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The purpose of the study was to perform a node-by-node comparison of an ADC-based diagnosis and various size-based criteria on T2-weighted imaging (T2WI) with regard to their correlation with PET/CT findings in patients with uterine cervical cancer. In 163 patients with 339 pelvic lymph nodes (LNs) with short-axis diameter >5 mm, the minimum apparent diffusion coefficient (ADC), mean ADC, short- and long-axis diameters, and ratio of long- to short-axis diameters (L/S ratio) were compared in PET/CT-positive and -negative LNs. On PET/CT, 118 (35%) LNs in 58 patients were positive. The mean value of minimum and mean ADCs, short- and long-axis diameters, and L/S ratio were different in PET/CT-positive (0.6436 x 10(-3) mm(2)/s, 0.756 x 10(-3) mm(2)/s, 10.3 mm, 13.2 mm, 1.32, respectively) and PET/CT-negative LNs (0.8893 x 10(-3) mm(2)/s, 1.019 x 10(-3) mm(2)/s, 7.4 mm, 11.0 mm, 1.49, respectively) (P < 0.05). The Az value of the minimum ADC (0.864) was greater than those of mean ADC (0.836), short-axis diameter (0.764), long-axis diameter (0.640) and L/S ratio (0.652) (P < 0.05). The sensitivity and accuracy of the minimum ADC (86%, 82%) were greater than those of the short-axis diameter (55%, 74%), long-axis diameter (73%, 58%) and L/S ratio (52%, 66%) (P < 0.05). ADC showed superior correlation with PET/CT compared with conventional size-based criteria on T2WI. [ABSTRACT FROM AUTHOR]

This study was conducted to assess the accuracy of US-guided directional vacuum-assisted removal (US-DVAR) in evaluating nonmalignant papillary breast lesions. This retrospective study was approved by the institutional review board at our institution; patient consent was not required. We reviewed the clinical and pathology findings from a total of 39 papillary lesions diagnosed at vacuum-assisted removal in 37 patients (age range, 26-60 years; mean age, 44.5 years). Over the follow-up period, we evaluated whether any histologic upgrade occurred and whether or not residual lesions were detected on follow-up imaging. US-DVAR of 39 lesions yielded tissue that was classified as benign in 35 and atypical in 4. Of the 35 lesions that were diagnosed as histologically benign at US-DVAR, 2 were surgically excised. Both of them yielded benign results. Of the 33 benign lesions that were not surgically excised, 28 (85%) were not seen at radiographic follow-up. Of the four lesions diagnosed as atypical at US-DVAR that were surgically excised, all the four were benign. None proved to be malignant. The upgrade rate was 0.0% (95% confidence interval, 0-9%). Among our patients, diagnosis by US-DVAR of benign papillary lesions proved to be accurate, and benign papillary lesions at US-DVAR did not need to be surgically excised for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST., Methods: This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model., Results: Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42-2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12-4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%)., Conclusions: SLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi., (© 2024. The Author(s).)

Background: Epicardial adipose tissue (EAT) is associated with the development of cardiovascular disease and long-term survival. This study aimed to assess the characteristics of EAT according to the metabolic health and obesity status using low-dose chest computed tomography (CT)., Methods: A total of 1074 asymptomatic adults who underwent a medical health check-up were enrolled. Subjects were categorized into the following four groups according to the metabolic health and obesity status: metabolically healthy non-obese (MHNO); metabolically unhealthy non-obese (MUNO); metabolically healthy obese (MHO); and metabolically unhealthy obese (MUO). EAT on low-dose chest CT was measured by using automatic, quantitative measurement software., Results: MUO showed the highest EAT volume and lowest EAT radiodensity in comparison with MHNO (p < 0.001). The MUNO (n = 70), MHO (n = 259), and MUO (n = 231) groups had increased EAT volume (β [95 % CI], 37.65 [23.11,52.18], 56.79 [47.56,66.02], 84.85 [74.59,95.11] respectively, all p < 0.001), decreased EAT radiodensity (β [95 % CI], - 3.22 [- 4.59,- 1.85], - 4.48 [- 5.30,- 3.66], - 6.03 [- 6.90,- 5.16] respectively, all p < 0.001) in comparison with the MHNO (n = 514) group by using multivariable linear regression models., Conclusions: Both metabolic abnormalities and obesity were closely associated with EAT characteristics. Characteristics of EAT are similar in MHO and MUNO. This finding suggests that MHO is not a favorable condition in terms of cardiac health, as assessed by the characteristics of EAT. The combination of obesity and metabolically unhealthy status has a synergistic adverse effect on EAT. Measurement of EAT could be a useful imaging biomarker for evaluation of an individual's metabolic health/obesity status., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Objective: Serum hemoglobin (Hb) level affects the viscosity of blood. Several studies have reported that Hb level is associated with adverse cardiovascular outcome. However, there is a paucity of evidence on the association between serum Hb level and the risk of subclinical atherosclerosis. Thus, the objective of this study was to investigate the relationship between Hb level and risk of carotid plaque in a health checkup cohort., Methods: This retrospective study analyzed a total of 3,805 individuals without history of cardiovascular disease (CVD) who underwent carotid ultrasonography (USG) between January 2016 and June 2018. Participants were divided into 4 groups based on Hb quartiles in each of male and female. Carotid plaque score was calculated based on USG reports. Multivariable logistic regression analysis was performed for each index of quartile groups regarding the risk of carotid plaque., Results: Of 3,805 individuals (mean age, 52.62±10.25 years; 2,674 [70.28%] males), mean Hb level was 15.11±0.75 g/dL in male and 13.35±0.74 g/dL in female. When the Q1 group was compared to the Q4, increasing quartile of Hb was associated with the presence of significant carotid plaque (plaque score ≥3) in male (adjusted odds ratio [OR], 1.538; 95% confidence interval [CI], 1.182-2.001; p =0.001) and female (adjusted OR, 1.749; 95% CI, 1.058-2.676; p =0.01)., Conclusion: A high Hb level is associated with an increased risk of carotid plaques in individuals without history of CVD. This finding may support the need for early screening of CVD in individuals with high Hb levels., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© 2024 The Korean Society of Lipid and Atherosclerosis.)

Background: Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI., Results: HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-β1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis., Conclusions: Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart., (© 2024. The Author(s).)

Purpose: Lymphovascular invasion (LVI) is a well-known poor prognostic factor for early breast cancer. However, the effect of LVI on breast cancer subtype and node status remains unknown. In this study, we aimed to evaluate the clinical significance of LVI on the recurrence and long-term survival of patients with early breast cancer by comparing groups according to the subtype and node status., Methods: We retrospectively reviewed the medical records of 4554 patients with breast cancer who underwent breast cancer surgery between January 2010 and December 2017. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors related to the DFS and OS according to the nodal status and breast cancer subtype., Results: During a follow-up period of 94 months, the median OS and DFS were 92 and 90 months, respectively. The LVI expression rate was 8.4%. LVI had a negative impact on the DFS and OS, regardless of the lymph node status. LVI was associated with higher recurrence and lower survival in the luminal A, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes. The Cox proportional hazards model showed that LVI was a significant prognostic factor for both DFS and OS. No correlation has been observed between LVI and the Oncotype Dx results in terms of prognostic value in early breast cancer., Conclusion: LVI is an independent poor prognostic factor in patients with early breast cancer, regardless of the node status and molecular subtype. Therefore, the LVI status should be considered when making treatment decisions for patients with early stage breast cancer; however, further prospective studies are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Go, Ahn, Ahn, Kim, Park, Kim, Park and Park.)

Purpose: Few studies have reported on patient prognosis according to residual cancer burden after neoadjuvant chemotherapy (NAC). Herein, we evaluated the survival of patients based on residual disease after NAC to identify subpopulations with distinct prognoses., Methods: We retrospectively reviewed 728 patients treated with NAC from 2010 to 2017. Patients were divided into four subgroups depending on post-surgical residual disease according to the staging system: pathological complete response (pCR) (ypT0/TisN0), minimal residual disease (MRD) (ypT1mi/T1aN0 or ypT0/Tis ypN0i+/N1mic), node-only pCR (≥ ypT1b ypN0), and breast-only pCR (ypT0/Tis ≥ ypN1a). Clinicopathological characteristics and survival outcomes were analyzed by adjusting for factors affecting survival., Results: Overall, 50.4% (n = 367) of patients achieved pCR, with the MRD group accounting for 16.5% (n = 120). Although age and clinical stage were not different among the study groups, histologic grade, subtypes, chemotherapy response, and local treatment showed differences. Event-free survival (EFS) and overall survival (OS) demonstrated no significant difference between the pCR and MRD groups. In the multivariate analysis, pCR status was the only significant factor in EFS, and no statistical difference was noted between the pCR and MRD groups. However, clinical stage, pCR status, and subtype significantly affected the OS. MRD showed favorable outcomes in terms of both EFS and OS in all subtypes, except for those with triple-negative breast cancer (TNBC)., Conclusion: Patients with MRD showed outcomes comparable to those of patients who achieved pCR and may be candidates for de-escalation of post-NAC treatment, except for those with a TNBC subtype., (© 2023. Society of Surgical Oncology.)

Background: This study used a single-institution cohort, the Severance dataset, validated the results by using the surveillance, epidemiology, and end results (SEER) database, adjusted with propensity-score matching (PSM), and analyzed by using a machine learning method. To determine whether the 5-year, disease-free survival (DFS) and overall survival (OS) of patients undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) are not inferior to those of women treated with total mastectomy/skin-sparing mastectomy (TM/SSM)., Methods: The Severance dataset enrolled 611 patients with early, invasive breast cancer from 2010 to 2017. The SEER dataset contained data for 485,245 patients undergoing TM and 14,770 patients undergoing NSM between 2000 and 2018. All patients underwent mastectomy and IBR. Intraoperative, frozen-section biopsy for the retro-areolar tissue was performed in the NSM group. The SEER dataset was extracted by using operation types, including TM/SSM and NSM. The primary outcome was DFS for the Severance dataset and OS for the SEER dataset. PSM analysis was applied. Survival outcomes were analyzed by using the Kaplan-Meier method and Cox proportional hazard (Cox PH) regression model. We implemented XGBSE to predict mortality with high accuracy and evaluated model prediction performance using a concordance index. The final model inspected the impact of relevant predictors on the model output using shapley additive explanation (SHAP) values., Results: In the Severance dataset, 151 patients underwent NSM with IBR and 460 patients underwent TM/SSM with IBR. No significant differences were found between the groups. In multivariate analysis, NSM was not associated with reduced oncologic outcomes. The same results were observed in PSM analysis. In the SEER dataset, according to the SHAP values, the individual feature contribution suggested that AJCC stage ranks first. Analyses from the two datasets confirmed no impact on survival outcomes from the two surgical methods., Conclusions: NSM with IBR is a safe and feasible procedure in terms of oncologic outcomes. Analysis using machine learning methods can be successfully applied to identify significant risk factors for oncologic outcomes., (© 2023. Society of Surgical Oncology.)

Purpose: Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)-positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia., Materials and Methods: Patients with HR-positive, human epidermal growth factor receptor 2-negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups., Results: During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality., Conclusion: Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

Background: Low-pass whole-genome sequencing (LP-WGS)-based circulating tumor DNA (ctDNA) analysis is a versatile tool for somatic copy number aberration (CNA) detection, and this study aims to explore its clinical implication in breast cancer., Methods: We analyzed LP-WGS ctDNA data from 207 metastatic breast cancer (MBC) patients to explore prognostic value of ctDNA CNA burden and validated it in 465 stage II-III triple-negative breast cancer (TNBC) patients who received neoadjuvant chemotherapy in phase III PEARLY trial (NCT02441933). The clinical implication of locus level LP-WGS ctDNA profiling was further evaluated., Results: We found that a high baseline ctDNA CNA burden predicts poor overall survival and progression-free survival of MBC patients. The post hoc analysis of the PEARLY trial showed that a high baseline ctDNA CNA burden predicted poor disease-free survival independent from pathologic complete response (pCR), validating its robust prognostic significance. The 24-month disease-free survival rate was 96.9% and 55.9% in [pCR(+) and low I-score] and [non-pCR and high I-score] patients, respectively. The locus-level ctDNA CNA profile classified MBC patients into 5 molecular clusters and revealed targetable oncogenic CNAs. LP-WGS ctDNA and in vitro analysis identified the BCL6 amplification as a resistance factor for CDK4/6 inhibitors. We estimated ctDNA-based homologous recombination deficiency status of patients by shallowHRD algorithm, which was highest in the TNBC and correlated with platinum-based chemotherapy response., Conclusions: These results demonstrate LP-WGS ctDNA CNA analysis as an essential tool for prognosis prediction and molecular profiling. Particularly, ctDNA CNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ischemic heart disease remains the primary cause of morbidity and mortality worldwide. Despite significant advancements in pharmacological and revascularization techniques in the late 20th century, heart failure prevalence after myocardial infarction has gradually increased over the last 2 decades. After ischemic injury, pathological remodeling results in cardiomyocytes (CMs) loss and fibrosis, which leads to impaired heart function. Unfortunately, there are no clinical therapies to regenerate CMs to date, and the adult heart's limited turnover rate of CMs hinders its ability to self-regenerate. In this review, we present novel therapeutic strategies to regenerate injured myocardium, including (1) reconstruction of cardiac niche microenvironment, (2) recruitment of functional CMs by promoting their proliferation or differentiation, and (3) organizing 3-dimensional tissue construct beyond the CMs. Additionally, we highlight recent mechanistic insights that govern these strategies and identify current challenges in translating these approaches to human patients., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2023. The Korean Society of Cardiology.)

Objective: Mammographic density is an independent risk factor for breast cancer that can change after neoadjuvant chemotherapy (NCT). This study aimed to evaluate percent changes in volumetric breast density (ΔVbd%) before and after NCT measured automatically and determine its value as a predictive marker of pathological response to NCT., Materials and Methods: A total of 357 patients with breast cancer treated between January 2014 and December 2016 were included. An automated volumetric breast density (Vbd) measurement method was used to calculate Vbd on mammography before and after NCT. Patients were divided into three groups according to ΔVbd%, calculated as follows: Vbd (post-NCT - pre-NCT)/pre-NCT Vbd × 100 (%). The stable, decreased, and increased groups were defined as -20% ≤ ΔVbd% ≤ 20%, ΔVbd% < -20%, and ΔVbd% > 20%, respectively. Pathological complete response (pCR) was considered to be achieved after NCT if there was no evidence of invasive carcinoma in the breast or metastatic tumors in the axillary and regional lymph nodes on surgical pathology. The association between ΔVbd% grouping and pCR was analyzed using univariable and multivariable logistic regression analyses., Results: The interval between the pre-NCT and post-NCT mammograms ranged from 79 to 250 days (median, 170 days). In the multivariable analysis, ΔVbd% grouping (odds ratio for pCR of 0.420 [95% confidence interval, 0.195-0.905; P = 0.027] for the decreased group compared with the stable group), N stage at diagnosis, histologic grade, and breast cancer subtype were significantly associated with pCR. This tendency was more evident in the luminal B-like and triple-negative subtypes., Conclusion: ΔVbd% was associated with pCR in breast cancer after NCT, with the decreased group showing a lower rate of pCR than the stable group. Automated measurement of ΔVbd% may help predict the NCT response and prognosis in breast cancer., Competing Interests: Min Jung Kim, a contributing editor of the Korean Journal of Radiology, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Objectives: To investigate reproducibility of quantitative measurement and radiomic features in vessel wall MRI (VW-MRI), evaluate the impact of lesion size, and identify reproducible radiomic features., Methods: This retrospective, single-center study included 251 patients (mean age, 53 ± 12 years; 128 women) with atherosclerosis, dissection, aneurysm, moyamoya disease, and vasculitis of the intracranial arteries who underwent three-dimensional turbo spin echo T1-weighted image. Lesion thickness, volume, and signal intensity were measured, and 157 radiomic features were extracted. Intra-observer reproducibility of quantitative measurement and radiomic features was evaluated by calculating the concordance correlation coefficient (CCC) and proportion of radiomic features above the predefined CCC. The reproducibility of quantitative measurement and radiomic features according to lesion size (binary comparison and stratification into 5 and 18 groups) was evaluated., Results: There was an overall serial increase in CCC for thickness measurement when stratified by lesion thickness and volume. There was an overall serial increase in the median CCC for radiomic features and proportion of radiomic features with CCC > 0.85 when stratified by lesion thickness and volume. Reproducibility of radiomic features was higher in the lesions with thickness ≥ 2.5 mm (median CCC, 0.97 vs. 0.89, p < .001; proportion with CCC > 0.85, 88.5% vs. 59.6%, p < .001) and volume ≥ 50 mm 3 (median CCC, 0.97 vs. 0.88, p < .001; proportion with CCC > 0.85, 90.4% vs. 59.0%, p < .001). Intensity-based statistical features remained most reproducible in the thinnest and smallest lesions., Conclusions: Intra-observer reproducibility of thickness measurement and radiomic features was affected by lesion size in VW-MRI although intensity-based statistical features remained most reproducible., Key Points: • There was an overall serial increase in CCC for thickness measurement when stratified by lesion size. • There was an overall serial increase in the median CCC for radiomic features and proportion of radiomic features with CCC > 0.85 when stratified by lesion size. • Intensity-based statistical features remained most reproducible in the thinnest and smallest lesions., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Aims: Glomerular hyperfiltration (GHF) is a hemodynamic change of the kidney as an adaptive response to nephron loss. Although GHF is associated with metabolic risk factors and cardiovascular disease (CVD), the mechanisms that explain these relationships remain largely unknown. This is partially caused by a non-unified definition of GHF based on pathophysiologic vascular changes. Thus, the objective of this study was to evaluate the association between various definitions of GHF and carotid plaque in a health checkup cohort., Methods: A total of 4493 individuals without history of CVD who had carotid ultrasonography (USG) results available between January 2016 and June 2018 were enrolled. GHF was defined as >90th percentile of eGFR residuals after adjusting for confounding factors. Carotid plaque score was calculated based on carotid USG results., Results: Of 4493 individuals (mean age, 52.3 ± 10.1 years; 3224 [71.8%] males), 449 subjects were included in the GHF group (mean eGFR, 107.0 ± 7.1 ml/min/1.73 m 2 ) and 4044 subjects were included in the non-GHF group (mean eGFR, 92.5 ± 12.3 ml/min/1.73 m 2 ). When the GHF group was compared to the non-GHF group, GHF was associated with the presence of significant carotid plaque (carotid plaque score ≥2) (adjusted OR: 1.46; 95% CI: 1.16 to 1.83; p = 0.001). GHF defined in this study showed higher sensitivity to the presence of carotid plaque than other definitions of GHF., Conclusions: GHF status was associated with risk of carotid plaque in individuals without history of CVD. Presence of subclinical carotid plaque was associated with risk of future CVD. Therefore, GHF based on creatinine could be a useful surrogate marker for surveillance of CVD in asymptomatic individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of alkylammonium lead trihalide perovskite (ALHP) photovoltaics has grown rapidly over the past decade. However, there are remaining critical challenges, such as proton defects, which can lead to the material instability of ALHPs. Although specific strategies, including the use of halide additives, have significantly reduced the defects, a fundamental understanding of the defect passivation mechanism remains elusive. Herein, an approach and mechanism for minimizing proton defects in ALHP crystals by adding ionized halides to the perovskite precursor solution are reported. This work clarifies that the ionized halides induced proton transfer from H 2 O to the alkylammonium cation in the precursor solution, stabilizing the ALHP crystals. The fundamental characteristics of ALHP and its precursors are examined by X-ray diffraction, transmittance electron microscopy, in situ extended X-ray absorption fine structure, Fourier transform NMR spectroscopy, and Fourier transform infrared spectroscopy. The findings from this work will guide the development of highly stable ALHP crystals, enabling efficient and stable optoelectronic ALHP devices., (© 2023 Wiley-VCH GmbH.)

This study evaluated how the efficacy of intense pulsed light (IPL) was influenced by biological factors such as the incubation time and the population of Escherichia coli. According to the 4D value, the microorganisms in the exponential phase were more susceptible to IPL (0.51 J/cm 2 ), while those in the stationary phase were the most resistant (0.67 J/cm 2 ). The microorganisms in the exponential phase could have more critical DNA damage. In addition, the degree of inactivation was affected by the microbial population. When the population was 10 9 CFU/ml, a maximum 3.4-log reduction was observed after applying IPL at 12.5 J/cm 2 . In contrast, a population with a density of 10 10 CFU/ml showed maximally 0.13-log reduction when IPL was applied at 18.7 J/cm 2 . This large difference might have been due to cell distribution and aggregation. The study is expected to contribute to the analytical confirmation of the microbial reduction mechanism through non-thermal technologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated., Methods: Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics., Results: In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency., Conclusions: On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment., (© 2023. The Author(s).)

Direct cardiac reprogramming has emerged as a promising therapeutic approach for cardiac regeneration. Full chemical reprogramming with small molecules to generate cardiomyocytes may be more amenable than genetic reprogramming for clinical applications as it avoids safety concerns associated with genetic manipulations. However, challenges remain regarding low conversion efficiency and incomplete cardiomyocyte maturation. Furthermore, the therapeutic potential of chemically induced cardiomyocytes (CiCMs) has not been investigated. Here, we report that a three-dimensional microenvironment reconstituted with decellularized heart extracellular matrix can enhance chemical reprogramming and cardiac maturation of fibroblasts to cardiomyocytes. The resultant CiCMs exhibit elevated cardiac marker expression, sarcomeric organization, and improved electrophysiological features and drug responses. We investigated the therapeutic potential of CiCMs reprogrammed in three-dimensional heart extracellular matrix in a rat model of myocardial infarction. Our platform can facilitate the use of CiCMs for regenerative medicine, disease modeling, and drug screening.

Purpose: Chemotherapy-induced cardiotoxicity is a critical issue for patients with breast cancer. Change of epicardial adipose tissue (EAT) is associated with cardiac dysfunction. The objective of this study was to investigate the relationship between EAT and chemotherapy-induced cardiotoxicity., Methods: This retrospective study analyzed EAT on chest computed tomography (CT) of patients with early breast cancer using automatic, quantitative measurement software between November 2015 and January 2020. Changes in EAT before and after initiation of chemotherapy were compared according to the type of anticancer drug. Subclinical cardiotoxicity was defined as worsening ≥ 10% in left ventricular ejection fraction to an absolute value > 50% with a lower limit of normal measured with standard echocardiography., Results: Among 234 patients with breast cancer, 85 were treated with adjuvant anthracycline-based (AC) and 149 were treated with non-anthracycline-based (non-AC) chemotherapy. There was a significant increase in EAT volume index (mL/kg/m 2 ) at the end of chemotherapy compared to that at the baseline in the AC group (3.33 ± 1.53 vs. 2.90 ± 1.52, p < 0.001), but not in the non-AC group. During the follow-up period, subclinical cardiotoxicity developed in 20/234 (8.6%) patients in the total population [13/85 (15.3%) in the AC group and 7/149 (4.8%) in the non-AC group]. In the multivariable analysis, EAT volume index increment after chemotherapy was associated with a lower risk of subclinical cardiotoxicity in the AC group (Odds ratio: 0.364, 95% CI 0.136-0.971, p = 0.044)., Conclusions: Measurement of EAT during anthracycline-based chemotherapy might help identify subgroups who are vulnerable to chemotherapy-induced cardiotoxicity. Early detection of EAT volume change could enable tailored chemotherapy with cardiotoxicity prevention strategies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: There is a potential risk that lobular carcinoma in situ (LCIS) on preoperative biopsy might be diagnosed as ductal carcinoma in situ (DCIS) or invasive carcinoma in the final pathology. This study aimed to evaluate the rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive carcinoma., Materials and Methods: Data of 55 patients with LCIS on preoperative biopsy were analyzed. All patients underwent surgery between 1991 and 2016 at Severance Hospital in Seoul, Korea. We analyzed the rate of upgrade of preoperative LCIS to DCIS or invasive cancer in the final pathology. The clinicopathologic features related to the upgrade were evaluated., Results: The rate of upgrade of LCIS to DCIS or invasive carcinoma was 16.4% (9/55). In multivariate analysis, microcalcification and progesterone receptor expression were significantly associated with the upgrade of LCIS (p=0.023 and p=0.044, respectively)., Conclusion: The current study showed a relatively high rate of upgrade of LCIS on preoperative biopsy to DCIS or invasive cancer. The presence of microcalcification and progesterone receptor expression may be potential predictors of upgradation of LCIS on preoperative biopsy. Surgical excision of the LCIS during preoperative biopsy could be a management option to identify the concealed malignancy.

Since an impaired coronary blood supply following myocardial infarction (MI) negatively affects heart function, therapeutic neovascularization is considered one of the major therapeutic strategies for cell-based cardiac repair. Here, to more effectively achieve therapeutic neovascularization in ischemic hearts, we developed a dual stem cell approach for effective vascular regeneration by utilizing two distinct types of stem cells, CD31 + -endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) and engineered human mesenchymal stem cells that continuously secrete stromal derived factor-1α (SDF-eMSCs), to simultaneously promote natal vasculogenesis and angiogenesis, two core mechanisms of neovascularization. To induce more comprehensive vascular regeneration, we intramyocardially injected hiPSC-ECs to produce de novo vessels, possibly via vasculogenesis, and a 3D cardiac patch encapsulating SDF-eMSCs (SDF-eMSC-PA) to enhance angiogenesis through prolonged secretion of paracrine factors, including SDF-1α, was implanted into the epicardium of ischemic hearts. We verified that hiPSC-ECs directly contribute to de novo vessel formation in ischemic hearts, resulting in enhanced cardiac function. In addition, the concomitant implantation of SDF1α-eMSC-PAs substantially improved the survival, retention, and vasculogenic potential of hiPSC-ECs, ultimately achieving more comprehensive neovascularization in the MI hearts. Of note, the newly formed vessels through the dual stem cell approach were significantly larger and more functional than those formed by hiPSC-ECs alone. In conclusion, these results provide compelling evidence that our strategy for effective vascular regeneration can be an effective means to treat ischemic heart disease., (© 2022. The Author(s).)

The valence band of lead halide hybrid perovskites with a mixed I/Br composition is investigated using electronic structure calculations and complementarily probed with hard X-ray photoelectron spectroscopy. In the latter, we used high photon energies giving element sensitivity to the heavy lead and halide ions and we observe distinct trends in the valence band as a function of the I : Br ratio. Through electronic structure calculations, we show that the spectral trends with overall composition can be understood in terms of variations in the local environment of neighboring halide ions. From the computational model supported by the experimental evidence, a picture of the microheterogeneity in the valence band maximum emerges. The microheterogeneity in the valence band suggests that additional charge transport mechanisms might be active in lead mixed halide hybrid perovskites, which could be described in terms of percolation pathways., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Stem cell therapy has emerged as a novel treatment for heart failure after myocardial infarction (Ml). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are commonly considered because of their accessibility and usability. However, their therapeutic potential remains controversial. In our previous in vitro study, chorion-derived mesenchymal stem cells (C-MSCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) demonstrated an ability to differentiate into cardiomyocytes and neural cells, respectively. Thus, we examined whether C-MSCs had a better differentiation potential in an MI animal model., Methods: MI was induced by ligation of the left anterior descending artery, and DiI-labeled MSCs were injected into the border of the infarcted myocardium. The left ventricular ejection fraction (LVEF) and fractional shortening (FS) were measured using echocardiograms. Masson's Trichrome staining was performed to evaluate the viable myocardium. Alpha-sarcomeric actin (α-SA), cardiac troponin-T (cTnT), and isolectin were immunolabeled to evaluate differentiation and capillary formation., Results: After 8 weeks, the LVEF and FS significantly increased to a greater extent in the C-MSC-injected group with maintenance of viable myocardium, as compared to in the control, UC-MSC-, and BM-MSC-injected groups (p < 0.05). Compared to UC-MSCs and BM-MSCs, C-MSCs significantly increased the capillary density (p < 0.05) and demonstrated higher expressions of cTnT and α-SA., Conclusions: In conclusion, compared to UC-MSCs and BM-MSCs, C-MSCs showed a better therapeutic efficacy in a rat MI model., Competing Interests: Conflict of interest None., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to identify the association between Ki-67 level and the prognosis of patients with breast cancer, regardless of the timing of Ki-67 testing (using preoperative biopsy vs. postoperative specimen)., Methods: A total of 4177 patients underwent surgery between January 2008 and December 2016. Immunohistochemical Ki-67 levels, using either preoperative (1673) or postoperative (2831) specimens, were divided into four groups using cutoff points of 10%, 15%, and 20%., Results: Groups with higher-Ki-67 levels, in both the pre- and postoperative periods, showed significantly larger tumor size, higher grade, more frequent hormone receptor-negativity and human epidermal growth factor receptor 2 overexpression, and active adjuvant treatments than groups with lower-Ki-67 levels. High-Ki-67 levels were also significantly associated with poor survival, irrespective of the timing of specimen examination., Conclusion: Despite the problems associated with Ki-67, Ki-67 level is an important independent prognostic factor, regardless of the timing of Ki-67 testing, i.e., preoperative or postoperative testing., (© 2022. The Author(s).)

Ischemia-reperfusion (I/R) injury accelerates the cardiomyocytes (CMs) death by oxidative stress, and thereby deteriorates cardiac function. There has been a paradigm shift in the therapeutic perspective more towards the prevention or amelioration of damage caused by reperfusion. Cardiac microvascular endothelial cells (CMECs) are more vulnerable to reperfusion injury and play the crucial roles more than CMs in the pathological process of early I/R injury. In this study, we investigate that CU06-1004, as a vascular leakage blocker, can improve cardiac function by inhibiting CMEC's hyperpermeability and subsequently reducing the neutrophil's plugging and infiltration in infarcted hearts. CU06-1004 was delivered intravenously 5 min before reperfusion and the rats were randomly divided into three groups: (1) vehicle, (2) low-CU06-1004 (1 mg/kg, twice at 24 h intervals), and (3) high-CU06-1004 (5 mg/kg, once before reperfusion). CU06-1004 treatment reduced necrotic size and cardiac edema by enhancing vascular integrity, as demonstrated by the presence of intact junction proteins on CMECs and surrounding pericytes in early I/R injury. It also decreased the expression of vascular cell adhesion molecule 1 (VCAM-1) on CMECs, resulting in reduced infiltration of neutrophils and macrophages. Echocardiography showed that the CU06-1004 treatment significantly improved cardiac function compared with the vehicle group. Interestingly, single high-dose treatment with CU06-1004 provided a greater functional improvement than repetitive low-dose treatment until 8 weeks post I/R. These findings demonstrate that CU06-1004 enhances vascular integrity and improves cardiac function by preventing lethal myocardial I/R injury. It can provide a promising therapeutic option, as potential adjunctive therapy to current reperfusion strategies., (© 2021. The Author(s).)

This study aimed to determine whether post-mastectomy radiotherapy (PMRT) is beneficial for the prognosis of patients who achieved pathologic complete response (pCR), or who had minimal residual disease, after undergoing neoadjuvant chemotherapy (NAC). Patients who underwent a total mastectomy between 2006 and 2018, after NAC, were included. Patients who did not receive PMRT were matched using 1:3 propensity score matching (PSM). Kaplan-Meier survival curves were used to compare locoregional recurrence-free survival (LRRFS) and overall survival (OS). A total of 368 patients were included after 1:3 PSM. PMRT improved the LRRFS ( p = 0.016) and OS ( p = 0.017) rates of patients who underwent NAC. However, PMRT did not affect the prognosis of patients with pCR (LRRFS: p = 0.999; OS: p = 0.453). In addition, PMRT had a limited effect on LRRFS and OS in patients who responded well to NAC, with a neoadjuvant response index (NRI) value of 0.7-1.0 (LRRFS: p = 0.568; OS: p = 0.875). PMRT improved the OS of patients with a large residual tumor burden, such as nodal metastases or pathologic stage II/III. The benefits of PMRT vary depending on the patients' response to NAC, although PMRT is useful for treating patients who underwent NAC. PMRT can be omitted, not only in patients with pCR, but also in good responders with an NRI value of 0.7-1.0.

Background: Stress cardiomyopathy (SCMP) is an acute but reversible heart failure syndrome with varying clinical outcomes. Although low triiodothyronine (T3) levels are closely associated with heart failure, it is uncertain whether total T3 levels on admission might be correlated with clinical outcomes in patients with SCMP. The aim of this study was to investigate the prognostic value of total T3 level for in-hospital mortality in patients with SCMP., Methods: Patients presenting with SCMP at a single tertiary hospital between January 2013 and May 2019 were retrospectively reviewed. The diagnosis of SCMP was confirmed using the International Takotsubo Diagnostic Criteria and echocardiography was performed at least twice at the time of admission. Comorbidities, antecedent triggers, and other cardiac and metabolic parameters were measured in the survivor group compared with the non-survivor group. We evaluated the correlation between these parameters, especially total T3 and the prevalence of in-hospital mortality and the predictive values of total T3., Results: Of the 134 SCMP patients (69.4 ± 15.5 years old, 94 women), 29 (21.6%) died during hospitalisation. The median follow-up period (interquartile range) was 480 days (63.25-1052.50). Total T3 levels were significantly lower in the non-survival group than in the survival group (33.38 ± 22.58 ng/dL vs. 65.72 ± 34.68 ng/dL, p  < 0.0001). Receiver operating characteristic curve analysis showed the cut-offs of total T3 levels (≤64.37 ng/dL) for in-hospital mortality (area under curve [AUC] = 0.764, p  < 0.001). In multivariable analysis, the T3 level (odds ratio [OR], 0.957; 95% confidential interval [CI], 0.934 to 0.982; p  < 0.001), left ventricular ejection in follow-up echocardiography (OR, 0.935; 95% CI, 0.889-0.983; p  = 0.008), and shock at initial presentation (OR, 3.389; 95% CI, 1.076-10.669; p  = 0.037) were independent predictors for in-hospital mortality in SCMP patients. In patients with low T3 (<64.37 ng/dL), the 30-day survival rate was also significantly lower (81.58 vs. 100%, Log rank p  = 0.001)., Conclusions: Lower levels of total T3 were strongly correlated with in-hospital mortality in patients with SCMP. A low T3 level might suggest poor prognosis in patients with SCMP.

The radiodensity and volume of epicardial adipose tissue (EAT) on computed tomography angiography (CTA) may provide information regarding cardiovascular risk and long-term outcomes. EAT volume is associated with mortality in patients undergoing incident hemodialysis. However, the relationship between EAT radiodensity/volume and all-cause mortality in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis remains elusive. In this retrospective study, EAT radiodensity (in Hounsfield units) and volume (in cm 3 ) on coronary CTA were quantified for patients with ESRD using automatic, quantitative measurement software between January 2012 and December 2018. All-cause mortality data (up to December 2019) were obtained from the Korean National Statistical Office. The prognostic values of EAT radiodensity and volume for predicting long-term mortality were assessed using multivariable Cox regression models, which were adjusted for potential confounders. A total of 221 patients (mean age: 64.88 ± 11.09 years; 114 women and 107 men) with ESRD were included. The median follow-up duration (interquartile range) after coronary CTA was 29.63 (range 16.67-44.7) months. During follow-up, 82 (37.1%) deaths occurred. In the multivariable analysis, EAT radiodensity (hazard ratio [HR] 1.055; 95% confidence interval [CI] 1.015-1.095; p = 0.006) was an independent predictor of all-cause mortality in patients with ESRD. However, EAT volume was not associated with mortality. Higher EAT radiodensity on CTA is associated with higher long-term all-cause mortality in patients undergoing prevalent hemodialysis, highlighting its potential as a prognostic imaging biomarker in patients undergoing hemodialysis., (© 2021. The Author(s).)

Myocardial ischemia-reperfusion (IR) generates stress-induced senescent cells (SISCs) that play an important role in the pathophysiology of adverse cardiac remodeling and heart failure via secretion of pro-inflammatory molecules and matrix-degrading proteases. Thus, removal of senescent cells using a senolytic drug could be a potentially effective treatment. However, clinical studies on cancer treatment with a senolytic drug have revealed that systemic administration of a senolytic drug often causes systemic toxicity. Herein we show for the first time that local delivery of a senolytic drug can effectively treat myocardial IR injury. We found that biodegradable poly(lactic-co-glycolic acid) nanoparticle-based local delivery of a senolytic drug (ABT263-PLGA) successfully eliminated SISCs in the IR-injured rat hearts without systemic toxicity. Consequently, the treatment ameliorated inflammatory responses and attenuated adverse remodeling. Surprisingly, the ABT263-PLGA treatment restored the cardiac function over time, whereas the cardiac function decreased over time in the no treatment group. Mechanistically, the ABT263-PLGA treatment not only markedly reduced the expression of pro-inflammatory molecules and matrix-degrading proteases, but also induced macrophage polarization from the inflammatory phase to the reparative phase via efferocytosis of apoptotic SISCs by macrophages. Therefore, the senolytic strategy with ABT263-PLGA in the early stage of myocardial IR injury may be an effective therapeutic option for myocardial infarction. STATEMENT OF SIGNIFICANCE: This study describes a local injection of senolytic drug-loaded nanoparticles that selectively kills stress-induced senescent cells (SISCs) in infarcted heart. Removal of SISCs decreases inflammatory cytokines and normal cell death. We firstly revealed that further efferocytosis of apoptotic senescent cells by macrophages restores cardiac function after myocardial ischemia-reperfusion injury. Importantly, a local injection of senolytic drug did not exhibit systemic toxicity, but a systemic injection did. Our findings not only spotlight the basic understanding of therapeutic potential of senolysis in infarcted myocardium, but also pave the way for the further application of senolytic drug for non-aging related diseases., Competing Interests: Declaration of Competing Interest The authors report no commercial or proprietary interest in any product or concept discussed in this article., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The present study extensively aimed to evaluate the underlying mechanism of the immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium (PLM)., Methods: To assess whether PLM influences the production of markers related to inflammation, Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with PLM (50, 100, 200, and 500 μg/mL). Splenocyte, thymus, peritoneal exudate cells (PEC), and peripheral blood mononuclear cells (PBMC) were isolated from the Balb/c mice treated with Korean red ginseng or PLM once a day for 5 weeks. Moreover, all mice except normal mice were stimulated with 10% proteose peptone (PP) treated 3 days before the sacrifice and 2% starch treated 2 days before the sacrifice. Subsequently, the cytotropic substance was evaluated by using flow cytometry analysis and ELISA assay., Results: PLM200 treatment significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and inhibited the release of proinflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α dose-dependently in the LPS-stimulated RAW264.7 cells. PLM200 supplementation showed a significant increase in IL-2, IL-12, and interferon (IFN)-γ production and upregulated the ratio of IFN-γ (T-helper type 1, Th1) to IL-4 (T-helper type 2, Th2) in splenocytes. After PLM200 treatment, the significant elevation of CD4 + CD25 + , CD4 + &CD8 + , and CD4 + CD69 + treatment were detected in thymus. Moreover, CD4 + and CD4 + CD69 + in PBMC and CD69 + in PEC were also shown in a significant increase., Conclusions: Taken together, these results showed an immunomodulatory effect of PLM about an elevated INF-γ/IL4 ratio, as an index of Th1/Th2, as well as the anti-inflammatory effect in the LPS-stimulated RAW264.7 cells. Therefore, our findings demonstrate that PLM possesses immunostimulatory and anti-inflammatory effects., (© 2021. The Author(s).)

Background and Objectives: Appropriate catheter selection when conducting transradial coronary angiography (CAG) helps shorten examination time, preventing vascular complications and lowering medical expense. However, catheter selection is made based on the practitioner's experience in almost all cases. Therefore, we undertook this study to define radiologic and echocardiographic indices that would enable physicians to anticipate appropriate catheter selection. Materials and Methods: This is a retrospective study of 244 undergoing transradial diagnostic CAG at an established center from February 2006 to April 2014. Patients who successfully underwent angiography with a JL3.5 catheter were defined as the control group, and patients who successfully underwent angiography after the catheter was replaced with a JL4.0 or higher were defined as the switched group. To identify predictors for appropriate catheter selection, radiologic and echocardiographic indices were analyzed. Results: A total of 122 patients in the switched group and 122 patients in the control group were analyzed in this study. Average age was 64.65 ± 8.6 years. In the radiographic index, the switched group exhibited a significantly higher mediastinal-thoracic ratio (0.27 ± 0.05 vs. 0.23 ± 0.03, p < 0.001. Additionally, the mediastinal-cardiac ratio was significantly greater in the switched group (0.50 ± 0.08 vs. 0.45 ± 0.05, p < 0.001). Aortic root diameter, which is used here as the echocardiographic index, was significantly larger in the switched group compared to the control group (34.94 ± 4.18 mm vs. 32.66 ± 3.99 mm, p < 0.001). In the multivariable logistic regression model, mediastinal-cardiac ratio (OR 5.197, 95% CI 2.608-10.355, p < 0.001) and increased aortic root (OR 2.115, 95% CI 1.144-3.912, p = 0.017) were significantly associated with catheter change. Conclusions: Mediastinal-cardiac ratio and aortic root diameter provide helpful and effective indices for appropriate catheter selection during transradial coronary angiography.

Incorporating dual human epidermal growth factor receptor 2 (HER2) blockade into neoadjuvant systemic therapy (NST) led to higher response in patients with HER2-positive breast cancer. However, axillary response to treatment regimens, including single or dual HER2 blockade, in patients with clinically node-positive breast cancer remains uncertain. Our study aimed to examine the pathologic axillary response according to the type of NST, that is, single or dual HER2 blockade. In our study, 546 patients with clinically node-positive, HER2-positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into three groups: chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab. The primary outcome was the axillary pathologic complete response (pCR). Among 471 patients undergoing axillary lymph node dissection, the axillary pCR rates were 43.5%, 74.5% and 68.8% in patients who received chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab, respectively. There was no difference in axillary pCR rates between patients who received single or dual HER2 blockade (P = .379). Among patients receiving chemotherapy + trastuzumab, patients without breast pCR had the greatest risk for residual axillary metastases (relative risk, 9.8; 95% confidence interval, 3.2-14.9; P < .0001). In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node-positive, HER2-positive breast cancer; furthermore, dual HER2-blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node-positive patients treated with HER2-targeting therapy., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Reactive oxygen species (ROS) and intracellular iron levels are critical modulators of lipid peroxidation that trigger iron-dependent non-apoptotic ferroptosis in myocardial ischemia-reperfusion (I/R) injury. Histochrome (HC), with a potent antioxidant moiety and iron-chelating capacity, is now available in clinical practice. However, limited data are available about the protective effects of HC on ferroptotic cell death in myocardial I/R injury. In this study, we investigated whether the intravenous administration of HC (1 mg/kg) prior to reperfusion could decrease myocardial damage by reducing ferroptosis. Rats undergoing 60 min of ischemia and reperfusion were randomly divided into three groups as follows: (1) Sham, (2) I/R control, and (3) I/R + HC. Serial echocardiography up to four weeks after I/R injury showed that intravenous injection of HC significantly improved cardiac function compared to the I/R controls. In addition, the hearts of rats who received intravenous injection of HC exhibited significantly lower cardiac fibrosis and higher capillary density. HC treatment decreased intracellular and mitochondrial ROS levels by upregulating the expression of nuclear factor erythroid 2-related factor ( Nrf2 ) and its downstream genes. HC also inhibited erastin- and RSL3-induced ferroptosis in rat neonatal cardiomyocytes by maintaining the intracellular glutathione level and through upregulated activity of glutathione peroxidase 4. These findings suggest that early intervention with HC before reperfusion rescued myocardium from I/R injury by preventing ferroptotic cell death. Therefore, HC is a promising therapeutic option to provide secondary cardioprotection in patients who undergo coronary reperfusion therapy.

Hormone receptor (HR)-positive breast cancer has a heterogeneous pattern according to the level of receptor expression. Patients whose breast cancers express low levels of estrogen receptor (ER) or progesterone receptor (PgR) may be eligible for adjuvant endocrine therapy, but limited data are available to support this notion. We aimed to determine whether HR expression level is related to prognosis. Tumors from 6042 patients with breast cancer were retrospectively analyzed for combined HR levels of ER and PgR. Low expression was defined as ER 1-10% and PgR 1-20%. Four HR groups were identified by combining ER and PgR expression levels. Patients whose tumors expressed high levels of a single receptor showed the worst survival outcomes, and their risk continuously increased even after the 10-year follow-up. Endocrine therapy had a significant benefit for patients whose tumors expressed high HR levels and a favorable tendency for patients with tumors expressing low HR levels. We established the possible benefit of endocrine therapy for patients whose breast tumors expressed low HR levels. Thus, HR level was a prognostic factor and might be a determinant of extended therapy, especially for patients with high expression of a single receptor.

The inhalation toxicology of multifaceted particulate matter from the environment, cigarette smoke, and e-cigarette liquid vapes is a major research topic concerning the adverse effect of these items on lung tissue. In vitro air-liquid interface (ALI) culture models hold more potential in an inhalation toxicity assessment. Apropos to e-cigarette toxicity, the multiflavor components of the vapes pose a complex experimental bottleneck. While an appropriate ALI setup has been one part of the focus to overcome this, parallel attention towards the development of an ideal exposure system has pushed the field forward. With the advent of microfluidic devices, lung-on-chip (LOC) technologies show enormous opportunities in in vitro smoke-related inhalation toxicity. In this review, we provide a framework, establish a paradigm about smoke-related inhalation toxicity testing in vitro, and give a brief overview of breathing LOC experimental design concepts. The capabilities with optimized bioengineering approaches and microfluidics and their fundamental pros and cons are presented with specific case studies. The LOC model can imitate the structural, functional, and mechanical properties of human alveolar-capillary interface and are more reliable than conventional in vitro models. Finally, we outline current perspective challenges as well as opportunities of future development to smoking lungs-on-chip technologies based on advances in soft robotics, machine learning, and bioengineering.

Background: Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM., Methods: In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database., Results: In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392-1.707, p < 0.001) and 1.405 (95% CI 1.183-1.668, p < 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476-2.328, p < 0.001) and 1.807 (95% CI 1.186-2.752, p = 0.006), respectively., Conclusions: Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients., (© 2021. Society of Surgical Oncology.)

Background: Patients on haemodialysis (HD) are at high risk of infective endocarditis (IE). Research comparing the microbiological features as well as clinical characteristics and outcomes of HD and non-HD patients with IE is limited. Specifically, no data focussed on vascular access infections (VAIs) have been reported., Methods: The medical records of patients with IE were retrospectively reviewed from January 2010 to February 2020 in a referral hospital in Korea. Those with definite or possible IE by modified Duke criteria were included in the study. The clinical characteristics, microbiological features, echocardiographic findings and outcomes of the patients were analysed., Results: Of the 80 patients with IE, 34 had undergone HD and 46 had not. HD patients with IE had a higher in-hospital mortality rate (50% vs. 17.4%, p  = .004) than non-HD patients. In multivariable stepwise Cox proportional hazards regression analysis, HD (hazard ratio = 2.633; 95% confidential interval: 1.053-6.582; p  = .038) was predictors of 60-day mortality in IE patients. In HD patients, the presence of VAI was associated with a high in-hospital mortality rate (70.59% vs. 29.41%, p  = .039) and all of the patients with VAIs (100%) had methicillin-resistant S. aureus (MRSA) as a causative pathogen., Conclusions: HD patients with IE showed high in-hospital mortality. HD, high C-reactive protein levels and lower left ventricular ejection fraction were predictors of 60-day mortality in IE patients. In particular, HD patients with VAIs had higher mortality rates and MRSA should be considered as the causative microorganism.

Respiratory toxicology remains a major research area in the 21st century since current scenario of airborne viral infection transmission and pollutant inhalation is expected to raise the annual morbidity beyond 2 million. Clinical and epidemiological research connecting human exposure to air contaminants to understand adverse pulmonary health outcomes is, therefore, an immediate subject of human health assessment. Important observations in defining systemic effects of environmental contaminants on inhalation metabolic dysfunction, liver health, and gastrointestinal tract have been well explored with in vivo models. In this review, a framework is provided, a paradigm is established about inhalation toxicity testing in vitro, and a brief overview of breathing Lungs-on-Chip (LoC) as design concepts is given. The optimized bioengineering approaches and microfluidics with their fundamental pros, and cons are presented. There are different strategies that researchers apply to inhalation toxicity studies to assess a variety of inhalable substances and relevant LoC approaches. A case study from published literature and frame arguments about reproducibility as well as in vitro/in vivo correlations are discussed. Finally, the opportunities and challenges in soft robotics, systems inhalation toxicology approach integrating bioengineering, machine learning, and artificial intelligence to address a multitude model for future toxicology are discussed., (© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Stem cell-based therapies with clinical applications require millions of cells. Therefore, repeated subculture is essential for cellular expansion, which is often complicated by replicative senescence. Cellular senescence contributes to reduced stem cell regenerative potential as it inhibits stem cell proliferation and differentiation as well as the activation of the senescence-associated secretory phenotype (SASP). In this study, we employed MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, and examined its long-term priming effect on the activities of senile human cardiac stem cells (hCSCs) and the functional benefits of primed hCSCs after transplantation. In vitro experiments showed that the MHY-1685‒primed hCSCs exhibited higher viability in response to oxidative stress and an enhanced proliferation potential compared to that of the unprimed senile hCSCs. Interestingly, priming MHY-1685 enhanced the expression of stemness-related markers in senile hCSCs and provided the differentiation potential of hCSCs into vascular lineages. In vivo experiment with echocardiography showed that transplantation of MHY-1685‒primed hCSCs improved cardiac function than that of the unprimed senile hCSCs at 4 weeks post-MI. In addition, hearts transplanted with MHY-1685-primed hCSCs exhibited significantly lower cardiac fibrosis and higher capillary density than that of the unprimed senile hCSCs. In confocal fluorescence imaging, MHY-1685‒primed hCSCs survived for longer durations than that of the unprimed senile hCSCs and had a higher potential to differentiate into endothelial cells (ECs) within the infarcted hearts. These findings suggest that MHY-1685 can rejuvenate senile hCSCs by modulating autophagy and that as a senescence inhibitor, MHY-1685 can provide opportunities to improve hCSC-based myocardial regeneration., (© 2021. The Author(s).)

Aim: To develop and validate a radiomics-based model for predicting response to neoadjuvant chemotherapy (NAC) using baseline computed tomography (CT) images in patients with muscle-invasive bladder cancer (MIBC)., Materials and Methods: A radiomics signature for predicting pathological complete response (pCR) was developed using radiomics features selected by a random forest classifier on baseline CT images, and imaging predictors were identified in the training set (87 patients). By incorporating imaging predictors and radiomics signature, an imaging-based model was constructed using multivariate logistic regression analysis and validated in an independent validation set consisting of 48 patients with CT from outside institutions. The performance and clinical usefulness of the imaging-based model for predicting pCR were evaluated using area under the receiver operating characteristic curve (AUC) and decision curve analysis. Using a cut-off determined in the training set, the positive likelihood ratios of the imaging-based model were calculated and compared with imaging and histological predictors., Results: The radiomics signature was developed based on six stable radiomics features. An imaging-based model incorporating radiomics signature, tumour shape, tumour size, and clinical stage showed good performance for predicting pCR in both the training (AUC, 0.85; 95% confidence interval [CI], 0.78-0.93) and validation (AUC, 0.75; 95% CI, 0.60-0.86) sets, providing a larger net benefit in decision curve analysis. The imaging-based model showed a higher positive likelihood ratio (1.91) for pCR than imaging and histological predictors (1.33-1.63)., Conclusions: The radiomics-based model using baseline CT images may predict the response of patients with MIBC to NAC., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Since triple-negative breast cancers (TNBCs) have varying prognoses, it is important to identify subgroups with particularly poor prognosis. The aim of this study was to assess whether changes in the neutrophil-to-lymphocyte ratio (NLR) during the treatment process were associated with poor prognosis in TNBC patients. This study included 600 TNBC patients who underwent surgery from January 2005 to December 2016. The associations of the NLR and clinicopathologic factors with breast cancer recurrence and survival in patients who underwent both definitive local treatment (total mastectomy or breast-conserving surgery with radiotherapy) and systemic chemotherapy were analyzed. The NLRs at four time points (before surgery, before chemotherapy, before radiotherapy, and 1 year after surgery) were assessed. The univariate analysis showed that changes in the NLR before the start of radiotherapy (odds ratio: 1.115, confidence interval: 1.011-1.229) and 1 year after surgery (odds ratio: 1.196, confidence interval: 1.057-1.354) significantly increased the risk of recurrence or death. In multivariate analysis, T stage, N stage, and changes in the NLR were significant factors. A time-sequenced NLR may reflect the prognosis of TNBC patients. A poor prognosis is expected in patients whose NLR increases during treatment compared to the preoperative NLR, and additional treatment is needed.