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Semiconductor intellectual property (SIP) represents a crucial component of integrated circuit design activities. However, many small SIP firms fail to create value and adopt a viable business model. This article aims to investigate the value creation mechanism within the SIP business by drawing on the business model and dynamic capabilities views of the firm. First, the authors classify the forms and types of SIP from a technology and market perspective. Analyzing ten leading SIP firms, three SIP business models based on resources, competencies, and strategies are then identified. Dynamic capabilities are then linked to the selection and implementation of classified business models. Findings of the study suggest that existing SIP business models primarily favor large vendors. Keystone business model is proposed as a possible successful business model for small vendors. Consequently, this article provides insights and opportunities for leveraging the SIP ecosystem and business model innovation for small firms in the industry.

Objectives This study assessed the efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations in adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). Methods PubMed, Web of Science, the Cochrane Library, Ovid MEDLINE, Embase and EBSCO databases were searched for randomized controlled trials (RCTs) published before September 13, 2020. Only RCTs comparing the treatment efficacy of novel β-lactam/β-lactamase inhibitor combinations with other antibiotics for HAP/VAP in adult patients were included in this integrated analysis. Results Three RCTs were included, and no significant difference in clinical cure rate of the test of cure (TOC) was observed between the novel β-lactam/β-lactamase inhibitor combination and comparators (odds ratio [OR], 1.01; 95% CI, 0.81-1.27; I2 = 35%). The 28-day all-cause mortality was 16.2% and 17.6% for patients receiving the novel β-lactam/β-lactamase inhibitor combination and those receiving comparators, respectively, and no significant difference was noted (OR, 0.90; 95% CI, 0.69-1.16; I2 = 11%). Compared with the comparators, the novel β-lactam/β-lactamase inhibitor combination was associated with a similar microbiological response (OR, 1.06; 95% CI, 0.73-1.54; I2 = 64%) and a similar risk of AEs (treatment-emergent AEs [TEAEs]: OR, 1.04; 95% CI, 0.83-1.30; I2 = 0%; serious AEs: OR, 1.14; 95% CI, 0.79-1.63; I2 = 68%; treatment discontinuation for TEAE: OR, 0.90; 95% CI, 0.62-1.31; I2 = 11%). Conclusions The clinical and microbiological responses of novel β-lactam/β-lactamase inhibitor combinations in the treatment of HAP/VAP were similar to those of other available antibiotics. These combinations also shared a similar safety profile to that of comparators.

In image processing, smoke may degrade visibility and deteriorate the performance of high-level vision applications. Therefore, single image smoke removal is crucial for computer vision. Currently, existing smoke removal algorithms mainly leverage handcrafted priors. Moreover, these methods usually apply haze removal methods to perform smoke removal due to the similarity between smoke and haze. However, these methods cannot sufficiently address the degradation of thick smoke and may suffer from residual smoke and color distortion problems due to the non-global and non-homogeneous distribution of smoke. In this paper, to solve the aforementioned problems, an end-to-end deep neural network called DesmokeNet is proposed. We construct a two-stage recovered pipeline to remove the smoke in different thicknesses. The light and thick smoke is first removed locally by the smoke removal network (SRN). The missing pixels in the thick smoke are then recovered by the pixel compensation network (PCN). Moreover, we proposed the thickness-aware pixel loss and the dark channel loss to suppress the residual smoke. To further increase the discriminative ability of the DesmokeNet, we proposed self-attentive feature consensus loss and multi-level contrastive regularization loss to improve the performance of smoke removal. Finally, to train the proposed method, we construct the first large-scale dataset containing synthetic and real-world data. Extensive experiments show that the proposed method outperforms favorably against other state-of-the-art methods quantitatively and qualitatively.

STUDY OBJECTIVES: Biological models suggest that obstructive sleep apnea (OSA) is potentially carcinogenic. We aimed to clarify the inconsistent epidemiological literature by considering various traditional and novel OSA severity indices. METHODS: We systematically searched PubMed, Embase, Scopus, and the Cochrane Library for observational or randomized studies of associations of OSA, measured by diagnostic codes or any index, each with all-cancer incidence or mortality in adults, compared with participants with no/mild OSA. Two reviewers independently selected studies, extracted data, and evaluated study bias using the Newcastle-Ottawa scale and quality of evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). We performed inverse variance-weighted, random-effects meta-analyses and sensitivity analyses. RESULTS: We included 20 observational studies (5,340,965 participants), all with moderate/low bias, from 1,698 records. Based on T90 (sleep duration with oxygen saturation < 90%), patients with OSA who had moderate (T90 > 1.2%, hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.07–1.54) and severe nocturnal hypoxemia (T90 > 12%, HR = 1.43, 95% CI = 1.16–1.76) experienced 30%–40% higher pooled all-cancer risk than normoxemic patients, after multiple adjustment for covariates including obesity. Furthermore, severe nocturnal hypoxemia nearly tripled all-cancer mortality (HR = 2.66, 95% CI = 1.21–5.85). Patients with apnea-hypopnea index–defined severe OSA, but not moderate OSA, had higher all-cancer risk (HR = 1.18, 95% CI = 1.03–1.35) but similar all-cancer mortality as patients without OSA. An OSA diagnosis was not associated with all-cancer risk. Evidence quality ranged from low to moderate. Insufficient evidence was available on the oxygen desaturation index, lowest/median saturation, and arousal index. CONCLUSIONS: In patients with OSA, nocturnal hypoxemia is independently associated with all-cancer risk and mortality. Future studies should explore if risk differs by cancer type, and whether cancer screening and OSA treatment are beneficial. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220836; Identifier: CRD42021220836. CITATION: Tan BKJ, Teo YH, Tan NKW, et al. Association of obstructive sleep apnea and nocturnal hypoxemia with all-cancer incidence and mortality: a systematic review and meta-analysis. J Clin Sleep Med. 2022;18(5):1427–1440.

COVID-19 has not only affected the respiratory but the cardiovascular system. Taiwan has encountered a less severe COVID-19 pandemic. We reported the current situation in Taiwan. In this study, we retrospectively analyzed the data from our cardio-oncology program since October of 2019 to April of 2020 (the initial months of COVID-19 pandemic). In our cardio-oncology program, newly diagnosed breast cancer patients preparing for epirubicin therapy were included. Echocardiography, 6-min walking distance and major adverse cardiovascular events (MACEs) were recorded. To evaluate whether the social atmosphere affects cardio-oncology care, we analyzed the objective (physical) and subjective (emotional) parameters before and after January 21, 2020, when the first case of COVID-19 was confirmed in Taiwan. There was no significant decrease in patients’ return ratio and LVEFs. However, there was a trend of subjective shortness of breath reported by the patients but no decline in 6 MWT. Notably, none of the enrolled patients reported MACEs during the COVID pandemic. We observed an impact of anxiety on patients receiving epirubicin but it did not influence their return ratio.

Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies.Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years.The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies.Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.

RATIONALE In 2020, lung cancer was the leading cause of cancer deaths, and was the most common cancer in men. Though obstructive sleep apnea (OSA) has been postulated to be carcinogenic, epidemiological studies are inconclusive. OBJECTIVES We conducted this systematic review and meta-analysis to investigate the associations between OSA and the incidence and mortality of lung cancer. METHODS Four electronic databases (PubMed, Embase, Cochrane Library, and Scopus) were searched from inception till 6 June 2021 for randomized controlled trials and observational studies examining the association between sleep apnea and incident lung cancer. Two reviewers selected studies, extracted data, graded the risk of bias using the Newcastle-Ottawa scale and the quality of evidence using GRADE. Random-effects models were used to meta-analyze the maximally covariate-adjusted associations. RESULTS Seven studies were included in our systematic review; among which four were suitable for meta-analysis, comprising a combined cohort of 4,885,518 patients. Risk of bias was low to moderate. OSA was associated with a higher incidence of lung cancer (HR 1.25, 95%CI 1.02 to 1.53), with substantial heterogeneity (I²=97%). Heterogeneity was eliminated, with a stable pooled effect size, when including the three studies with at least 5 years of median follow-up (HR 1.32, 95%CI 1.27 to 1.37, I²=0%). CONCLUSIONS In this meta-analysis of 4,885,518 patients from four observational studies, patients with OSA had approximately 30% higher risk of lung cancer, compared to those without OSA. We suggest more clinical studies with longer follow-up as well as biological models of lung cancer be performed to further elucidate this relationship.

PURPOSE The US Food and Drug Administration has granted regulatory approval for the use of nivolumab—an immune checkpoint inhibitor (ICI)—in the first-line treatment of advanced gastric or esophageal adenocarcinoma (GEAC), regardless of programmed death-ligand 1 (PD-L1) expression. However, the efficacy of ICIs in low PD-L1–expressing tumors remains unclear. MATERIALS AND METHODS This study aims to reconstruct unreported Kaplan-Meier (KM) plots of PD-L1 combined positive score (CPS) subgroups of randomized phase III trials comparing the addition of ICIs with conventional chemotherapy in the first-line treatment of GEAC. A graphical reconstructive algorithm was adopted to estimate time-to-event outcomes from reported overall survival and progression-free survival (OS and PFS) KM plots describing overall or subgroup cohorts. Using reconstructed time-to-event outcomes, KMSubtraction conducts bipartite matching of patients from the reported subgroup among the overall cohort. By excluding matched patients, KM plots and survival analyses of the unreported subgroups were retrieved. RESULTS CheckMate-649, KEYNOTE-062, and KEYNOTE-590 were included. Two PD-L1 subgroups were identified with data unreported in the primary manuscripts: PD-L1 CPS 1-4 from CheckMate-649 and PD-L1 CPS 1-9 from KEYNOTE-062. No significant differences in OS and PFS were demonstrated in ICI-chemotherapy combinations when compared with chemotherapy among CheckMate-649 PD-L1 CPS 1-4 (OS: hazard ratio [HR] = 0.950, 95% CI, 0.747 to 1.209, P = .678; PFS: HR = 0.958, 95% CI, 0.743 to 1.236, P = .743) and KEYNOTE-062 PD-L1 CPS 1-9 subgroups. In the KEYNOTE-062 PD-L1 CPS 1-9 subgroup, patients treated with pembrolizumab had an increased hazard of tumor progression (HR = 2.092, 95% CI, 1.661 to 2.635, P < .001). CONCLUSION Using KMSubtraction, data of PD-L1 subgroups previously unreported by primary manuscripts of pivotal clinical trials were retrieved. These data suggest the lack of benefit in the addition of ICI to chemotherapy in low PD-L1–expressing GEAC tumors.

Background Chest pain is the most common symptom of aortic dissection (AD), but it is often confused with other prevalent cardiopulmonary diseases. We aimed to develop deep-learning models (DLMs) with ECG and CXR features to detect AD and evaluate their performance. Methods This study included 43,473 patients in the emergency department (ED) between July 2012 and December 2019 for retrospective DLM development. A development cohort including 49,071 ED records (120 AD-type A and 64 AD-type B) was used to train DLMs for ECG and CXR, and 9,904 independent ED records (40 AD-type A and 34 AD-type B) were used to validate DLM performance. Human–machine competitions of ECG and CXR were conducted. Patient characteristics and laboratory results were used to enhance the diagnostic accuracy. The DLM-enabled AD diagnostic process was prospectively evaluated in 25,885 ED visits. Results The AUCs of the ECG and CXR models were 0.918 and 0.857 for detecting AD in a human–machine competition, respectively, which were better than those of the participating physicians. In the validation cohort, the AUCs of the integrated model were 0.882, 0.960, and 0.813 in all AD, AD-type A, and AD-type B patients, respectively, with a sensitivity of 100.0% and a specificity of 81.7% for AD-type A. In patients with chest pain and D-dimer tests, the DLM could predict more precisely, achieving a positive predictive value of 62.5% in the prospective evaluation. Conclusions DLMs may serve as decision-supporting tools for AD identification and facilitate differential diagnosis in patients with acute chest pain.

Background To identify the outcome-associated predictors and develop predictive models for patients receiving targeted temperature management (TTM) by artificial neural network (ANN). Methods The derived cohort consisted of 580 patients with cardiac arrest and ROSC treated with TTM between January 2014 and August 2019. We evaluated the predictive value of parameters associated with survival and favorable neurologic outcome. ANN were applied for developing outcome prediction models. The generalizability of the models was assessed through 5-fold cross-validation. The performance of the models was assessed according to the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results The parameters associated with survival were age, duration of cardiopulmonary resuscitation, history of diabetes mellitus (DM), heart failure, end-stage renal disease (ESRD), systolic blood pressure (BP), diastolic BP, body temperature, motor response after ROSC, emergent coronary angiography or percutaneous coronary intervention (PCI), and the cooling methods. The parameters associated with the favorable neurologic outcomes were age, sex, DM, chronic obstructive pulmonary disease, ESRD, stroke, pre-arrest cerebral-performance category, BP, body temperature, motor response after ROSC, emergent coronary angiography or PCI, and cooling methods. After adequate training, ANN Model 1 to predict survival achieved an AUC of 0.80. Accuracy, sensitivity, and specificity were 75.9%, 71.6%, and 79.3%, respectively. ANN Model 4 to predict the favorable neurologic outcome achieved an AUC of 0.87, with accuracy, sensitivity, and specificity of 86.7%, 77.7%, and 88.0%, respectively. Conclusions The ANN-based models achieved good performance to predict the survival and favorable neurologic outcomes after TTM. The models proposed have clinical value to assist in decision-making.

In this paper, we study the problem of federated learning over a wireless channel with user sampling, modeled by a fading multiple access channel, subject to central and local differential privacy (DP/LDP) constraints. It has been shown that the superposition nature of the wireless channel provides a dual benefit of bandwidth efficient gradient aggregation, in conjunction with strong DP guarantees for the users. Specifically, the central DP privacy leakage has been shown to scale as $\mathcal {O}(1/K^{1/2})$ , where $K$ is the number of users. It has also been shown that user sampling coupled with orthogonal transmission can enhance the central DP privacy leakage with the same scaling behavior. In this work, we show that, by jointly incorporating both wireless aggregation and user sampling, one can obtain even stronger privacy guarantees. We propose a private wireless gradient aggregation scheme, which relies on independently randomized participation decisions by each user. The central DP leakage of our proposed scheme scales as $\mathcal {O}(1/K^{3/4})$ . In addition, we show that LDP is also boosted by user sampling. We also present analysis for the convergence rate of the proposed scheme and study the tradeoffs between wireless resources, convergence, and privacy theoretically and empirically for two scenarios when the number of sampled participants are $(a)$ known, or $(b)$ unknown at the parameter server.

Whether the electrocardiography (ECG) serial changes predict outcomes in cardiac arrest survivors undergoing therapeutic hypothermia remains unclear.This retrospective observational study enrolled 366 adult nontraumatic cardiac arrest survivors who underwent therapeutic hypothermia in a tertiary transfer center during 2006-2018. The ECG at return of spontaneous circulation (ROSC), during hypothermia and after rewarming were analyzed. 295 cardiac arrest survivors were included. Compared with the survivors, the non-survivors had longer QRS durations at the ROSC (118.33 ± 32.47 ms vs 106.88 ± 29.78 ms, p 0.001) and after rewarming (99.26 ± 25.07 ms vs 93.03 ± 19.09 ms, p = 0.008). The enrolled patients were classified into 4 groups based on QRS duration at the ROSC and after rewarming, namely (1) narrow-narrow (narrow QRS at ROSC and narrow QRS after rewarming, n = 156), (2) narrow-wide (n = 29), (3) wide-narrow (n = 87), and (4) wide-wide (n = 23) group. The wide-wide group had the worst survival rates [odds ratio (OR) = 0.141, p = 0.001], followed by the narrow-wide group (OR 0.223, p = 0.003) and the wide-narrow group (OR 0.389, p = 0.003).In cardiac arrest survivors given therapeutic hypothermia, QRS durations at the ROSC, after rewarming and their changes may predict survival to hospital discharge.

Background Melanoma is the most aggressive and lethal form of skin cancer. While emerging in-vivo evidence suggests that intermittent hypoxia, a hallmark feature of obstructive sleep apnea (OSA), may induce melanoma tumorigenesis, the epidemiological association between OSA and melanoma has been inconsistent. Methods We performed a literature search of PubMed, Embase, Scopus and Cochrane Library from inception until 6 June 2021. Two reviewers independently selected randomized trials or observational studies that reported the association of OSA with melanoma incidence or mortality in adults, in comparison to participants with no OSA. Two reviewers independently extracted relevant data and assessed the quality of evidence using the GRADE framework and the Newcastle–Ottawa Scale (NOS). We pooled data using an inverse variance-weighted meta-analysis and ran pre-specified subgrourp analyses. Results The meta-analysis included six studies out of 1897 records, comprising a combined cohort of 5,276,451 patients. All studies were adjusted for covariates, with majority of studies adjusting for age (N=5) and sex (N = 4). Compared to those without OSA, patients with OSA had 71% higher pooled hazards of melanoma (HR = 1.71; 95% CI: 1.08–2.69, I2 = 99%). Subgroup analyses for studies with (1) median follow-up duration of at least five years, (2) prospective study design, (3) adjustment for obesity yielded HRs of 1.88 (95%CI:1.32–2.67, N = 5), 1.11 (95%CI:0.77–1.60, N = 2) and 1.52 (95%CI:0.75–3.08, N = 3) respectively. One study investigating the relationship between OSA and melanoma mortality detected no association. There were insufficient studies to assess publication bias. Conclusions Meta-analysis of mainly retrospective observational studies, with significant heterogeneity, suggests increased melanoma incidence in OSA patients. Future studies should prospectively explore the differential risk of melanoma for varying OSA severity, and whether timely OSA treatment may mitigate this risk.

Summary Background Excessive use of digital smart devices, including smartphones and tablet computers, could be a risk factor for myopia. We aimed to review the literature on the association between digital smart device use and myopia. Methods In this systematic review and meta-analysis we searched MEDLINE and Embase, and manually searched reference lists for primary research articles investigating smart device (ie, smartphones and tablets) exposure and myopia in children and young adults (aged 3 months to 33 years) from database inception to June 2 (MEDLINE) and June 3 (Embase), 2020. We included studies that investigated myopia-related outcomes of prevalent or incident myopia, myopia progression rate, axial length, or spherical equivalent. Studies were excluded if they were reviews or case reports, did not investigate myopia-related outcomes, or did not investigate risk factors for myopia. Bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklists for analytical cross-sectional and cohort studies. We categorised studies as follows: category one studies investigated smart device use independently; category two studies investigated smart device use in combination with computer use; and category three studies investigated smart device use with other near-vision tasks that were not screen-based. We extracted unadjusted and adjusted odds ratios (ORs), β coefficients, prevalence ratios, Spearman's correlation coefficients, and p values for associations between screen time and incident or prevalent myopia. We did a meta-analysis of the association between screen time and prevalent or incident myopia for category one articles alone and for category one and two articles combined. Random-effects models were used when study heterogeneity was high (I2>50%) and fixed-effects models were used when heterogeneity was low (I2≤50%). Findings 3325 articles were identified, of which 33 were included in the systematic review and 11 were included in the meta-analysis. Four (40%) of ten category one articles, eight (80%) of ten category two articles, and all 13 category three articles used objective measures to identify myopia (refraction), whereas the remaining studies used questionnaires to identify myopia. Screen exposure was measured by use of questionnaires in all studies, with one also measuring device-recorded network data consumption. Associations between screen exposure and prevalent or incident myopia, an increased myopic spherical equivalent, and longer axial length were reported in five (50%) category one and six (60%) category two articles. Smart device screen time alone (OR 1·26 [95% CI 1·00–1·60]; I2=77%) or in combination with computer use (1·77 [1·28–2·45]; I2=87%) was significantly associated with myopia. The most common sources of risk of bias were that all 33 studies did not include reliable measures of screen time, seven (21%) did not objectively measure myopia, and nine (27%) did not identify or adjust for confounders in the analysis. The high heterogeneity between studies included in the meta-analysis resulted from variability in sample size (range 155–19 934 participants), the mean age of participants (3–16 years), the standard error of the estimated odds of prevalent or incident myopia (0·02–2·21), and the use of continuous (six [55%] of 11) versus categorical (five [46%]) screen time variables Interpretation Smart device exposure might be associated with an increased risk of myopia. Research with objective measures of screen time and myopia-related outcomes that investigates smart device exposure as an independent risk factor is required. Funding None.

Objects This study compared the clinical efficacy and safety of anti-methicillin-resistant Staphylococcus aureus (MRSA) quinolones for treating acute bacterial skin and skin structure infections (ABSSSIs). Methods PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant articles from inception to July 21, 2021. RCTs comparing the clinical efficacy and safety of anti-MRSA quinolones with other antibiotics for treating adult patients with ABSSSIs were included. Results Six RCTs were included. A total of 1,264 and 1,307 participants received the anti-MRSA quinolone-based study group and the control group. In the study group receiving anti-MRSA quinolone-based treatment, 935, 246, and 83 patients received delafloxacin, levonadifloxacin, and acorafloxacin, respectively. No significant difference was observed in the clinical cure rate at test of cure between the study and control groups (OR, 1.08; 95% CI, 0.91-1.29; I2 = 0%). In patients with MRSA-associated ABSSSIs, the clinical cure rate (OR, 1.09; 95% CI, 0.71-1.65; I2 = 0%) and microbiological response rate (OR, 1.24; 95% CI, 0.48-3.21; I2 = 0%) of anti-MRSA quinolones were similar to those of other antibiotics. Conclusions The efficacy of anti-MRSA quinolone-based treatment is comparable to that of other anti-MRSA antibiotics for treating ABSSSIs.

Background This meta-analysis of randomized controlled trials (RCTs) investigated the usefulness of Janus kinase (JAK) inhibitors among hospitalized patients with COVID-19. Methods PubMed, Web of Science, the Cochrane Library, and Ovid MEDLINE were searched for RCTs published before 7 September 2021. Only RCTs that compared the clinical efficacy and safety of JAK inhibitors with other alternative treatments or placebos in the treatment of hospitalized patients with COVID-19 were included. Results Overall, patients receiving JAK inhibitors exhibited a lower 28-day mortality rate than the control group (risk ratio [RR], 0.60; 95% CI, 0.47–0.77; I2 = 0%). Compared with the control group, the study group also had a lower 14-day mortality rate (RR, 0.60; 95% CI, 0.42–0.85; I2 = 0%), a higher rate of clinical improvement (RR, 1.05; 95% CI, 1.02–1.09; I2 = 0%), and less need of mechanical ventilation or extracorporeal membrane oxygenation (RR, 0.64; 95% CI, 0.50–0.84; I2 = 0%). Finally, JAK inhibitor use was associated with a similar risk of adverse events and infections as that observed in the control group. Conclusions JAK inhibitors can help reduce mortality and improve clinical outcomes among hospitalized patients with COVID-19. Additionally, JAK inhibitors can be used safely in this clinical entity.

This study aimed to investigate whether early surgical decompression was associated with favorable neurological recovery in patients with traumatic spinal cord injury (tSCI). We searched PubMed and Embase from the database inception through December 2020 and selected studies comparing the impact of early versus late surgical decompression on neurological recovery as assessed by American Spinal Injury Association Impairment Scale (AIS) for adult patients sustaining tSCI. We pooled the effect estimates in random-effects models and quantified the heterogeneity by the

Cord blood transplantation (CBT) provides a treatment scheme for hematologic diseases and leukemia in both children and adults. However, adverse reactions and transplantation-related death may still occur in patients receiving CBT even when donor and recipient have fully matched HLA in high-resolution HLA typing analysis. Single nucleotide polymorphisms (SNPs) of HLA-related and unrelated genes are known to associate with disease status of patients with unrelated stem cell transplantation. In this study, the genomic regions ranging from 500 base pairs upstream to 500 base pairs downstream of the eight SNPs that were reported as transplantation determinants by Petersdorf et al. were analyzed to evaluate whether genetic variants were associated with the survival status of patients, and the risk for severe (grades 3–4) graft-versus-host disease (GVHD) or cytomegalovirus (CMV) infection/reactivation. The analyses were performed in the mode of recipient genotype, donor genotype, and recipient-donor mismatching, respectively. By analysis of sixty-five patients and their HLA-matched unrelated donors, we found that five SNPs were associated with patient survival which included the recipient genotype with SNPs of rs107822 in the RING1 gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene; and the recipient-donor mismatching with SNPs of rs9282369 in HLA-DOA gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene. Five SNPs were associated with the risk for severe GVHD which included the donor genotype with SNPs of rs213210 and rs2523675; the recipient genotype with SNPs of rs9281491 in the HCP5 gene; and the recipient-donor mismatching with SNPs of rs209130 in the TRIM27 gene, and rs986522 in the COL11A2 gene. Six SNPs were related to the risk for CMV infection/reactivation which included the donor genotype with SNPs of rs435766, rs380924, and rs2523957; and the recipient-donor mismatching with SNPs of rs2070120, rs17220087, and rs17213693 in the HLA-DOB gene; and rs435766 and rs380924 in the MICD gene. This study provides the basis for larger analyses and if the results are confirmed, a way of selecting better unrelated CBT candidate donors.

Background Z scores are the method of choice to report dimensions in pediatric echocardiography. Z scores based on body surface area (BSA) have been shown to cause systematic biases in overweight and obese children. Using aortic valve (AoV) diameters as a paradigm, the aims of this study were to assess the magnitude of z score underestimation in children with increased body mass index z score (BMI-z) and to determine if a predicting model with height and weight as independent predictors would minimise this bias. Methods In this multicentre, retrospective, cross-sectional study, 15,006 normal echocardiograms in healthy children 1-18 years old were analyzed. Residual associations with body size were assessed for previously published z score. BSA-based and alternate prediction models based on height and weight were developed and validated in separate training and validation samples. Results Existing BSA-based z scores incompletely adjusted for weight, BSA, and BMI-z and led to an underestimation of > 0.8 z score units in subjects with higher BMI-z compared with lean subjects. BSA-based models led to overestimation of predicted AoV diameters with increasing weight or BMI-z. Models using height and weight as independent predictors improved adjustment with body size, including in children with higher BMI-z. Conclusions BSA-based models result in underestimation of z scores in patients with high BMI-z. Prediction models using height and weight as independent predictors minimise residual associations with body size and generate well fitted predicted values that could apply to all children, including those with low or high BMI-z.

Topic To provide updated estimates on the global prevalence and number of people with diabetic retinopathy (DR) through 2045. Clinical Relevance The International Diabetes Federation (IDF) estimated the global population with diabetes mellitus (DM) to be 463 million in 2019 and 700 million in 2045. Diabetic retinopathy remains a common complication of DM and a leading cause of preventable blindness in the adult working population. Methods We conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020. Random effect meta-analysis with logit transformation was performed to estimate global and regional prevalence of DR, vision-threatening DR (VTDR), and clinically significant macular edema (CSME). Projections of DR, VTDR, and CSME burden were based on population data from the IDF Atlas 2019. Results We included 59 population-based studies. Among individuals with diabetes, global prevalence was 22.27% (95% confidence interval [CI], 19.73%–25.03%) for DR, 6.17% (95% CI, 5.43%–6.98%) for VTDR, and 4.07% (95% CI, 3.42%–4.82%) for CSME. In 2020, the number of adults worldwide with DR, VTDR, and CSME was estimated to be 103.12 million, 28.54 million, and 18.83 million, respectively; by 2045, the numbers are projected to increase to 160.50 million, 44.82 million, and 28.61 million, respectively. Diabetic retinopathy prevalence was highest in Africa (35.90%) and North American and the Caribbean (33.30%) and was lowest in South and Central America (13.37%). In meta-regression models adjusting for habitation type, response rate, study year, and DR diagnostic method, Hispanics (odds ratio [OR], 2.92; 95% CI, 1.22–6.98) and Middle Easterners (OR, 2.44; 95% CI, 1.51–3.94) with diabetes were more likely to have DR compared with Asians. Discussion The global DR burden is expected to remain high through 2045, disproportionately affecting countries in the Middle East and North Africa and the Western Pacific. These updated estimates may guide DR screening, treatment, and public health care strategies.

Aims Fabry cardiomyopathy (FC) is characterized by progressive left ventricular hypertrophy (LVH). Conventional echocardiography is not sensitive in detecting preclinical FC before the development of LVH. We aim to investigate whether myocardial deformation analysis is useful to detect preclinical FC before LVH. Methods and results One hundred and sixty patients carrying mutated gene were prospectively enrolled, including 86 patients without LVH and 74 patients with LVH. Another 33 healthy individuals were also included for comparison. Standard transthoracic two-dimensional, Doppler, tissue Doppler echocardiography and deformation analysis were performed. The mean age of the overall 193 subjects was 48 ± 15 years, with 51% men. Fabry patients with LVH were older, more often to be men. They also had the worst diastolic function as evidenced by the largest left atrium, lowest E/A, and highest E/e′ ratio. The global longitudinal strain (GLS) deteriorated with the development of LVH (control vs. LVH− patients vs. LVH+ patients = −21.2 ± 2.7 vs. −19.0 ± 2.9 vs. −16.5 ± 4.2%, P Conclusion Reduced GLS could be a marker of early FC before the development of LVH.

Background and Aim Biliary tract infection (BTI) is an inflammatory disease and commonly associated with bacteremia. Delays in diagnosis or treatment of BTI cause high morbidity and mortality. However, an early diagnosis depends on appropriate clinical investigations. Appropriate biomarkers are urgently needed to improve the BTI diagnostic rate. We hypothesized that intestinal fatty acid‐binding protein (I‐FABP) might be a potential biomarker for BTI diagnosis. Methods We examined data from subjects aged ≥18 years diagnosed with BTI, including cholangitis and cholecystitis, whose blood samples were adequate for I‐FABP and zonulin assessment. We also collected blood samples from healthy volunteers as the control group. We excluded subjects in both groups who received steroids, antibiotics, or probiotics within 1 month before hospital admission (BTI cohort) or participation in this research (controls). The main study endpoint was to compare the diagnostic ability of I‐FABP to detect BTI in comparison with high‐sensitivity C‐reactive protein (hs‐CRP) and zonulin. Results The study collected the data of 51 patients with BTI and 35 healthy subjects. The receiver operating characteristic (ROC) area under the curve (AUC) for I‐FABP was 0.884 (95% confidence interval [CI]: 0.814–0.954), numerically higher than that for hs‐CRP (0.880; 0.785–0.976) and zonulin (0.570; 0.444–0.697). We estimated that the optimal cutoff value of I‐FABP was 2.1 ng/mL (sensitivity: 0.804; specificity: 0.829) for the diagnosis of BTI. Conclusions In summary, this study suggests that I‐FABP may be a potential alternative biomarker to hs‐CRP for diagnosing BTI. Further research should verify the use of I‐FABP as a marker for BTI diagnosis, but also for other inflammatory diseases., Our study revealed the diagnostic performance of intestinal fatty acid‐binding protein (I‐FABP) was comparable to that of C‐reactive protein (CRP) and superior to zonulin for detecting biliary tract infection (BTI).

ObjectivesMAP4K3 (GLK) overexpression in T cells induces interleukin (IL)-17A production and autoimmune responses. GLK overexpressing T-cell population is correlated with severity of human systemic lupus erythematosus (SLE); however, it is unclear how GLK is upregulated in patients with SLE.MethodsWe enrolled 181 patients with SLE and 250 individuals without SLE (93 healthy controls and 157 family members of patients with SLE) in two independent cohorts from different hospitals/cities. Genomic DNAs of peripheral blood mononuclear cells were subjected to next-generation sequencing to identify GLK gene variants. The functional consequences of the identified GLK germline or somatic variants were investigated using site-directed mutagenesis and cell transfection, followed by reporter assays, mass spectrometry, immunoblotting, coimmunoprecipitation, and in situ proximity ligation assays.ResultsWe identified 58 patients with SLE from Cohort #1 and #2 with higher frequencies of a somatic variant (chr2:39 477 124 A>G) in GLK 3′-untranslated region (UTR); these patients with SLE showed increased serum anti-double-stranded DNA levels and decreased serum C3/C4 levels. This somatic variant in 3′-UTR enhanced GLK mRNA levels in T cells. In addition, we identified five patients with SLE with GLK (A410T) germline variant in Cohort #1 and #2, as well as two other patients with SLE with GLK (K650R) germline variant in Cohort #1. Another GLK germline variant, A579T, was also detected in one patient with SLE from Cohort #2. Both GLK (A410T) and GLK (K650R) mutants inhibited GLK ubiquitination induced by the novel E3 ligase makorin ring-finger protein 4 (MKRN4), leading to GLK protein stabilisation.ConclusionsMultiple GLK germline and somatic variants cause GLK induction by increasing mRNA or protein stability in patients with SLE.

Background With emerging evidence on the efficacy of adding dapagliflozin to standard care for patients with heart failure with reduced ejection fraction (HFrEF), this study assessed the cost-effectiveness of add-on dapagliflozin to standard care versus standard care alone for HFrEF from the perspective of healthcare systems in the Asia–Pacific region. Methods A Markov model was applied to project the outcomes of treatment in terms of lifetime medical cost and quality-adjusted life-years. The transition probabilities between health states in the model were obtained from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. Country-specific costs and utilities were extracted for modeling. The incremental cost-effectiveness ratio against a country-specific willingness-to-pay threshold was applied to determine the cost-effectiveness of treatment. A series of sensitivity analyses were performed to ensure the robustness of the study results. Costs are presented in 2020 United States dollars. Results The incremental cost-effectiveness ratios for add-on dapagliflozin versus standard care alone were $5277, $9980, $12,305, $16,705, and $23,227 per quality-adjusted life-year gained in Korea, Australia, Taiwan, Japan, and Singapore, respectively. When using add-on dapagliflozin to standard care versus standard care alone, ~ 100% of simulations were cost-effective at a willingness-to-pay threshold of one gross domestic product per capita of the given Asia–Pacific country; however, the probability of being cost-effective for using add-on dapagliflozin decreased when the time horizon for simulation was restricted to 18 months and when the cardiovascular mortality for the two treatments (43.8% and 33.0%, respectively) was assumed to be the same. The cost-effectiveness results were most sensitive to cardiovascular mortality of treatment. Conclusions Adding dapagliflozin to standard care is cost-effective for HFrEF in healthcare systems in the Asia–Pacific region, which supports the rational use of dapagliflozin for HFrEF in this region.

The highly infectious and serious nature of coronavirus disease 2019 (COVID-19) has highlighted the need for hospital space disinfection technology and the prevention of human exposure to pathogenic environments. This research developed novel chlorine dioxide (ClO2) sterilization technology to reduce bacteria and viruses in the air and on surfaces. A smart sterilization robot system was also developed to spray disinfectants in operating theaters or patients’ rooms, designed according to the results of controlled experiments and the requirements for hospital disinfection. The system was built incorporated a semi-automatic remote-controlled module and an automatic intelligent disinfection function; that is, it could operate independently according to specific epidemic prevention strategies, which were implemented using a combination of Internet of Things (IoT) applications and a gesture recognition function. The elimination of Escherichia coli ( E. coli ) bacteria on sample plates was 99.8 % effective. This paper reviews the evolution of various disinfection technologies and describes a disinfection robot system in detail.

BACKGROUND AND AIM Pancreatic elastase-1 (PE-1) has been investigated in pancreatic disorders. However, the reference interval (RI) of PE-1 in blood remains unconfirmed. We aimed to establish the blood RI of PE-1 in an adult population. METHODS In this prospective cross-sectional study, we enrolled 400 adults who had received the whole-body physical check-up program between May 1, 2019 and November 20, 2019. The serum and plasma PE-1 levels were measured by latex turbidimetric immunoassay in different storage conditions (fresh, refrigerated, and frozen). The 95% and 99% RI of PE-1 were calculated according to the Clinical & Laboratory Standards Institute guidelines. The correlations between PE-1 and other parameters were analyzed using multivariable regression models. Ultimately, 38 patients with acute pancreatitis were prospectively recruited as the validation cohort. RESULTS The PE-1 levels in fresh serum were highly correlated with those in refrigerated (R2 = 0.998) or frozen (R2 = 0.942) samples; however, plasma should not be suggested in frozen conditions (plasma vs serum: R2 = 0.185). In the RI study population (202 male & 198 female participants), the median age was 52.6 (25-75% interquartile range: 43.1-61.0). The 95% and 99% RIs of PE-1 were 30.0-221.0 and 22.0-359.0 ng/dL, respectively. Triglycerides (β = 0.106, P = 0.033), lipase (β = 0.154, P = 0.007), and CA19-9 (β = 0.130, P = 0.008) were independent factors associated with PE-1. In the pancreatitis validation cohort, with a cut-off value of 359.0 ng/dL, the sensitivity and specificity were 100% and 99.8%, respectively. CONCLUSION The RI of PE-1 established in this study can be used for further applications. Serum is the suggested form for frozen sample storage.

Purpose: To construct, apply, and evaluate a multidisciplinary approach in teaching radiology to Canadian medical students. Methods: A multidisciplinary team of radiology and other disciplines experts designed an online 5-session course that was delivered to medical students. The topics of each session were clinical cases involving different systems. The target audience was medical students of Canadian schools. Pretests and post-tests were administered before and after each session respectively. An evaluation survey was distributed at the end of the course to gauge students’ perceptions of this experience. Results: An average of 425 medical students attended the live sessions. For each session, 405 students completed both the pre-tests and post-tests. In general, students scored an average of 56% higher on the post-test than on the pre-test. The final course survey was completed by 469 students. The survey results show that more than 98% of students found the course to meet or exceed their expectations. Over 80% of students agreed that the course increased their interest in radiology and about 81% agree that the topics presented were excellent and clinically important. The ratings in the final survey results also indicate that students increased their confidence in basic radiology skills after completing the course. Conclusions: The implementation of an integrative clinical approach to teaching radiology in a virtual setting is achievable. It provides efficient use of educational resources while being accessible by a large number of students across different medical schools.

Patients with head and neck cancer (HNC) are vulnerable to psychiatric comorbidities, particularly anxiety and depression, and also suffer from cancer stigma. This study aimed to comprehensively compare HNC patients’ stigma, depression, and anxiety, and elucidate the underlying relationships among them. This cross-sectional study recruited inpatients with HNC from a medical center. Measurements included a psychiatric diagnostic interview, the Shame and Stigma Scale (SSS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Explanatory Model Interview Catalogue (EMIC), and stressors of HNC patients. Structural equation modeling was used to establish models of potential mechanisms. Those patients having stressors of worry about health (t = 5.21, p

Type 2 diabetes mellitus (T2DM) is one of the fastest growing public health concerns around the world. Sugar-sweetened beverage (SSB) consumption has been proven to be associated with adverse health consequences in the diabetic population. Reducing SSB consumption, body weight control, healthy diets, and increased physical activity have been suggested as strategies to improve diabetes prevention and management. This literature review provides an overview of: (1) The association between SSB consumption and the risk of T2DM; (2) Types of SSB consumption and T2DM; (3) The effect of obesity and inflammation on the association between SSB consumption and risk of T2DM; and (4) SSB consumption in T2DM patients. There is still work to be done to determine how SSB consumption is related to T2DM, but the current research on identifying the association between SSB consumption and T2DM is promising, with the most promising studies confirming the connection between SSBs, T2DM risk, and diabetes management. Future studies should explore more effective SSB related diabetes prevention and management interventions.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case‐control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53‐2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04‐1.85) (heterogeneity‐P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2‐deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Objectives Cognitive impairment is an important non-motor aspect of Parkinson's disease (PD). Amyloid-β and tau pathologies are well-established in Alzheimer's disease and commonly coexist with synucleinopathy in PD. However, the levels of these biomarkers in the plasma of patients with PD and their relationship with specific cognition domains remain to be clarified. The current study compared the motor severity and neuropsychological assessment of general and specific cognition, with plasma levels of α-synuclein (α-syn), amyloid-β 42 (Aβ42), and total tau (t-tau) in PD subjects. Methods Plasma levels of α-syn, Aβ42, and t-tau were measured in 55 participants with PD through immunomagnetic reduction assay. The evaluation of motor severity and comprehensive neuropsychological assessment was performed in all participants. Results The level of plasma α-syn was negatively correlated with the scores of Unified Parkinson's Disease Rating Scale part III [r = (-.352), p = .008]. The level of plasma t-tau was negatively correlated with the scores of digits recall forwards and digits recall backwards [r = (-.446), p = .001; r = (-.417), p = .002, respectively]. No correlations were found between the levels of α-syn and Aβ42 and any neuropsychological tests. Conclusions This study concluded a lower level of plasma α-syn was correlated with motor dysfunction in PD patients, and a higher level of plasma t-tau was correlated with lower cognitive performance, especially for attention and executive function. These results propose the possibility of using plasma biomarkers to predict specific cognitive performance in PD subjects.

Background Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and a highly variable survival rate. Few studies have focused on outcomes in rural and urban groups while also evaluating underlying diseases and prehospital factors for OHCAs. Objective To investigate the relationship between the patient's underlying disease and outcomes of OHCAs in urban areas versus those in rural areas. Methods We reviewed the emergency medical service (EMS) database for information on OHCA patients treated between January 2015 and December 2019, and collected data on pre-hospital factors, underlying diseases, and outcomes of OHCAs. Univariate and multivariate logistic regression analyses were used to evaluate the prognostic factors for OHCA. Results Data from 4225 OHCAs were analysed. EMS response time was shorter and the rate of attendance by EMS paramedics was higher in urban areas (p 24-h survival (odds ratio [OR] = 1.437, 95% confidence interval [CI]: 1.179–1.761). Age (OR = 0.986, 95% CI: 0.979–0.993). EMS response time (OR = 0.854, 95% CI: 0.811–0.898), cardiac arrest location (OR = 2.187, 95% CI: 1.707–2.795), attendance by paramedics (OR = 1.867, 95% CI: 1.483–2.347), and prehospital defibrillation (OR = 2.771, 95% CI: 2.154–3.556) were independent risk factors for survival to hospital discharge, although the influence of an urban area was not significant (OR = 1.211, 95% CI: 0.918–1.584). Conclusions Compared with rural areas, OHCA in urban areas are associated with a higher 24-h survival rate. Shorter EMS response time and a higher probability of being attended by paramedics were noted in urban areas. Although shorter EMS response time, younger age, public location, defibrillation by an automated external defibrillator, and attendance by Emergency Medical Technician-paramedics were associated with a higher rate of survival to hospital discharge, urban area was not an independent prognostic factor for survival to hospital discharge in OHCA patients.

Aims The Registry to Evaluate Early and Long‐Term PAH Disease Management (REVEAL) risk scores differentiate survivals in patients with pulmonary arterial hypertension (PAH). However, measurements of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) in the peripheral blood may not adequately reflect early‐stage decompensated heart failure (HF). Given that right heart catheterization (RHC) can facilitate measurements of intracardiac NT‐proBNP, in this study our aim was to evaluate the predictive role of right ventricular (RV) NT‐proBNP measurements in patients with PAH. Methods and results We prospectively collected intracardiac blood samples for NT‐proBNP measurements from patients diagnosed with World Health Organization Group I PAH during RHC. Clinical information including the aetiology of PAH (idiopathic, connective tissue disease, or congenital heart disease) and REVEAL scores were recorded. The primary endpoint was hospitalization for decompensated HF; median duration of follow‐up was 28 months. Among the 62 patients evaluated, 12 reached the designated endpoint. REVEAL risk scores were higher among patients hospitalized for HF. We detected no significant differences in plasma NT‐proBNP levels in peripheral circulation, in the right atrium, or in pulmonary arterial blood; however, significantly higher levels of NT‐proBNP were detected in the RV in patients diagnosed with PAH. RV NT‐proBNP was a sensitive predictor (cut‐off value 1500 pg/mL) of subsequent hospitalization for HF. Our findings indicate that RV NT‐proBNP levels add predictive value to REVEAL scores with respect to future hospitalization due to HF. Conclusions Right ventricular NT‐proBNP levels combined with REVEAL 2.0 could predict the development of subsequent HF in patients with PAH and may be a potential biomarker.

The 5-nm-thick Mg0.05Sn0.95O x thin film deposited using mist chemical vapor deposition is used as a channel layer of the thin-film transistor (TFT). Mg0.05Sn0.95O x improves the crystallinity, reduces the number of oxygen deficiencies, and enlarges the energy bandgap compared with SnO2. Mg0.05Sn0.95O x -based TFT shows higher field-effect mobility (144.9 cm2V−1s−1), steeper subthreshold slope (134 mV/decade), and significant ON/OFF current ratio (>109) than the SnO2-based TFT. Owing to fewer oxygen-related defects, wide energy bandgaps, and stable Mg-O chemical bonding, the Mg0.05Sn0.95O x -based TFT exhibits more stable electrical performance than the SnO2 TFT after negative bias illumination stress testing. These results suggest that Mg0.05Sn0.95O x is a promising material for high electron mobility TFT applications.

BACKGROUND: Electroencephalography (EEG) findings following cardiovascular collapse in death are uncertain. We aimed to characterize EEG changes immediately preceding and following cardiac death. METHODS: We retrospectively analyzed EEGs of patients who died from cardiac arrest while undergoing standard EEG monitoring in an intensive care unit. Patients with brain death preceding cardiac death were excluded. Three events during fatal cardiovascular failure were investigated: (1) last recorded QRS complex on electrocardiogram (QRS(0)), (2) cessation of cerebral blood flow (CBF(0)) estimated as the time that blood pressure and heart rate dropped below set thresholds, and (3) electrocerebral silence on EEG (EEG(0)). We evaluated EEG spectral power, coherence, and permutation entropy at these time points. RESULTS: Among 19 patients who died while undergoing EEG monitoring, seven (37%) had a comfort-measures-only status and 18 (95%) had a do-not-resuscitate status in place at the time of death. EEG(0) occurred at the time of QRS(0) in five patients and after QRS(0) in two patients (cohort median − 2.0, interquartile range − 8.0 to 0.0), whereas EEG(0) was seen at the time of CBF(0) in six patients and following CBF(0) in 11 patients (cohort median 2.0 min, interquartile range − 1.5 to 6.0). After CBF(0), full-spectrum log power (p < 0.001) and coherence (p < 0.001) decreased on EEG, whereas delta (p = 0.007) and theta (p = 0.007) permutation entropy increased. CONCLUSIONS: Rarely may patients have transient electrocerebral activity following the last recorded QRS (less than 5 min) and estimated cessation of cerebral blood flow. These results may have implications for discussions around cardiopulmonary resuscitation and organ donation.

Constant DNA damage occurs in cells, and the cells are programmed to respond constitutively. This study explored the roles of ataxia-telangiectasia mutated interactor (ATMIN), one of the impaired pathways involving the DNA damage response (DDR) in mismatch repair-deficient [microsatellite instability (MSI)-high] colorectal carcinoma (CRC). Expression of ATMIN messenger RNA (mRNA) was detected in CRC specimens with microsatellite instability (MSI) characteristics. The effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were evaluated in MSI-high cell lines, and liver metastasis ability was investigated in vivo. Protein-protein interactions were assessed by coimmunoprecipitation analyses in vitro. Decreased ATMIN expression was positively correlated with advanced stage of disease (P < 0.05), lymph node metastases (P < 0.05), and deeper invasion (P < 0.05) in MSI-high tumors. Transient or stable ATMIN knockdown significantly increased cell motility. Moreover, in the high-throughput microarray and gene set enrichment analysis, ATMIN was shown to act on the Wnt-signaling pathway via PARP1. This cascade influences β-catenin/transcription factor 4 (TCF4) binding affinity in MSI-high tumors, and PARP1 inhibition significantly decreased the number of metastases from ATMIN knockdown cancer cells. The results not only indicated the critical role of ATMIN, but also shed new light on PARP1 inhibitors, providing a basis for further clinical trials of MSI-high CRC.

Objectives: To investigate the clinical efficacy and safety of ceftobiprole for acute bacterial skin and skin structure infections (ABSSSIs).Methods: PubMed, Web of Science, EBSO, Ovid Medline, ClinicalTrial.gov and Cochrane Library were searched until December 25, 2020. Only randomized controlled trials that compared the treatment efficacy of ceftobiprole with that of other antibiotics for adult patients with ABSSSIs were included in this meta-analysis.Results: The 3 RCTs involving 2291 adult patients with ABSSSIs were included. No significant difference in clinical success, as measured by the TOC, was observed between ceftobiprole and comparators among the intention-to-treat population (OR, 1.06; 95% CI, 0.85-1.33; I2 = 0%) and clinical evaluable population (OR, 1.17; 95% CI, 0.76-1.79; I2 = 17%). Ceftobiprole was associated with a similar risk of adverse events (AEs) to that of comparators (treatment-emergent AE [TEAE]: OR, 1.09; 95% CI, 0.92-1.29; I2 = 0%; serious AEs: OR, 0.84; 95% CI, 0.58-1.21; I2 = 0%; treatment discontinuation for TEAE: OR, 0.95; 95% CI, 0.61-1.49; I2 = 0%; death: OR, 0.30; 95% CI, 0.05-1.97; I2 = 0%).Conclusions: Ceftobiprole can achieve similar clinical and microbiological responses as alternative antibiotics in patients with ABSSSIs. In addition, ceftobiprole shares a similar safety profile to comparators.

This study investigates how ambient/carrier gases affect the material characteristics of amorphous indium–gallium–zinc oxide (a-InGaZnO) thin films deposited using the ultrasonic spray pyrolysis deposition (USPD) method. Nitrogen and air are used as the ambient/carrier gases in this study. The crystallinity, oxygen deficiency, energy bandgap, and trap level in the a-InGaZnO thin films are analyzed. The performance of the thin-film transistors (TFTs) based on a-InGaZnO with different ambient/carrier gases is investigated as well. It is found that oxygen deficiency is suppressed when air is used as the ambient/carrier gas. When nitrogen is used as the ambient/carrier gas to deposit a-InGaZnO thin film, the TFT shows higher field-effect mobility and saturation mobility. However, when the a-InGaZnO thin film is deposited with air as the ambient/carrier gas, the subthreshold swing, ON-/ OFF-current ratio, interface trap density, and stability of the TFT are improved. This study demonstrates how ambient/carrier gases in the USPD system affect the performance of a-InGaZnO TFT.

Background and Purpose Oral anticoagulants (OACs) prevent stroke recurrence and vascular embolism in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Based on empirical consensus, current guidance recommends a “1–3–6–12 days” rule to resume OACs after AIS. This study investigated the suitability of guideline-recommended timing for OAC initiation. Methods Using data of 12,307 AF patients hospitalized for AIS, for the period 2012 to 2016, in Taiwan's National Health Insurance Research Database, we constructed a sequence of cohorts of OAC users and propensity score-matched nonusers, creating one cohort on each day of OAC initiation for 30 days since admission. Composite outcome included effectiveness (cardiovascular death, ischemic stroke, myocardial infarction, transient ischemic attack, systemic embolism, and venous thromboembolism) and safety (intracranial hemorrhage, gastrointestinal bleeding, and hematuria) outcomes. Comparing with nonusers, we examined the risks in the early OAC use (within 1–3–6–12 days) or guideline-recommended delayed use. Indirect comparison between the early and delayed use was conducted using mixed treatment comparison. Results Across the AIS severity, the risks of composite or effectiveness outcome were lower in OAC users than nonusers, and the risks were similar between the early and delayed use groups. In patients with severe AIS, early OAC use was associated with an increased risk of safety outcome, with a hazard ratio (HR) of 1.67 (confidence interval [CI]: 1·30–2·13) compared with nonusers and a HR of 1.44 (CI: 0·99–2·09) compared with the delayed use. Conclusion Our study findings support an early OAC initiation in AF patients with mild-to-moderate AIS and a routine delayed use of OACs can be considered in those with severe AIS to avoid a serious bleeding event.

Introduction Screening for cryptococcal antigen (CrAg) is recommended for people living with HIV (PLWH) who present with low CD4 lymphocyte counts. Real-world experience is important to identify gaps between the guidelines and clinical practice. We investigated the trends of CrAg testing and prevalence of cryptococcal antigenemia among PLWH at the time of HIV diagnosis and the related mortality in Taiwan from 2009 to 2018. Methods Medical records of newly diagnosed PLWH seeking care at six medical centers around Taiwan between 2009 and 2018 were reviewed. The annual trends of PLWH who had CrAg testing and cryptococcal antigenemia were examined by Cochran-Armitage test. Among PLWH with CD4

Right ventricular (RV) function is a critical determinant of survival in patients with pulmonary arterial hypertension (PAH). While miR-21 is known to associate with vascular remodeling in small animal models of PAH, its role in RV remodeling in large animal models has not been characterized. Herein, we investigated the role of miR-21 in RV dysfunction using a sheep model of PAH secondary to pulmonary arterial constriction (PAC). RV structural and functional remodeling were examined using ultrasound imaging. Our results showed that post PAC, RV strain significantly decreased at the basal region compared with t the control. Moreover, such dysfunction was accompanied by increases in miR-21 levels. To determine the role of miR-21 in RV remodeling secondary to PAC, we investigated the molecular alteration secondary to phenylephrine induced hypertrophy and miR21 overexpression in vitro using neonatal rat ventricular myocytes (NRVMs). We found that overexpression of miR-21 in the setting of hypertrophic stimulation augmented only the expression of proteins critical for mitosis but not cytokinesis. Strikingly, this molecular alteration was associated with an eccentric cellular hypertrophic phenotype similar to what we observed in vivo PAC animal model in sheep. Importantly, this hypertrophic change was diminished upon suppressing miR-21 in NRVMs. Collectively, our in vitro and in vivo data demonstrate that miR-21 is a critical contributor in the development of RV dysfunction and could represent a novel therapeutic target for PAH associated RV dysfunction.

Among non-small cell lung cancer (NSCLC) patients with therapeutically targetable tumor mutations in epidermal growth factor receptor (EGFR), not all patients respond to targeted therapy. Combining circulating-tumor DNA (ctDNA), clinical variables, and radiomic phenotypes may improve prediction of EGFR-targeted therapy outcomes for NSCLC. This single-center retrospective study included 40 EGFR-mutant advanced NSCLC patients treated with EGFR-targeted therapy. ctDNA data included number of mutations and detection of EGFR T790M. Clinical data included age, smoking status, and ECOG performance status. Baseline chest CT scans were analyzed to extract 429 radiomic features from each primary tumor. Unsupervised hierarchical clustering was used to group tumors into phenotypes. Kaplan–Meier (K–M) curves and Cox proportional hazards regression were modeled for progression-free survival (PFS) and overall survival (OS). Likelihood ratio test (LRT) was used to compare fit between models. Among 40 patients (73% women, median age 62 years), consensus clustering identified two radiomic phenotypes. For PFS, the model combining radiomic phenotypes with ctDNA and clinical variables had c-statistic of 0.77 and a better fit (LRT p = 0.01) than the model with clinical and ctDNA variables alone with a c-statistic of 0.73. For OS, adding radiomic phenotypes resulted in c-statistic of 0.83 versus 0.80 when using clinical and ctDNA variables (LRT p = 0.08). Both models showed separation of K–M curves dichotomized by median prognostic score (p EGFR mutations.

Radiofrequency ablation (RFA) of medium-sized (3–5 cm) hepatocellular carcinoma (HCC) is suboptimal. Switching monopolar RFA (SW-RFA) enlarges the ablative volume to better cover larger tumors. This study aims to compare the long-term outcomes of medium-sized HCC treated by either SW-RFA or single-monopolar RFA (S-RFA). We retrospectively reviewed 139 cases (147 medium-size HCC) between 2008 and 2014. Under propensity score matching, a total of 43 paired patients with medium-size HCC and balanced clinical variables treated by either SW-RFA or S-RFA were selected for comparison. SW-RFA showed a higher rate of achieving an adequate safety margin (p = 0.002). After a mean follow-up period of 40.4 months, SW-RFA produced significantly lower global RFA failure rates (p < 0.001) and better overall survival (p = 0.005) compared to S-RFA. SW-RFA was independently associated with a decreased risk of global RFA failure (hazard ratio [HR]: 0.136, 95% confidence interval [CI]: 0.030–0.607, p = 0.009) and improved overall survival (HR: 0.337, 95% CI: 0.152–0.747, p = 0.007). By last follow-up, the SW-RFA group maintained a superior tumor-free rate (p = 0.010) and fewer progressions to Barcelona Clinic Liver Cancer stage C (p = 0.011). Major complication rates were comparable in both groups (SW-RFA: 2.3% vs. S-RFA: 4.7%, p = 1.000). The switching multi-monopolar ablation technique could be beneficial for patients with medium-sized HCCs given sustained control of larger tumors with better overall survival. • Switching monopolar ablation could provide a sustained local tumor control and better overall survival than single-monopolar ablation for the medium-sized hepatocellular carcinoma. • Compared to single-monopolar ablation, switching monopolar ablation could create a larger homogeneous coagulation volume by using a shorter total ablation time to achieve a higher rate of adequate safety margin for a medium-sized HCC. • Patients with medium-sized HCC can be maintained at a higher rate of tumor-free status and at a lower risk of progression into BCLC stage C in the follow-up period after ablation by switching monopolar than by single-monopolar ablation.