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Background: Total hip arthroplasty (THA) done in the aging population is associated with osteoporosis-related complications. The altered bone density in osteoporotic patients is a risk factor for revision surgery. This study aimed to develop and validate machine learning (ML) models to predict revision surgery in patients with osteoporosis after primary noncemented THA., Methods: We retrospectively reviewed a consecutive series of 350 patients with osteoporosis (T-score less than or equal to -2.5) who underwent primary noncemented THA at a tertiary referral center. All patients had a minimum 2-year follow-up (range: 2.1 to 5.6). Four ML algorithms were developed to predict the probability of revision surgery, and these were assessed by discrimination, calibration, and decision curve analysis., Results: The overall incidence of revision surgery was 5.2% at a mean follow-up of 3.7 years after primary noncemented THA in osteoporotic patients. Revision THA was done because of periprosthetic fracture in nine patients (50%), aseptic loosening/subsidence in five patients (28%), periprosthetic joint infection in two patients (11%) and dislocation in two patients (11%). The strongest predictors for revision surgery in patients after primary noncemented THA were female sex, BMI (>35 kg/m2), age (>70 years), American Society of Anesthesiology score (≥3), and T-score. All four ML models demonstrated good model performance across discrimination (AUC range: 0.78 to 0.81), calibration, and decision curve analysis., Conclusion: The ML models presented in this study demonstrated high accuracy for the prediction of revision surgery in osteoporotic patients after primary noncemented THA. The presented ML models have the potential to be used by orthopaedic surgeons for preoperative patient counseling and optimization to improve the outcomes of primary noncemented THA in osteoporotic patients., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Suicide is a leading cause of death worldwide, presenting a serious public health problem. We aimed to investigate the biological basis of suicide completion using proteomics on postmortem brain tissue. Thirty-six postmortem brain samples (23 suicide completers and 13 controls) were collected. We evaluated the proteomic profile in the prefrontal cortex (Broadmann area 9, 10) using tandem mass tag-based quantification with liquid chromatography-tandem mass spectrometry. Bioinformatics tools were used to elucidate the biological mechanisms related to suicide. Subgroup analysis was conducted to identify common differentially expressed proteins among clinically different groups. Of 9801 proteins identified, 295 were differentially expressed between groups. Suicide completion samples were mostly enriched in the endocannabinoid and apoptotic pathways (CAPNS1, CSNK2B, PTP4A2). Among the differentially expressed proteins, GSTT1 was identified as a potential biomarker among suicide completers with psychiatric disorders. Our findings suggest that the previously under-recognized endocannabinoid system and apoptotic processes are highly involved in suicide., (© 2022. The Author(s).)

Background: Highly sensitive and accurate malaria diagnostic tools are essential to identify asymptomatic low parasitaemia infections. This study evaluated the performance of histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (RDTs), microscopy and loop-mediated isothermal amplification (LAMP) for the detection of asymptomatic Plasmodium spp. infections in Northern Côte d'Ivoire, using nested polymerase chain reaction (nPCR) as reference., Methods: A household-based survey was carried out in July 2016, in the health district of Korhogo, involving 1011 adults without malaria symptom nor history of fever during the week before recruitment. The fresh capillary blood samples were collected to detect Plasmodium infections using on HRP-2-based RDTs, microscopy and LAMP and stored as dried blood spots (DBS). A subset of the DBS (247/1011, 24.4%) was randomly selected for nPCR analyses. Additionally, venous blood samples, according to LAMP result (45 LAMP positive and 65 LAMP negative) were collected among the included participants to perform the nested PCR used as the reference., Results: The prevalence of asymptomatic Plasmodium spp. infections determined by RDT, microscopy, and LAMP were 4% (95% confidence interval (CI) 2.8-5.3), 5.2% (95% CI 3.9-6.6) and 18.8% (95% CI 16.4-21.2), respectively. Considering PCR on venous blood as reference, performed on 110 samples, the sensibility and specificity were, respectively, 17.8% (95% CI 6.1-29.4) and 100% for RDT, 20.0% (95% CI 7.8-32) and 100% for microscopy, and 93.3% (95% CI 85.7-100) and 95.4% (95% CI 92.2-100) for LAMP., Conclusion: In Northern Côte d'Ivoire, asymptomatic Plasmodium infection was found to be widely distributed as approximately one out of five study participants was found to be Plasmodium infected. LAMP appears currently to be the only available diagnostic method that can identify in the field this reservoir of infections and should be the method to consider for potential future active case detection interventions targeting elimination of these infections., (© 2022. The Author(s).)

Alzheimer disease (AD) is a leading cause of dementia that has gained prominence in our aging society. Yet, the complexity of diagnosing AD and measuring its invasiveness poses an obstacle. To this end, blood-based biomarkers could mitigate the inconveniences that impede an accurate diagnosis. We developed models to diagnose AD and measure the severity of neurocognitive impairment using blood protein biomarkers. Multiple reaction monitoring-mass spectrometry, a highly selective and sensitive approach for quantifying targeted proteins in samples, was used to analyze blood samples from 4 AD groups: cognitive normal control, asymptomatic AD, prodromal AD), and AD dementia. Multimarker models were developed using 10 protein biomarkers and apolipoprotein E genotypes for amyloid beta and 10 biomarkers with Korean Mini-Mental Status Examination (K-MMSE) score for predicting Alzheimer disease progression. The accuracies for the AD classification model and AD progression monitoring model were 84.9% (95% CI 82.8 to 87.0) and 79.1% (95% CI 77.8 to 80.5), respectively. The models were more accurate in diagnosing AD, compared with single APOE genotypes and the K-MMSE score. Our study demonstrates the possibility of predicting AD with high accuracy by blood biomarker analysis as an alternative method of screening for AD., (© 2022. The Author(s).)

TurboID is a new and efficient proximity labeling system that was first developed in living mammalian cells. TurboID is a modified bacterial biotin ligase that can be fused to a bait protein, which can then modify proximal interacting proteins with biotin. Prey proteins subsequently labeled with biotin tags will be pulled down with streptavidin-coated beads and identified by mass spectrometry-based proteomics. TurboID has been recently applied to living plant cells and provided promising results in identification of interacting proteins. Mitogen-activated protein kinase 4 (MPK4) is important for plant growth, development, and defense; however, the molecular mechanisms underlying the range of MPK4 functions are not completely known. Here we use modern proteomics together with the TurboID in a proof-of-concept study to profile the MPK4 interactome and uncover the functions of MPK4 in plant signaling cascades., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To propose guidelines for lung stereotactic body radiation therapy (SBRT) when using Acuros XB (AXB) equivalent to the existing ones developed for convolution algorithms such as analytic anisotropic algorithm (AAA), considering the difference between the algorithms., Methods: A retrospective analysis was performed on 30 lung patients previously treated with SBRT. The original AAA plans, which were developed using dynamic conformal arcs, were recalculated and then renormalized for planning target volume (PTV) coverage using AXB. The recalculated and renormalized plans were compared to the original plans based on V100% and V90% PTV coverage, as well as V105%, conformality index, D 2cm , Rx/D max , R50, and D min . These metrics were analyzed nominally and on variations according to RTOG and NRG guidelines. Based on the relative difference between each metric in the AAA and AXB plans, new guidelines were developed. The relative differences in our cohort were compared to previously documented AAA to AXB comparisons found in the literature., Results: AAA plans recalculated in AXB had a significant reduction in most dosimetric metrics. The most notable changes were in V100% (4%) and the conformality index (7.5%). To achieve equal PTV coverage, AXB required an average of 1.8% more monitor units (MU). This fits well with previously published data. Applying the new guidelines to the AXB plans significantly increased the number of minor violations with no change in major violations, making them comparable to those of the original AAA plans., Conclusion: The relative difference found between AAA and AXB for SBRT lung plans has been shown to be consistent with previous works. Based on these findings, new guidelines for lung SBRT are recommended when planning with AXB., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Aims: Cardiogenic shock (CS) is associated with significant mortality, and there is a movement towards regional 'hub-and-spoke' triage systems to coordinate care and resources. Limited data exist on outcomes of patients treated at CS transfer hubs., Methods and Results: Cardiogenic shock hospitalizations were obtained from the Nationwide Readmissions Database 2010-2014. Centres receiving any interhospital transfers with CS in a given year were classified as CS transfer 'hubs'; those without transfers were classified as 'spokes.' In-hospital mortality was compared among three cohorts: (A) direct admissions to spokes, (B) direct admissions to hubs, and (C) interhospital transfer to hubs. Among hospitals treating CS, 70.6% were classified as spokes and 29.4% as hubs. A total of 130 656 (31.7%) hospitalizations with CS were direct admission to spokes, 253 234 (61.4%) were direct admissions to hubs, and 28 777 (7.0%) were transfer to hubs. CS mortality was 47.8% at spoke hospitals and was lower at hub hospitals, both for directly admitted (39.3%, P < 0.01) and transferred (33.4%, P < 0.01) patients. Hospitalizations at hubs had higher procedural frequency (including coronary artery bypass graft, right heart catheterization, mechanical circulatory support), greater length of stay, and greater costs. On multivariable analysis, direct admission to CS hubs [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.84-0.89, P < 0.01] and transfer to hubs (OR 0.72, 95% CI 0.69-0.76, P < 0.01) were both associated with lower mortality., Conclusion: While acknowledging the limited ability of the Nationwide Readmissions Database to classify CS severity on presentation, treatment of CS at transfer hubs was associated with significantly lower mortality within this large real-world sample., (© 2021 European Society of Cardiology.)

Hepatocellular carcinoma (HCC) is a malignant cancer with one of the highest mortality rates. Des-γ-carboxyprothrombin (DCP) is an HCC serologic surveillance marker that can complement the low sensitivity of alpha-fetoprotein (AFP). DCP exists in the blood as a mixture of proteoforms from an impaired carboxylation process at glutamic acid (Glu) residues within the N-terminal domain. The heterogeneity of DCP may affect the accuracy of measurements because DCP levels are commonly determined using an immunoassay that relies on antibody reactivity to an epitope in the DCP molecule. In this study, we aimed to improve the DCP measurement assay by applying a mass spectrometry (MS)-based approach for a more inclusive quantification of various DCP proteoforms. We developed a multiple-reaction monitoring-MS (MRM-MS) assay to quantify multiple noncarboxylated peptides included in the various des-carboxylation states of DCP. We performed the MRM-MS assay in 300 patients and constructed a robust diagnostic model that simultaneously monitored three noncarboxylated peptides. The MS-based quantitative assay for DCP had reliable surveillance power, which was evident from the area under the receiver operating characteristic curve (AUROC) values of 0.874 and 0.844 for the training and test sets, respectively. It was equivalent to conventional antibody-based quantification, which had AUROC values at the optimal cutoff (40 mAU/mL) of 0.743 and 0.704 for the training and test sets, respectively. The surveillance performance of the MS-based DCP assay was validated using an independent validation set consisting of 318 patients from an external cohort, resulting in an AUROC value of 0.793. Conclusion: Due to cost effectiveness and high reproducibility, the quantitative DCP assay using the MRM-MS method is superior to antibody-based quantification and has equivalent performance., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Background: Cardiovascular disease is the leading cause of death for women in the United States. Revascularization is considered the standard of care for treatment of ST-segment elevation myocardial infarction (STEMI) and is known to reduce readmission. However there is a paucity of data that examines the sex-dependent impact of revascularization on readmission. We aimed to investigate sex differences in revascularization rates, 30-day readmission rates, and primary cause of readmissions following STEMIs., Methods: STEMI hospitalizations were selected in the Nationwide Readmissions Database from 2010 to 2014. Revascularization rates, 30-day readmission rates, and primary cause of readmission were examined. Interaction between sex and revascularization was assessed. Multivariable regression analysis was performed to identify predictors of 30-day readmission and revascularization for both sexes., Results: 219,944 women and 489,605 men were admitted with STEMIs. Women were more likely to be older, and have more comorbidities. Women were less likely to undergo revascularization by percutaneous coronary intervention (adjusted odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.66-0.70) or coronary artery bypass graft surgery (adjusted OR 0.40; CI 0.39-0.44). Women had higher 30-day readmission rates (15.7% vs. 10.8%, p < 0.001; OR 1.20, CI 1.17-1.23), and revascularization in women was not associated with a decreased likelihood of 30-day readmission. The primary cardiac cause of readmission in women was heart failure., Conclusion: Compared to men, women with STEMIs had lower rates of revascularization and higher rates of 30-day readmission. When revascularized, women were still more likely to be readmitted as compared to non-revascularized women., Competing Interests: Declaration of competing interest The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although abdominal aortic aneurysms (AAA) are more common in men, women with AAA have increased morbidity and mortality. Additionally, there are discrepancies among professional society guidelines for AAA screening in women. In this retrospective study from the Nationwide Inpatient Sample (NIS) database from 2003 to 2014, we compared rates of AAA repair (rupture and elective) and AAA-related mortality in men vs. women to identify predictors of death among men and women with AAA. We divided the population into 1) AAA rupture 2) elective AAA repair. The main outcomes included temporal trends in AAA rupture, rupture-related death, AAA repair, in-hospital death, and predictors of AAA-related death. There were 570,253 discharge records for AAA admissions between 2003 and 2014, including 22.8% women and 77.2% men. Women had a higher proportion of rupture (18.4% vs 12.6%, p <0.01). A smaller proportion of women underwent endovascular aortic repair (EVAR) compared with men in the ruptured AAA (13.9% vs. 20.3%, p <0.01) and elective repair (55.7% vs. 67.4%, p <0.01) cohorts. Within the ruptured cohort, a higher proportion of women did not receive repair (46.4% vs. 26.1%, p <0.01). On multivariable analysis, female gender was a significant predictor of death with rupture (OR 1.39, 95% CI 1.16 to 1.66) and elective repair (OR 1.74, 95% CI 1.36 to 2.22), with both elective EVAR (OR 2.52, 95% CI 2.06 to 3.09) and elective open aortic repair (OAR; OR 1.50, 95% CI 1.33 to 1.68). Propensity score matching confirmed a higher risk of death in women in both the rupture (OR 1.19, 95% CI 1.09 to 1.30) and elective repair (OR 1.50, 95% CI 1.35 to 1.67) cohorts. In conclusion, AAA poses significant morbidity and mortality, especially in women. Women were more likely to die before repair with AAA rupture and female gender was an independent predictor of mortality in both the rupture and elective repair groups., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The association between malignancy and readmission after Takotsubo syndrome (TTS) hospitalization has not been fully described. We sought to examine the rates, cause, and cost of 30-day readmissions of TTS, with or without malignancy, by utilizing Nationwide Readmissions Databases from 2010 to 2014. We identified 61,588 index hospitalizations for TTS. TTS patients with malignancy tended to be older (70.6 ± 0.2 vs. 66.1 ± 0.1, p < 0.001), and the overall burden of comorbidities was higher than in those without malignancy. TTS patients with malignancy had significantly higher 30-day readmission rates than those without malignancy (15.9% vs. 11.0%; odds ratio (OR), 1.35; 95% confidence interval (CI), 1.18-1.56). Non-cardiac causes were the most common causes of readmission for TTS patients with malignancy versus without malignancy (75.5% vs. 68.1%, p < 0.001). The 30-day readmission rate due to recurrent TTS was very low in both groups (0.4% and 0.5%; p = 0.47). The total costs were higher by 25% ( p < 0.001) in TTS patients with vs. without malignancy. In summary, among patients hospitalized with TTS, the presence of malignancy was associated with increased risk of 30-day readmission and increased costs. These findings highlight the importance of optimized management for TTS patients with malignancy.

As the workforce shrinks, the demand for automatic, labor-saving, anomaly detection technology that can perform maintenance on advanced equipment such as vehicles has been increasing. In a vehicular environment, noise in the cabin, which directly affects users, is considered an important factor in lowering the emotional satisfaction of the driver and/or passengers in the vehicles. In this study, we provide an efficient method that can collect acoustic data, measured using a large number of microphones, in order to detect abnormal operations inside the machine via deep learning in a quick and highly accurate manner. Unlike most current approaches based on Long Short-Term Memory (LSTM) or autoencoders, we propose an anomaly detection (AD) algorithm that can overcome the limitations of noisy measurement and detection system anomalies via noise signals measured inside the mechanical system. These features are utilized to train a variety of anomaly detection models for demonstration in noisy environments with five different errors in machine operation, achieving an accuracy of approximately 90% or more.

Background: There are limited data on the characteristics of 30-day readmission after hospitalization with coronavirus disease 2019 (COVID-19)., Objectives: To examine the rate, timing, causes, predictors and outcomes of 30-day readmission after COVID-19 hospitalization., Methods: From 13 March to 9 April 2020, all patients hospitalized with COVID-19 and discharged alive were included in this retrospective observational study. Multivariable logistic regression was used to identify the predictors of 30-day readmission, and a restricted cubic spline function was utilized to assess the linearity of the association between continuous predictors and 30-day readmission., Results: A total of 1062 patients were included in the analysis, with a median follow-up time of 62 days. The mean age of patients was 56.5 years, and 40.5% were women. At the end of the study, a total of 48 (4.5%) patients were readmitted within 30 days of discharge, and a median time to readmission was 5 days. The most common primary diagnosis of 30-day readmission was a hypoxic respiratory failure (68.8%) followed by thromboembolism (12.5%) and sepsis (6.3%). The patients with a peak serum creatinine level of ≥1.29 mg/dL during the index hospitalization, compared to those with a creatinine of <1.29 mg/dL, had 2.4 times increased risk of 30-day readmission (adjusted odds ratio: 2.41; 95% CI: 1.23-4.74). The mortality rate during the readmission was 22.9%., Conclusion: With 4.5% of the thirty-day readmission rate, COVID-19 survivors were readmitted early after hospital discharge, mainly due to morbidities of COVID-19. One in five readmitted COVID-19 survivors died during their readmission., (© 2021 The Association for the Publication of the Journal of Internal Medicine.)

Because major depressive disorder (MDD) and bipolar disorder (BD) manifest with similar symptoms, misdiagnosis is a persistent issue, necessitating their differentiation through objective methods. This study was aimed to differentiate between these disorders using a targeted proteomic approach. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was performed to quantify protein targets regarding the two disorders in plasma samples of 270 individuals (90 MDD, 90 BD, and 90 healthy controls (HCs)). In the training set (72 MDD and 72 BD), a generalizable model comprising nine proteins was developed. The model was evaluated in the test set (18 MDD and 18 BD). The model demonstrated a good performance (area under the curve (AUC) >0.8) in discriminating MDD from BD in the training (AUC = 0.84) and test sets (AUC = 0.81) and in distinguishing MDD from BD without current hypomanic/manic/mixed symptoms (90 MDD and 75 BD) (AUC = 0.83). Subsequently, the model demonstrated excellent performance for drug-free MDD versus BD (11 MDD and 10 BD) (AUC = 0.96) and good performance for MDD versus HC (AUC = 0.87) and BD versus HC (AUC = 0.86). Furthermore, the nine proteins were associated with neuro, oxidative/nitrosative stress, and immunity/inflammation-related biological functions. This proof-of-concept study introduces a potential model for distinguishing between the two disorders.

Introduction: Poor sleep is a pervasive problem for hospitalized patients and can contribute to adverse health outcomes., Methods: We aimed to improve self-reported sleep for patients on a general medicine ward as measured by the Richards-Campbell Sleep Questionnaire (RCSQ) as well as the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) question addressing quietness at night. We utilized a non-pharmacologic sleep hygiene bundle composed of a short script with sleep hygiene prompts, such as whether patients would like the shades closed or the lights turned off, as well as a sleep package including an eye mask, earplugs, lavender scent pad, and non-caffeinated tea. Relaxing music was played at bedtime and signs promoting the importance of quietness at night were placed around the unit. Front-line champions were identified to aid with implementation., Results: A total of 931 patients received the intervention. In a sample of surveyed patients, we observed an increase in the RCSQ global score from 6.0 (IQR 3.0-7.0) to 6.2 (IQR 4.0-7.8) from the pre- to post- intervention periods (p = 0.041), as well as increases in three of the five individual survey components. Additionally, HCAHPS "quietness at night" score increased on the unit from 34.1% pre-intervention to 42.5% post-intervention., Conclusion: A nonpharmacologic sleep hygiene protocol paired with provider education and use of champions was associated with modest improvements in patients' perceived sleep and unit HCAHPS scores., (Copyright © 2021 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Background: Adverse local tissue reactions (ALTRs) in metal-on-polyethylene (MoP) total hip arthroplasty (THA) with head-neck taper corrosion are multifactorial, involving implant and patient factors. This study aimed to identify any potential clinical risk factors associated with failed MoP THA due to head-neck taper corrosion., Methods: A series of 146 MoP THA patients was investigated: (1) ALTR (n = 42) on metal artifact sequence MRI and (2) non-ALTR (n = 104). Both cohorts were compared regarding femoral neck shaft angle, acetabular implant orientation, component size, femoral head offset, measurement of medial and vertical femoral offsets, and femoral stem alloy., Results: The occurrence of ALTR was associated with increased radiographic femoral stem offset (36.0 ± 7.7 mm versus 40.8 ± 7.3 mm, P = 0.008), increased femoral head offset (0.7 ± 3.4 versus 4.5 ± 3.7, P < 0.001), and the use of Ti-12Mo-6Zr-2Fe alloy stems (P = 0.041). The presence of ALTR was notably associated with higher chromium (2.0 versus 0.5 μg/L) and cobalt (7.4 versus 0.7 μg/L, P < 0.001)., Discussion: This study identified increased femoral head and stem offset and the use of Ti-12Mo-6Zr-2Fe alloy stems as risk factors for clinically relevant ALTR due to head-neck taper corrosion in MoP THA patients. This provides evidenced-based practical information for surgeons in identifying "at-risk" symptomatic MoP THA patients with head-neck taper corrosion for systematic risk stratification., (Copyright © 2020 by the American Academy of Orthopaedic Surgeons.)

Purpose: To develop and validate a protein-based, multi-marker panel that provides superior pancreatic ductal adenocarcinoma (PDAC) detection abilities with sufficient diagnostic performance., Experimental Design: A total of 959 plasma samples from patients at multiple medical centers were used. To construct an optimal, diagnostic, multi-marker panel, we applied data preprocessing procedure to biomarker candidates. The multi-marker panel was developed using a training set comprised of 261 PDAC cases and 290 controls. Subsequent evaluations were performed in a validation set comprised of 65 PDAC cases and 72 controls. Further validation was performed in an independent set comprised of 75 PDAC cases and 47 controls., Results: A multi-marker panel containing 14 proteins was developed. The multi-marker panel achieved AUCs of 0.977 and 0.953 for the training set and validation set, respectively. In an independent validation set, the multi-marker panel yielded an AUC of 0.928. The diagnostic performance of the multi-marker panel showed significant improvements compared with carbohydrate antigen (CA) 19-9 alone (training set AUC = 0.977 vs. 0.872, P < 0.001; validation set AUC = 0.953 vs. 0.832, P < 0.01; independent validation set AUC = 0.928 vs. 0.771, P < 0.001). When the multi-marker panel and CA 19-9 were combined, the diagnostic performance of the combined panel was improved for all sets., Conclusions: This multi-marker panel and the combined panel showed statistically significant improvements in diagnostic performance compared with CA 19-9 alone and has the potential to complement CA 19-9 as a diagnostic marker in clinical practice., (©2021 American Association for Cancer Research.)

Background: Pseudo-Wellens syndrome is a rare entity characterized by the presence of electrocardiogram (ECG) changes of Wellens syndrome but without the stenosis of the left anterior descending (LAD) coronary artery. In previous reports, pseudo-Wellens syndrome most commonly resulted from recreational drug use or unidentified etiologies. We present a unique case of pseudo-Wellens syndrome due to sepsis-induced cardiomyopathy and a review of the literature., Case Presentation: A 62-year-old Caucasian woman was admitted for sepsis from left foot cellulitis. Laboratory data were notable for elevated lactate of 2.5 mmol/L and evidence of acute kidney injury. She developed chest pain on the third day of hospitalization. ECG showed symmetric T-wave inversion in leads V1-V4. Serial troponin I levels were within normal limits. Chest imaging showed no pulmonary embolism. Echocardiogram showed ejection fraction of 25%, left ventricular diastolic diameter of 4.6 cm, and multiple segmental wall motion abnormalities. Cardiac catheterization showed patent coronary arteries. The hospital course was complicated by transient sinus bradycardia and hypotension. She was hospitalized for a total of 17 days. ECG prior to discharge showed resolution of T-wave changes., Conclusion: Pseudo-Wellens syndrome may result from myocardial ischemia due to vasospasm or myocardial edema from external insults. In our case, we suspect sepsis-related cytokine production resulting in cardiomyopathy and pseudo-Wellens syndrome. The clinical manifestations were indistinguishable between Wellens and pseudo-Wellens syndrome. Physicians should include the diagnosis of pseudo-Wellens syndrome when considering the presence of LAD coronary artery occlusion given risk stratifications.

Background The independent prognostic value of troponin and other biomarker elevation among patients with coronavirus disease 2019 (COVID-19) are unclear. We sought to characterize biomarker levels in patients hospitalized with COVID-19 and develop and validate a mortality risk score. Methods and Results An observational cohort study of 1053 patients with COVID-19 was conducted. Patients with all of the following biomarkers measured-troponin-I, B-type natriuretic peptide, C-reactive protein, ferritin, and d-dimer (n=446) -were identified. Maximum levels for each biomarker were recorded. The primary end point was 30-day in-hospital mortality. Multivariable logistic regression was used to construct a mortality risk score. Validation of the risk score was performed using an independent patient cohort (n=440). Mean age of patients was 65.0±15.2 years and 65.3% were men. Overall, 444 (99.6%) had elevation of any biomarker. Among tested biomarkers, troponin-I ≥0.34 ng/mL was the only independent predictor of 30-day mortality (adjusted odds ratio, 4.38; P <0.001). Patients with a mortality score using hypoxia on presentation, age, and troponin-I elevation, age (HA 2 T 2 ) ≥3 had a 30-day mortality of 43.7% while those with a score <3 had mortality of 5.9%. Area under the receiver operating characteristic curve of the HA 2 T 2 score was 0.834 for the derivation cohort and 0.784 for the validation cohort. Conclusions Elevated troponin and other biomarker levels are commonly seen in patients hospitalized with COVID-19. High troponin levels are a potent predictor of 30-day in-hospital mortality. A simple risk score can stratify patients at risk for COVID-19-associated mortality.

[Figure: see text].

Background: The accurate diagnosis of periprosthetic joint infection (PJI) in the setting of adverse local tissue reactions in patients with metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to head-neck taper junction corrosion is challenging as it frequently has the appearance of purulence. The aim of this study is to evaluate the utility of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and synovial fluid markers in diagnosing PJI in failed MoP THA due to head-neck taper corrosion., Methods: A total of 89 consecutive patients with MoP THA with head-neck taper corrosion in 2 groups was evaluated: (1) infection group (n = 11) and (2) noninfection group (n = 78). All patients had highly crossed polyethylene with cobalt chromium femoral heads and had preoperative synovial fluid aspiration. In addition, serum cobalt and chromium levels were analyzed., Results: The optimal cutoff value for synovial white blood cell was 2144 with 93% sensitivity and 84% specificity. Neutrophil count optimal cutoff value was 82% with 93% sensitivity and 82% specificity. Receiver operating characteristic analysis of ESR and CRP determined optimal cutoff at 57 mm/h and 35 mg/L with 57% sensitivity and 94% specificity and 93% sensitivity and 76% specificity, respectively. There were no significant differences in metal ion levels between the infected and noninfected groups., Conclusion: The results of this study suggest that ESR and CRP are useful in excluding PJI, whereas both synovial white blood cell count and neutrophil percentage in hip aspirate are useful markers for diagnosing infection in MoP THA patients with head-neck taper corrosion associated adverse local tissue reaction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Adverse local tissue reaction (ALTR) associated with mechanically assisted crevice corrosion of metal-on-polyethylene (MoP) head-neck modular total hip arthroplasty (THA), similarly observed in the metal-on-metal bearing, is a growing concern in MoP THA patients. Given the complex pathogenesis as well as variable clinical presentation, the diagnosis can be challenging. This article focuses on providing surgeons with an evidence-based update on (1) implant, surgical, and patient risk factors associated with ALTRs; (2) clinical systematic evaluation; and (3) surgical management options for ALTRs in MoP THA patients based on the currently available evidence.

Catechol-conjugated chitosan (CCs), used as tissue adhesive, wound dressing, and hemostatic materials, has been drawing much more attention. However, most CCs tissue adhesives exhibit poor adhesion strength, and few studies on optimization of cohesion and adhesion strength of CCs derivatives have been conducted. This work focused on the balance between cohesion and adhesion strength of catechol-conjugated chitosan (CCs) derivatives via different mechanisms of chemical and enzymatic conjugation. CCs derivatives were characterized regarding its mechanical property, cytotoxicity, platelet adhesion and wound healing test. Mechanical properties could be optimized by the degree of catechol substitution, pH and the presence of oxidizing agent, resulting in that the highest value of adhesive shear strength to the porcine tissue is 64.8 ± 5.7 kPa. In addition, CCs derivatives exhibit decreased toxicity and promoted in vivo wound healing effects as comparing to a commercially available adhesive (Dermabond®). All the results demonstrate that CCs derivatives can be used as well-optimized tissue adhesives as well as a hemostat., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) has been recommended as a cross-sectional imaging modality in clinical evaluation of adverse local tissue reactions (ALTRs) in metal-on-metal (MoM) patients and metal-on-polyethylene (MoP) patients with taper corrosion. The aim of the study was to compare MARS MRI characteristics of ALTR in MoM total hip arthroplasty (THA) with ALTR in MoP THA with modular taper corrosion., Methods: A total of 197 patients with ALTR were evaluated: 86 patients with MoM THA; 37 MoP patients with head-neck taper corrosion; and 74 MoP patients with neck-stem dual taper corrosion. MARS MRI scans were evaluated to identify location, size, type of ALTR (I-III), and associated ALTR synovitis (cystic, solid, and mixed)., Results: MARS MRI characteristics of ALTR were significantly different between the MoM and MoP groups (P = .017). The MoP group demonstrated the highest proportion of thick-walled cystic masses type II (56.7% in head-neck taper corrosion MoP and 46.5% in dual taper corrosion MoP vs 28.7% in MoM), whereas the MoM group had the highest proportion of thin-walled cystic masses type I. MoM implants (96.8%) were significantly more likely to have ALTR in multiple locations compared with both MoP groups (P = .001)., Conclusion: This study demonstrates that MARS MRI characteristics of ALTR differ by bearing type with a significantly higher percentage of mixed type and solid type ALTR in the taper corrosion MoP THA compared with MoM THA. This information provides clinically useful information in evaluation of symptomatic MoP and MoM THA patients for ALTRs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: The complex relationship between acetabular component position and spinopelvic mobility in patients following total hip arthroplasty (THA) renders it difficult to optimize acetabular component positioning. Mobility of the normal lumbar spine during postural changes results in alterations in pelvic tilt (PT) to maintain the sagittal balance in each posture and, as a consequence, markedly changes the functional component anteversion (FCA). This study aimed to investigate the in vivo association of lumbar degenerative disc disease (DDD) with the PT angle and with FCA during postural changes in THA patients., Methods: A total of 50 patients with unilateral THA underwent CT imaging for radiological evaluation of presence and severity of lumbar DDD. In all, 18 patients with lumbar DDD were compared to 32 patients without lumbar DDD. In vivo PT and FCA, and the magnitudes of changes (ΔPT; ΔFCA) during supine, standing, swing-phase, and stance-phase positions were measured using a validated dual fluoroscopic imaging system., Results: PT, FCA, ΔPT, and ΔFCA were significantly correlated with the severity of lumbar DDD. Patients with severe lumbar DDD showed marked differences in PT with changes in posture; there was an anterior tilt (-16.6° vs -12.3°, p = 0.047) in the supine position, but a posterior tilt in an upright posture (1.0° vs -3.6°, p = 0.005). A significant decrease in ΔFCA during stand-to-swing (8.6° vs 12.8°, p = 0.038) and stand-to-stance (7.3° vs 10.6°,p = 0.042) was observed in the severe lumbar DDD group., Conclusion: There were marked differences in the relationship between PT and posture in patients with severe lumbar DDD compared with healthy controls. Clinical decision-making should consider the relationship between PT and FCA in order to reduce the risk of impingement at large ranges of motion in THA patients with lumbar DDD. Cite this article: Bone Joint J 2020;102-B(11):1505-1510.

Background: Human epidermal growth factor receptor 2 (HER2) is often overexpressed in breast cancer and correlates with a worse prognosis. Thus, the accurate detection of HER2 is crucial for providing the appropriate measures for patients. However, the current techniques used to detect HER2 status, immunohistochemistry and fluorescence in situ hybridization (FISH), have limitations. Specifically, FISH, which is mandatory for arbitrating 2+ cases, is time-consuming and costly. To address this shortcoming, we established a multiple reaction monitoring-mass spectrometry (MRM-MS) assay that improves on existing methods for differentiating HER2 status., Methods: We quantified HER2 expression levels in 210 breast cancer formalin-fixed paraffin-embedded (FFPE) tissue samples by MRM-MS. We aimed to improve the accuracy and precision of HER2 quantification by simplifying the sample preparation through predicting the number of FFPE slides required to ensure an adequate amount of protein and using the expression levels of an epithelial cell-specific protein as a normalization factor when measuring HER2 expression levels., Results: To assess the correlation between MRM-MS and IHC/FISH data, HER2 quantitative data from MRM-MS were divided by the expression levels of junctional adhesion molecule A, an epithelial cell-specific protein, prior to statistical analysis. The normalized HER2 amounts distinguished between HER2 2+/FISH-negative and 2+/FISH-positive groups (AUROC = 0.908), which could not be differentiated by IHC. In addition, all HER2 status were discriminated by MRM-MS., Conclusions: This MRM-MS assay yields more accurate HER2 expression levels relative to immunohistochemistry and should help to guide clinicians toward the proper treatment for breast cancer patients, based on their HER2 expression., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Non-traumatic osteonecrosis of the femoral head (ONFH) is a plausible complication in brain tumor patients. Frequent use of corticosteroid therapy, chemotherapy, and oxidative stress for managing brain tumors may be associated with the development of ONFH. However, there is little knowledge on the prevalence and risk factors of ONFH from brain tumor. This study aimed to investigate the prevalence and risk factors of ONFH in patients with primary brain tumors., Methods: This retrospective cohort study included data from consecutive patients between December 2005 and August 2016 from a tertiary university hospital in South Korea. A total of 73 cases of ONFH were identified among 10,674 primary brain tumor patients. After excluding subjects (25 out of 73) with missing data, history of alcohol consumption or smoking, history of femoral bone trauma or surgery, comorbidities such as systemic lupus erythematosus (SLE), sickle cell disease, cancer patients other than brain tumor, and previous diagnosis of contralateral ONFH, we performed a 1:2 propensity score-matched, case-control study (ONFH group, 48; control group, 96). Risk factors of ONFH in primary brain tumor were evaluated by univariate and multivariate logistic regression analyses., Results: The prevalence of ONFH in patients with surgical resection of primary brain tumor was 683.9 per 100,000 persons (73 of 10,674). In this cohort, 55 of 74 patients (74.3%) underwent THA for ONFH treatment. We found that diabetes was an independent factor associated with an increased risk of ONFH in primary brain tumor patients (OR = 7.201, 95% CI, 1.349-38.453, p = 0.021). There was a significant difference in univariate analysis, including panhypopituitarism (OR = 4.394, 95% CI, 1.794-11.008, p = 0.002), supratentorial location of brain tumor (OR = 2.616, 95% CI, 1.245-5.499, p = 0.011), and chemotherapy (OR = 2.867, 95% CI, 1.018-8.069, p = 0.046)., Conclusions: This study demonstrated that the prevalence of ONFH after surgical resection of primary brain tumor was 0.68%. Diabetes was an independent risk factor for developing ONFH, whereas corticosteroid dose was not. Routine screening for brain tumor-associated ONFH is not recommended; however, a high index of clinical suspicion in these patients at risk may allow for early intervention and preservation of the joints., Competing Interests: Youn-Soo Park is a paid consultant for DePuy Synthes and Corentec and has received royalties for Corentec products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: The real-world distribution of hospital atrial fibrillation (AF) ablation volume and its impact on outcomes are not well-established. We sought to examine patient characteristics, complications, and readmissions after AF ablation stratified by hospital procedural volume., Methods and Results: Using the nationally representative inpatient Nationwide Readmissions Database, we evaluated 54 597 admissions for AF ablation between 2010 and 2014. Hospitals were categorized according to tertiles of annual AF ablation volume. Index complications, 30-day readmissions, and early mortality were examined. Multivariable logistic regression was performed to assess the predictors of adverse outcomes. Between 2010 and 2014, low volume tertile hospitals accounted for 79.3% of hospitals performing AF ablations. When stratified by first, second, and third volume tertiles, complication and early mortality rates were higher in low volume centers (8.9% and 0.67% vs 6.1% and 0.33%, vs 4.5% and 0.16%, respectively; P < .001). Patients undergoing AF ablation at low volume centers were older and had a higher prevalence of congestive heart failure, coronary artery disease, and other comorbidities. Low volume hospitals were associated with increased cardiac perforation (adjusted odds ratio [aOR], 4.79; P < .001), vascular complications (aOR 1.49; P < .001), and any complication (aOR 2.06; P < .001) during index admission as well as increased early mortality (aOR 2.43; P = .039)., Conclusions: Among patients hospitalized for AF ablation, low inpatient AF ablation hospital volume was associated with worse outcomes following ablation, which was exacerbated by a greater comorbidity burden among patients at these centers., (© 2020 Wiley Periodicals LLC.)

Multiple reaction monitoring-mass spectrometry became a mainstream method for quantitative proteomics, which made the validation of a method and the analyzed data important. In this portal for validation of the MRM-MS assay, we developed a website that automatically evaluates uploaded MRM-MS data, based on biomarker assay guidelines from the European Medicines Agency, the US Food & Drug Administration, and the Korea Food & Drug Administration. The portal reads a Skyline output file and produces the following results-calibration curve, specificity, sensitivity, carryover, precision, recovery, matrix effect, recovery, dilution integrity, stability, and QC-according to the standards of each independent agency. The final tables and figures that pertain to the 11 evaluation categories are displayed in an individual page. Spring boot was used as a framework for development of the webpage, which follows MVC Pattern. JSP, HTML, XML, and Java Script were used to develop the webpage. A server was composed of Apache Tomcat, MySQL. Input files were skyline-derived output files (csv file), and each files were organized by specific columns in order. SQL, JAVA were interworked to evaluate all the categories and show the results. Method Validation Portal can be accessed via any kind of explorer from https://pnbvalid.snu.ac.kr.

We investigate the quantum confinement effects on excitons in several types of strain-free GaAs/Al 0 . 3 Ga 0 . 7 As droplet epitaxy (DE) quantum dots (QDs). By performing comparative analyses of energy-dispersive X-ray spectroscopy with the aid of a three-dimensional (3D) envelope-function model, we elucidate the individual quantum confinement characteristics of the QD band structures with respect to their composition profiles and the asymmetries of their geometrical shapes. By precisely controlling the exciton oscillator strength in strain-free QDs, we envisage the possibility of tailoring light-matter interactions to implement fully integrated quantum photonics based on QD single-photon sources (SPSs).

Background Readmission after ST-segment-elevation myocardial infarction (STEMI) poses an enormous economic burden to the US healthcare system. There are limited data on the association between length of hospital stay (LOS), readmission rate, and overall costs in patients who underwent primary percutaneous coronary intervention for STEMI. Methods and Results All STEMI hospitalizations were selected in the Nationwide Readmissions Database from 2010 to 2014. From the patients who underwent primary percutaneous coronary intervention, we examined the 30-day outcomes including readmission, mortality, reinfarction, repeat revascularization, and hospital charges/costs according to LOS (1-2, 3, 4, 5, and >5 days) stratified by infarct locations. The 30-day readmission rate after percutaneous coronary intervention for STEMI was 12.0% in the anterior wall (AW) STEMI group and 9.9% in the non-AW STEMI group. Patients with a very short LOS (1-2 days) were readmitted less frequently than those with a longer LOS regardless of infarct locations. However, patients with a very short LOS had significantly increased 30-day readmission mortality versus an LOS of 3 days (hazard ratio, 1.91; CI, 1.16-3.16 [ P =0.01]) only in the AW STEMI group. Total costs (index admission+readmission) were the lowest in the very short LOS cohort in both the AW STEMI group ( P <0.001) and the non-AW STEMI group ( P <0.001). Conclusions For patients who underwent primary percutaneous coronary intervention for STEMI, a very short LOS was associated with significantly lower 30-day readmission and lower cumulative cost. However, a very short LOS was associated with higher 30-day mortality compared with at least a 3-day stay in the AW STEMI cohort.

Purpose: This technology evaluation study assesses the limits of agreement between the mammographic density (MD) measurement of Quantra™ from different breasts and mammographic views and its agreement with the Royal Australian and New Zealand College of Radiologists (RANZCR) synoptic scale. Approach: MD of 800 women was assessed by Quantra™ and seven radiologists using the RANZCR synoptic scale. Bland-Altman analysis was used to assess the limits of agreement between Quantra™ MD measures from both breasts and mammographic views. The agreement between Quantra™ and the RANZCR synoptic scale was assessed using weighted kappa ( K w ). The receiver operating characteristics area under the curve (AUC) was used to assess the performance of Quantra™ in reproducing RANZCR MD ratings. Results: There was no significant bias in the mean MD of Quantra™ from both breasts: left versus right craniocaudal (CC) views ( B = - 0.14 ; p = 0.36 ) and right versus left mediolateral oblique (MLO) ( B = - 0.021 ; p = 0.18 ). However, MD measures from the same breast but different views showed significant bias: right CC versus right MLO ( B = 0.064 ; p < 0.0001 ) and left CC versus left MLO ( B = 0.56 ; p < 0.0001 ). Quantra™ demonstrated substantial agreement with the RANZCR synoptic scale on four- and two-category scales ( K w = 0.62 ; 0.59 to 0.66 and 0.76; 0.72 to 0.81, respectively). Quantra™ better reproduced the RANZCR synoptic scale on a two-category scale ( AUC = 0.88 ; 0.84 to 0.91) than a four-category scale ( AUC = 0.62 ; 0.58 to 0.67 to 0.78; 0.74 to 0.82). Conclusions: Quantra™ reproduces MD classification using the RANZCR synoptic scale on a two-category scale and should help in identification of women with dense breasts who may need adjunctive imaging for early detection of breast cancer., (© 2020 Society of Photo-Optical Instrumentation Engineers (SPIE).)

There is an urgent need for new biomarkers that address the shortcomings of current screening methods which fail to detect a large proportion of cases with hepatocellular carcinoma (HCC) at early stage. To develop a robust, multiple-biomarker panel based on multiple reaction monitoring-mass spectrometry with high performance in detecting early-stage HCC within at-risk populations. In the discovery set, 150 samples were analyzed to identify candidate biomarkers. The resulting list of candidates was tested in the training set (713 samples) to establish a multimarker panel, which was evaluated in the validation set (305 samples). We identified 385 serum HCC biomarker candidates in the discovery set and developed a multimarker panel consisting of 28 peptides that best differentiated HCC from controls. The area under the receiver operating characteristic curve of multimarker panel was significantly higher than alpha-fetoprotein (AFP) in the training (0.976 vs. 0.804; P  < 0.001) and validation (0.898 vs. 0.778; P  < 0.001) sets. In the validation set, this multimarker panel, compared with AFP, showed significantly greater sensitivity (81.1% vs. 26.8%; P  < 0.001) and lower specificity (84.8% vs. 98.8%; P  < 0.001) in detecting HCC cases. Combining AFP with the multimarker panel did not significantly improve the area under the receiver operating characteristic curve compared with the panel alone in the training (0.981 vs. 0.976; P  = 0.37) and validation set (0.906 vs. 0.898; P  = 0.75). Conclusion: The multiple reaction monitoring-mass spectrometry multimarker panel consisting of 28 peptides discriminates HCC cases from at-risk controls with high performance and may have potential for clinical application in HCC surveillance., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

The purpose of this study is to propose a reconstruction method of a target and its neighborhood, representative of the moment of radiotherapy delivery, based on differences in its transit images between the time of planning computed tomography (pCT) and the time of treatment beam delivery. To validate the method, a lung phantom with a target object was constructed, and CT-scanned before and after making a shift of the target. The latter scan was intended to simulate a potential organ movement at the time of treatment, and to serve as ground-truth images. Treatment planning using arc-beam delivery was done on the first pCT images. The planned beams were irradiated to the phantom after the shift, while cine transit images were acquired. Cine transit images were also calculated through the pCT images before the shift. From the ratio of the measured and calculated transit images, the amount of image changes due to the organ movement between the time of pCT and that of treatment was three-dimensionally reconstructed. By adding the reconstructed images to the pCT images before the shift, the CT images of the phantom at the time of the beam delivery were generated and compared with the ground truth images. The phantom after the shift was also scanned by on-board cone-beam computer tomography (CBCT) and reconstructed from the measured transit images (MVCT) for comparison. The proposed method reconstructed images that are very close to the ground-truth images in the volume and HU values of the target and the dose-volume coverage of the target and lung. Similar agreement was not found in the CBCT and MVCT images. The method may be used for 4D target image reconstruction, and, combined with the reconstructed image of un-irradiated areas, may offer clinically useful images of the entire region of interest.

Purpose: Highly cross-linked polyethylene has been introduced to decrease osteolysis secondary to polyethylene wear debris generation. However, few long-term data on revision total hip arthroplasty (THA) using highly cross-linked polyethylene liners are available. The objective of this study was to determine long-term outcomes of a highly cross-linked polyethylene liner in revision THA., Materials & Methods: We evaluated 63 revision THAs performed in 63 patients using a highly cross-linked polyethylene liner between April 2000 and February 2005. Of these, nine died and four were lost to follow-up. Thus, the final study cohort consisted of 50 patients (50 hips), including 26 males and 24 females with a mean age of 53 years (range, 27-75 years). Mean follow-up was 11 years (range, 10-14 years)., Results: The mean Harris hip score improved from 44 points preoperatively to 85 points at the final follow-up. No radiographic evidence of osteolysis was found in any hip. The mean rate of polyethylene liner wear was 0.029 mm/year (range, 0.003 to 0.098 mm/year). A total of 5 hips (10%) required re-revision arthroplasty, including one cup loosening, one recurrent dislocation, and three deep infections. Kaplan-Meier survivorship with an end point of re-revision for any reason was 91.1% and for aseptic cup loosening was 97.9% at 11 years., Conclusion: At a minimum of 10 years, the highly cross-linked polyethylene liners showed excellent clinical performance and implant survivorship, and were not associated with osteolysis in our patients with revision THAs., (© 2019. The Author(s).)

Herein, we present the calculated strain-induced control of single GaAs/AlGaAs quantum dots (QDs) integrated into semiconductor micropillar cavities. We show precise energy control of individual single GaAs QD excitons under multi-modal stress fields of tailored micropillar optomechanical resonators. Further, using a three-dimensional envelope-function model, we evaluated the quantum mechanical correction in the QD band structures depending on their geometrical shape asymmetries and, more interestingly, on the practical degree of Al interdiffusion. Our theoretical calculations provide the practical quantum error margins, obtained by evaluating Al-interdiffused QDs that were engineered through a front-edge droplet epitaxy technique, for tuning engineered QD single-photon sources, facilitating a scalable on-chip integration of QD entangled photons.

A power and area efficient CMOS stochastic neuron for resistive computing device-based neural networks is presented. The stochastic neuron performs both quantization and activation function simultaneously by using a single dynamic comparator and allows power-hungry analog to digital and digital to analog converters to be removed at the cost of the increased computation time. A network learning method utilizing a noisy sigmoid function is also presented to minimize the computation time with little accuracy degradation. A prototype neuron chip fabricated in 0.18μm CMOS process successfully demonstrates the neuron's performance and the learning method is verified through network simulations.

Background: Although procedure-related deaths during index admission following catheter ablation of AF have been reported to be low, adverse outcomes can occur after discharge. There are limited data on mortality early after AF ablation., Objectives: This study aimed to identify rates, trends, and predictors of early mortality post-atrial fibrillation (AF) ablation., Methods: Using the all-payer, nationally representative Nationwide Readmissions Database, we evaluated 60,203 admissions of patients 18 years of age or older for AF ablation between 2010 and 2015. Early mortality was defined as death during initial admission or 30-day readmission. Based on International Classification of Diseases-9th Revision, Clinical Modification codes, we identified comorbidities, procedural complications, and causes of readmission following AF ablation. Multivariable logistic regression was performed to assess predictors of early mortality., Results: Early mortality following AF ablation occurred in 0.46% cases, with 54.3% of deaths occurring during readmission. From 2010 to 2015, quarterly rates of early mortality post-ablation increased from 0.25% to 1.35% (p < 0.001). Median time from ablation to death was 11.6 (interquartile range [IQR]: 4.2 to 22.7) days. After adjustment for age and comorbidities, procedural complications (adjusted odds ratio [aOR]: 4.06; p < 0.001), congestive heart failure (CHF) (aOR: 2.20; p = 0.011) and low AF ablation hospital volume (aOR: 2.35; p = 0.003) were associated with early mortality. Complications due to cardiac perforation (aOR: 2.98; p = 0.007), other cardiac (aOR: 12.8; p < 0.001), and neurologic etiologies (aOR: 8.72; p < 0.001) were also associated with early mortality., Conclusions: In a nationally representative cohort, early mortality following AF ablation affected nearly 1 in 200 patients, with the majority of deaths occurring during 30-day readmission. Procedural complications, congestive heart failure, and low hospital AF ablation volume were predictors of early mortality. Prompt management of post-procedure complications and CHF may be critical for reducing mortality rates following AF ablation., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Although catheter ablation has emerged as an important therapy for patients with symptomatic atrial fibrillation (AF), there are limited data on sex-based differences in outcomes. We sought to compare in-hospital outcomes and 30-day readmissions of women and men undergoing AF ablation., Methods and Results: Using the United States Nationwide Readmissions Database, we analysed patients undergoing AF ablation between 2010 and 2014. Based on ICD-9-CM codes, we identified co-morbidities and outcomes. Multivariable logistic regression and inverse probability-weighting analysis were performed to assess female sex as a predictor of endpoints. Of 54 597 study patients, 20 623 (37.7%) were female. After adjustment for age, co-morbidities, and hospital factors, women had higher rates of any complication [adjusted odds ratio (aOR) 1.39; P < 0.0001], cardiac perforation (aOR 1.39; P = 0.006), and bleeding/vascular complications (aOR 1.49; P < 0.0001). Thirty-day all-cause readmission rates were higher for women compared to men (13.4% vs. 9.4%; P < 0.0001). Female sex was independently associated with readmission for AF/atrial tachycardia (aOR 1.48; P < 0.0001), cardiac causes (aOR 1.40; P < 0.0001), and all causes (aOR 1.25; P < 0.0001). Similar findings were confirmed with inverse probability-weighting analysis. Despite increased complications and readmissions, total costs for AF ablation were lower for women than men due to decreased resource utilization., Conclusions: Independent of age, co-morbidities, and hospital factors, women have higher rates of complications and readmissions following AF ablation. Sex-based differences and disparities in the management of AF need to be explored to address these gaps in outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Purpose: To evaluate the clinical characteristics and surgical outcomes of pediatric retinal detachments (RDs) in an Asian population., Methods: Retrospective review of 171 eyes of 152 pediatric patients with rhegmatogenous RD over a 20-year period., Results: Myopia was the most common risk factor in our population. At 6 months, primary anatomical success was 60.7%, and overall anatomical success was 86.7%. A total of 46.8% had best-corrected visual acuity of 20/40 or better, and 81.6% had best-corrected visual acuity of 20/200 or better. In primary RDs, high myopia (≤-6D) patients had a lower primary anatomical success compared to patients with moderate myopia (≤-2D) (59.3 vs. 100% P = 0.03). Increasing age and absence of proliferative vitreoretinopathy were associated with anatomical and visual success. Pars plana vitrectomy as the primary procedure was associated with decreased odds of anatomical success. A longer duration of symptoms, cataract, and a larger RD extent were associated with poorer functional outcome., Conclusion: Myopia was the commonest risk factor for pediatric RD in our population. Good anatomical and functional outcome can be achieved with surgery. Increasing age at presentation and absence of proliferative vitreoretinopathy was associated with anatomical and functional success. High myopia was associated with poorer anatomical and functional outcome.

Purpose: To assess the ability of optical coherence tomography (OCT) alone and in combination with OCT angiography (OCTA) to differentiate polypoidal choroidal vasculopathy (PCV) from neovascular age-related macular degeneration, as compared to fluorescein angiography and indocyanine green angiography., Methods: This is a cross-sectional study. All participants had a standardized history, clinical examination including measurement of best-corrected visual acuity, slit-lamp biomicroscopy, and indirect fundus examination, and underwent standardized imaging (color photography, fluorescein and indocyanine green angiography, OCT, and OCTA) after predefined protocols. We used a 2-step approach (Step 1: spectral domain OCT; Step 2: addition of OCTA) combining structural OCT and OCTA to differentiate 50 treatment-naive eyes with PCV, choroidal neovascularization, and retinal angiomatous proliferation and compared with the diagnosis based on fluorescein angiography and indocyanine green angiography. Spectral domain OCT signs used to diagnose PCV included presence of two out of three of any retinal pigment epithelium detachment (pigment epithelial detachment/double-layer sign), notched or narrow-peaked pigment epithelial detachment, or round subretinal pigment epithelium structure. Optical coherence tomography angiography signs used to diagnose PCV included presence of a localized subretinal pigment epithelium hyperflow signal in the cross-sectional OCTA and/or presence of a focal hyperflow sign in en face OCTA based on outer retina slab., Results: Based on fluorescein angiography and indocyanine green angiography, the diagnosis was choroidal neovascularization in 24 eyes, PCV in 23 eyes, and retinal angiomatous proliferation in 3 eyes. Based on spectral domain OCT signs, PCV was diagnosed in 19/23 (82.6%) eyes; however, specificity of OCT was only 51.9%. Cross-sectional OCTA showed a diffuse hyperflow signal in all 24 (100.0%) eyes with choroidal neovascularization, whereas a localized subretinal pigment epithelium hyperflow signal was detected in 19/23 (82.6%) eyes with PCV. En face OCTA only detected a nodular hyperflow signal in 10/23 eyes (43.5%) with PCV. Combination of OCT and OCTA achieved 82.6% sensitivity and 100.0% specificity for differentiating PCV from choroidal neovascularization/retinal angiomatous proliferation., Conclusion: Cross-sectional OCTA is more sensitive than en face OCTA in detecting flow signal in polyps. Combination of structural OCT and OCTA can be used to screen for PCV with a high level of sensitivity and specificity.

Spreading processes associated with slow-spreading ridges are a complex interplay of volcanic accretion and tectonic dismemberment of the oceanic crust, resulting in an irregular seafloor morphology made up of blocks created by episodes of intense volcanic activity or tectonic deformation. These blocks undergo highly variable evolution, such as tilts or dissection by renewed tectonic extension, depending on their positions with respect to the spreading axis, core complexes, detachment or transform faults. Here, we use near-seafloor magnetic and bathymetric data and seismic profiles collected over the TAG Segment of the Mid-Atlantic Ridge to constrain the tectonic evolution of these blocks. Our study reveals that the presence and evolution of oceanic core complexes play a key role in triggering block movements. The deep subvertical detachment fault roots on the plate boundary, marked by a thermal anomaly and transient magma bodies. Thermal and magmatic variations control the structure and morphology of the seafloor above the subhorizontal detachment surface, occasionally leading to relocating the detachment.

MitraClip therapy has shown increasing use since it was commercially adopted among US hospitals in October 2013. However, the relation of institutional MitraClip volume with outcomes is unclear. This study sought to examine the association between hospital volume and outcomes after transcatheter mitral valve repair using the MitraClip device. Using the Nationwide Readmissions Database, we identified all patients who underwent a MitraClip procedure and categorized hospitals into tertiles based on their annual procedure volume: low (≤3 procedures/year), medium (4 to 13/year), and high (≥14/year) volume centers. Multivariable logistic and Cox regression analyses were performed to examine the impact of institutional MitraClip volume on in-hospital and 90-day outcomes, respectively. From 2014 to 2015, a total of 3,420 procedures were performed at 266 hospitals with a median annual procedural volume of 5 per hospital. Low (n = 81), medium (n = 86), and high (n = 99) volume hospitals performed 147 (4.3%), 403 (11.8%), and 2,870 (83.9%) MitraClip procedures, respectively. The low versus high hospital volume was independently associated with increased in-hospital mortality (7.8% vs 3.0%; adjusted odds ratio [aOR] 2.64; p = 0.04), acute myocardial infarction (10.2% vs 2.2%; aOR 2.93; p = 0.02), and acute respiratory failure (19.3% vs 7.7%; aOR 2.24; p = 0.02) during index admission as well as 90-day all-cause readmissions (37.8% vs 26.6%; adjusted hazard ratio 1.54; p = 0.03), and 90-day infective endocarditis (2.4% vs 0.3%; adjusted hazard ratio 10.06; p = 0.003). In conclusion, low hospital MitraClip volume is an independent determinant of worse outcomes including in-hospital mortality and 90-day readmissions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to examine the correlation between the tongue coating thickness (TCT) and ultraviolet (UV) fluorescence and propose a new method for the estimation of TCT using a computerized tongue image acquisition system (CTIS).In this prospective and observational single-center study, we acquired tongue images under visible light and near-UV light for 60 patients with functional dyspepsia. Tongue images were acquired twice within a 30-minute interval to assess the reliability of CTIS. Then, the tongue coating was scraped and weighed to derive the wet weight of the tongue coating (WWTC). The percentage of the tongue coating area was calculated from the tongue images acquired under visible light. Mean color values (mCVs) for the UV fluorescence of the dorsal surface of the tongue were also computed.The reliabilities of the derived mCVs and percentage of the tongue coating area were acceptable (intraclass correlation coefficients, 0.907-0.947). The mCVs were more strongly correlated with WWTC than with the area, with mCV of modified lightness showing the strongest association (r = 0.785, P < .01). Finally, we suggested an estimation model for TCT based on the results.The results of this study suggest that both UV fluorescence of the dorsal tongue and the distribution area of tongue coating are useful parameters for the quantitative assessment of tongue coating. We believe that these findings will contribute to the development of a clinically useful CTIS.

Background: With the expected growth in the elderly segment of the U.S. population particularly in women, the prevalence of valvular heart disease is bound to increase in the coming years. We sought to delineate the impact of gender on in-hospital clinical outcomes in Medicare-age patients undergoing isolated left-side heart valve surgery., Methods: Using the National Inpatient Sample files from 2003 to 2014, we compared the in-hospital major adverse cardiac and cerebral events (MACCE: all-cause mortality, stroke, or myocardial infarction) and composite complications (MACCE, permanent pacemaker implantation, bleeding requiring transfusion, iatrogenic vascular complications, acute respiratory failure, acute kidney injury requiring hemodialysis, sepsis and prolonged hospital stay) following isolated mitral or aortic surgery between genders with 1:1 propensity score analysis. Further, we examined gender-specific temporal trends of in-hospital clinical outcomes over the study period., Results: There were 336,506 isolated left-side heart valve surgeries over the study period. Following propensity score matching, 24,637 unweighted pairs were identified for gender-specific comparison. Female gender was independently associated with a higher in-hospital MACCE (9.4% vs. 8.3%; OR = 1.14, 95% CI = 1.07-1.21, P < 0.0001) driven mostly by all-cause mortality (5.2% vs. 4.3%; OR = 1.33, 95% CI = 1.12-1.33, P < 0.0001). The composite complication rate (37.9% vs. 35.3%; OR = 1.12, 95% CI-1.08-1.16, P < 0.0001) was also higher in women. Significant reduction in both in-hospital MACCE and all-cause mortality was observed over time regardless of gender., Conclusions: Following isolated left-side heart valve surgery, women experienced higher in-hospital MACCE including all-cause mortality compared to men. Continued temporal improvements in in-hospital clinical outcomes were observed in both genders., Summary for the Annotated Table of Contents: The influence of gender on surgical aortic or mitral valve replacement/repair outcome is unclear. The current study showed that women fared worse than men including all-cause mortality following isolated left-side valve surgery and significant temporal improvements have been made in in-hospital clinical outcomes in both genders during the 12-year study period. Further research in gender-specific approach in management of valve disease is warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Reproducible sample preparation remains a significant challenge in large-scale clinical research using selected reaction monitoring-mass spectrometry (SRM-MS), which enables a highly sensitive multiplexed assay. Although automated liquid-handling platforms have tremendous potential for addressing this issue, the high cost of their consumables is a drawback that renders routine operation expensive. Here we evaluated the performance of a liquid-handling platform in preparing serum samples compared with a standard experiment while reducing the outlay for consumables, such as tips, wasted reagents, and reagent stock plates. A total of 26 multiplex assays were quantified by SRM-MS using four sets of 24 pooled human serum aliquots; the four sets used a fixed number (1, 4, 8, or 24) of tips to dispense digestion reagents. This study demonstrated that the use of 4 or 8 tips is comparable to 24 tips (standard experiment), as evidenced by their coefficients of variation: 13.5% (for 4 and 8 tips) versus 12.0% (24 tips). Thus we can save 37% of the total experimental cost compared with the standard experiment, maintaining nearly equivalent reproducibility. The routine operation of cost-effective liquid-handling platforms can enable researchers to process large-scale samples with high throughput, adding credibility to their findings by minimizing human error.

Background: Discovering reliable protein biomarkers is one of the most important issues in biomedical research. The ELISA is a traditional technique for accurate quantitation of well-known proteins. Recently, the multiple reaction-monitoring (MRM) mass spectrometry has been proposed for quantifying newly discovered protein and has become a popular alternative to ELISA. For the MRM data analysis, linear mixed modeling (LMM) has been used to analyze MRM data. MSstats is one of the most widely used tools for MRM data analysis that is based on the LMMs. However, LMMs often provide various significance results, depending on model specification. Sometimes it would be difficult to specify a correct LMM method for the analysis of MRM data. Here, we propose a new logistic regression-based method for Significance Analysis of Multiple Reaction Monitoring (LR-SAM)., Results: Through simulation studies, we demonstrate that LMM methods may not preserve type I error, thus yielding high false- positive errors, depending on how random effects are specified. Our simulation study also shows that the LR-SAM approach performs similarly well as LMM approaches, in most cases. However, LR-SAM performs better than the LMMs, particularly when the effects sizes of peptides from the same protein are heterogeneous. Our proposed method was applied to MRM data for identification of proteins associated with clinical responses of treatment of 115 hepatocellular carcinoma (HCC) patients with the tyrosine kinase inhibitor sorafenib. Of 124 candidate proteins, LMM approaches provided 6 results varying in significance, while LR-SAM, by contrast, yielded 18 significant results that were quite reproducibly consistent., Conclusion: As exemplified by an application to HCC data set, LR-SAM more effectively identified proteins associated with clinical responses of treatment than LMM did.