Effects of Glucagon-Like Peptide-1 Receptor Agonist on Bone Mineral Density and Bone Turnover Markers: A Meta-Analysis.

AIMS: Glucagon-like peptide-1 receptor agonist (GLP-1RA) may promote bone formation, but conversely, they could also weaken bones due to the reduction in mechanical load associated with weight loss. However, the clinical effects in humans have not been clearly demonstrated. This meta-analysis aimed to evaluate whether GLP-1RAs affect BMD and bone turnover markers. MATERIAL AND METHODS: PubMed, Embase, and Scopus were searched on June 13, 2024. The eligibility criteria were: (1) human studies, (2) receiving a GLP-1RA for more than 4 weeks, (3) an untreated control group or a placebo group, (4) reporting of at least one BMD or bone turnover marker, and (5) an RCT design. The risk of bias was assessed using the Cochrane risk of bias 2 tool. Fixed- or random-effects meta-analysis was performed according to heterogeneity. RESULTS: Seven studies were included in the meta-analysis. GLP-1RAs did not significantly change BMD in the femoral neck (mean difference [MD], 0.01 g/cm2; 95% CI, -0.01-0.04 g/cm2), in the total hip (MD, -0.01 g/cm2; 95% CI, -0.02-0.01 g/cm2), and in the lumbar spine (MD, 0 g/cm2; 95% CI, -0.02-0.02 g/cm2). C-terminal telopeptide of type 1 collagen (CTX), a bone resorption marker, significantly increased after GLP-1RA treatment (MD, 0.04 µg/L; 95% CI, 0.01-0.07 µg/L). GLP-1RAs did not significantly change bone formation markers such as procollagen type 1 N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin. CONCLUSIONS: GLP-1RA did not affect BMD and bone formation markers. However, GLP-1RAs led to a significant increase in CTX.

Transporter Genes and statin-induced Hepatotoxicity.

PURPOSE: Hepatotoxicity has emerged as a major cause of statin treatment interruption. Although organic anion-transporting polypeptide 1B1 (SLCO1B1), multidrug resistance protein 1 (ABCB1), and breast cancer resistance protein (ABCG2) have been identified as transporters of statins, knowledge of their role in statin-associated hepatotoxicity remains limited. Therefore, we aimed to conduct a comprehensive analysis to elucidate the association between hepatotoxicity and SLCO1B1, ABCB1, and ABCG2 polymorphisms. METHODS: This study retrospectively analyzed prospectively collected samples. We selected 10 single nucleotide polymorphisms (SNPs) of SLCO1B1, 9 SNPs of ABCB1, and 12 SNPs of ABCG2. We developed two models for multivariable analyses (Model I: clinical factors only; Model II: both clinical and genetic factors), and the attributable risk (%) of variables in Model II was determined. RESULTS: Among 851 patients, 66 (7.8%) developed hepatotoxicity. In Model I, lipophilic statins, atrial fibrillation (Afib), and diabetes mellitus showed a significant association with hepatotoxicity. In Model II, lipophilic statins and Afib, SLCO1B1 rs11045818 A allele, SLCO1B1 rs4149035 T allele, and ABCG2 rs2622629 TT genotype were associated with higher hepatotoxicity risk. Among them, the SLCO1B1 rs11045818 A allele exhibited the highest attributable risk (93.2%). The area under the receiver operating characteristic curve in Model I was 0.62 (95% CI: 0.55-0.69), and it was increased to 0.71 in Model II (95% CI: 0.64-0.77). CONCLUSION: This study investigated the correlation between hepatotoxicity and polymorphisms of transporter genes in patients taking statins. The findings could help improve personalized treatments for patients receiving statin therapy.

Mid-term outcomes of hybrid debranching endovascular aortic arch repair in landing zones 0-2.

OBJECTIVES: The aim of this study is to summarize a single-center experience of hybrid debranching endovascular repair of the aortic arch and proximal descending thoracic aorta (DTA) with regard to the mid-term outcomes with highlighting the difference between the landing zones 0-2. METHODS: A retrospective review of data from a prospectively collected registry (Gangnam Severance Endovascular Aortic Registry) was performed. From among 332 patients whose aortic pathology was managed with TEVAR, 112 patients who underwent hybrid arch repair during the study period between 2012 and 2016 were identified. The patients were grouped into three cohorts according to the proximal landing zones (0, 1, and 2) of Ishimaru. The early outcome (30-days) in terms of mortality, morbidity, supra-aortic vessels patency, and presence of endoleak were analyzed. The survival, freedom from re-intervention, and major complications during follow-up were demonstrated. RESULTS: During the study period. 112 patients (mean age 65±7, 79% males) were included. The patients were distributed in three cohorts: 8 (7%) patients with proximal landing zone 0, 20 (18%) with zone 1, and 80 (75%) with zone 2 hybrid aortic arch repair. Technical success was achieved in 7 (88%), 19 (90%), and 79 (94%) patients for zones 0, 1, and 2, respectively. The mean intensive care unit (ICU) stay was shorter in zone 2 (p = .005). The mean total hospital stay was shorter in zone 2 (p = .03). The overall in-hospital mortality rate was 5% (4/112). There was no spinal cord ischemia or early surgical conversion. Renal function deterioration was seen more but not significantly in zone 0 patients (p = .08). Respiratory failure was seen significantly in zone 0 patients (p = .01). Stroke occurred in 6/44 (14%) patients with degenerative aneurysm versus 1/60 (2%) patients with aortic dissection (p =.06). Early CTA showed 100% patency of the supra-aortic vessels. The early endoleak rate was significant in zone 0 patients (p = .008). The mean follow-up period was (32±19 months). The survival rates and freedom from re-intervention were not statistically significant among the three zones. However, the survival rate and freedom from intervention tend to be higher in zone 2 versus zone 0 (p = .07 and .09), respectively. CONCLUSION: Hybrid debranching endovascular aortic arch repair is feasible and relatively safe with acceptable mid-term outcomes. Zone 0 patients has worse early and late outcomes in comparison to other zones. Careful patient selection and improved endovascular technology may be the key to improve the outcomes.

Associations between breastfeeding intention, breastfeeding practices and post-natal depression during the COVID-19 pandemic: A multi-country cross-sectional study.

Associations between breastfeeding intention, duration and post-natal depression (PND) have been shown in pre-COVID-19 studies. However, studies during COVID-19 have not examined the associations between breastfeeding intention, breastfeeding practices, and PND in an international sample of post-natal women, taking into consideration COVID-19 related factors. This is the first study to address this gap as both PND and breastfeeding may be affected by COVID-19, and have important long-term effects on women's and infant's health. A cross-sectional internet-based survey was conducted with 3253 post-natal women from five countries: Brazil, South Korea, Taiwan, Thailand, and the United Kingdom from July to November 2021. The results showed that women who intended to breastfeed during pregnancy had lower odds of having PND than women who did not intend to. Women who had no breastfeeding intention but actually breastfed had greater odds (AOR 1.75) of having PND than women who intended to breastfeed and actually breastfed. While there was no statistical significance in expressed breast milk feeding in multivariable logistic regression models, women who had shorter duration of breastfeeding directly on breast than they planned had greater odds (AOR 1.58) of having PND than those who breastfed longer than they planned even after adjusting for covariates including COVID-19-related variables. These findings suggested the importance of working with women on their breastfeeding intention. Tailored support is required to ensure women's breastfeeding needs are met and at the same time care for maternal mental health during and beyond the pandemic.

Bacillus subtilis as a robust host for biochemical production utilizing biomass.

Bacillus subtilis is regarded as a suitable host for biochemical production owing to its excellent growth and bioresource utilization characteristics. In addition, the distinct endogenous metabolic pathways and the suitability of the heterologous pathways have made B. subtilis a robust and promising host for producing biochemicals, such as: bioalcohols; bioorganic acids (lactic acids, α-ketoglutaric acid, and γ-aminobutyric acid); biopolymers (poly(γ-glutamic acid, polyhydroxyalkanoates (PHA), and polysaccharides and monosaccharides (N-acetylglucosamine, xylooligosaccharides, and hyaluronic acid)); and bioflocculants. Also for producing oligopeptides and functional peptides, owing to its efficient protein secretion system. Several metabolic and genetic engineering techniques, such as target gene overexpression and inactivation of bypass pathways, have led to the improvement in production titers and product selectivity. In this review article, recent progress in the utilization of robust B. subtilis-based host systems for biomass conversion and biochemical production has been highlighted, and the prospects of such host systems are suggested.

Characteristics of cytomegalovirus enterocolitis in patients with or without inflammatory bowel diseases.

OBJECTIVES: Cytomegalovirus (CMV) disease is more common in immunocompromised patients but may occur in people with normal immune function. In addition, CMV enterocolitis can aggravate inflammatory bowel diseases (IBD), but there was little knowledge of differences in clinical and endoscopic features of CMV enterocolitis between patients with IBD and without IBD. The aim of this study was to determine the difference in clinical implication in CMV enterocolitis between the IBD patients and non-IBD patients. METHODS: This was a retrospective study of 82 patients with CMV enterocolitis based on the pathologic findings at two tertiary referral hospitals from 2003 to 2013. Clinical and endoscopic characteristics and clinical course were analyzed according to the presence of IBD. RESULTS: Of the 82 patients, 25 (30.5%) had IBD and 57 (69.5%) did not have IBD. Hematochezia was more common in IBD patients (84.0% vs. 35.1%; p = .001), but fever and positive CMV antigenemia were more common in non-IBD patients (50.9% vs. 12.0%; p = .001; 54.4% vs. 28.0; p = .027). Endoscopic findings showed more ulcer with inflammation in IBD patients (68.0% vs. 35.2%; p = .005). Sixty-four patients were treated with antiviral agents and 12 patients who did not receive antiviral agents recovered spontaneously. All naturally healed patients were in normal immune status. CONCLUSIONS: Hematochezia is more common in IBD patients and fever/CMV antigenemia is more common in patients without IBD. In patients without IBD, the natural resolution of CMV enterocolitis is expected at least in normal immune function.

Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer.

BACKGROUND: This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohn's disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). MATERIALS AND METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above. RESULTS: Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio [HR] = 12.193, 95% confidence interval [95% CI] 1.039-143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917-25.525, P = 0.063). CONCLUSION: The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.

A comparison of endoscopic treatments in rectal carcinoid tumors.

BACKGROUND: Various endoscopic techniques for rectal carcinoid tumors have been developed recently. In this study, we compared the outcomes of conventional endoscopic mucosal resection (EMR), strip biopsy, and EMR after circumferential precutting (EMR-P). METHODS: From March 2004 to July 2014, the medical records of 188 patients (190 rectal carcinoid tumors) who were treated with an endoscopic procedure for rectal carcinoid tumors were investigated retrospectively. The characteristics of the patients and tumors, the selection of the treatment method, the rate of complete resection, and the rate of complications were analyzed retrospectively. RESULTS: Forty-seven, 75 and 68 cases of EMR, strip biopsy and EMR-P were performed, respectively. The mean procedure time was not significantly different between the EMR, strip biopsy and EMR-P cases (5.6, 6.5 and 7.4 min, respectively, P = 0.119). En bloc resection was achieved in most of the cases (97.8, 98.7 and 95.5 % in the EMR, strip biopsy and EMR-P cases, respectively). However, histologic examination showed positive lateral or deep resection margins in 57 out of 190 cases (30.0 %). Multivariate analysis showed that the strip biopsy and EMR-P methods were independent factors for pathologic complete resection (negative in both lateral and deep resection margins), with odds ratios for margin involvement of 0.20 and 0.43 with 95 % confidence intervals from 0.08 to 0.47 and 0.19 to 0.96, respectively. In all the follow-up cases (81 of 190, 42.6 %), no local recurrence or distal metastasis was found. CONCLUSIONS: Compared to conventional EMR, strip biopsy and EMR-P had a lower risk of incomplete resection. The procedure time and complication rate did not differ between the three groups, and no recurrence was detected during the follow-up period. Strip biopsy and EMR-P are safe and effective methods for the treatment of rectal carcinoid tumors.

Association between basal-like phenotype and BRCA1/2 germline mutations in Korean breast cancer patients.

INTRODUCTION: BRCA mutation testing allows index patients and their families to be provided with appropriate cancer risk-reduction strategies. Because of the low prevalence of BRCA mutations in unselected breast cancer patients and the high cost of genetic testing, it is important to identify the subset of women who are likely to carry BRCA mutations. In the present study, we examined the association between BRCA1/2 germline mutations and the immunohistochemical features of breast cancer. METHODS: In a retrospective review of 498 breast cancer patients who had undergone BRCA testing at Seoul National University Bundang Hospital between July 2003 and September 2012, we gathered immunohistochemical information on estrogen receptor (er), progesterone receptor (pr), her2 (human epidermal growth factor receptor 2), cytokeratin 5/6, egfr (epidermal growth factor receptor), and p53 status. RESULTS: Among the 411 patients eligible for the study, 50 (12.2%) had germline mutations in BRCA1 or BRCA2. Of the 93 patients with triple-negative breast cancer (tnbc), 25 with BRCA1/2 mutations were identified (BRCA1, 20.4%; BRCA2, 6.5%). On univariate analysis, er, pr, cytokeratin 5/6, egfr, and tnbc were found to be related to BRCA1 mutations, but on multivariate analysis, only tnbc was significantly associated with BRCA1 mutations. Among patients with early-onset breast cancer or with a family history of breast or ovarian cancer, BRCA1 mutations were significantly more prevalent in the tnbc group than in the non-tnbc group. CONCLUSIONS: In the present study, tnbc was the only independent predictor of BRCA1 mutation in patients at high risk of hereditary breast and ovarian cancers. Other histologic features of basal-like breast cancer did not improve the estimate of BRCA1 mutation risk.

Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance. METHODS: We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab. RESULTS: Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting. CONCLUSIONS: Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.

Clinicopathologic and prognostic significance of c-MYC copy number gain in lung adenocarcinomas.

BACKGROUND: c-MYC copy number gain (c-MYC gain) has been associated with aggressive behaviour in several cancers. However, the role of c-MYC gain has not yet been determined in lung adenocarcinomas classified by genetic alterations in epidermal growth factor receptor (EGFR), KRAS, and anaplastic lymphoma kinase (ALK) genes. We investigated the clinicopathologic and prognostic significance of c-MYC gain for disease-free survival (DFS) and overall survival (OS) according to EGFR, KRAS, and ALK gene status and stages in lung adenocarcinomas. METHODS: In 255 adenocarcinomas resected in Seoul National University Bundang Hospital from 2003 to 2009, fluorescence in situ hybridisation (FISH) with c-MYC probe and centromeric enumeration probe 8 (CEP8) was analysed using tissue microarray containing single representative core per each case. EGFR (codon 18 to 21) and KRAS (codon 12, 13, and 61) mutations were analysed by polymerase chain reaction and direct sequencing method from formalin-fixed, paraffin-embedded tissue sections. ALK rearrangement was determined by FISH method. c-MYC gain was defined as >2 copies per nucleus, chromosome 8 gain as ⩾3 copies per nucleus, and gain of c-MYC:CEP8 ratio (hereafter, c-MYC amplification) as ⩾2. RESULTS: We observed c-MYC gain in 20% (51 out of 255), chromosome 8 gain in 5.5% (14 out of 255), c-MYC amplification in 2.4% (6 out of 255), EGFR mutation in 49.4% (118 out of 239), KRAS mutation in 5.7% (7 out of 123), and ALK rearrangement in 4.9% (10 out of 205) of lung adenocarcinomas. c-MYC gain was observed in 19% (22 out of 118) of patients with lung adenocarcinomas with an EGFR mutation, but not in any patients with a KRAS mutation, or an ALK rearrangement. c-MYC gain (but not chromosome 8 gain or c-MYC amplification) was an independent poor-prognostic factor in the full cohort of lung adenocarcinoma (P=0.022, hazard ratio (HR)=1.71, 95% confidence interval (CI), 1.08-2.69 for DFS; P=0.032, HR=2.04, 95% CI, 1.06-3.91 for OS), as well as in stage I subgroup (P=0.023, HR=4.70, 95% CI, 1.24-17.78 for DFS; P=0.031, HR=4.65, 95% CI, 1.15-18.81 for OS), and in EGFR-mutant subgroup (P=0.022; HR=2.14; 95% CI, 1.11-4.10 for DFS). CONCLUSIONS: c-MYC gain (but not chromosome 8 gain or c-MYC amplification) was an independent poor-prognostic factor for DFS and OS in lung adenocarcinomas, both in full cohort and stage I cancer, and possibly for DFS in EGFR-mutant adenocarcinomas. Additional studies are required to determine if patients with lung adenocarcinoma with c-MYC gain are candidates for additional first-line treatment to mitigate their increased risk for disease progression and death.

Effects of low-intensity ultrasound on gramicidin D-induced erythrocyte edema.

OBJECTIVES: To determine whether low-intensity ultrasound (US) can reduce red blood cell (RBC) edema and, if so, whether the US activity is associated with aquaporin 1 (AQP-1), a water channel in the cell membrane. METHODS: Red blood cell edema was induced by gramicidin D treatment at 40 ng/mL for 20 minutes and evaluated by a hematocrit assay. Low-intensity continuous wave US at 1 MHz was applied to RBCs for the last 10 minutes of gramicidin D treatment. To determine whether US activity was associated with AQP-1, RBCs were treated with 40 µM mercuric chloride (HgCl(2)), an AQP-1 inhibitor, for 20 minutes at the time of gramicidin D treatment. Posttreatment morphologic changes in RBCs were observed by actin staining with phalloidin. RESULTS: Red blood cell edema increased significantly with gramicidin D at 20 (1.8%), 40 (6.7%), 60 (16.7%), and 80 (11.3%) ng/mL, reaching a peak at 60 ng/mL, compared to the control group (20 ng/mL, P = .019; 40, 60, and 80 ng/mL, P < .001). No significant RBC hemolysis was observed in any group. Edema induced by gramicidin D at 40 ng/mL was significantly reduced by US at 30 (3.4%; P = .003), 70 (4.4%; P = .001), and 100 (2.9%; P = .001) mW/cm(2). Subsequent experiments showed that edema reduction by US ranged from 7% to 10%. Cotreatment with HgCl(2) partially reversed the US effect and showed a significantly different level of edema compared to gramicidin D-alone and US-cotreated groups (P = .001). These results were confirmed by microscopic observation of RBC morphologic changes. CONCLUSIONS: Low-intensity US could reduce gramicidin D-induced RBC edema, and its effect appeared to at least partly involve regulation of AQP-1 activity. These results suggest that low-intensity US can be used as an alternative treatment to control edema and related disorders.

Virtual reality education program for women with uterine tumors treated by high-intensity focused ultrasound.

This study aimed to develop and determine the effects of a nursing education program using virtual reality (VR) for women with uterine tumors undergoing treatment with high-intensity focused ultrasound (HIFU). Various nursing education methods need to be developed alongside new treatment methods and their effects should be clinically verified. Nursing intervention using VR has recently been attempted. The study comprises a pre- and post-test design with a non-equivalent control group. We assigned 54 women to experimental (n = 26) and control (n = 28) groups. The patients were diagnosed with benign uterine tumors and were treated with HIFU at two women's hospitals in D city. Data collected from these hospitals were analyzed using descriptive statistics, a pre-test of homogeneity, independent t-tests, and repeated measures analysis of variance. In the experimental group, uncertainty (t = 4.26, p < 0.001) and anxiety (t = 4.09, p < 0.001) were significantly lower compared to the control group. However, nursing satisfaction was significantly higher in the experimental group than in the control group (t = -4.50, p < 0.001). The VR education program is an educational nursing intervention that reduces uncertainty and anxiety and improves nursing satisfaction among women with uterine tumors treated by HIFU. We suggest that future nursing research integrates and converges disciplines according to progressive treatment methods and technological advancements for patients.

Association between coenzyme Q 10-related genetic polymorphisms and statin-associated myotoxicity in Korean stroke patients.

Introduction: The purpose of this study is to identify the relationship between coenzyme Q 10 (CoQ10)-related gene polymorphisms and statin-related myotoxicity (SRM). Methods: We retrospectively analyzed prospectively collected samples from February to May 2021. To investigate the association between CoQ10-related genetic factors and SRM, we selected 37 single nucleotide polymorphisms from five genes (COQ2, COQ3, COQ5, COQ6, and COQ7). The odds ratio (OR) and adjusted OR with 95% confidence intervals (CI) were calculated for univariate and multivariable logistic regression analyses, respectively. Results: A total of 688 stroke patients were included in the analysis, including 56 SRM cases. In the multivariable analysis, two models were constructed using demographic factors only in model I, and demographic and genetic factors in model II. Compared to other statins, atorvastatin decreased the SRM risk whereas ezetimibe use increased the SRM risk in model I and model II. Patients with COQ2 rs4693075 G allele, COQ3 rs11548336 TT genotype, and COQ5 rs10849757 A allele had a 2.9-fold (95% CI: 1.6-5.3), 1.9-fold (95% CI: 1.1-3.5), and 3.3-fold (95% CI: 1.5-8.3) higher risk of SRM, respectively. Conclusion: This study could be utilized to develop a personalized medicine strategy in patients treated with statins.

Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are known to be associated with response to primary systemic therapy (PST) in breast cancer. This study was conducted to assess the association of TIL subsets with pathological complete response (pCR) after PST in breast cancer in relation to breast cancer subtype, breast cancer stem cell (BCSC) phenotype and epithelial-mesenchymal transition (EMT). METHODS: The pre-chemotherapeutic biopsy specimens of 153 breast cancer patients who underwent surgical resection after anthracycline- or anthracycline/taxane-based PST were analysed. TIL subsets (CD4+, CD8+, and FOXP3+ TILs), BCSC phenotype, and the expression of EMT markers were evaluated by immunohistochemistry and were correlated with pCR after PST. RESULTS: Infiltration of CD4+ and CD8+ T lymphocytes was closely correlated with BCSC phenotype and EMT. High levels of CD4+, CD8+, and FOXP3+ TILs were associated with pCR, and CD8+ TILs were found to be an independent predictive factor for pCR. In addition, CD8+ TILs were associated with pCR irrespective of breast cancer subtype, CD44+/CD24- phenotype, EMT, and chemotherapeutic regimen in subgroup analyses. CONCLUSION: These findings indicate that CD8+ cytotoxic T lymphocytes are a key component of TILs associated with chemo-response and can be used as a reliable predictor of response to anthracycline- or anthracycline/taxane-based PST in breast cancer.

Construction of a risk scoring system using clinical factors and RYR2 polymorphisms for bleeding complications in patients on direct oral anticoagulants.

Introduction: Bleeding is one of the most undesirable complications of direct oral anticoagulants (DOACs). While the ryanodine receptor (RYR2) has been related to cardiac diseases, research on bleeding complications is lacking. This study aimed to elucidate the association between RYR2 and bleeding risk to develop the risk scoring system in patients treated with DOACs. Methods: This study was a retrospective analysis of prospectively collected samples. We selected ten SNPs within the RYR2 gene, and two models were constructed (Model I: demographic factors only, Model II: demographic and genetic factors) in multivariable analysis. Independent risk factors for bleeding were used to develop a risk scoring system. Results: A total of 447 patients were included, and 49 experienced either major bleeding or clinically relevant non-major bleeding. In Model I, patients using rivaroxaban and experiencing anemia exhibited an increased bleeding risk after adjusting for covariates. Upon incorporating genetic factors into Model I, a significant association with bleeding was also observed in cases of overdosing on DOACs and in patients with a creatinine clearance (CrCl) < 30 mL/min, in addition to rivaroxaban and anemia (Model II). Among genetic factors, RYR2 rs12594 GG, rs17682073 AA, rs3766871 GG, and rs6678625 T alleles were associated with bleeding complications. The area under the receiver operating characteristic curve (AUROC) of Model I was 0.670, whereas that of Model II increased to 0.803, demonstrating better performance with the inclusion of genetic factors. Using the significant variables in Model II, a risk scoring system was constructed. The predicted bleeding risks for scores of 0, 1-2, 3-4, 5-6, 7-8, and 9-10 points were 0%, 1.2%, 4.6%, 15.7%, 41.7%, and 73.3%, respectively. Conclusion: This study revealed an association between RYR2 and bleeding complications among patients taking DOACs and established a risk scoring system to support individualized DOAC treatment for these patients.

The impact of circulatory arrest with selective antegrade cerebral perfusion on brain functional connectivity and postoperative cognitive function.

Aortic surgery is one of the most challenging types of surgeries, which is possibly related to cognitive sequelae. We aimed to investigate the changes in resting-state functional connectivity (rsFC) associated with intraoperative circulatory arrest (CA) in aortic surgery, exploring the relationship between the altered connectivity and postoperative cognitive functions. Thirty-eight patients participated in this study (14 with CA, 24 without). Functional magnetic resonance imaging was scanned on the fifth day after surgery or after the resolution of delirium if it was developed. We assessed the differences in the development of postoperative cognitive changes and rsFC between patients with and without CA. The occurrence of postoperative delirium and postoperative cognitive dysfunction was not significantly different between the patients with and without the application of CA. However, patients with CA showed increased in posterior cingulate cortex-based connectivity with the right superior temporal gyrus, right precuneus, and right hippocampus, and medial prefrontal cortex-based connectivity with the dorsolateral prefrontal cortex. The application of moderate hypothermic CA with unilateral antegrade cerebral perfusion is unlikely to affect aspects of postoperative cognitive changes, whereas it may lead to increased rsFC of the default mode network at a subclinical level following acute brain insults.

CAPS markers using mitochondrial consensus primers for molecular identification of Panax species and Korean ginseng cultivars (Panax ginseng C. A. Meyer).

Cleaved amplified polymorphic sequence (CAPS) marker system using mitochondrial consensus primers was applied for molecular identification of Korean ginseng cultivars (Panax ginseng). Initially, a total of 34 primers were tested to six Korean ginseng cultivars and two foreign Panax species, P. quinquefolius and P. notoginseng. In the polymerase chain reaction (PCR) amplification results, four primers (mt7, mt11, mt13, and mt18) generated co-dominant polymorphic banding patterns discriminating the Korean ginseng cultivars from P. quinquefolius and P. notoginseng. In the CAPS analysis results, the majority of the cleaved PCR products also yielded additional latent polymorphisms between the Korean ginseng cultivars and two foreign Panax species. Specific latent CAPS polymorphisms for cultivar Gopoong and Chunpoong were detected from internal region amplified with mt9 primer by treating HinfI and Tsp509I endonucleases, respectively. Sequencing analysis revealed that the length of amplified region of Korean ginseng cultivars was 2,179 bp, and those of P. quinquefolius and P. notoginseng were 2,178 and 2,185 bp, respectively. Blast search revealed that the amplified region was a mitochondrial cytochrome oxidase subunit 2 (cox2) gene intron II region. Nineteen single nucleotide polymorphisms (SNP) including each specific SNP for Gopoong and Chunpoong, and three insertion and deletion (InDel) polymorphisms were detected by sequence alignment. The CAPS markers developed in this study, which are specific to Gopoong and Chunpoong, and between the Korean ginseng cultivars and two foreign Panax species, will serve as a practical and reliable tool for their identification, purity maintenance, and selection of candidate lines and cultivars.

Evaluation of optimal conditions for anionic surfactant removal in wastewater.

This study was conducted to find the optimal conditions for removing anionic surfactants in wastewater using the coagulant-flocculant method. Optimal conditions must be found to minimize the amount of metal materials that can cause secondary contamination and to improve performance. Five parameters were selected to investigate their influence on surfactant removal. The ranges of the independent variables were 0.5-5% for coagulant concentration, 0.1-1% for flocculant concentration, and 20-650 mg/L for surfactant concentration; the coagulant type was FeCl3·6H2O or Ca(OH)2; and the pH ranged from 2 to 10. The experimental results were analyzed with Minitab 19.1 to find the optimal conditions to maximize the removal rate of surfactant. In this study, a total of 20 experiments were carried out using a half fractional factorial design (FFD) including two center points with a resolution of 5 and a pseudo-center point. The results demonstrated that coagulant concentration, flocculant concentration, and pH were significant independent variables with respect to surfactant removal. The fitted regression equation confirmed that the surfactant removal rate was maximized when the coagulant concentration was 5%, the flocculant concentration was 0.1%, and the pH was 10.