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Purpose: Pediatric drug poisoning is a frequent reason for emergency department (ED) visits. Considering the increasing number of mental illnesses in adolescents, it has become a serious public health problem. We aimed to investigate the drug poisoning in the ED.Methods: We retrospectively analyzed children aged 1-17 years with diagnostic codes related to drug poisoning who visited the ED from January 1, 2010 through October 7, 2022. Exclusion criteria were non-pharmaceutical poisoning, insufficient data, and poisoning via respiratory, dermal or ocular route. Baseline characteristics, clinical manifestations, and outcomes of drug poisoning were analyzed in the study population, according to intention of poisoning and drug category.Results: A total of 197 cases of 161 children were analyzed. Compared with non-intentional poisoning, intentional poisoning was associated a higher age, a longer time from ingestion to visit, and higher proportions of girls, antipyretics/analgesics or psychotropic drugs, symptoms related to the gastrointestinal, neurologic or cardiopulmonary systems (P = 0.034), psychiatric comorbidity, multiple drug ingestion, suicide attempt, decontamination (P = 0.017), the use of antidote, history of drug poisoning, and hospitalization (P = 0.004; all other Ps < 0.001). Acetaminophen, a representative of antipyretics/analgesics, was associated with a longer time from ingestion to visit and higher proportions of girls (P = 0.004), the presence of initial gastrointestinal symptoms, suicide attempt (P = 0.001), the use of antidote, and hospitalization (all other Ps < 0.001). Psychotropic drug was associated with higher proportions of psychiatric comorbidity (P < 0.001) and multiple drug ingestion (P = 0.012).Conclusion: This study will enable pediatricians or emergency physicians to obtain an overview of the management of drug poisoning in EDs.

Robotic surgical systems enable surgeons to perform precise movement in the surgical field using high-resolution 3D vision and flexible robotic instruments. We aimed to evaluate the feasibility and safety of performing axillary lymph node dissection using a robotic surgical system in patients with node-positive breast cancer.Thirty-two women with breast cancer who underwent robot-assisted nipple-sparing mastectomy (RNSM) and level I/II axillary lymph node dissection were analyzed. Patients were divided into two groups: RNSM with conventional axillary lymph node dissection (CALND) vs. RNSM with robotic axillary lymph node dissection (RALND). Clinicopathological features and surgical outcomes were analyzed.The median age of the patients was 44 (range 20-59) years. Eleven patients underwent RALND. None of the clinicopathologic features differed between the two groups. There were no statistically significant differences in surgical outcomes, except for the final incision size, between the two groups. The proportion of cases with an incision ≤ 40 mm was 63.6% in the RALND group and 36.4% in the CALND group (p = 0.020).RALND can be safely performed in RNSM. RNSM with RALND is comparable to RNSM with CALND in terms of early surgical outcomes. The incision size can be reduced when using RALND.

Information systems play an important role in business management, especially in personnel, budget, and financial management. If an anomaly ensues in an information system, all operations are paralyzed until their recovery. In this study, we propose a method for collecting and labeling datasets from actual operating systems in corporate environments for deep learning. The construction of a dataset from actual operating systems in a company’s information system involves constraints. Collecting anomalous data from these systems is challenging because of the need to maintain system stability. Even with data collected over a long period, the training dataset may have an imbalance of normal and anomalous data. We propose a method that utilizes contrastive learning with data augmentation through negative sampling for anomaly detection, which is particularly suitable for small datasets. To evaluate the effectiveness of the proposed method, we compared it with traditional deep learning models, such as the convolutional neural network (CNN) and long short-term memory (LSTM). The proposed method achieved a true positive rate (TPR) of 99.47%, whereas CNN and LSTM achieved TPRs of 98.8% and 98.67%, respectively. The experimental results demonstrate the method’s effectiveness in utilizing contrastive learning and detecting anomalies in small datasets from a company’s information system.

We sought to investigate the utility of ebastine (EBA), a second-generation antihistamine with potent anti-metastatic properties, in the context of breast cancer stem cell (BCSC)-suppression in triple-negative breast cancer (TNBC). EBA binds to the tyrosine kinase domain of focal adhesion kinase (FAK), blocking phosphorylation at the Y397 and Y576/577 residues. FAK-mediated JAK2/STAT3 and MEK/ERK signaling was attenuated after EBA challenge in vitro and in vivo. EBA treatment induced apoptosis and a sharp decline in the expression of the BCSC markers ALDH1, CD44 and CD49f, suggesting that EBA targets BCSC-like cell populations while reducing tumor bulk. EBA administration significantly impeded BCSC-enriched tumor burden, angiogenesis and distant metastasis while reducing MMP-2/-9 levels in circulating blood in vivo. Our findings suggest that EBA may represent an effective therapeutic for the simultaneous targeting of JAK2/STAT3 and MEK/ERK for the treatment of molecularly heterogeneous TNBC with divergent profiles. Further investigation of EBA as an anti-metastatic agent for the treatment of TNBC is warranted.

Purpose: The purpose of this study was to investigate the effects of 17 essential oils (EOs) on Escherichia coli (E. coli), including their antibacterial activity according to the concentration used and its extraction site.Methods: All 17 EOs were prepared by step dilution at concentrations of 0.5% (v/v) and 1% (v/v). EOs were dispensed into 96-well plates with bacterial culture aliquots and incubated for 18 h; then, their absorbance was measured using a microplate reader.Results: Culture absorbance showed that thyme white (TM), palmarosa (PR) and rosemary verbenone (RM) at concentrations of 0.5% (v/v) and 1% (v/v) showed high antibacterial activity, similar to that of ampicillin. Melisa true (MS), RM, PR, lavender Bulgarian (LV), lemon (LM), peppermint premium (PM) and eucalyptus bluegum (EC) also showed increased antibacterial activity in a concentration-dependent manner. Finally, TM, MS, RM, PR, and lemongrass (LG) extracted from leaves showed higher antibacterial activity than extracts from other organs.Conclusion: TM extracted from leaves showed an excellent antibacterial effect; it exhibited bacterial growth at the same level of ampicillin. It is a natural substance that suppresses the action of bacteria in the inflammatory reaction of the skin and that may be used as a raw material for customized cosmetics.

Purpose: To determine the postoperative changes in vessel density according to macular hole and macular pseudohole (MPH) subtypes and to investigate the differences in the mechanisms underlying their development. We also investigated whether changes in vessel density are correlated with changes in the multifocal electroretinogram (mfERG) and best corrected visual acuity (BCVA).Methods: We reviewed the medical records of patients with MPH or a macular hole who underwent pars plana vitrectomy. We included 15 eyes of 15 patients with a full thickness macular hole (FTMH), nine eyes of nine patients with a tractional lamellar macular hole (LMH), eight eyes of eight patients with a degenerative LMH, and nine eyes of eight patients with a MPH. The BCVA, foveal avascular zone (FAZ), foveal and parafoveal vessel density, and mfERG ring 1 and ring 2 P1 amplitudes were analyzed before and 1 and 6 months after surgery.Results: One month postoperatively, the foveal vessel density of patients with a MPH or tractional LMH increased (p = 0.011, p = 0.008). The parafoveal vessel density of patients with a MPH, tractional LMH, and FTMH increased (p = 0.007, p = 0.038, p = 0.031). There was no significant increase in foveal or parafoveal vessel density in patients with a degenerative LMH (p = 0.201, p = 0.171). There was a significant correlation between the change in parafoveal vessel density and that in BCVA 6 months postoperatively in patients with a FTMH (r = -0.543, p = 0.037).Conclusions: By assessing changes in vessel density after vitrectomy, it is possible to estimate the effect of traction according to the type of macular hole. There was a significant correlation between parafoveal vessel density and BCVA in patients with a FTMH. Restoration of the retinal structure and vessel density might improve visual acuity.

Backgroud Since the results of TAILORx trial were published, it was shown that premenopausal young patients with intermediate Oncotype Dx(ODx) recurrence score(RS) (16-25) may benefit from adjuvant chemotherapy. In secondary analysis of the TAILORx trial, clinicopathological features can provide complementary information in addition to Oncotype Dx results. Although ambiguous benefit of adjuvant chemotherapy in premenopausal women with intermediate risk makes clinical decision difficult, the baseline characteristic may vary depending on menopausal status. This study intends to analyze whether the intermediate-risk group shows differences in characteristics by menopausal status. Materials and Methods 760 early breast cancer patients with ER positive, HER2 negative and lymph node negative patients who have been tested ODx from July 2013 to December 2020 at Severance Hospital were retrospectively reviewed. Results Of the 760 patients, 262 patients were postmenopausal status and 498 patients were premenopausal status. Among 262 postmenopausal patients, 152 patients were in low-risk group(RS 0-20), 43 patients were in intermediate-risk group(RS 21-25), 67 patients were in high-risk group(RS 26-100). Among 498 patients, 353 patients were in low-risk group(RS 0-20), 75 patients were in intermediate-risk group(RS 21-25), 70 patients were in high-risk group(RS 26-100), respectively. In premenopausal patients with intermediate risk, clinical risk group, PR score, and Ki-67 showed a significant difference from the low risk group(p-value 0.003, Citation Format: Jung Min Park, Jee Hyun Ahn, Soon Bo Choi, Jieon Ko, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park. Distinctive clinicopathological features of premenopausal women with intermediate 21-gene recurrence score [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-13.

Background: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is known important for predicting survival. However, few studies have reported prognosis of minimal residual disease. In this study, we evaluated the long term survival of the patients with breast or nodal pCR and compare patients with minimal residual disease to the breast and node pCR group. As it is difficult to analyze residual cancer burden and tumor-infiltrating lymphocytes in the retrospective study, we assessed the residual tumor or nodal status according to the pathologic report after surgery based on the AJCC 8th edition staging system. Methods: This study retrospectively reviewed 753 patients who achieved pCR of breast or node after NAC from 2010 to 2017 at Severance Hospital. We divided patients into five groups based on the residual disease; breast and node pCR (ypT0/TisN0), minimal residual disease (ypT1mi/T1aN0, ypT0/TisN0i+/N1+), breast-only pCR (ypT0/TisN1+), node-only pCR with residual tumor size no larger than 20mm (ypT1b/T1cN0), and node-only pCR with residual tumor size larger than 20mm (ypT2+N0). The basic characteristics and the 10-year event free survival (EFS) were evaluated. EFS was defined as time from surgery to last follow-up date without any events. Results: We analyzed the data until May 26, 2021, and 50.2% (n=378) of the patients achieved breast and node pCR. Minimal residual disease, defined as residual tumor size no larger than 5mm and residual nodal size 2mm, included 126 patients (16.7%). Overall, there was significant difference in 10-year EFS among five groups (ypT0/TisN0; 94.7%, ypT1mi/T1aN0, ypT0/TisN0i+/N1+; 93.7%, ypT1b/T1cN0; 86.8%, ypT0/TisN1+; 87.9%, ypT2+N0; 71.9%, p Citation Format: Jieon Go, Jee Hyun Ahn, Jung Min Park, Soon Bo Choi, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park. Long-term prognosis of minimal residual disease in breast cancer patients with breast or nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-14.

Background: Ki67 has been studied a lot as a prognostic factor, but ambiguity exists as a value of a prognostic factor that conforms to the guideline due to analytical and methodological issues. However, Ki67 is still represented as IHC representing proliferation, and it is evaluated as an important prognostic factor in many studies. Recently, the international Ki67 in breast cancer working group (IKWG) suggested that in early breast cancer with Estrogen receptor positive (ER+) and HER2 negative (HER2-), Ki67 5% or less could predict a good prognosis and 30% or more could predict a bad prognosis. However, the reality and limitation is that it is still difficult to predict the prognosis at Ki67 5% to 30%. The aim of our study intends to identify that if Progestrone receptor (PR) information is added to Ki67, which has such an ambiguous section, it can give additional prognostic information. Methods: We selected 2668 patients with early breast cancer who underwent surgery and were pathologically diagnosed with ER+ and HER2-. We divided these patients into three groups by Ki67 30%. PR was divided into low and high based on 20%. In each of the three groups, multivariate analysis was performed to identify whether PR is an important factor in prognosis. We set the Ki67 cutoff to 15% in the 5%≤Ki67≤30% group. In this group, we made three combinations of Ki67 and PR with Low group (Ki-6730%. Multivariate analysis was performed in total patients, and hazard ratio(HR) of Ki67 30% was 1, 2.978, and 6.203, respectively, and also it was statistically significant (p=0.004). In the clinical risk (combination of T size, N status, and Histologic grade), HR of clinical high was significantly higher than clinical low (HR: Clinical low : Clinical high = 1: 2.234, p20%, which was statistically significant (HR: PR >20 : PR ≤20% = 1: 1.550, p=0.016). Multivariate analysis was performed for each of the three groups. In the Ki67 30% groups, PR had no statistical significance, but in 5%≤ Ki67 ≤30%, PR was statistically significant (HR: PR >20% vs PR ≤20% = 1 vs 1.613, p= 0.029). In the multivariate analysis of 5%≤ Ki67 ≤30% performed with the Ki67/PR combination, HR of Low, intermediated, and high was 1, 2.139, and 2,054, respectively, and also it was statistically significant (p=0.003, and 0.030). Conclusion: Ki67 can be used as a single prognostic value in at least 30% of early breast cancer with ER+ and HER2-. In the case of 5% ≤Ki67≤ 30%, additional prognostic prediction is possible with the combination of Ki67 and PR. Keywords: Ki67, Progesterone receptor, Prognosis, Estrogen receptor positive, HER2 negative, Early breast cancer Citation Format: Soon Bo Choi, Jung Min Park, Jee Hyun Ahn, Jieon Go, Jeeye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park. The prognostic significance of Ki67 and progesterone receptor; could they really have prognostic importance in early breast cancer with estrogen receptor positive, HER-2 negative? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-13.

Background: Adjuvant endocrine therapy against hormone receptor for more than 5 years has a better prognosis in a subset of patients with hormone receptor-positive breast cancer. The Clinical Treatment Score post-5 years(CTS5) is well known as a promising tool to predict survival outcomes such as distant recurrence after 5-years adjuvant endocrine therapy. The purpose of this study was to determine whether CTS5 is sufficiently relevant to predict the effectiveness of extended endocrine therapy. Method: 3193 breast cancer patients treated between January 2001 and December 2014 were reviewed. The extracted patients were free from disease recurrence or death for 5 years after surgical treatment. The duration of prior adjuvant endocrine therapy was defined as 4.5 to 5.5 years with patients receiving anti-hormonal agents. We investigated the risk of disease-free survival(DFS) and overall survival(OS) according to the premenopausal(age≤50) and postmenopausal(age>50) status, and additionally applied three CTS5 risk groups (low-risk 3.86) to predict the prognosis. Result: The median follow-up period was 8.1(4.5-15.5) years. For total patients, CTS5 showed a distinct division of survival outcomes according to risk groups (p Citation Format: Jee Hyun Ahn, Jung Min Park, Soon Bo Choi, Jieon Go, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park. Clinical treatment score post-5 years (CTS5) and the prediction of survival benefit from extended endocrine therapy for breast cancer patients under and over 50 years of age [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-07-03.

To evaluate the prevalence of insomnia in patients with laryngopharyngeal reflux (LPR) and to analyze the relationship between the severity of insomnia and LPR-related symptoms.We analyzed 69 patients with LPR and 61 healthy controls. The LPR was confirmed via the 24-h hypopharyngeal-esophageal multichannel intraluminal impedance pH monitoring. Reflux symptoms and sleep disturbances were assessed using the Reflux Symptom Index and Insomnia Severity Index. We compared the prevalence of insomnia between the two groups. We analyzed the relationship between reflux symptoms and severity of insomnia.The prevalence of insomnia was significantly higher in patients with LPR than in healthy controls (46.3% vs. 29.5%; p = 0.049). The severity of reflux-related symptoms was correlated with insomnia severity (rho = 0.44; p 0.001). Patients with LPR with nighttime reflux were more likely to have sleep disturbances than patients with LPR without nighttime reflux.Patients with LPR are more likely to experience insomnia than healthy controls, and the severity of reflux symptoms was related to the severity of insomnia.

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.

Purpose: Recent findings suggest that combination treatment with antiestrogen and anti-RET may offer a novel treatment strategy in a subset of patients with breast cancer. We investigated the role of RET in potentiating the effects of antiestrogen response and examined whether RET expression predicted the ability for tyrosine kinase inhibitor (TKI) to affect extracellular signal–regulated kinase 1/2 (ERK1/2) activation in primary breast cancer.Experimental Design: Growth response, ERK1/2 activation, Ki-67, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling were assessed in breast cancer cell lines in vitro and in xenografts with vandetanib and/or tamoxifen. Thirty tumors with matched normal breast tissue were evaluated for RET expression and response to TKI treatment.Results: Vandetanib potentiated the inhibitory effect of tamoxifen in hormone responsive (P = 0.01) and hormone insensitive (P < 0.001) estrogen receptor α (ERα)-positive breast cancer cells. Vandetanib significantly repressed tumorigenesis of MCF-7 xenografts (P < 0.001), which displayed decreased activation of ERK1/2 and AKT. Vandetanib and tamoxifen reduced the growth of established tumors with a greater effect of dual therapy compared with single agent (P = 0.003), with tamoxifen-reducing proliferative index and vandetanib-inducing apoptosis. In primary breast cancers, RET expression correlated with the ERα-positive subtype. Relative decrease in ERK1/2 phosphorylation with TKI treatment was 42% (P < 0.001) in RET-positive tumors versus 14% (P = ns) in RET-negative tumors.Conclusions: Vandetanib potentiated the antigrowth effects of tamoxifen in breast cancer, which was mediated through RET activation. RET predicted response to TKI therapy with minimal effects on ERK1/2 activation in RET-negative tumors. The preclinical data support evaluation of antiestrogen in combination with TKI as a potential treatment strategy for RET-positive luminal breast cancer. Clin Cancer Res; 20(8); 2115–25. ©2014 AACR.

PDF file 70K, Supplementary Figure 1. RET expression with Drug Treatment; Supplementary Figure 2. RET Protein Expression in a Subset of Primary Cancers

BACKGROUND: Hair follicles are among a handful of organs that exhibit immune privilege. Dysfunction of the hair follicle immune system underlies the development of inflammatory diseases, such as alopecia areata. METHODS: Quantitative reverse transcription PCR and immunostaining was used to confirm the expression of major histocompatibility complex class I in human dermal papilla cells. Through transcriptomic analyses of human keratinocyte stem cells, major histocompatibility complex class I was identified as differentially expressed genes. Organ culture and patch assay were performed to assess the ability of WNT3a conditioned media to rescue immune privilege. Lastly, CD8+ T cells were detected near the hair bulb in alopecia areata patients through immunohistochemistry. RESULTS: Inflammatory factors such as tumor necrosis factor alpha and interferon gamma were verified to induce the expression of major histocompatibility complex class I proteins in dermal papilla cells. Additionally, loss of immune privilege of hair follicles was rescued following treatment with conditioned media from outer root sheath cells. Transcriptomic analyses found 58 up-regulated genes and 183 down-regulated genes related in MHC class I+ cells. Using newborn hair patch assay, we demonstrated that WNT3a conditioned media with epidermal growth factor can restore hair growth. In alopecia areata patients, CD8+ T cells were increased during the transition from mid-anagen to late catagen. CONCLUSION: Identification of mechanisms governing epithelial and mesenchymal interactions of the hair follicle facilitates an improved understanding of the regulation of hair follicle immune privilege. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13770-021-00392-7.

To determine whether the concentration of pepsin in the saliva sample changes according to the storage period of the sample.Forty eight patients with suspected laryngopharyngeal reflux were included in this study. Saliva samples were collected from each patient and each sample divided into six and stored for different period of time. Pepsin concentration was measured using enzyme-linked immunosorbent assay. A comparison was made between the pepsin concentration measured immediately and the concentration measured after storage for 1 week, 2 weeks, 1 month, 3 months, and 6 months.No significant difference in pepsin concentrations were detected between the sample analyzed immediately and those analyzed at 1 week, 2 weeks, 1 month, and 3 months after saliva collection. A significant difference in pepsin concentration was observed in the sample analyzed immediately and the sample analyzed 6 months after saliva collection.Pepsin concentration in saliva samples did not demonstrate a significant difference between the concentration measured immediately and the concentration measured 3 months after saliva collection, although a significant difference was observed in the concentration measured 6 months after collection.

Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis. Adult human tissues from diverse sites around the body are used to reconstruct cellular phylogenies from early development, using somatic mutations as an internal barcode.

In resource-constrained IoT networks, the use of conventional message authentication codes (MACs) to provide message authentication and integrity is not possible due to the large size of the MAC output. A straightforward yet naive solution to this problem is to employ a truncated MAC which undesirably sacrifices cryptographic strength in exchange for reduced communication overhead. In this paper, we address this problem by proposing a novel approach for message authentication called \textit{Cumulative Message Authentication Code} (CuMAC), which consists of two distinctive procedures: \textit{aggregation} and \textit{accumulation}. In aggregation, a sender generates compact authentication tags from segments of multiple MACs by using a systematic encoding procedure. In accumulation, a receiver accumulates the cryptographic strength of the underlying MAC by collecting and verifying the authentication tags. Embodied with these two procedures, CuMAC enables the receiver to achieve an advantageous trade-off between the cryptographic strength and the latency in processing of the authentication tags. Furthermore, for some latency-sensitive messages where this trade-off may be unacceptable, we propose a variant of CuMAC that we refer to as \textit{CuMAC with Speculation} (CuMAC/S). In addition to the aggregation and accumulation procedures, CuMAC/S enables the sender and receiver to employ a speculation procedure for predicting future message values and pre-computing the corresponding MAC segments. For the messages which can be reliably speculated, CuMAC/S significantly reduces the MAC verification latency without compromising the cryptographic strength. We have carried out comprehensive evaluation of CuMAC and CuMAC/S through simulation and a prototype implementation on a real car.

Background and Objectives: Biomarkers of allergic rhinitis (AR) have been studied; however, little is known regarding their practical application in the diagnosis of AR. Previous studies collected samples using saline lavage, nasal brushing, or nasal biopsy. To utilize nasal fluid as a diagnostic tool, we need to standardize the method of sample collection. Therefore, this study aimed to evaluate the difference in concentration of biomarkers depending on the method of nasal fluid collection.Materials and Method: Forty-five AR patients who had greater than moderate AR symptoms and who had positive results on skin prick test and serum-specific IgE tests were enrolled in this study. Nasal fluid was collected using the direct method or saline lavage method. The concentration of each biomarker was analyzed using enzyme-linked immunosorbent assay and the values compared.Results: Nasal fluid samples were collected directly from 14 patients and were collected via saline lavage in 31 patients. No significant differences were found in the median value of each biomarker between the two methods of nasal sample collection.Conclusion: Nasal fluid collection method does not significantly affect biomarker concentration.

Purpose: The prevalence and risk factors of neovascular glaucoma (NVG) after diabetic vitrectomy were evaluated. Methods: This retrospective study included 171 eyes of 141 patients who underwent diabetic vitrectomy in-hospital between March 2013 and July 2019 and were followed for >12 months postoperatively. Regardless of the presence or absence of neovascularization in the anterior segment, all patients received injections of intravitreal bevacizumab during vitrectomy. Patients with preoperative neovascularization in iris (NVI) or angle (NVA) received both intracameral and intravitreal bevacizumab injections. Data were collected regarding baseline demographics, preoperative best-corrected visual acuity, intraocular pressure, hypertension, NVG in the fellow eye, panretinal photocoagulation history, iris and angle neovascularization, and postoperative findings (e.g., rebleeding and residual retinal detachment). Results: In total, 141 patients and 171 eyes were included in the study, and the incidence of postoperative NVG was 5.85% (10 patients). Five patients (27.78%) with preoperative NVI or NVA developed postoperative NVG. Significant risk factors for postoperative NVG were preoperative NVA or NVI (odds ratio [OR] = 16.428, p = 0.003), shorter diabetic duration (OR = 0.853, p = 0.033), and the absence of preoperative panretinal photocoagulation (OR = 0.006, p = 0.035). Conclusions: There is a high possibility of postoperative NVG in patients with preoperative NVI or NVA, a short duration of diabetes, and no preoperative panretinal photocoagulation. In such patients, close monitoring is required after diabetic vitrectomy.

This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring.Prospective cohort study.A tertiary care otolaryngology clinic.Patients with typical LPR symptoms showing1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student'sEighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.

Herein, a novel analytical method using a high-performance liquid chromatography-fluorescence detector (HPLC/FLD) is developed for rapidly measuring an L-carnitine ester derivative in infant powdered milk. In this study, solid-phase extraction cartridges filled with derivatized methanol and distilled water were used to effectively separate L-carnitine. Protein precipitation pretreatment was carried out to remove the protein and recover the analyte extract with a high recovery (97.16%–106.56%), following which carnitine in the formula was derivatized to its ester form. Precolumn derivation with 1-aminoanthracene (1AA) was carried out in a phosphate buffer using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) as the catalyst. Method validation was performed following the AOAC guidelines. The calibration curves were linear in the L-carnitine concentration range of 0.1–2.5 mg/L. The lower limit of quantitation and limit of detection of L-carnitine were 0.076 and 0.024 mg/L, respectively. The intra- and interday precision and recovery results were within the allowable limits. The results showed that our method helped reduce the sample preparation time. It also afforded higher resolution and better reproducibility than those obtained by traditional methods. Our method is suitable for detecting the quantity of L-carnitine in infant powdered milk containing a large amount of protein or starch.

Alström syndrome is a rare, multisystemic genetic disorder, and dilated cardiomyopathy occurs in approximately two-thirds of patients with this condition. Because of donor organ shortage and unfavorable prognosis of multiple organ dysfunction, heart transplant is not the most desirable therapeutic option for patients with dilated cardiomyopathy with Alström syndrome. However, eliminating heart dysfunction elements at an appropriate time itself plays a pivotal role in preventing or even reversing other organ failures. Herein, we report the case of a 17-year-old boy who underwent successful isolated heart transplant despite severe liver dysfunction.

Background The emergence of de novo or intrinsic trastuzumab resistance is exceedingly high in breast cancer that is HER2 positive and correlates with an abundant cancer stem cell (CSC)-like population. We sought to examine the capacity of β-escin, an anti-inflammatory drug, to address trastuzumab resistance in HER2-positive breast cancer cells. Methods The effect of β-escin on trastuzumab-resistant and -sensitive cell lines in vitro was evaluated for apoptosis, expression of HER2 family members, and impact on CSC-like properties. An in vivo model of trastuzumab-resistant JIMT-1 was used to examine the efficacy and toxicity of β-escin. Results β-escin induced mitochondrial-mediated apoptosis accompanied by reactive oxygen species (ROS) production and increased active p18Bax fragmentation, leading to caspase-3/-7 activation. Attenuation of CSC-related features by β-escin challenge was accompanied by marked reductions in CD44high/CD24low stem-like cells and aldehyde dehydrogenase 1 (ALDH1) activity as well as hindrance of mammosphere formation. β-escin administration also significantly retarded tumor growth and angiogenesis in a trastuzumab-resistant JIMT-1 xenograft model via downregulation of CSC-associated markers and intracellular domain HER2. Importantly, β-escin selectively inhibited malignant cells and was less toxic to normal mammary cells, and no toxic effects were found in liver and kidney function in animals. Conclusions Taken together, our findings highlight β-escin as a promising candidate for the treatment of trastuzumab-resistant HER2-positive breast cancers.

This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. One hundred twenty-one patients who visited our clinic with a chief complaint of LPR-related symptoms and underwent 24-h MII-pH monitoring were enrolled prospectively. Also, 27 healthy subjects were enrolled and underwent 24-h MII-pH monitoring during the same period. We analyzed sensitivity, specificity, and accuracy comprehensively to determine appropriate cut-off values of pharyngeal reflux episodes in 24-h MII-pH monitoring to diagnose patients with LPR. Twenty-nine of 121 patients with suspected LPR showed no pharyngeal reflux episodes, while 92 showed more than one pharyngeal reflux event. In contrast, the 22 healthy subjects showed no pharyngeal reflux episodes, three showed one reflux event, and two showed two reflux events. A cut-off value of ≥ 1 showed best accuracy reflected by combined sensitivity and specificity values, while ≥ 2 demonstrated better specificity with slight loss of sensitivity and slightly lower overall accuracy, suggesting cut-off value of ≥ 1 pharyngeal reflux episodes is a good clinical indicator. A cut-off value of ≥ 1 in pharyngeal reflux episodes on 24-h MII-pH monitoring in patients with suspected LPR might be an acceptable diagnostic tool for LPR.

To evaluate differences between manual and automated analyses of 24-hour multichannel intraluminal impedance-pH monitoring for diagnosis of laryngopharyngeal reflux.Case series with planned data collection.Academic center outpatient clinic.The study group comprised 127 patients with symptoms suspicious of laryngopharyngeal reflux, who underwent 24-hour multichannel intraluminal impedance-pH monitoring. Automated and manual analyses were performed for each patient. The following parameters were compared between analyses: number of proximal reflux episodes, proximal exposure time, symptom index, and symptom association probability.The number of proximal reflux episodes detected by manual analysis was significantly lower than that detected by automated analysis, except in acid reflux cases. The false positive of automated analysis was 39.8%. In addition, the proximal exposure time for manual analysis was significantly lower than that for automated analysis, except in cases of acid reflux. Symptom index and symptom association probability values based on manual analysis were significantly lower than in automated analysis, except in heartburn cases.Automated analysis demonstrated a tendency of excessive reflux measurement when compared with manual analysis. It is necessary to increase the accuracy of laryngopharyngeal reflux diagnosis through manual analysis.

Triple-negative breast cancer (TNBC) harbors a higher cancer stem cell (CSC)-like population and exhibits a more aggressive metastatic phenotype. Due to the limitations of currently available targeted therapies, there remains a significant unmet need for the development of new targeted therapies for TNBC. Molecular chaperone heat shock protein 90 (HSP90) is attracting attention as an ideal therapeutic target due to it regulates essential biological functions such as cell proliferation, angiogenesis and metastasis. Although N-terminal HSP90 inhibitors have had little clinical success to date, C-terminal HSP90 inhibitors have received relatively little attention. We sought to investigate the effects of a new rationally designed NCT-547 on apoptosis, breast cancer stem cell (BCSC)-like properties, migration ability and heat shock response (HSR) in vitro and tumor growth and metastasis in CSC-enriched allograft model in vivo. NCT-547 inhibits TNBC cell proliferation by simultaneously inactivating several survival factors including AKT, MEK, and STAT3. In addition, NCT-547 effectively targets BCSC-like properties with impairment of ALDH1 activity, CD44+/CD24- phenotype, and 3D mammosphere-forming ability. The expression of HSF-1 target genes such as Hsp90, Hsp70, Hsp27, Hsp40 and Hsp65 is highly overexpressed in TNBC patients. The mRNA abundances of target genes were significantly decreased after NCT-547 challenge. NCT-547 effectively targets both the proliferating TNBC tumor cells and CSCs, markedly reducing tumor growth, coinciding with decreased Ki-67 proliferation index and enhanced apoptosis. Anti-tumor effect of NCT-457 was independent of heat shock response as evidenced by significant downregulation of HSF1 phosphorylation and expression of downstream targets HSPs members. It is noteworthy that NCT-547 did not affect markers of hepatic and renal acute toxicity and was not cytotoxic in non-malignant cells. NCT-547 may therefore have potential to address current limitations in the treatment of TNBC. Citation Format: Eunsun Jung, Seojin Jang, Daeil Sung, Soeun Park, Minsu Park, Dongmi Ko, Seongjae Kim, Juyeon Seo, Kee Dal Nam, Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo, Yong koo Kang, So Ra Seock, Jung Min Park. A novel C-terminal of HSP90 inhibitor NCT-547 eliminates cancer stem-like subpopulation in triple-negative breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4911.