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Abstract In recent years, human anatomy education has faced challenges with traditional donor dissection, leading to the emergence of virtual dissection as an alternative. This study aims to investigate the academic performance and satisfaction of medical students by comparing the virtual and donor dissections. An open-labeled crossover randomized controlled trial was conducted with 154 first-year medical students in Human Anatomy and Neuroanatomy laboratories, which were divided into three classes. Students were randomly assigned to either the virtual (virtual dissection followed by donor dissection) or donor (donor dissection followed by virtual dissection) groups in each class. A curriculum, incorporating head-mounted displays (HMDs), a life-sized touchscreen, and tablets, was developed. Data was evaluated through quizzes and surveys. In the Human Anatomy laboratory, each class of the donor group conducted heart extraction, dissection and observation. In observation class, the virtual group had a significantly higher mean quiz score than the donor group (p

Abstract Kirsten rat sarcoma viral oncogene homologue (KRAS) is a frequent oncogenic driver of solid tumors, including non-small cell lung cancer (NSCLC). The treatment and outcomes of KRAS-mutant cancers have not been dramatically revolutionized by direct KRAS-targeted therapies because of the lack of deep binding pockets for specific small molecule inhibitors. Here, we demonstrated that the mRNA and protein levels of the class III histone deacetylase SIRT1 were upregulated by the KRASMut-Raf-MEK-c-Myc axis in KRASMut lung cancer cells and in lung tumors of a mouse model with spontaneous KrasG12D expression. KRASMut-induced SIRT1 bound to KRASMut and stably deacetylated KRASMut at lysine 104, which increased KRASMut activity. SIRT1 knockdown (K/D) or the SIRT1H363Y mutation increased KRASMut acetylation, which decreased KRASMut activity and sensitized tumors to the anticancer effects of cisplatin and erlotinib. Furthermore, in KrasG12D/+;Sirt1co/co mice, treatment with cisplatin and erlotinib robustly reduced the tumor burden and increased survival rates compared with those in spontaneous LSL-KrasG12D/+;Sirt1+/+ mice and mice in each single-drug treatment group. Then, we identified p300 as a KRASMut acetyltransferase that reinforced KRASMut lysine 104 acetylation and robustly decreased KRASMut activity. KRASMut lysine 104 acetylation by p300 and deacetylation by SIRT1 were confirmed by LC‒MS/MS. Consistent with this finding, the SIRT1 inhibitor EX527 suppressed KRASMut activity, which synergistically abolished cell proliferation and colony formation, as well as the tumor burden in KRASMut mice, when combined with cisplatin or erlotinib. Our data reveal a novel pathway critical for the regulation of KRASMut lung cancer progression and provide important evidence for the potential application of SIRT1 inhibitors and p300 activators for the combination treatment of KRASMut lung cancer patients.

Background/Aims Some sessile serrated lesions (SSLs) progress into dysplasia and colorectal cancer, however, the clinical and endoscopic characteristics of SSLs with dysplasia remain to be determined. In this study, we elucidated these characteristics in SSLs with dysplasia/carcinoma, compared with those of SSLs without dysplasia. Methods We retrospectively collected the clinical, endoscopic, and pathological data of 254 SSLs from 216 patients endoscopically resected between January 2009 and December 2020. Results All SSLs included 179 without dysplasia and 75 with dysplasia/carcinoma, including 55 with low-grade dysplasia, 10 with high-grade dysplasia, and 10 with submucosal cancer. In clinical characteristics, SSLs with dysplasia/carcinoma were significantly associated with advanced age, metabolic diseases, and high-risk adenomas. In endoscopic characteristics, SSLs with dysplasia/carcinoma were significantly associated with the distal colon, large size, polypoid morphology, surface-changes, no mucus cap, and narrow-band imaging international colorectal endoscopic classification (NICE) type 2/3. In the multivariate analysis, high-risk adenomas (odds ratio [OR], 2.98; p = 0.01), large size (OR, 1.18; p < 0.01), depression (OR, 11.74; p = 0.03), and NICE type 2/3 (OR, 14.97; p < 0.01) were significantly associated with SSLs with dysplasia/carcinoma. Conclusions SSLs had a higher risk of dysplasia in the distal colon than in the proximal colon. SSLs with large size, depression, and adenomatous surface-patterns, as well as those in patients with high-risk adenomas, increased the risk of dysplasia/carcinoma. This suggests that the clinical and endoscopic characteristics can aid in the diagnosis and management of SSLs with dysplasia/carcinoma.

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02–0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86–182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment.

Abstract Objective For thoracoscopy, the usefulness of a dye mixture of indigo carmine and Lipiodol for localizing lung lesions has been reported. However, little is known about the stability and safety of this dye mixture injected on the visceral pleura through a bronchoscope. Methods Porcine models were divided into three groups according to the detection time of the dye mixture: group A with a detection time of 4 h; group B, 8 h; and group C, 24 h. A dye mixture of indigo carmine and Lipiodol (0.5 mL each) was sprayed onto the visceral pleura both in the ventral and dorsal regions via a spray catheter. Results Twelve markings were created on the visceral pleura of the porcine lung (six ventral and six dorsal) in the six porcine models. At predetermined detection times, all 12 dye markings (100%) were visible on the visceral pleura. The mean longest diameter of the dye marking in the ventral and dorsal regions was 18.8 mm and 24.3 mm, respectively. In groups B and C, pathological changes in the lymphatic system, such as lymphatic dilatations, were found; minimal changes were found in group B, however, these changes with oval‐shaped lymphatic cysts and Lipiodol accumulation, were more evident in group C. Conclusions The dye mixture of indigo carmine and Lipiodol had reliable stability and visibility. In terms of safety, it may be necessary to check the dye mixture on the lung surface within 8 h.

Abstract Background Clear cell Renal cell carcinoma (ccRCC) is an immunogenic tumor. B7 family members, such as CTLA-4, PD-1, and PD-L1, are the main components of immune checkpoints that regulate various immune responses. Specifically, B7-H3 regulates T cell-mediated immune responses against cancer. This study aimed to analyze the association between B7-H3 and CTLA-4 expression and the prognostic factors of ccRCC to provide a basis for their potential use as predictive factors and in immunotherapy. Methods Formalin-fixed paraffin-embedded specimens were obtained from 244 ccRCC patients, and B7-H3, CTLA-4, and PD-L1 expressions were evaluated using immunohistochemical staining. Results B7-H3 and CTLA-4 were positive in 73 (29.9%) and 57 (23.4%) of the 244 patients, respectively. B7-H3 expression was significantly associated with PD-L1 expression (P

Abstract Background B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC). The present study aimed to elucidate whether B7-H4 is involved in immune evasion and examine whether B7-H4 is associated with cancer stemness or EMT in ovarian serous carcinoma, the most common type of EOC. The clinical significance of B7-H4 was also investigated to evaluate its potential as a therapeutic target. Methods A total of 145 patients included in this study. The degree of stromal TILs was evaluated using hematoxylin and eosin (H&E)-stained slides. Immunohistochemical analysis of B7-H4, CSC-related biomarkers (CD24, CD44s, CD133, and ALDH1), and EMT-related biomarkers (E-cadherin, N-cadherin, and vimentin) was performed using tissue microarray. qRT-PCR for VTCN1, CD24, CD44, PROM1, ALDH1, CDH1, CDH2, and VIM genes was performed on 38 frozen tissue samples. The mRNA expression levels were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool. Results B7-H4 protein expression positively correlated with the degree of stromal TILs. CD24, CD44s, and CD133 expression showed a positive correlation with B7-H4 expression at both the protein and mRNA levels, but ALDH1 correlated only at the protein level. E-cadherin expression was positively correlated with B7-H4 expression at both the protein and mRNA levels. N-cadherin and vimentin expression was inversely related to B7-H4 expression only at the mRNA level. B7-H4 positive patients were associated with higher tumor grade and lower overall survival rate than B7-H4 negative patients, especially in ovarian serous carcinoma with low stromal TILs. Conclusions The present study demonstrates that B7-H4 may not be involved in the immune evasion mechanism, but is involved in cancer stemness and mesenchymal-epithelial transition. In addition, B7-H4 may be a therapeutic target for the treatment of ovarian serous carcinoma, especially with low stromal TILs.

The progression of idiopathic pulmonary fibrosis (IPF) is diverse and unpredictable. We identified and validated a new biomarker for IPF progression. To identify a candidate gene to predict progression, we assessed differentially expressed genes in patients with advanced IPF compared with early IPF and controls in three lung sample cohorts. Candidate gene expression was confirmed using immunohistochemistry and Western blotting of lung tissue samples from an independent IPF clinical cohort. Biomarker potential was assessed using an enzyme-linked immunosorbent assay of serum samples from the retrospective validation cohort. We verified that the final candidate gene reflected the progression of IPF in a prospective validation cohort. In the RNA-seq comparative analysis of lung tissues, CD276, COL7A1, CTSB, GLI2, PIK3R2, PRAF2, IGF2BP3, and NUPR1 were up-regulated, and ADAMTS8 was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting (n = 12; p < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort (n = 78), serum CTSB levels were higher in the progressive group (n = 25) than in the control (n = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, p < 0.001) and nonprogressive groups (n = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, p < 0.001). In the prospective validation cohort (n = 129), serum CTSB levels were higher in the progressive group than in the nonprogressive group (mean 8.30 ng/mL vs. 3.00 ng/mL, p < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, p < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, p < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control.

(1) Background: Advancements in the field of liver surgery have led to a critical need for precise estimations of preoperative liver function to prevent post-hepatectomy liver failure (PHLF), a significant cause of morbidity and mortality. This study introduces a novel application of artificial intelligence (AI) in determining safe resection volumes according to a patient’s liver function in major hepatectomies. (2) Methods: We incorporated a deep learning approach, incorporating a unique liver-specific loss function, to analyze patient characteristics, laboratory data, and liver volumetry from computed tomography scans of 52 patients. Our approach was evaluated against existing machine and deep learning techniques. (3) Results: Our approach achieved 68.8% accuracy in predicting safe resection volumes, demonstrating superior performance over traditional models. Furthermore, it significantly reduced the mean absolute error in under-predicted volumes to 23.72, indicating a more precise estimation of safe resection limits. These findings highlight the potential of integrating AI into surgical planning for liver resections. (4) Conclusion: By providing more accurate predictions of safe resection volumes, our method aims to minimize the risk of PHLF, thereby improving clinical outcomes for patients undergoing hepatectomy.

Background: The delta neutrophil index (DNI), a prognostic and diagnostic marker for sepsis, is based on the leukocyte count. Platelet activation, similar to leukocyte activation, plays a crucial role in host defense against pathogens and may serve as a predictor of sepsis outcome. However, the combined evaluation of mean platelet component (MPC) and DNI has rarely been used to assess sepsis. Methods: To assess the prognostic and diagnostic validity of the simultaneous evaluation of DNI and MPC in cases of human febrile sepsis, we conducted measurements of cellular indices, including DNI and MPC, as well as molecular biomarkers, including procalcitonin (PCT) and C-reactive protein (CRP). This study was carried out in patients admitted to the emergency department with suspected sepsis. Results: Using a cutoff value of 2.65%, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the DNI in sepsis were found to be 69%, 73.9%, 77.9%, and 64.1%, respectively. Furthermore, significant differences in DNI and MPC levels were observed between the sepsis and non-sepsis groups (6.7 ± 7.8% versus 2.1 ± 2.2% (p = 0.000) and 26.0 ± 1.9 g/dL versus 26.8 ± 1.4 g/dL (p = 0.002), respectively). Notably, there was a negative correlation between DNI and MPC, with the strength of the correlation varying based on the cause of sepsis. By setting the cutoff value of the DNI to 6.2%, its sensitivity, specificity, and NPV improved to 100%, 80.3%, and 100%, respectively, although the PPV remained at 10.6%. Conclusions: In our study, the DNI demonstrates superior effectiveness compared with other molecular biomarkers, such as CRP and procalcitonin, in distinguishing septic febrile patients from non-septic febrile patients. Additionally, a negative correlation exists between MPC and DNI, making MPC a valuable marker for differentiating the etiology of sepsis. These findings hold significant clinical implications, as DNI/MPC evaluation is a cost-effective and readily applicable approach in various impending sepsis scenarios. Notably, this study represents the first examination of the prognostic and diagnostic validity of employing the simultaneous evaluation of DNI and MPC in human cases of febrile sepsis.

Abstract Weak interlayer couplings at 2D van der Waals (vdW) interfaces fundamentally distinguish out‐of‐plane charge flow, the information carrier in vdW‐assembled vertical electronic and optical devices, from the in‐plane band transport processes. Here, the out‐of‐plane charge transport behavior in 2D vdW semiconducting transition metal dichalcogenides (SCTMD) is reported. The measurements demonstrate that, in the high electric field regime, especially at low temperatures, either electron or hole carrier Fowler–Nordheim (FN) tunneling becomes the dominant quantum transport process in ultrathin SCTMDs, down to monolayers. For few‐layer SCTMDs, sequential layer‐by‐layer FN tunneling is observed to dominate the charge flow, thus serving as a material characterization probe for addressing the Fermi level positions and the layer numbers of the SCTMD films. Furthermore, it is shown that the physical confinement of the electron or hole carrier wave packets inside the sub‐nm thick semiconducting layers reduces the vertical quantum tunneling probability, leading to an enhanced effective mass of tunneling carriers.

In‐memory computing using memristor‐based stateful logic reveals high efficiency in the computing paradigm where the memory and computation are colocated. Still, variations in the memristor induce reliability issues for practical applications. Previous error detection and correction modules in the inmemory logic gates can handle the errors but only account for nonswitching errors of the output memristor, while the highly probable switching error of the output memristor is neglected, reducing overall efficiency. Moreover, the module operations use other added stateful logic gates, which may add errors. Herein, modules to handle both nonswitching and switching error cases within the three average steps using reliable logic gates consisting of five memristors are proposed. Detecting both error cases allows logic gates to be still operated in the optimized region for high‐energy efficiency and stability. In addition, combining two different logic families of stateful and sequential logic gates provides the reliability of the stateful logic gates and a possible solution to the peripheral complexity of cascading sequential logic gates. Although detection and correction are demonstrated in NOR and NAND logic gates with the memristor model, the other logic gates can be applied with the same algorithm with the appropriate module‐enable signal and input‐checker bits.

Background d‐Dimer level is a marker of hypercoagulability, which is associated with thrombus formation and resolution. We investigated the value of d‐dimer levels in predicting outcomes of acute ischemic stroke in patients who underwent endovascular treatment (EVT). Methods We analyzed data of patients who underwent only EVT from the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) registry. d‐Dimer levels were routinely measured in 10 of 15 participating hospitals. Patients were grouped into tertiles (tertile 1, tertile 2, and tertile 3) according to d‐dimer levels (lowest, moderate, and highest, respectively). We compared serial scores on the National Institutes of Health Stroke Scale at baseline, on day 1 of hospitalization, and at discharge; functional outcome 3 months after EVT; and rate of mortality within 6 months after EVT. Results In the 170 patients, the median d‐dimer level was 477 ng/mL (interquartile range, 249–988 ng/mL). In tertile 3, the National Institutes of Health Stroke Scale score was higher at discharge than on day 1 of hospitalization. Poor outcome 3 months after EVT (modified Rankin Scale score, ≥3) was more common with high d‐dimer levels (26.3% of tertile 1, 57.1% of tertile 2, and 76.4% of tertile 3; P

Objective To understand the domestication and spread of horses in history, genetic information is essential. However, mitogenetic traits of ancient or medieval horses have yet to be comprehensively revealed, especially for East Asia. This study thus set out to reveal the maternal lineage of skeletal horse remains retrieved from a 15th century archaeological site (Gongpyeongdong) at Old Seoul City in South Korea. Methods We extracted DNA from the femur of Equus caballus (SNU-A001) from Joseon period Gongpyeongdong site. Mitochondrial (mt) DNA (HRS 15128-16116) of E. caballus was amplified by polymerase chain reaction. Cloning and sequencing were conducted for the mtDNA amplicons. The sequencing results were analyzed by NCBI/BLAST and phylogenetic tool of MEGA7 software. Results By means of mtDNA cytochrome b and D-loop analysis, we found that the 15th century Korean horse belonged to haplogroup Q representing those horses that have historically been raised widely in East Asia. Conclusion The horse is unique among domesticated animals for the remarkable impact it has on human civilization in terms of transportation and trade. Utilizing the Joseon-period horse remains, we can obtain clues to reveal the genetic traits of Korean horse that existed before the introduction of Western horses.

Background Chronic kidney disease (CKD) is a common condition leading to renal dysfunction and is closely related to increased cardiovascular and mortality risk. CKD is an important public health issue, and recent genetic studies have verified common CKD susceptibility variants. This research examines the interrelationship between candidate genes polymorphisms of interferon lambda (IFNL) induction, its signaling pathway, and CKD. Methods Seventy-five patients with advanced CKD and 312 healthy subjects (as controls) participated in this research. A replication set composed of 172 patients with advanced CKD and 365 controls was used for additional analysis. The genotype of single nucleotide polymorphisms (SNPs) was determined by the Axiom Genome-Wide Human Assay and SNaPshot assay. Results The SNP of IFNL3 was significantly associated with CKD in the codominant (p = 0.02) and dominant models (p = 0.02). In addition, the SNPs of IFNL2 were significantly associated with CKD in the dominant model (p = 0.03), and the SNP of interferon alpha receptor 2 (IFNAR2) was significantly associated with CKD in the log-additive model (p = 0.03). Concerning rs148543092, in the IFNL3 gene, a significant association was observed after pooling the original and replication sets. Conclusion These results indicate that SNPs in the IFNL induction and signal pathway may be associated with CKD risk in the Korean population. Finally, our results also show that the IFNL3 gene variant may be associated with CKD risk.

Background Mac-2 binding protein glycosylation isomer (M2BPGi) was introduced as a noninvasively measurable serologic marker for liver fibrosis. Acoustic radiation force impulse imaging (ARFI) elastography is another noninvasive method of measuring hepatic fibrosis. There are limited data about the correlations between histologic fibrosis grade and noninvasively measured markers, including M2BPGi and ARFI. Methods This prospective study was conducted among patients admitted consecutively for liver resection, cholecystectomy, or liver biopsy. ARFI elastography, serum M2BPGi levels, and the aspartate aminotransferase to platelet ratio index (APRI) score were evaluated before histologic evaluation. Histologic interpretation was performed by a single pathologist using the METAVIR scoring system. Results In patients with high METAVIR scores, M2BPGi levels and ARFI values showed statistically significant differences between patients with fibrosis and those without fibrosis. In 41 patients with hepatocellular carcinoma, as METAVIR scores increased, M2BPGi levels also tended to increase (p=0.161). ARFI values changed significantly as METAVIR scores increased (p=0.039). In 33 patients without hepatocellular carcinoma, as METAVIR scores increased, M2BPGi levels significantly increased (p=0.040). ARFI values also changed significantly as METAVIR scores increased (p=0.033). M2BPGi levels were significantly correlated with ARFI values (r=0.604, p

Alcohol-related liver disease (ALD) has become the major cause of liver transplantation (LT) in Korea, and is currently the most common cause of LT in Europe and the United States. Although, ALD is one of the most common indications for LT, it is traditionally not considered as an option for patients with ALD due to organ shortages and concerns about relapse. To select patients with terminal liver disease due to ALD for transplants, most LT centers in the United States and European countries require a 6-month sober period before transplantation. However, Korea has a different social and cultural background than Western countries, and most organ transplants are made from living donors, who account for approximately twice as many procedures as deceased donors. Most LT centers in Korea do not require a specific period of sobriety before transplantation in patients with ALD. As per the literature, 8%–20% of patients resume alcohol consumption 1 year after LT, and this proportion increases to 30%–40% at 5 years post-LT, among which 10%–15% of patients resume heavy drinking. According to previous studies, the risk factors for alcohol relapse after LT are as follows: young age, poor familial and social support, family history of alcohol use disorder, previous history of alcohol-related treatment, shorter abstinence before LT, smoking, psychiatric disorders, irregular follow-up, and unemployment. Recognition of the risk factors, early detection of alcohol consumption after LT, and regular follow-up by a multidisciplinary team are important for improving the short- and long-term outcomes of LT patients with ALD.

Summary: The inherent properties of 2D materials—light mass, high out-of-plane flexibility, and large surface area—promise great potential for precise and accurate nanomechanical mass sensing, but their application is often hampered by surface contamination. Here we demonstrate a tri-layer graphene nanomechanical resonant mass sensor with sub-attogram resolution at room temperature, fabricated by a bottom-up process. We found that Joule-heating is effective in cleaning the graphene membrane surface, which results in a large improvement in the stability of the resonance frequency. We characterized the sensor by depositing Cr metal using a stencil mask and found a mass-resolution that is sufficient to weigh very small particles, like large proteins and protein complexes, with potential applications in the fields of nanobiology and medicine.

Neuromodulation using high-energy focused ultrasound (FUS) has recently been developed for various neurological disorders, including tremors, epilepsy, and neuropathic pain. We investigated the safety and efficacy of low-energy FUS for patients with chronic neuropathic pain. We conducted a prospective single-arm trial with 3-month follow-up using new transcranial, navigation-guided, focused ultrasound (tcNgFUS) technology to stimulate the anterior cingulate cortex. Eleven patients underwent FUS with a frequency of 250 kHz and spatial-peak temporal-average intensity of 0.72 W/cm2. A clinical survey based on the visual analog scale of pain and a brief pain inventory (BPI) was performed during the study period. The average age was 60.55 ± 13.18 years-old with a male-to-female ratio of 6:5. The median current pain decreased from 10.0 to 7.0 (p = 0.021), median average pain decreased from 8.5 to 6.0 (p = 0.027), and median maximum pain decreased from 10.0 to 8.0 (p = 0.008) at 4 weeks after treatment. Additionally, the sum of daily life interference based on BPI was improved from 59.00 ± 11.66 to 51.91 ± 9.18 (p = 0.021). There were no side effects such as burns, headaches, or seizures, and no significant changes in follow-up brain magnetic resonance imaging. Low-energy tcNgFUS could be a safe and noninvasive neuromodulation technique for the treatment of chronic neuropathic pain

Abstract This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). Clinical records of patients diagnosed with CD or RPD with multimodal imaging was reviewed for patients diagnosed with both CD and RPD. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. Of the 220 eyes of 110 patients diagnosed with CD and 926 eyes of 463 patients diagnosed with RPD, 13 eyes of seven patients met the diagnostic criteria for both CD and RPD. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.

Background The level of surgical difficulty in laparoscopic cholecystectomy might be predictable based on preoperative imaging and intraoperative findings indicative of cholecystitis severity. Several scales for laparoscopic cholecystectomy have been developed, but most are complex, unverified, and not widely adopted. This study evaluated the association of the cystic duct fibrosis score (range, 0–3) with surgical difficulty in laparoscopic cholecystectomy. Methods Between July 2018 and November 2018, 163 laparoscopic cholecystectomy cases were retrospectively reviewed at a single center. Patients’ demographics, preoperative laboratory data, operation time, complications, hospital stay, and cholecystitis severity grade were investigated. We also evaluated the associations of the Tokyo Guidelines 2018 and the Parkland grading scale with the cystic fibrosis score. Results The cystic duct fibrosis score was associated with preoperative white blood cells (p

The early rectal cancer (ERC) has increased with the national cancer screening project for early detection of colorectal cancer. The gold standard treatment for low rectal cancer is low anterior resection (LAR) based on total mesorectal excision. However, radical resection results in a high mortality and complication rate, and the deterioration of quality of life due to LAR syndrome, genitourinary dysfunction, and possible permanent stoma. Local excision with chemoradiation therapy could be one of the alternative therapeutic strategies for the organ preservation and a cure of cancer. To decide the treatment strategies, it is important to establish sophisticated indications that can maximize the therapeutic effect. ERC has heterogeneous pathological features, including aggressive behavior and occult lymph node metastasis, with different responses to chemoradiotherapy. Therefore, radiologic, endoscopic and pathologic evaluation to predict the risk of lymph node metastasis and local recurrence has been evolving to determine the optimal treatment strategy in the patient-tailored medicine. Recently, the long-term outcomes of prospective randomized clinical trials provide new hope for organ preservation in patients with ERC. In this paper, we aim to review various risk factors related to local recurrence and discuss the optimal treatment strategy for ERC.

BackgroundAlthough the PRISMS study did not demonstrate the benefit of intravenous alteplase administration in patients with mild stroke within 3 h, about 30% of patients presenting with mild symptoms showed unfavorable functional outcomes. We investigated the factors predictive of functional disability at 90 days in patients who were excluded from alteplase administration due to the National Institutes of Health Stroke Scale (NIHSS) scores of 0–5 and a score between 0 and 2 for each NIHSS score item.MethodsAll patients were diagnosed with acute ischemic stroke or transient ischemic attack within 4.5 h of admission to a tertiary hospital and did not receive alteplase due to a minor stroke between January 2013 and December 2020. Radiological data and clinical information were collected, including baseline and discharge NIHSS scores and modified Rankin Scale (mRS) scores at 90 days. Early neurological deterioration (END) was defined as an increase of two or more NIHSS scores. We defined moderate motor weakness as a NIHSS limb motor score of more than 3 and defined a favorable outcome as a mRS score at 90 days that was 0 or 1.ResultsDuring the investigation period, 400 patients did not receive alteplase. END occurred significantly more frequently in patients with large artery disease (LAD) than in those with other TOAST classifications. In the multivariate regression analysis, NIHSS per 1-point increase, presenting as moderate motor weakness, and LAD were independent predictors of poor functional outcome (OR, 1.811 NIHSS per 1-point increase; 95% confidence interval [CI], 1.503–2.182; P < 0.0001; OR, 2.173 moderate motor weakness; 95% CI 1.028–4.595; P = 0.042; OR, 2.033 LAD; 95% CI 1.099–3.762; P = 0.024, respectively).ConclusionModerate motor weakness presentation and LAD may be important factors associated with poor functional outcomes in patients with acute stroke excluded from alteplase administration due to mild symptoms.

Neuromelanin (NM)-sensitive MRI using a magnetization transfer (MT)-prepared T1-weighted sequence has been suggested as a tool to visualize NM contents in the brain. In this study, a new NM-sensitive imaging method, sandwichNM, is proposed by utilizing the incidental MT effects of spatial saturation RF pulses in order to generate consistent high-quality NM images using product sequences. The spatial saturation pulses are located both superior and inferior to the imaging volume, increasing MT weighting while avoiding asymmetric MT effects. When the parameters of the spatial saturation were optimized, sandwichNM reported a higher NM contrast ratio than those of conventional NM-sensitive imaging methods with matched parameters for comparability with sandwichNM (SandwichNM: 23.6 ± 5.4%; MT-prepared TSE: 20.6 ± 7.4%; MT-prepared GRE: 17.4 ± 6.0%). In a multi-vendor experiment, the sandwichNM images displayed higher means and lower standard deviations of the NM contrast ratio across subjects in all three vendors (SandwichNM vs. MT-prepared GRE; Vendor A: 28.4 ± 1.5% vs. 24.4 ± 2.8%; Vendor B: 27.2 ± 1.0% vs. 13.3 ± 1.3%; Vendor C: 27.3 ± 0.7% vs. 20.1 ± 0.9%). For each subject, the standard deviations of the NM contrast ratio across the vendors were substantially lower in SandwichNM (SandwichNM vs. MT-prepared GRE; subject 1: 1.5% vs. 8.1%, subject 2: 1.1 % vs. 5.1%, subject 3: 0.9% vs. 4.0%, subject 4: 1.1% vs. 5.3%), demonstrating consistent contrasts across the vendors. The proposed method utilizes product sequences, requiring no alteration of a sequence and, therefore, may have a wide practical utility in exploring the NM imaging.

Testicular carcinoid tumors are very rare, accounting for less than 1% of all testicular tumors. We report a rare case of a testicular carcinoid tumor with extensive lymphatic invasion. A 42-year-old man presented with a painless, enlarged right testicular mass. There was no history of injury or discomfort in this region. Right radical orchiectomy was performed, which showed a well-defined, non-encapsulated solid white mass with calcification (7.0 × 4.5 × 3.5 cm) and absence of cystic components. Microscopic examination using hematoxylin and eosin staining of the tumor sections identified organoid, trabecular, and solid patterns with rosette formation. Extensive multifocal lymphatic invasion was observed. Immunohistochemistry was positive for synaptophysin, chromogranin, and CD56. Testicular carcinoid tumors usually show good prognoses; however, there was extensive lymphovascular invasion in this case. Thus, in the case of unusual presentation of the disease, close follow-up is necessary.

Background and Objectives: BRAF mutational status in resected non-small cell lung cancer (NSCLC) in the Korean population is poorly understood. We explored BRAF (particularly BRAF V600E) mutational status among Korean patients with NSCLC. Materials and Methods: This study included 378 patients with resected primary NSCLC who were enrolled from January 2015 to December 2017. The authors obtained formalin-fixed paraffin-embedded (FFPE) tissue blocks and performed peptide nucleic acid (PNA)-clamping polymerase chain reaction (PCR) for detecting BRAF V600, real-time PCR for detecting BRAF V600E, and immunohistochemical analyses using the mutation-specific Ventana VE1 monoclonal antibody. For positive cases in any methods mentioned above, direct Sanger sequencing was additionally performed. Results: The PNA-clamping method revealed the BRAF V600 mutation in 5 (1.3%) of the 378 patients. Among these five patients, real-time PCR, direct Sanger sequencing detected BRAF V600E mutations in three (0.8%) patients. Thus, two cases showed differences in their PNA-clamping and the others. Direct Sanger sequencing of PNA-clamping PCR product was performed for two cases showing negative results on direct Sanger sequencing; both contained BRAF mutations other than V600E. All patients harboring BRAF mutations had adenocarcinomas, and all patients with V600E mutation exhibited minor micropapillary components. Conclusions: Despite the low incidence of the BRAF mutation among Korean patients with NSCLC, lung adenocarcinoma patients with micropapillary components should be prioritized in terms of BRAF mutation testing. Immunohistochemical staining using Ventana VE1 antibody may serve as a screening examination for BRAF V600E.

Abstract Under ER stress conditions, the ER form of transmembrane proteins can reach the plasma membrane via a Golgi‐independent unconventional protein secretion (UPS) pathway. However, the targeting mechanisms of membrane proteins for UPS are unknown. Here, this study reports that TMED proteins play a critical role in the ER stress‐associated UPS of transmembrane proteins. The gene silencing results reveal that TMED2, TMED3, TMED9 and TMED10 are involved in the UPS of transmembrane proteins, such as CFTR, pendrin and SARS‐CoV‐2 Spike. Subsequent mechanistic analyses indicate that TMED3 recognizes the ER core‐glycosylated protein cargos and that the heteromeric TMED2/3/9/10 complex mediates their UPS. Co‐expression of all four TMEDs improves, while each single expression reduces, the UPS and ion transport function of trafficking‐deficient ΔF508‐CFTR and p.H723R‐pendrin, which cause cystic fibrosis and Pendred syndrome, respectively. In contrast, TMED2/3/9/10 silencing reduces SARS‐CoV‐2 viral release. These results provide evidence for a common role of TMED3 and related TMEDs in the ER stress‐associated, Golgi‐independent secretion of transmembrane proteins.

Background Cutaneous metastasis (CM) is the spread of cancer cells from a primary site to the skin and is rarely the first sign of silent cancer. We investigated the clinicopathological characteristics of CM from internal malignancies in Korean patients treated at our institution over 20 years. Methods The clinicopathological findings of 112 patients (62 females, 50 males) with CM diagnosed at Yeungnam University Hospital between 2000 and 2020 were retrospectively reviewed. Results Mean patient age was 58.6 years (range, 26 to 87 years), and the most common primary cancer site was breast (74.2%) in women and lung (36.0%) in men. Ninety-six patients (85.7%) presented with CM after primary tumor diagnosis. CM from the lung or biliary tract usually occurred within 2 years of primary tumor diagnosis, whereas metastases from the breast and kidney occurred several years later. The chest, abdomen, and scalp were common sites of CM. Breast cancer usually metastasized to chest skin, while gastrointestinal tract cancers commonly metastasized to the abdomen. The scalp was a common location for CM from various tumors. The most common dermatologic presentations were nodules and masses. Immunohistochemical studies helped identify underlying malignancies when primary tumors were unknown. Conclusions The relative frequency of CM parallels the overall incidence of primary malignant tumors, and CMs usually occur at anatomic sites close to the primary tumor. CM can be diagnosed based on clinical, radiological, and histological features; however, immunohistochemical study is required in some cases.

Purpose Rectal neuroendocrine tumors (NETs)

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

ABSTRACT To optimize antibiotic use, the US CDC has outlined core elements of antimicrobial stewardship programs (ASP). However, they are difficult to implement in limited-resource settings. We report on the successful implementation of a series of ASP with insufficient number of infectious diseases specialists. We retrospectively collected data regarding antibiotic administration and culture results of all patients admitted to a tertiary care teaching hospital, Seoul National University Bundang Hospital (SNUBH), from January 2010 to December 2019. Trends of antibiotic use and antibiotic resistance rates were compared with those from Korean national data. Trend analyses were performed using nonparametric, two-sided, correlated seasonal Mann–Kendall tests. Total antibiotic agent usage has significantly decreased with ASP implementation at SNUBH since 2010. National claim data from tertiary care hospitals have revealed an increase in the use of all broad-spectrum antibiotics except for third-generation cephalosporins (3GC). In contrast, at SNUBH, glycopeptide and fluoroquinolone use gradually decreased, and 3GC and carbapenem use did not significantly change. Furthermore, the rate of colonization with methicillin-resistant Staphylococcus aureus showed a consistently decreasing trend, while that with 3GC- and fluoroquinolone-resistant Escherichia coli significantly increased. Unlike the national rate, the rate of colonization with antibiotic resistant-Klebsiella pneumoniae did not increase and that of 3GC- and fluoroquinolone-resistant Pseudomonas aeruginosa significantly decreased. Stepwise implementation of core ASP elements was effective in reducing antibiotic use despite a lack of sufficient manpower. Long-term multidisciplinary teamwork is necessary for successful and sustainable ASP implementation. IMPORTANCE Antimicrobial stewardship programs aimed to optimize antibiotic use are difficult to implement in limited-resource settings. Our study indicates that stepwise implementation of core antimicrobial stewardship program elements was effective in reducing antibiotic use in a tertiary care hospital despite the lack of sufficient manpower.

Background: Resuming anticoagulation after an intracranial hemorrhage (ICH) poses a clinical conundrum. The absence of relevant guidelines has led to wide variations in the decision on resuming anticoagulation therapies after ICH. This study aimed to evaluate the risks of an anticoagulation therapy on severe thrombotic events (STE) and severe hemorrhage events (SHE) in Korea and compare the effects of novel direct oral anticoagulants (NOACs) and warfarin in patients with AF. Methods: This study was performed using the Korean national health insurance claims data obtained between 2002 and 2017 from individuals who had recently survived an ICH with comorbid AF. The endpoints of this study were STE and SHE. Anticoagulants, antiplatelet agents, and non-antithrombotic users were analyzed for survival with propensity score matching. Results: Among the 4,964 participants analyzed, 878 (17.7%) and 2,070 (41.7%) used anticoagulant and antiplatelet agents, respectively. Anticoagulant (hazard ratio [HR] for STE: 0.385, P

Backgrounds/Aims: Post-hepatectomy liver failure (PHLF) is a major concern for patients with hepatocellular carcinoma (HCC) who have undergone liver resection. The albumin-bilirubin (ALBI) score is a novel model for assessing liver function. We aimed to investigate the effectiveness of the ALBI score as a predictor of PHLF in HCC patients who have undergone hepatectomy in South Korea. Methods: Between January 2014 and November 2018, HCC patients who underwent hepatectomy and indocyanine retention rate at 15 min (ICG-R15) test were enrolled in this study. Results: A total of 101 patients diagnosed with HCC underwent hepatectomy. Thirty-two patients (31.7%) experienced PHLF. The ALBI score (OR 2.83; 95% CI 1.22-6.55; p=0.015), ICG-R15 (OR 1.07; 95% CI 1.02-1.12; p=0.007) and ALBI grade (OR 2,86; 95% CI 1.08-7.58; p=0.035) were identified as independent predictors of PHLF by multivariable analysis. The area under the receiver operating characteristic curve of the ALBI score and ICG-R15 were 0.676 (95% CI 0.566-0.785) and 0.632 (95% CI 0.513-0.752), respectively. The optimal cutoff value of the ALBI score in predicting PHLF was -2.62, with a sensitivity of 75.0% and a specificity of 56.5%. Conclusions: The ALBI score is an effective predictor of PHLF in patients with HCC, and its predictive ability is comparable to that of ICG-R15.

Abstract The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p

In field-effect transistors, a semiconducting channel is indispensable for device switching. Here, the authors demonstrate semiconductor-less switching via modulation of the field emission barrier height across a graphene-hBN interface with ON/OFF ratio of 106.

Chemotherapy is a common treatment technique that uses chemical drugs to kill cancer cells. This technique affects normal healthy tissues being unspecific and has toxic adverse effects. Nowadays, nanotechnology applications in cancer chemotherapy have helped to solve the uncontrolled problems involving distribution of medicine particles and other side effects. Nanoparticles (NPs) can offer significant advantages over conventional drug delivery to have magnificent properties such as controlled mode of action, various methods of administration, and the ability to transport both organic/inorganic drug particles. Special ligands containing polymeric NPs preferentially hit the tumour site because of their chemical affinity to malignant tissues. This article, reviews the fabrication, characterization, and applications of NPs being used in chemotherapy. Furthermore, different forms of polymeric and especially polymeric chemotherapy were also explored and discussed to understand better the effects of NPs on cancer chemotherapy.

Anatomical examination of animal bones found at archaeological sites can provide information that historical studies alone cannot. As related in this report, we performed morphological analyses on cattle and horse bones retrieved from Joseon-period ruins found at the Gongpyeongdong site (Seoul, South Korea). By anatomical and histological comparisons, we confirmed that the slaughter of Gongpyeongdong cattle and horses was done at a later age than is the case today. This was likely due to the fact that cattle and horses in Joseon society were raised primarily as beasts of burden and only secondarily for food; and so, the Joseon government strictly prohibited what it considered to be premature slaughter.

An extragastrointestinal stromal tumor (EGIST) is a gastrointestinal stromal tumor that arises outside of the gastrointestinal tract. Most EGISTs are located in the omentum, mesentery, and retroperitoneum. The occurrence of an EGIST at the perianal region is very rare. Herein, we report our experience with EGISTs in the perianal area and review the literature. A 70-year-old man presented to our hospital with a 2-year history of anal discomfort. A pelvic magnetic resonance imaging scan showed a homogenous, well-defined, soft tissue density mass. The patient underwent mass excision, and the pathological examination confirmed that the mass was an EGIST. The size of the tumor was 4.3×3.2 cm, and the mitotic count was 1 per 50 high-power fields. The tumor cells were immunohistochemically positive for KIT and CD34 but were negative for S-100 and alpha-smooth muscle actin. There were no other abnormal findings in the gastrointestinal tract; upon pathological review, this case was confirmed as perianal EGIST. Therefore, EGIST should be considered as a differential diagnosis of perianal masses.

In adoptive T cell therapy (ACT), the transfer of tumor-specific T cells is paralleled by the conditioning regimen to increase therapeutic efficacy. Pre-conditioning depletes immune-suppressive cells and post-conditioning increases homeostatic signals to improve the persistence of administered T cells. Identifying the favorable immunological factors involved in a conditioning regimen is important to design effective strategies in ACT. Here, by using an ACT model of murine melanoma, we evaluate the effect of the total body irradiation (TBI) and interleukin-2 (IL-2) treatment combination. The use of a Rag1 knock-out strain, which lacks endogenous T cells, enables the identification of factors in a way that focuses more on transferred T cells. We demonstrate that the TBI/IL-2 combination has no additive effect in ACT, although each conditioning improves the therapeutic outcome. While the combination increases the frequency of transferred T cells in lymphoid and tumor tissues, the activation intensity of the cells is reduced compared to that of the sole TBI treatment. Notably, we show that in the presence of TBI, the IL-2 treatment reduces the frequency of intra-tumoral dendritic cells, which are crucial for T cell activation. The current study provides insights into the immunological events involved in the TBI/IL-2 combination in ACT.

Abstract Background The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS). Case presentation A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for 1 week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G > T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G > A/p.E542K in exon 10). Conclusions We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic substantially undermined medical education and healthcare systems. Owing to the pandemic in South Korea, most medical schools needed to be flexible when conducting online and offline classes, but the guidelines did not reflect the specificity of medical schools. This study described the impact of modified anatomy education schedules at the Seoul National University College of Medicine (SNUCM) on students' academic performance and satisfaction.MethodsAnatomy education in SNUCM is divided into three regional units (the upper and lower limbs, trunk, and head and neck). Owing to the COVID-19 pandemic, the schedule was mixed with simultaneous and rotating schedules. The authors conducted exceptions for online lectures, cadaver dissections, and written and practical examinations in three classes of approximately 50 students each. Furthermore, the authors assessed students' performance using three sets of written and practical examinations, and students completed a questionnaire regarding modified anatomy laboratory schedules.ResultsDespite the pandemic events in Seoul and South Korea during the laboratory sessions, all sessions were completed without any confirmed COVID-19 cases among the students, faculty, and staff. Most of the scores on the written and practical examinations significantly decreased in 2020 compared to those in 2019. However, in the trunk session that used the virtual anatomy application, the score on the practical examination in 2020 was significantly higher than that in 2019. Over 70% (79 and 77 out of 105 respondents on the upper and lower limbs and trunk, respectively) and 53% (55/105) students reported that there were no significant difficulties in studying anatomy in a face-to-face laboratory.ConclusionsIn conclusion, an adequate education program for cadaver dissection should be developed and provided to overcome the pandemic restrictions. The study findings could serve as a reference for anatomy education during the COVID-19 pandemic.

Abstract Cuticular drusen show some similarities to and differences from soft drusen in age-related macular degeneration (AMD) and might thus be a unique AMD subtype. Previous studies on cuticular drusen were performed mainly in white ethnic groups, but AMD shows ethnic differences. We investigated clinical manifestations of cuticular drusen in Korean patients to evaluate possible ethnic differences. Clinical records of Korean patients with cuticular drusen were retrospectively reviewed. Fundus distribution pattern, imaging features, and presence of large drusen, drusenoid pigment epithelial detachment (PED), and macular complications, including geographic atrophy (GA), choroidal neovascularization (CNV), and acquired vitelliform lesion (AVL), were assessed via multimodal imaging in 162 eyes with cuticular drusen (n = 81 patients; 67 females; mean age: 66.6 ± 9.1 years). Diffuse distribution was found in 61.7% and peripapillary involvement in 75.3% of eyes. Large drusen, drusenoid PED, GA, CNV, and AVL were observed in 59.3%, 26.5%, 18.5%, 3.7%, and 1.2% of eyes, respectively. The macular complication prevalence was similar between patients ≤ 60 and those > 60 years old. In Korean patients, cuticular drusen were less frequently associated with macular complications than in white patients, and the proportion of macular complications differed significantly, with AVL representing an uncommon complication.

Abstract Background Carbapenem is frequently used when gram negative bacilli (GNB) bacteremia is detected especially in neutropenic patients. Consequently, appropriate treatment could be delayed in GNB bacteremia cases involving organisms which are not susceptible to carbapenem (carba-NS), resulting in a poor clinical outcomes. Here, we explored risk factors for carba-NS GNB bacteremia and its clinical outcomes in patients with acute myelogenous leukemia (AML) that underwent chemotherapy. Methods We reviewed all GNB bacteremia cases that occurred during induction or consolidation chemotherapy, over a 15-year period, in a tertiary-care hospital. Results Among 489 GNB bacteremia cases from 324 patients, 45 (9.2%) were carba-NS and 444 (90.8%) were carbapenem susceptible GNB. Independent risk factors for carba-NS GNB bacteremia were: carbapenem use at bacteremia onset (adjusted odds ratio [aOR]: 91.2; 95% confidence interval [95%CI]: 29.3–284.1; P

Backgraoud & Aims: Aberrant epithelial bicarbonate (HCO3−) secretion caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with several diseases including cystic fibrosis and pancreatitis. Dynamically regulated ion channel activity and anion selectivity of CFTR by kinases sensitive to intracellular chloride concentration ([Cl−]i) play an important role in epithelial HCO3− secretion. However, the molecular mechanisms of how [Cl−]i-dependent mechanisms regulate CFTR are unknown. Methods: We examined the mechanisms of the CFTR HCO3− channel regulation by [Cl−]i-sensitive kinases using an integrated electrophysiological, molecular, and computational approach including whole-cell, outside-out, and inside-out patch clamp recordings and molecular dissection of WNK1 and CFTR proteins. In addition, we analyzed the effects of pancreatitis-causing CFTR mutations on the WNK1-mediated regulation of CFTR. Results: Among the WNK1, SPAK, and OSR1 kinases that constitute a [Cl−]i-sensitive kinase cascade, the expression of WNK1 alone was sufficient to increase the CFTR bicarbonate permeability (PHCO3/PCl) and conductance (GHCO3) in patch clamp recordings. Molecular dissection of the WNK1 domains revealed that the WNK1 kinase domain is responsible for CFTR PHCO3/PCl regulation by direct association with CFTR, while the surrounding N-terminal regions mediate the [Cl−]i-sensitivity of WNK1. Furthermore, the pancreatitis-causing R74Q and R75Q mutations in the elbow helix 1 of CFTR hampered WNK1-CFTR physical associations and reduced WNK1-mediated CFTR PHCO3/PCl regulation. Conclusion: The CFTR HCO3− channel activity is regulated by [Cl−]i and a WNK1-dependent mechanism. Our results provide new insights into the regulation of the ion selectivity of CFTR and the pathogenesis of CFTR-related disorders. Keywords: Bicarbonate Secretion, Epithelia, Pancreatitis, Ion Selectivity

Background Embolic stroke undetermined source (ESUS), which is defined as nonlacunar infarction in the absence of cardioembolic sources, proximal artery stenosis excluded by echocardiogram, holter monitoring and vascular images, is reported to account for 9% to 25% of ischemic stroke. Because the source of embolism remains unclear, it is an important task to find the etiology for secondary prevention of stroke recurrent. Case Report We report a case of uterine myoma found in an embolic stroke patient with incidentally found a huge uterine myoma and related deep vein thrombosis. Conclusion Uterine myoma in a middle-aged woman can be thought to be the etiological cause that can contributor to deep vein thrombosis, and it is necessary to pay attention as the etiology of ESUS.

Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3–6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290–1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041–1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.

In the general context of rescue archaeology or in any emergency salvage operation, especially where human bones are involved that need to be cremated within a short time frame, anthropologists cannot conduct their work carefully at a university or institute lab. Thus, they have sought ever-more efficient and effective investigative protocols by which work can be conducted in cases of urgent time constraints. A recent anthropological survey conducted at a small town in South Korea (Goryeung) is thus significant. A joint team of anthropologists and dress historians performed collaborative research work in a “field lab” set up at the excavation site. Our novel protocol, by which academic data demonstrably can be successfully secured in the field instead of having to be sent to a university or institute lab, could be useful for the purposes of rescue archaeology.

Background Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis. Methods Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy. Results CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001). Conclusions Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.