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Alterations in PIEZO2 can result in distal arthrogryposis, which is characterized by non-progressive contracture in two or more areas of the body prior to birth. Here, we present a 29-year-old man born with multiple joint contractures and cleft palate. He showed short stature, low-set ears, macrotia, hearing impairment, micrognathia, a triangular face, blepharophimosis, deep-set eyes, high arched eyebrows, decreased facial expressions, retrognathia, arachnodactyly, absent phalangeal crease, shortening of the first and fifth toes, short stature, pectus excavatum, epicanthus, bilateral ptosis, and ophthalmoplegia. He also complained of dyspnea and severe kyphoscoliosis. Pulmonary function tests showed a severe restrictive pattern. An electrodiagnostic study did not reveal any neurogenic or myogenic features. Next-generation sequencing revealed a novel de novo heterozygous pathogenic variant in PIEZO2 (c.7251G>T; p.Trp2417Cys). Our study is the first report of a pathogenic variant in PIEZO2 in a Korean patient with distal arthrogryposis.

We examined the relative effectiveness of a college-level self-management (SM) course and a physical exercise (PE) course on improving self-control. In Study 1, Barratt Impulsiveness Scale (BIS-11) and general regulatory behavior questionnaire were administered before and after the courses to students from an SM course (experimental group 1

Objective: This study investigated the clinical, pathological, and genetic characteristics of 5 Korean patients with selenoprotein N-related myopathy (SELENON-RM).Methods: Five unrelated patients were genetically diagnosed with SELENON-RM by whole-exome or targeted gene panel sequencing. We then analyzed their clinical, pathological, and genetic spectra.Results: The median age at symptom onset was 3 years (interquartile range, 2–10 years). The most common clinical finding was proximal muscle weakness in all 5 patients, followed by spinal scoliosis and respiratory distress in 4 patients and delayed motor development in 2 patients. Other uncommon clinical findings were winged scapula in one patient and cardiomegaly in one patient. Magnetic resonance imaging of muscles revealed that fatty replacement was predominant in the paraspinal muscles, adductors, semimembranosus, semitendinosus, long head of the biceps femoris, and medial gastrocnemius. Muscle biopsies in 2 patients showed type 1 predominance and multiple eccentric cores within the fibers. We identified 5 pathogenic variants of SELENON. The most common variant was the c.1574T > G variant in 5 alleles (50%) in 4 patients (80%).Conclusion: In the first report of SELENON-RM in Korea, we identified 5 SELENON-RM patients and expanded existing knowledge on the clinical and genetic spectrum of these patients.

Background: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. Results: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, −8.5% [95% CI, −17.8% to 0.8%]; P =0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, −6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. Conclusions: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03284827.

We reported an age 32 male with progressive proximal muscle weakness. The serum creatine kinase was 1,908 IU/L. The muscle biopsy from biceps brachii muscle showed nonspecific myopathic changes. The whole exome sequencing identified a heterozygous variant (c.296A>C) in CAV3. It was previously reported as a likely pathogenic variant. It was also detected in the male’s mother and brother. However, his mother and brother had only hyperCKemia without muscle weakness. Our case showed phenotypic heterogeneity in a family, with the same variant in CAV3.

Aims The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning. Methods and results Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834–0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034). Conclusion A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors.

Computational microscopy, which merges cutting-edge optical methods with intricate algorithms, offers significant potential for applications such as resolution improvement and quantitative phase retrieval. However, it faces challenges due to high computational demands and the need for precise algorithms. Recent advancements in data-driven deep-learning-based techniques have emerged to mitigate these challenges; however, incorporating physics-based constraints can further address the limitations. In this paper, we propose a deep-learning framework for image reconstruction in computational microscopy that combines the advantages of single-pass, end-to-end inversion and physics-informed learning approaches, while considering the challenges in obtaining exact physics-informed constraints. Our network learns the forward imaging process, which accurately estimates position-dependent optical aberrations and serves as an effective physical prior in the training of the reconstruction model. Validated on Fourier Ptychography (FP), our proposed framework demonstrates fast and robust FP reconstructions that outperform conventional model-based methods with significantly fewer input measurements and exhibits generalizability to unseen samples, as demonstrated by quantitative comparisons with existing methods. We evaluated our approach on various datasets, including human breast cancer pathology samples, the HeLA dataset, and the USAF phase target dataset, demonstrating that our method improves the practicality of computational microscopy by offering high-quality reconstructions with faster speeds over different sample types.

We present a design and construction of a lensless camera where the phase-modulating mask is integrated directly on a sensor using the UV-imprint lithography. Our method delivers a rigid device with a small form-factor.

The decision to perform an intervention for asymptomatic severe aortic stenosis (AS) requires careful weighing of the risks of early intervention against those of watchful observation, and the optimal timing of intervention remains controversial. With improvements in surgical and postoperative care, long-term survival after surgical aortic valve (AV) replacement (AVR) is excellent in low-risk patients, and the emergence of transcatheter AVR may change the thresholds for early preemptive intervention, although a durability issue has to be resolved. A watchful observation strategy also has a risk of sudden death, irreversible myocardial damage, and increase in operative risk while waiting for symptoms to develop. We have been waiting for a prospective randomized trial to solve the intense debate between early AVR and watchful observation, and the RECOVERY (Randomized Comparison of Early Surgery versus Conventional Treatment in Very Severe Aortic Stenosis) trial provides the evidence to support early AVR for asymptomatic severe AS. Risk assessment with severity of AS and staging classification may help to facilitate the identification of patients who may benefit from early intervention. Based on the results of the RECOVERY trial, early surgical AVR is reasonable for asymptomatic patients with very severe AS (aortic jet velocity ≥4.5 m/s) and low surgical risk. Further evidence is required to extend the indications of surgical AVR and to consider transcatheter AVR in asymptomatic patients with severe AS.

Increasing evidence has shown that small ubiquitin-like modifier (SUMO) modification plays an important role in metabolic regulation. We previously demonstrated that SUMO-specific protease 2 (SENP2) is involved in lipid metabolism in skeletal muscle and adipogenesis. In this study, we investigated the function of SENP2 in pancreatic β cells by generating a β cell-specific knockout (Senp2-βKO) mouse model. Glucose tolerance and insulin secretion were significantly impaired in the Senp2-βKO mice. In addition, glucose-stimulated insulin secretion (GSIS) was decreased in the islets of the Senp2-βKO mice without a significant change in insulin synthesis. Furthermore, islets of the Senp2-βKO mice exhibited enlarged mitochondria and lower oxygen consumption rates, accompanied by lower levels of S616 phosphorylated DRP1 (an active form of DRP1), a mitochondrial fission protein. Using a cell culture system of NIT-1, an islet β cell line, we found that increased SUMO2/3 conjugation to DRP1 due to SENP2 deficiency suppresses the phosphorylation of DRP1, which possibly induces mitochondrial dysfunction. In addition, SENP2 overexpression restored GSIS impairment induced by DRP1 knockdown and increased DRP1 phosphorylation. Furthermore, palmitate treatment decreased phosphorylated DRP1 and GSIS in β cells, which was rescued by SENP2 overexpression. These results suggest that SENP2 regulates mitochondrial function and insulin secretion at least in part by modulating the phosphorylation of DRP1 in pancreatic β cells.

Objectives The aim of this study was to compare the incidence and prognostic significance of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) according to racial groups. Background PPM after TAVR may be of more concern in Asian populations considering their relatively small annular and valve sizes compared with Western populations. Methods TP-TAVR (Transpacific TAVR Registry) was an international multicenter cohort study of patients with severe aortic stenosis who underwent TAVR in the United States and South Korea from January 2015 to November 2019. PPM was defined as moderate (0.65-0.85 cm2/m2) or severe ( Results Among 1,101 eligible patients (533 Asian and 569 non-Asian), the incidence of PPM was significantly lower in the Asian population (33.6%; moderate, 26.5%; severe, 7.1%) than in the non-Asian population (54.5%; moderate, 29.8%; severe, 24.7%). The 1-year rate of the primary outcome was similar between the PPM and non-PPM groups (27.5% vs 28.1%; P = 0.69); this pattern was consistent between Asian (25.4% vs 25.2%; P = 0.31) and non-Asian (28.7% vs 32.1%; P = 0.97) patients. After multivariable adjustment, the risk for the primary outcome did not significantly differ between the PPM and non-PPM groups in the overall population (HR: 0.95; 95% CI: 0.74-1.21), in Asian patients (HR: 1.07; 95% CI: 0.74-1.55), and in non-Asian patients (HR: 0.86; 95% CI: 0.63-1.19). Conclusions In this study of patients with severe aortic stenosis who underwent TAVR, the incidence of PPM was significantly lower in Asian patients than in non-Asian patients. The 1-year risk for the primary composite outcome was similar between the PPM and non-PPM groups regardless of racial group. (Transpacific TAVR Registry [TP-TAVR]; NCT03826264 )

Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the β-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.

PURPOSE We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. FINDINGS Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p

To understand the characteristics of Korean patients with anti-HMGCR myopathy, we measured anti-HMGCR antibodies and analyzed clinical, radiological, and pathological features. We measured titers of anti-HMGCR antibodies in the sera of 99 patients with inflammatory myopathy using the enzyme-linked immunosorbent assay. We tested 16 myositis-specific autoantibodies (MSAs) in all patients with anti-HMGCR myopathy. Positivity for the anti-HMGCR antibody was observed in 17 (4 males and 13 females) of 99 patients with inflammatory myopathy. The median age at symptom onset was 60 years. Ten (59%) of the anti-HMGCR positive patients had taken statins. The most common symptoms were proximal muscle weakness in 15 (88%), followed by myalgia in 9 (53%), neck weakness in 4 (24%), dysphagia in 3 (18%), and skin lesions in 2 (12%). The median titer of anti-HMGCR antibody was 202 U/ml. We found eight different MSAs in nine (53%) patients. The median disease duration from symptom onset to diagnosis was significantly shorter in the MSA-positive group than in the MSA-negative group (p = 0.027). In conclusion, our study is the first to measure anti-HMGCR antibodies with inflammatory myopathy, and identify new findings including the coexistence of other MSAs in Korean patients.

Background: Shoulder subluxation occurs in 17–64% of hemiplegic patients after stroke and develops mostly during the first three weeks of hemiplegia. A range of shoulder orthoses has been used in rehabilitation to prevent subluxation. However, there is little evidence of their efficacy. AIM: This study aimed to investigate whether there is a difference in the subluxation distance, pain, and functional level of the hemiplegic upper extremity among patients with two different shoulder orthoses. Design: This is a prospective, randomized controlled trial with intention-to-treat analysis. SETTING: Multicenter, rehabilitation medicine department of two university hospitals in South Korea. Population: Forty-one patients with subacute stroke with shoulder subluxation with greater than 0.5 finger width within 4 weeks of stroke were recruited between January 2016 and October 2021. Methods: The experimental group used an elastic dynamic sling while sitting and standing to support the affected arm for eight weeks. The control group used a Bobath sling while sitting and standing. The primary outcome was to assess the distance of the shoulder subluxation on radiography. The secondary outcomes were upper-extremity function, muscle power, activities of daily living, pain and spasticity. Result: The horizontal distance showed significant improvement in the elastic dynamic sling group, but there were no significant differences in the vertical distance between the elastic dynamic and Bobath sling groups. Both groups showed improvements in upper-extremity movements and independence in daily living after 4 and 8 weeks of using shoulder orthoses, and the differences within the groups were significant (p < 0.05). However, there were no significant differences in upper-extremity movements and independence in daily living between the two groups. Conclusions: The subluxation distance showed better results in the elastic dynamic sling, which has both proximal and distal parts, than in the Bobath sling, which holds only the proximal part. Both shoulder orthoses showed improvements in the modified Barthel index, upper-extremity function, and manual muscle testing.

Human-Biology Interaction (HBI) is a field that aims to provide first-hand experience with living matter and the modern life-sciences to the lay public. Advances in optical, bioengineering, and digital technologies as well as interaction design now also enable real and direct experiences at the microscale, such as with living cells and molecules, motivating the sub-field of “micro-HBI.” This is distinct from simulating any biological processes. There is a significant need for HBI as new educational modalities are required to enable all strata of society to become informed about new technologies and biology in general, as we face challenges like global pandemics, environmental loss, and species extinctions. Here we review this field in order to provide a jump-off point for future work and to bring stakeholder from different disciplines together. By now, the field has explored and demonstrated many such interactive systems, the use of different microorganisms, new interaction design principles, and versatile applications, such as museum exhibits, biotic games, educational cloud labs, citizen science platforms, and hands-on do-it-yourself (DIY) Bio maker activities. We close with key open questions for the field to move forward.

This paper explores the dynamics between globalization and local culture in analyzing how higher education (HE) has expanded in Qatar and the United Arab Emirates (UAE) through internationalization. It contends that HE expands through internationalization in part because these Arab Gulf states use higher education institutions (HEIs) to legitimate themselves and gain prominence as internationally competitive societies in a globalized world. At the same time, however, these Arab Gulf states face push back from their more conservative, traditional constituents who criticize the state for “Westernizing” education. Hence, these states simultaneously pursue anti-liberal practices in public HEIs to manage state–society relations, enabling them to maintain both national and global legitimacy. This effort to balance what appears to be two competing interests creates a “dual higher education system.”

Purpose We evaluate outcomes of our single center using vertical rectus abdominis myocutaneous (VRAM) flaps for reconstruction after abdominoperineal resection (APR). Our goal was to analyze factors that may affect perineal wound healing, a problematic complication with APR reconstructions due to location and high frequency of neoadjuvant chemoradiation. Methods This single-center, retrospective study analyzed all VRAM flap perineal reconstruction patients after APR defect over a 10-year period (from July 2008 to June 2018). Outcome measures focused on factors that may affect perineal wound healing complication rates: cancer stage (I/II vs III/IV), neoadjuvant chemoradiation, surgeon's years in practice ( 5 years), and pelvic closed suction drain use. Results Twenty-eight patients met inclusion criteria. The overall major perineal wound complication rate was 14.3% (4 patients). Lack of perioperative closed suction pelvic drain use was associated with a significantly higher rate of major perineal wound complications (28.6% vs 0% and p = 0.031). All four major wound complications occurred in patients who did not have a pelvic drain. The major perineal wound complication rate for patients who underwent neoadjuvant chemoradiation was 22% vs 0% with no neoadjuvant chemoradiation (p = 0.107). Conclusion While our cohort represents a relatively small single-center study, our 14.3% rate of major perineal wound complications is consistent with previous studies in the literature. Our findings show that perioperative pelvic closed suction drain use is associated with a lower rate of perineal wound complications. While neoadjuvant chemoradiation trended toward a higher incidence of perineal wound complications, it did not reach statistical significance.

The longitudinal effect of B12 insufficiency on sarcopenia has not yet been investigated in older adults. We aimed to study the impact of B12 levels on alterations in muscle mass, function and strength over two years. Non-sarcopenic older adults (n = 926) aged 70–84 were included. Using the Korean Frailty and Aging Cohort Study, this two-year longitudinal study used data across South Korea. The tools used for assessing muscle criteria were based on the Asian Working Group for Sarcopenia guidelines. Participants were divided into the insufficiency (initial serum B12 concentration < 350 pg/mL) and sufficiency groups (≥350 pg/mL). Logistic regression analyses were performed to evaluate the effect of initial B12 concentration on sarcopenia parameters over a two-year period. In women, multivariate analysis showed that the B12 insufficiency group had a significantly higher incidence of low SPPB scores (odds ratio [OR] = 3.28, 95% confidence interval [CI] = 1.59–6.76) and sarcopenia (OR = 3.72, 95% CI = 1.10–12.62). However, the B12 insufficiency group did not have a greater incidence of sarcopenia or other parameters in men. Our findings suggest B12 insufficiency negatively impacts physical performance and increases the incidence of sarcopenia only in women.

Background: In patients with breast cancer after Neoadjuvant Chemotherapy (NAC), pathological Complete Response (pCR) was associated with better long-term outcomes. We here attempted to predict pCR using machine learning. Patients and Methods: From 2008 to 2017, 1308 breast cancer patients underwent NAC before surgery, of whom 377 patients underwent Cancer SCANTM for gene data. Of 377, 238 were analyzed here, with 139 excluded due to incomplete medical data. Results: The pCR (-) vs. (+) group had 200 vs. 38 patients. In our predictive model with gene data, the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve was 0.909 and accuracy was 0.875. In another model without gene data, the AUC of ROC curve was 0.743 and accuracy was 0.800. We also conducted internal validation with 72 patients undergoing NAC and Cancer SCANTM during July 2017 and April 2018. When we applied a 0.4 threshold value, accuracy was 0.806 and 0.778 in the predictive model with vs. without gene profiles, respectively. Conclusion: The present predictive model may be a useful and easy-to-access tool for pCR-prediction in breast cancer patients treated with NAC.

ObjectivesPatients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery.MethodsThe retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery.ResultsDuring follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1–3) and two older groups (group 4–5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1–5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; pConclusionFive phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.

Pancreatic cancer is a devastating disease and is highly resistant to anticancer drugs because of its complex microenvironment. Cancer-associated fibroblasts (CAFs) are an important source of extracellular matrix (ECM) components, which alter the physical and chemical properties of pancreatic tissue, thus impairing effective intratumoral drug delivery and resulting in resistance to conventional chemotherapy. The objective of this study was to develop a new cancer organoid model, including a fibrous tumor microenvironment (TME) using CAFs. The CAF-integrated pancreatic cancer organoid (CIPCO) model developed in this study histologically mimicked human pancreatic cancer and included ECM production by CAFs. The cancer cell–CAF interaction in the CIPCO promoted epithelial–mesenchymal transition of cancer cells, which was reversed by CAF inhibition using all-trans retinoic acid. Deposition of newly synthesized collagen I in the CIPCO disturbed the delivery of gemcitabine to cancer cells, and treatment with collagenase increased the cytotoxic effect of gemcitabine. This model may lead to the development of next-generation cancer organoid models recapitulating the fibrous TME.

The accurate estimation of acute ischemic stroke (AIS) using diffusion-weighted imaging (DWI) is crucial for assessing patients and guiding treatment options. This study aimed to propose a method that estimates AIS volume in DWI objectively, quickly, and accurately. We used a dataset of DWI with AIS, including 2159 participants (1179 for internal validation and 980 for external validation) with various types of AIS. We constructed algorithms using 3D segmentation (direct estimation) and 2D segmentation (indirect estimation) and compared their performances with those annotated by neurologists. The proposed pretrained indirect model demonstrated higher segmentation performance than the direct model, with a sensitivity, specificity, F1-score, and Jaccard index of 75.0%, 77.9%, 76.0, and 62.1%, respectively, for internal validation, and 72.8%, 84.3%, 77.2, and 63.8%, respectively, for external validation. Volume estimation was more reliable for the indirect model, with 93.3% volume similarity (VS), 0.797 mean absolute error (MAE) for internal validation, VS of 89.2% and a MAE of 2.5% for external validation. These results suggest that the indirect model using 2D segmentation developed in this study can provide an accurate estimation of volume from DWI of AIS and may serve as a supporting tool to help physicians make crucial clinical decisions.

Background Obesity is a chronic disease that causes various medical health problems, increases morbidity, and reduces the quality of life. Obesity (especially central obesity) in older adults is expected to act with the development of sarcopenia. However, the relationship between obesity, central obesity, and sarcopenia remains controversial. This study aimed to investigate the impact of obesity on sarcopenia. Methods In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 1,827 community-dwelling older adults (883 men and 944 women) aged 70–84 years were recruited. The Asian Working Group for Sarcopenia (AWGS) criteria were used to evaluate sarcopenia. Subjects with a low appendicular skeletal muscle mass index (ASMI; men: 2, women: 2) and either low handgrip strength (HGS; men: 2, while central obesity was defined as WC measurements of ≥ 90 cm in men and ≥ 85 cm in women. Logistic regression analyses were performed to evaluate the impact of obesity and central obesity on sarcopenia and the parameters of sacropenia. Results In both sexes, the obese group, defined based on the BMI, had a significantly low prevalence of low ASMI (odds ratio [OR] = 0.14, 95% confidence interval CI = 0.10–0.20 in men, OR = 0.17, 95% CI = 0.12–0.25 in women) and sarcopenia (OR = 0.28, 95% CI = 0.16–0.50 in men, OR = 0.17, 95% CI = 0.08–0.35 in women) in the multivariable logistic regression analysis. In women, the central obese group had a low prevalence of sarcopenia (OR = 0.46, 95% CI = 0.27–0.77) in the multivariable logistic regression analysis. Meanwhile, the obese group had a significantly higher prevalence of low SPPB in women (OR = 1.75, 95% CI = 1.18–2.59). Conclusions Obesity may have a protective effect on low ASMI and sarcopenia, as defined by the AWGS criteria. Central obesity was associated with a low prevalence of sarcopenia in women only. However, obesity did not have a positive impact on functional parameters of sarcopenia including muscle strength and physical performance.

Halitosis is referred to as an unpleasant odor coming from the mouth. Recently, probiotics have been studied as an alternative prevention for halitosis. The aim of this study was to evaluate the ef...

BACKGROUND Hypertensive patients are at increased risk of diastolic dysfunction. The hypothesis of this study was that addition of amlodipine would be superior to valsartan in improving diastolic dysfunction associated with hypertension. METHODS In this randomized trial, we randomly assigned 104 controlled, hypertensive patients with diastolic dysfunction to receive either amlodipine 2.5 mg or valsartan 40 mg, in addition to antihypertensive therapy. The primary end point was the change in the ratio of early mitral inflow velocity to early mitral annular relaxation velocity (E/E') from baseline to the 6-month follow-up. Secondary end points included changes in systolic blood pressure (SBP), left ventricular (LV) mass index, and left atrial volume index. RESULTS SBP decreased significantly from baseline in both treatment groups (p < 0.001). E/E' decreased significantly from 13.0 ± 2.2 to 12.0 ± 2.7 in the amlodipine arm and from 14.4 ± 4.3 to 12.7 ± 3.7 in the valsartan arm (p < 0.01 in both groups). The change of E/E' was not significantly different between treatment groups (p = 0.25). There were also no significant between-group differences regarding the changes in SBP, LV mass index, and left atrial volume index. Two patients (3.8%) in the amlodipine group and 1 (16%) in the valsartan group had serious adverse event. CONCLUSIONS In this randomized trial involving controlled hypertensive patients, addition of amlodipine or valsartan was associated with an improvement of diastolic dysfunction, but the effects on diastolic dysfunction did not differ significantly between the treatment groups.

Background: Recently CDK4/6 inhibitors are being widely used to treat advanced HR-positive breast cancer. Despite promising clinical outcomes, almost all patients eventually acquire resistance to CDK4/6 inhibitors. Hence, understanding the mechanisms of acquired resistance to CDK4/6 inhibitors is crucial to develop alternate treatment strategy. Therefore, we screened genes associated with palbociclib resistance through genomics and transcriptomics in breast cancer preclinical models. Methods: We generated palbociclib-resistant cell lines, MCF7-PR and T47D-PR by exposing MCF7 and T47D cells to palbociclib for over 9 months. After confirming the acquired resistance through in vitro assays, we performed whole exome sequencing (WES) and mRNA microarray to compare genomic and transcriptomic landscape between palbociclib-sensitive and resistant cells. Real-time PCR was performed to confirm differentially expressed genes. Results: Microrray analysis revealed 651 differentially expressed genes (DEGs) (fold change ≥2) by comparing MCF7 vs. MCF7-PR cells. WES also revealed 107 mutated genes by comparing T47D vs. T47D-PR cells. Further, GO annotation of both the DEGs and mutated genes found deregulation of immune pathway commonly in MCF7-PR and T47D-PR (FDR Citation Format: Yong Wha Moon, Eunbyeol Lee, Sohyun Hwang, Kamal Pandey, Nahee Park, Jin Hur, Young Bin Cho, Seung Ki Kim, Seung Ah Lee, Hee-Jung An, Joohyuk Sohn. Deregulated immune pathway associated with palbociclib resistance in breast cancer preclinical models: Integrative analysis of genomics and transcriptomics [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-21-06.