p < 0.001). CONCLUSION: The FF and R2 * measured using T2 *-corrected 6-echo Dixon VIBE imaging can serve as predictors of osteopenia and osteoporosis. R2 * might be useful for predicting osteoporosis, especially in postmenopausal women.
Area Under Curve ; Bias (Epidemiology) ; Bone Density ; Bone Diseases, Metabolic ; Bone Marrow ; Female ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Menopause ; Osteoporosis ; Spine

The Clinical Research Center for Dementia of South Korea (CREDOS), a nation-wide clinical dementia research group, has prepared clinical practice guidelines (CPG) for dementia tailored to the Korean population. In this article, a summary of the CREDOS CPG is presented with the Korean and English version of full report included in the appendix. The CREDOS CPG in intended not only for psychiatrists and neurologists, but also internists, family physicians, and other primary care physicians involved in the prevention and early diagnosis of dementia. While our CPG for dementia mainly covers Alzheimer's disease (AD) and vascular dementia (VaD), it also includes mild cognitive impairment (MCI) and vascular MCI, which are currently known to be the preclinical stages of AD or VaD, respectively, with emphasis placed on early diagnosis. The CREDOS CPG aims to achieve the following goals by developing CPG for dementia: to establish evidence-based, objective and clear clinical standards for dementia; to improve the clinical decision-making process for patients with dementia; to provide scientific and systematic scales to aid in the work of dementia specialists; to suggest comprehensive and systematic healthcare services tailored to each dementia subtype. The CREDOS CPG focuses on diagnosis and evaluation of clinical practice available domestically, and provides useful concepts of dementia. Its emphasis is on etiologies and epidemiology, diagnostic criteria and evaluation, neuropsychological tests, behavioral and psychological symptoms, the activities of daily living, laboratory tests, and brain imaging.
Activities of Daily Living ; Alzheimer Disease ; Appendix ; Delivery of Health Care ; Dementia ; Dementia, Vascular ; Early Diagnosis ; Humans ; Mild Cognitive Impairment ; Neuroimaging ; Neuropsychological Tests ; Physicians, Family ; Physicians, Primary Care ; Psychiatry ; Republic of Korea ; Weights and Measures

BACKGROUND/AIMS: Mirocam(R) capsule endoscopy has been widely used in Korea; however, data with respect to Mirocam(R) capsule endoscopy is lacking. We have assessed the factors affecting complete small bowel studies and diagnostic yield in Mirocam(R) capsule endoscopic studies. METHODS: We retrospectively analyzed 103 cases that were assessed with Mirocam(R) capsule endoscopy between June 2007 and February 2010 at Guro Korea University Hospital. RESULTS: The mean age of the 103 cases was 55.47 years (range, 16-99 years) and 67 cases (65%) were male. The indications for capsule endoscopy were hematochezia/melena (77 cases, 74.8%), anemia (8 cases, 7.8%), abdominal pain (12 cases, 11.7%), and miscellaneous (weight loss and chronic diarrhea; 6 cases, 5.8%). The mean stomach transit time was 59.9+/-88.3 minutes (range, 1-630 minutes) and the mean small bowel transit time was 396.0+/-131.7 minutes (range, 117-708 minutes). The rate of successfully performing a complete small bowel study was 82.5% (85 cases), and the stomach transit time was a significant factor for a complete small bowel study (OR=0.991, 95% CI=0.984-0.998, P=0.012). The diagnostic yield was 51.5% (53 cases); visual quality was a significant factor in determining the diagnostic yield (OR=6.776, 95% CI=1.32-34.70, P=0.022). CONCLUSIONS: In a Mirocam(R) capsule endoscopic study, short stomach transit time was a significant factor affecting completion of the small bowel study. Achieving excellent visual quality by good bowel preparation was a significant factor for improving the diagnostic yield.
Abdominal Pain ; Anemia ; Capsule Endoscopy ; Humans ; Korea ; Male ; Retrospective Studies ; Stomach

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that is associated with mutation in the tuberous sclerosis genes, renal angiomyolipomas, lymphatic spread and a remarkable female gender predilection. The pathology of LAM is represented by the proliferation of immature smooth muscle cells in the walls of airways, and venules and lymphatic vessels in the lung. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax and collections of chylous fluid. The diagnosis of pulmonary LAM can be made on chest X-ray, a high-resolution CT scan and lung biopsy. We experienced a case of pulmonary lymphangioleiomyomatosis in a 28-years-old female patient who had suffered from progressive dyspnea on exertion, so we report on it along with a brief review of the relevant literature.
Angiomyolipoma ; Biopsy ; Dyspnea ; Female ; Humans ; Lipopolysaccharides ; Lung ; Lung Diseases ; Lymphangioleiomyomatosis ; Lymphatic Vessels ; Myocytes, Smooth Muscle ; Pneumothorax ; Thorax ; Tuberous Sclerosis ; Venules

Pulmonary alveolar proteinosis (PAP) is a rare disorder that's characterized by accumulation of surfactant components in the alveolar space. Idiopathic PAP is recognized as an autoimmune disease that's due to impaired alveolar macrophage function and this caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We report here a case of pulmonary alveolar proteinosis that was deemed interstitial lung disease at the initial diagnosis. A 61-year-old man presented with intermittent blood tinged sputum and dyspnea on exertion. The man was a painter for 30 years and he had a 10 pack-years smoking history. Chest computerized tomography (CT) revealed multifocal ground-glass opacity with interstitial thickening at both lungs. His pulmonary function tests and methacholine test revealed non specific results. He was diagnosed with interstitial lung disease on the basis of the chest CT finding and occupational history. However, seven months later, his symptoms progressed. Follow-up chest CT was performed. Wedge resection via video-assisted thoracoscopic surgery (the anterior basal segment of the left lower lobe) was done. Microscopic examination showed large groups of alveoli with excessive amounts of surfactant and a complex mixture of protein and lipid (fat) molecules. Finally, he was diagnosed as having pulmonary alveolar proteinosis.
Autoantibodies ; Autoimmune Diseases ; Benzeneacetamides ; Dyspnea ; Follow-Up Studies ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Lung ; Lung Diseases, Interstitial ; Macrophages, Alveolar ; Methacholine Chloride ; Middle Aged ; Piperidones ; Pulmonary Alveolar Proteinosis ; Respiratory Function Tests ; Smoke ; Smoking ; Sputum ; Thoracic Surgery, Video-Assisted ; Thorax ; Tolnaftate