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Background: The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA).Methods: Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody.Results: Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression.Conclusions: Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Sei Han Song,1 Seung Ho Choi,2 Hae Ri Park,1 Soo Yeon Jeon,1 Seung Hyun Kim2 1Department of Anesthesiology and Pain Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; 2Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, KoreaCorrespondence: Seung Hyun Kim, Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea, Tel +82-2-2224-1055, Fax +82-2-2227-7897, Email anesshkim@yuhs.acIntroduction: Anesthesiologists are exposed to the risk of infection from various secretions or droplets from the respiratory tract of patients. We aimed to determine bacterial exposure to anesthesiologists’ faces during endotracheal intubation and extubation.Methods: Six resident anesthesiologists performed 66 intubation and 66 extubation procedures in patients undergoing elective otorhinolaryngology surgeries. Sampling was performed by swabbing the face shields twice in an overlapping slalom pattern, before and after each procedure. Samples for pre-intubation and pre-extubation were collected immediately after wearing the face shield at the time of anesthesia induction and at the end of the surgery, respectively. Post-intubation samples were collected after the injection of anesthetic drugs, positive pressure mask ventilation, endotracheal intubation, and confirmation of intubation success. Post-extubation samples were collected after endotracheal tube suction, oral suction, extubation, and confirmation of spontaneous breathing and stable vital signs. All swabs were cultured for 48 h, and bacterial growth was confirmed by colony forming unit (CFU) count.Results: There was no bacterial growth in either pre- or post-intubation bacterial cultures. In contrast, while there was no bacterial growth in pre-extubation samples, 15.2% of post-extubation samples were CFU+ (0/66 [0%] vs 10/66 [15.2%], p=0.001). All the CFU+ samples belonged to 47 patients with post-extubation coughing, and the CFU count was correlated with the number of coughing episodes during the process of extubation (P < 0.01, correlation coefficient= 0.403).Conclusion: The current study shows the actual chance of bacterial exposure to the anesthesiologist’s face during the patient awakening process after general anesthesia. Given the correlation between the CFU count and the number of coughing episodes, we recommend anesthesiologists to use appropriate facial protection equipment during this procedure.Keywords: bacterial exposure, cough, extubation, face shield, intubation

Background A deep learning (DL) model to identify lung cancer screening candidates based on their chest radiographs requires external validation with a recent real-world non-U.S. sample. Purpose To validate the DL model and identify added benefits to the 2021 U.S. Preventive Services Task Force (USPSTF) recommendations in a health check-up sample. Materials and Methods This single-center retrospective study included consecutive current and former smokers aged 50-80 years who underwent chest radiography during a health check-up between January 2004 and June 2018. Discrimination performance, including receiver operating characteristic curve analysis and area under the receiver operating characteristic curve (AUC) calculation, of the model for incident lung cancers was evaluated. The added value of the model to the 2021 USPSTF recommendations was investigated for lung cancer inclusion rate, proportion of selected CT screening candidates, and positive predictive value (PPV). Results For model validation, a total of 19 488 individuals (mean age, 58 years ± 6 [SD]; 18 467 [95%] men) and the subset of USPSTF-eligible individuals (

Objectives: We introduced the cohort studies included in the Korean Cohort Consortium (KCC), focusing on large-scale cohort studies established in Korea with a prolonged follow-up period. Moreover, we also provided projections of the follow-up and estimates of the sample size that would be necessary for big-data analyses based on pooling established cohort studies, including population-based genomic studies.Methods: We mainly focused on the characteristics of individual cohort studies from the KCC. We developed “PROFAN”, a Shiny application for projecting the follow-up period to achieve a certain number of cases when pooling established cohort studies. As examples, we projected the follow-up periods for 5000 cases of gastric cancer, 2500 cases of prostate and breast cancer, and 500 cases of non-Hodgkin lymphoma. The sample sizes for sequencing-based analyses based on a 1:1 case-control study were also calculated.Results: The KCC consisted of 8 individual cohort studies, of which 3 were community-based and 5 were health screening-based cohorts. The population-based cohort studies were mainly organized by Korean government agencies and research institutes. The projected follow-up period was at least 10 years to achieve 5000 cases based on a cohort of 0.5 million participants. The mean of the minimum to maximum sample sizes for performing sequencing analyses was 5917-72 102.Conclusions: We propose an approach to establish a large-scale consortium based on the standardization and harmonization of existing cohort studies to obtain adequate statistical power with a sufficient sample size to analyze high-risk groups or rare cancer subtypes.

BackgroundIdentifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge.ObjectiveTo assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones.MethodsUsing data from the Parkinson’s Progression Markers Initiative (PPMI)de novoPD cohort, we monitored 25 milestones across six domains (“walking and balance”; “motor complications”; “cognition”; “autonomic dysfunction”; “functional dependence”; “activities of daily living”). Milestones were intended to be severe enough to reflect meaningful disability. We assessed the proportion of participants reaching any milestone; evaluated which occurred most frequently; and conducted a time-to-first-event analysis exploring whether baseline characteristics were associated with progression.ResultsHalf of participants reached at least one milestone within five years. Milestones within the cognitive, functional dependence, and autonomic dysfunction domains were reached most often. Among participants who reached a milestone at an annual follow-up visit and remained active in the study, 82% continued to meet criteria for any milestone at one or more subsequent annual visits and 55% did so at thenextannual visit. In multivariable analysis, baseline features predicting faster time to reaching a milestone included age (ppp=0.0341), lower dopamine transporter binding (p=0.0043), and lower CSF total α-synuclein levels (p=0.0033). Symptomatic treatment was not significantly associated with reaching a milestone (p=0.1639).ConclusionsClinically relevant milestones occur frequently, even in early PD. Milestones were significantly associated with baseline clinical and biological markers, but not with symptomatic treatment. Further studies are necessary to validate these results, further assess the stability of milestones, and explore translating them into an outcome measure suitable for observational and therapeutic studies.

Supplementary Figure Legends - PDF file 151K, Legend for Supplementary Figures S1-S6

Supplementary Figure S2 PDF - PDF file 414K, Activation of autophagy in AMC-HN-9 cells

Supplementary Figure Legends - PDF file 151K, Legend for Supplementary Figures S1-S6

Supplementary Figure S3 - PDF file 477K, Combinational treatment of mTOR inhibitor with radiation induces enhanced autophagy activation

Supplementary Methods - PDF file 168K, Additional experimental procedures, including western blot, RT-PCR, cell cycle analysis, etc. Also includes supplementary references

Supplementary Figure S6 - PDF file 499K, Inhibition of the mTOR pathway induces cellular senescence in irradiated U-87 cancer cells

Supplementary Figure S5 - PDF file 61K, Model of cellular senescence induction in human cancer cells

Supplementary Figure S4 - PDF file 302K, Suppression of autophagic flux decreases survival of radioresistant AMC-HN-9 cells

Supplementary Figure S1 - PDF file 214K, Clonogenic survival of cancer cell lines

SummaryBackgroundRecent research demonstrates that α-synuclein seed amplification assays (αSyn-SAA) accurately differentiate Parkinson’s disease (PD) patients from healthy controls (HC). We used the well-characterized, multicenter Parkinson’s Progression Markers Initiative (PPMI) cohort to further assess the diagnostic performance of αSyn-SAA and to examine whether the assay identifies heterogeneity among patients and enables early identification in at-risk groups.MethodsαSyn-SAA analysis of cerebrospinal fluid (CSF) was performed using previously described methods. We assessed sensitivity and specificity in PD and HC, including subgroups based on genetic and clinical features. We determined the frequency of positive αSyn-SAA results in prodromal participants (REM sleep behavior disorder and hyposmia) and non-manifesting carriers (NMCs) of genetic variants associated with PD and compared αSyn-SAA to clinical measures and other biomarkers.Findings1,123 participants were included: 545 PD, 163 HCs, 54 participants with scans without evidence of dopaminergic deficit (SWEDDs), 51 prodromal participants, and 310 NMCs. Sensitivity and specificity for PD versus HC were 88% and 96%, respectively. Sensitivity in sporadic PD with the typical olfactory deficit was 99%. The proportion of positive αSyn-SAA was lower in subgroups including LRRK2 PD (68%) and sporadic PD patients without olfactory deficit (78%). Participants with LRRK2 variant and normal olfaction had an even lower αSyn-SAA positivity rate (35%). Among prodromal and at-risk groups, 86% of RBD and hyposmic cases had positive αSyn-SAA. 8% of NMC (either LRRK2 or GBA) were positive.InterpretationThis study represents the largest analysis of αSyn-SAA for biochemical diagnosis of PD. Our results demonstrate that the assay classifies PD patients with high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals prior to diagnosis. These findings suggest a crucial role for αSyn-SAA in therapeutic development, both to identify pathologically defined subgroups of PD patients and to establish biomarker-defined at-risk cohorts.FundingPPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including: PPMI is supported by a consortium of private and philanthropic parnters: Abbvie, AcureX, Aligning Science Across Parkinson’s, Amathus Therapeutics, Avid Radiopharmaceuticals, Bial Biotech, Biohaven, Biogen, BioLegend, Bristol-Myers Squibb, Calico Labs, Celgene, Cerevel, Coave, DaCapo Brainscience, 4D Pharma, Denali, Edmond J. Safra Foundation, Eli Lilly, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, VanquaBio, Verily, Voyager Therapeutics, and Yumanity.Research in ContextEvidence before the studyWe searched PubMed with the terms Parkinson’s disease (PD), prodromal, Non-manifest carriers, GBA, LRRK2 and real-me quaking-induced conversion (RT-QuIC), protein misfolding cyclic amplification (PMCA), and seed amplification assay (SAA) for articles published in English on or before Oct 25, 2022, in any field. This is a large and rapidly growing literature, and a number of studies were identified, including case-series of PD patients with and without genetic variants, individuals with isolated REM sleep behavior disorder (RBD), and a small number of studies of non-manifesting carriers of genetic variants (4) associated with PD.Added value of the studyTo our knowledge, this is the largest report of comparative data from a cohort of PD patients, healthy controls, individuals with clinical syndromes prodromal to PD (hyposmia and RBD), and non-manifest carriers ofLRRK2 G2019SandGBA N370Smutations. The strengths of our data include a large sample size, robust clinical data set, a high percentage of DAT scans completed, and the ability to compare non-manifest carriers to similar aged healthy controls, which allows for inter-group comparisons and sub-group analysis. The key novel findings in this study include: 1) marked variability in rates of positive αSyn-SAA results particularly among LRRK2 variant carriers depending on olfactory performance and sex; 2) αSyn-SAA positivity in prodromal and NMCs without dopaminergic imaging abnormalities in a substantial number of cases, while the converse is less common, indicating that αSyn-SAA may be a very early indicator of synucleinopathy. We also confirmed the high diagnostic accuracy of αSyn-SAA for sporadic PD vs. HC and that αSyn-SAA is negative in the vast majority of NMC, suggesting that the presence of synuclein aggregates in CSF is not a life-long trait but rather acquired at some point relatively close to disease onset.Implications of all available evidenceOur results demonstrate that the assay classifies PD patients with high sensitivity and specificity, provides information about molecular heterogeneity, and detects prodromal individuals prior to diagnosis. These findings suggest a crucial role for αSyn-SAA in therapeutic development, both to identify pathologically defined subgroups of PD patients and to establish biomarker-defined at-risk cohorts.

A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear.This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung function decline rates were classified as "slow" and "accelerated" and compared among four different sonographic changes in steatosis status: "normal," "improved," "worsened," and "persistent." A genome-wide association study was conducted between the two groups: normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function.Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEVRegression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.

Injection laryngoplasty (IL) is performed to reduce the gap between vocal folds induced by unilateral vocal fold paralysis (UVFP). Voice quality after IL may be different due to other factors that influence voice quality. Voice therapy has been reported to improve voice quality after IL in patients with UVFP. This study evaluated the efficacy of voice therapy combined with IL.Patients with UVFP who underwent IL as primary therapy from March 2017 to June 2019 were evaluated. The enrolled patients were divided into two groups, those who did and did not receive voice therapy after IL. Voice quality was evaluated using perceptual, acoustic, and aerodynamic parameters, and voice handicap index-30 scores one month after IL and after completing each treatment.Of 261 patients who underwent IL during the study period, 40 were enrolled, including 21 who did and 19 who did not receive voice therapy. Voice parameters one month after IL did not differ between these two groups. Jitter, shimmer, noise-to-harmonic ratio, and mean flow rate decreased, while maximum phonation time increased after voice therapy (both P0.05). In the absence of voice therapy, improved voice parameters were maintained for six months after IL. Total voice handicap index-30 scores decreased, from 35.6 to 19.1 (P0.05), in patients who received voice therapy.Voice therapy following IL is beneficial to patients with UVFP. Combined treatment can help to maintain improved voice quality more than six months after IL.

Moyamoya disease, a rare chronic cerebrovascular disease with a fragile vascular network at the base of the brain, can cause ischemic or hemorrhagic strokes or seizures. Precise blood pressure control and adequate analgesia are important for patients with moyamoya disease to prevent neurological events such as ischemia and hemorrhage. This study aimed to compare the intraoperative mean arterial pressure of pregnant women with moyamoya disease according to the mode of anesthesia (general anesthesia versus spinal anesthesia) used during cesarean delivery.We retrospectively reviewed the medical records of 87 cesarean deliveries in 74 patients who had been diagnosed with moyamoya disease before cesarean delivery. The primary outcome, intraoperative maximum mean arterial pressure during anesthesia, was compared according to the type of anesthesia administered (general versus spinal anesthesia). Other perioperative hemodynamic data (lowest mean arterial pressure, incidence of hypotension, vasopressor use, and antihypertensive agent use), maternal neurologic symptoms, neonatal outcomes (Apgar scores7, ventilatory support, and intensive care unit admission), maternal and neonatal length of stay, postoperative pain scores, and rescue analgesic use were assessed as secondary outcomes.While the lowest blood pressure during anesthesia and incidence of hypotension did not differ between the 2 groups, the maximum mean arterial pressure during anesthesia was lower in the spinal anesthesia group than that in the general anesthesia group (104.8 ± 2.5 vs 122.0 ± 4.6; P = .002). Study data did not support the claim that maternal neurologic symptoms differ according to the type of anesthesia used (5.6% vs 9.3%; P = .628); all patients recovered without any sequelae. The postoperative pain scores were lower, and fewer rescue analgesics were used in the spinal anesthesia group than in the general anesthesia group. Other maternal and neonatal outcomes were not different between the 2 groups.Compared with general anesthesia, spinal anesthesia mitigated the maximum arterial blood pressure during cesarean delivery and improved postoperative pain in patients with moyamoya disease.

Regular safety inspections of existing reinforced concrete (RC) structures are required according to the regulations and criteria set by each country. In South Korea, the safety inspection regulations provided by the Korea Infrastructure Safety and Technology Corporation (KISTEC) are followed. These regulations were developed based on fuzzy theory to avoid subjective decisions, and provide standardized deterioration grades for member types, floors, and the entire structure. However, the safety inspection regulation by the KISTEC often provides unconservative evaluation results. In particular, as the importance factors of beam and slab members are set lower than those of other members, there are cases in which deteriorations occurring in beams and slabs are not properly reflected in the floor level evaluation. In this study, to overcome such limitations, case studies were carried out and modified importance factors for structural member types were proposed considering the failure probabilities of each member type based on the reliability theory. The importance modification factor was calculated based on the strength ratio of structural members so that the more dangerous the members are, the more impact they give on the evaluation. Overall, compared to the KISTEC method, the proposed method provided conservative but practical assessment results, and it was found that the proposed importance factors can be very useful to properly reflect the effects of damaged members on the deterioration status evaluation of the floors and the entire structure.

Background/Objectives: Shoulder function is an important aspect of health related quality of life (QOL). Neck dissection impairment index (NDII) is a simple shoulder-specific questionnaire. This study aimed to evaluate the association between QOL and NDII in patients who underwent neck dissection to validate the Korean version of NDII.Materials & Methods: This study enrolled 74 patients with head and neck cancer who underwent neck dissection from December 2013 to April 2014. Patients completed questionnaires on QOL including the European Organization of Research and Treatment of Cancer 30-item Core QOL questionnaire (EORTC QLQ-C30) and NDII which was translated into Korean. Validity was evaluated by calculating the Pearson correlation coefficient between NDII and EORTC QLQ-C30.Results: We compared preoperative, postoperative within a week, 1st and 3rd months NDII scores. The total NDII scores were 14.7, 47.4, 33.7 and 34.3 each. Clinical variables including gender, site of primary tumor, performing revision neck dissection, radiotherapy and flap reconstruction were not significantly associated with NDII. However NDII mean score of patients who underwent unilateral neck dissection over 3 levels is most increased after operation. During all periods NDII scores were significantly associated with functioning score. Although other scores are lower correlation than function scores, global health status scores and symptom scores are also correlation with NDII.Conclusion: NDII was valid instrument and can be used not only in the clinical practice to assess shoulder dysfunction but also in the simple instrument to evaluate global QOL in Korea patients with having neck dissection.

The prevalence and intensity of Opisthorchis viverrini metacercariae (OvMc) were investigated in fish from 3 southern administrative regions along the Mekong River in Cambodia, i.e., Phnom Penh, Takeo, and Kandal Provinces from 2017 to 2020. A total of 295 freshwater fish (24 species) were transported to our laboratory with ice and examined using the artificial digestion method. In Phnom Penh, among 4 fish species positive for OvMc, 9 (23.7%) of 38 specimens examined were infected, and their intensity of infection averaged 4.3 metacercariae per infected fish. In Takeo Province, among 10 fish species positive for OvMc, 24 (38.1%) out of 63 fish examined were infected, and their intensity of infection was av. 14.4 metacercariae per infected fish. In particular, all of 3 Osteochilus schlegelii fish examined were infected, and their infection intensity was high, 34.7 metacercariae per fish. In Kandal Province, among 6 fish species positive for OvMc, 46 (90.2%) out of 51 specimens examined were infected, and their infection intensity was 24.0 metacercaraie per infected fish. All fish of Systomus orphoides (n=17), Barbonymus altus (n=14), and Rasbora aurotaenia (n=2) were infected, and their intensity of infection averaged 37.7, 21.6, and 18.5 metacercariae per fish, respectively. Metacercariae of Haplochis yokogawai, Haplorchis taichui, and Centrocestus formosanus were detected in fish from Takeo and Kandal Provinces. From these results, it has been confirmed that a variety of fish species from Phnom Penh, Takeo, and Kandal Provinces are commonly infected with OvMc, and preventive measures to avoid human O. viverrini infection should be performed in Cambodia.

In this study, experiments were carried out to evaluate the seismic performance of a hybrid prestressed precast concrete (HPPC) system devised to ensure the integrity of precast concrete (PC) beam-column joints by introducing the post-tensioning method. A total of four full-scale HPPC beam-column joints were fabricated, and the presence of a topping slab, a post-tensioned length, and a type of tendon were set as the main variables. The quasi-static cyclic loading tests were performed to analyze the load-story drift ratio response, failure mode, ductility, residual deformation, and energy dissipation capacity of each specimen. The seismic performance of the specimen was then quantitatively evaluated based on the acceptance criteria of the ACI 374 report. The shear strength estimation model for the HPPC beam-column joints was also proposed and the proposed model was verified in detail using the test results.

Background and Objectives Scalp angiosarcoma is a rare but aggressive vascular malignancy. It is often found in the advanced state and tends to cause distant metastasis at an early stage. There is no consensus on a treatment modality, although wide excision followed by adjuvant therapy is currently used. The purpose of this study was to analyze the treatment results and disease progress pattern of scalp angiosarcoma in a single institution.Subjects and Method We enrolled patients who diagnosed with scalp angiosarcoma at Asan Medical Center from March 2011 to September 2019. Disease course and prognostic factors were analyzed by estimating overall survival rate and disease free survival.Results A total 12 patients were enrolled in this study. The median overall survival was 16.0 months. The 3-year-survival rate was 10.6%, and the median disease free survival was 5.0 months. On the average, it took 11.4 months till death after recurrence.Conclusion Although wide surgical excision and multiple adjuvant therapies are employed, scalp angiosarcoma showed frequent recurrences and metastasis which led to poor outcomes. Further investigations for scalp angiosarcoma are necessary to improve treatment outcomes.

We present theoretical and experimental results to obtain an intuitive understanding of bulk modulus of metamaterials composed of Helmholtz resonators (HR). Using transmission line theory, we introduce an intuitive method to determine the frequency domain in which the negative bulk modulus appears. The results obtained by simulations and experiments are consistent with theoretical results found using transmission line theory. The results suggest that wider negative (BNG) areas of bulk modulus can be obtained using two HRs than one HR of the same total cavity volume.

Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6 474 (1 484 cases and 4 990 controls) and 1 654 (557 cases and 1 097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10− 8; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15–1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1 757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (15 771 cases and 178 777 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms.

Bond–slip is an important characteristic that determines the stiffness, displacement, and load-bearing capacity of a reinforced concrete (RC) beam. It is essential for performing a precise numerical analysis of the beam. In most cases, bond–slip models can define the bond–slip curve only when there are experimental data. However, many bond test data have been obtained from pull-out tests, and the dominant view is that the bond–slip behavior observed in the pull-out test is quite different from that in an actual RC beam. Therefore, a mapping function that makes it possible to estimate the bond–slip behaviors of beam specimens using those of pull-out specimens was developed in this study. A total of 255 pull-out specimen data and 75 beam specimen data were collected from previous studies, and the importance and influence of each feature of the two groups were analyzed using random forest and K-means clustering. The mapping function was derived using genetic programming, and its accuracy was verified through a comparison with existing models. The proposed model exhibits a high degree of accuracy in estimating bond–slip and bond strength in beam specimens and can provide useful information for understanding the difference in bond–slip behaviors between the two groups.

Vocal cord paralysis caused by recurrent laryngeal nerve (RLN) injury during thyroidectomy results in hoarseness, aspiration, and dyspnea. We evaluated the usefulness of nerve guidance conduits (NGCs) constructed from an asymmetric polycaprolactone (PCL)/Pluronic F127 porous membrane and filled with platelet-rich plasma (PRP) for functional RLN regeneration. We evaluated the proliferation and migration of Schwann cells (SCs) after PRP treatment in vitro. For the in vivo study, rabbits were divided into a non-loaded NGC group and a PRP-loaded NGC group. The left RLNs were resected and interposed with the NGCs. Functional and histological examinations of the vocal cords were performed. SC proliferation and migration increased in a PRP dose-dependent manner, with the PRP increasing the levels of neurotrophic factors, myelin-associated glycoprotein, and ERK. In vivo, the PRP group showed significantly better vocal cord mobility and less vocalis muscle atrophy than the non-loaded NGC group. Histologically, the ingrowth of nerve endings occurred more rapidly in the PRP group, and acetylcholinesterase, neurofilament, and S-100 expression in neural endings were significantly higher in the PRP group. Furthermore, transmission electron microscopy showed that myelinated axons were more tightly packed in the PRP group. This study shows that PRP-loaded NGCs provide a favorable environment for neural regeneration and suggests that this technique has therapeutic potential for promoting RLN recovery.

In this study, three-dimensional K - E turbulence numerical simulations were conducted to analyze the extent of hazardous area for the sonic jet leakage of flammable gas. Incompressible fluid flows were simulated based on an inlet boundary condition estimated using the theory of “equivalent leak diameter” to prevent the direct simulation of sonic flows near the leakage hole. Numerical simulations of 20 methane leakage scenarios providing the lower explosive limit contour showed shapes of the hazardous area with a maximum height of approximately 12-14 times larger than the maximum width, owing to convection. The extents of hazardous area determined using computational fluid dynamics (CFD) were approximately 5%-10% lower than the results obtained with 1 m over based on IEC 60079-10-1. For scenarios in which quantitative data were not calculated using IEC 60079-10-1 due to low release rates, CFD provided quantitative data for the extent of hazardous area, showing nonlinear relationships with the pressure and diameter of leak holes.

Suppressor of cytokine signaling (SOCS) proteins are primarily feedback inhibitors of cytokine signaling. The two conserved domains of SOCS proteins have distinct functions. Src homology 2 (SH2) domain inhibits cytokine receptor, while SOCS box acts as an E3 ubiquitin ligase. SOCS2, a cytokine signaling suppressor, has been primarily implicated in regulating inflammatory conditions in neuronal diseases. However, SOCS proteins have been suggested to play diverse roles in healthy and diseased nervous system including neurodegenerative disorders. In this study, SOCS2 was found to be upregulated in Huntington's disease and was substantially induced in extended polyglutamine (polyQ)-expressing striatal cells. The induced level was augmented under aging conditions. In extended polyQ-expressing cells, downregulated SOCS2 improved autophagic dysfunction rather than altered inflammatory conditions. Overall, we suggest that SOCS2 involves in regulating autophagy by functioning as an E3 ligase in extended polyQ conditions, and consequently regulates cell damage and cell death type.

All-solid-state batteries (ASSBs) that employ anode-less electrodes have drawn attention from across the battery community because they offer competitive energy densities and a markedly improved cycle life. Nevertheless, the composite matrices of anode-less electrodes impose a substantial barrier for lithium-ion diffusion and inhibit operation at room temperature. To overcome this drawback, here, the conversion reaction of metal fluorides is exploited because metallic nanodomains formed during this reaction induce an alloying reaction with lithium ions for uniform and sustainable lithium (de)plating. Lithium fluoride (LiF), another product of the conversion reaction, prevents the agglomeration of the metallic nanodomains and also protects the electrode from fatal lithium dendrite growth. A systematic analysis identifies silver (I) fluoride (AgF) as the most suitable metal fluoride because the silver nanodomains can accommodate the solid-solution mechanism with a low nucleation overpotential. AgF-based full cells attain reliable cycling at 25 °C even with an exceptionally high areal capacity of 9.7 mAh cm

BackgroundClonal hematopoiesis of indeterminate potential (CHIP), defined as a clonal expansion of hematopoietic stem cells with age-related recurrent somatic mutations, has recently emerged as a novel cardiovascular risk factor. However, the pathogenic mechanism of CHIP in atherosclerotic cardiovascular disease (ASCVD) development is not yet fully understood.MethodsIn a cohort comprising 4,300 asymptomatic Korean participants aged 40–79 years, we investigated the risks associated with ASCVD by CHIP and the interplay of CHIP with other traditional risk factors for developing ASCVD. Using coronary computed tomography angiography (CCTA), we noninvasively assessed the changes in coronary arteries to evaluate CHIP-associated atherosclerosis.ResultsCHIP was present in 368 participants (8.6%). The most commonly mutated genes in CHIP included DNMT3A, TET2, and ASXL1. During follow-up (median, 4.7 years), 18 ASCVD cases (4.9%) were observed in CHIP carriers vs. 62 (1.6%) in non-carriers (pppS-index, 4.61; 95% CI 1.04–20.57, p=0.045). Serial CCTAs supported our findings by displaying de novo measurable coronary atherosclerosis with unstable plaque and in proximal lesions only in CHIP carriers with high LDL cholesterol.ConclusionThe presence of CHIP was significantly associated with the risk of ASCVD through synergy with LDL cholesterol in the general population, which might promote the early stage of coronary atherosclerosis.

As surface-enhanced Raman scattering (SERS) has been used to diagnose several respiratory viruses (e.g., influenza A virus subtypes such as H1N1 and the new coronavirus SARS-CoV-2), SERS is gaining popularity as a method for diagnosing viruses at the point-of-care. Although the prior and quick diagnosis of respiratory viruses is critical in the outbreak of infectious disease, ELISA, PCR, and RT-PCR have been used to detect respiratory viruses for pandemic control that are limited for point-of-care testing. SERS provides quantitative data with high specificity and sensitivity in a real-time, label-free, and multiplex manner recognizing molecular fingerprints. Recently, the design of Raman spectroscopy system was simplified from a complicated design to a small and easily accessible form that enables point-of-care testing. We review the optical design (e.g., laser wavelength/power and detectors) of commercialized and customized handheld Raman instruments. As respiratory viruses have prominent risk on the pandemic, we review the applications of handheld Raman devices for detecting respiratory viruses. By instrumentation and commercialization advancements, the advent of the portable SERS device creates a fast, accurate, practical, and cost-effective analytical method for virus detection, and would continue to attract more attention in point-of-care testing.

OBJECTIVES/HYPOTHESIS There may be an interobserver variation in the diagnosis of laryngeal disease based on laryngoscopic images according to clinical experience. Therefore, this study is aimed to perform computer-assisted diagnosis for common laryngeal diseases using deep learning-based disease classification models. STUDY DESIGN Experimental study with retrospective data METHODS: A total of 4106 images (cysts, nodules, polyps, leukoplakia, papillomas, Reinke's edema, granulomas, palsies, and normal cases) were analyzed. After equal distribution of diseases into ninefolds, stratified eightfold cross-validation was performed for training, validation process and remaining onefold was used as a test dataset. A trained model was applied to test sets, and model performance was assessed for precision (positive predictive value), recall (sensitivity), accuracy, F1 score, precision-recall (PR) curve, and PR-area under the receiver operating characteristic curve (PR-AUC). Outcomes were compared to those of visual assessments by four trainees. RESULTS The trained deep neural networks (DNNs) outperformed trainees' visual assessments in discriminating cysts, granulomas, nodules, normal cases, palsies, papillomas, and polyps according to the PR-AUC and F1 score. The lowest F1 score and PR-AUC of DNNs were estimated for Reinke's edema (0.720, 0.800) and nodules (0.730, 0.780) but were comparable to the mean of the two trainees' F1 score with the best performances (0.765 and 0.675, respectively). In discriminating papillomas, the F1 score was much higher for DNNs (0.870) than for trainees (0.685). Overall, DNNs outperformed all trainees (micro-average PR-AUC = 0.95; macro-average PR-AUC = 0.91). CONCLUSIONS DNN technology could be applied to laryngoscopy to supplement clinical assessment of examiners by providing additional diagnostic clues and having a role as a reference of diagnosis. LEVEL OF EVIDENCE 3 Laryngoscope, 131:2558-2566, 2021.

In a post-tensioned precast concrete beam–column connection, the precast beams are post-tensioned to ensure the integrity of the connection and to provide recentring characteristics when the connection is subjected to seismic loads. In this study, the post-tensioned precast concrete beam–column connections were tested under reverse-cyclic loading with the test variables of grout strength at the beam–column interface and prestressing stress of stands. The test results showed that the post-tensioned precast concrete beam–column connections have a seismic performance equivalent to that of a conventional reinforced concrete beam–column connection. When high prestress is applied, however, confinement reinforcement is required at the beam ends to secure sufficient deformation capacity without crushing of concrete. An analysis model for post-tensioned precast concrete beam–column connections is also proposed; the model considers the bond properties of prestressing strands, and provides good agreement with the experimental results.

Pulse oximetry is a non-invasive method for measuring blood oxygen saturation. However, its detection scheme heavily relies on single-point measurements. If the oxygen saturation is measured at a single location, the measurements are influenced by the profile of illumination, spatial variations in blood flow, and skin pigment. To overcome these issues, imaging systems that measure the distribution of oxygen saturation have been demonstrated. However, previous imaging systems have relied on red and near-infrared illuminations with different profiles, resulting in inconsistent ratios between transmitted red and near-infrared light over space. Such inconsistent ratios can introduce fundamental errors when calculating the spatial distribution of oxygen saturation. In this study, we developed a novel illumination system specifically designed for a pulse oximetry imaging system. For the illumination system, we customized the integrating sphere by coating a mixture of barium sulfate and white paint inside it and by coupling eight red and eight near-infrared LEDs. The illumination system created identical patterns of red and near-infrared illuminations that were spatially uniform. This allowed the ratio between transmitted red and near-infrared light to be consistent over space, enabling the calculation of the spatial distribution of oxygen saturation. We believe our developed pulse oximetry imaging system can be used to obtain spatial information on blood oxygen saturation that provides insight into the oxygenation of the blood contained within the peripheral region of the tissue.

Actinic keratosis is a premalignant skin lesion that develops into non-melanoma skin cancer. Various imaging techniques have been developed to find the actinic keratosis lesion. In this clinical study, the feasibility of a nonspectroscopic fluorescence imaging system is investigated for spatial assessment of the actinic keratosis lesion. Six patients between the ages of 70 and 80 years old are diagnosed with actinic keratosis by a board-certified dermatologist to obtain biopsy-proven clinical images. The patients were treated with 5-aminolevulinic acid, which is transformed into the protoporphyrin IX. After illuminating ultraviolet-A light on facial lesions, the protoporphyrin IX produces the exogenous fluorescence. The fluorescence is measured using both a hyperspectral camera and an RGB color camera to obtain spectroscopic and nonspectroscopic fluorescence images, respectively. It is found that fluorescence intensity of the actinic keratosis lesion is higher than that of normal skin. Based on combined fluorescence and physiological characteristics, the actinic keratosis lesion is distinguished from the adjacent normal skin area. For delineation of the actinic keratosis lesion, a linear unmixing algorithm is applied to spectroscopic image data and an erythema index is calculated from nonspectroscopic image data. Then, two extracted actinic keratosis lesions are compared for cross-validation. As a result, both spectroscopic and nonspectroscopic fluorescence images demarcate an identical lesion of actinic keratosis. Given the affordability and simplicity, an RGB camera and a 5-ALA photosensitizer can be used as a cost-effective nonspectroscopic imaging modality for accurate assessment of actinic keratosis margins.

Recently, more than 10 models have been developed to predict remission of type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of prediction of T2DM remission, but which of the two scoring systems is better remains controversial. Patient data from 463 obese East Asian patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or SG with duodenojejunal bypass (SG-DJB) as a primary operation and were followed for at least 3 years were retrospectively collected from 24 institutions. The correlation between the ABCD and IMS scoring systems and the discrimination power of the models was evaluated. The cut-off point for the IMS stage of T2DM severity was also revised to adjust the scoring system to obese East Asian patients. The two scoring systems were significantly well correlated. The IMS scoring system showed significant differences in T2DM remission rates between the procedures in the moderate stage, but the ABCD score showed no significant differences in each category. The discrimination power of the IMS score was comparable to that of the ABCD score at both 3 and 5 years. The revised IMS scoring system showed that SG-DJB had significantly higher T2DM remission rates in the moderate stage at 5 years than RYGB or SG. IMS score may be comparable to ABCD score to predict T2DM remission in obese East Asian patients. The revised IMS scoring system may also select candidates for SG or SG-DJB.

Introduction Sarcopenia may result in negative outcomes in patients with cancer, but its impact on surgical and oncological outcomes in older adult patients with head and neck squamous cell carcinoma (HNSCC) has not been systematically studied. This study evaluated the clinical impact of sarcopenia on postsurgical and oncological outcomes in older adult patients with HNSCC. Methods This is a prospective study of 190 consecutive HNSCC patients aged ≥65 years who underwent curative surgery at a tertiary referral hospital. Sarcopenia was determined from measurement of the cross-sectional area of skeletal muscles at the level of the third lumbar vertebra on pretreatment images of whole body 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Primary outcomes were early complications and overall survival. Factors of early complications and readmission were identified using binary logistic regression analyses, and factors of overall survival and disease-free survival were identified using univariate and multivariate Cox proportional hazards regression analyses. Results Pretreatment sarcopenia were found in 64 (33.7%) patients. In multivariate analysis, sarcopenia and N classification were significantly associated with early complications, while sarcopenia and T classification were associated with readmission. Independent factors of overall survival outcomes were age, sarcopenia, and extranodal extension (all P Conclusion Sarcopenia may predict early complications and survival after curative surgery in older adult patients with HNSCC.

ObjectivePostoperative delirium is known to have various adverse effects on head and neck surgery patients. This study was designed to identify possible risk factors of delirium following long periods of head and neck cancer surgery and to help prevent postoperative delirium.MethodsWe enrolled 197 patients who underwent long-time (>6 h) head and neck surgery at the Asan Medical Center from January 2017 to December 2018 in this study. Clinical covariates that may be associated with delirium were analyzed retrospectively using univariate and multivariate analyses.ResultsDelirium occurred in 18 patients (9.1%). Within the first 7 days, 16 patients (88.9%) experienced delirium. Upon univariate analysis, delirium was associated with old age (≥75, p = 0.001), past neurological history (p = 0.019), time to ambulation (p = 0.014), and postoperative hospital day (p = 0.048). In multivariate analysis, old age (≥75, odds ratios (OR) 6.16, CI 2.00–19.00, p = 0.002), time to ambulation (OR 1.04, CI 1.01–1.07, p = 0.017), and past neurological history (OR 5.26, CI 1.09–25.37, p = 0.039) were significant risk factors associated with postoperative delirium.ConclusionsOlder patients or patients with neurologic history must be attended with care, especially early after surgery. Encouraging early ambulation might lower the incidence of postoperative delirium and, subsequently, reduce adverse effects. This result could benefit patients by helping them avoid undesirable outcomes.