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Background: This study assessed health care system costs and resource utilization for adult women with breast cancer in Ontario, Canada. The goal was to update costs by stage, age, and phase of care from a health care system perspective., Data and Methods: A retrospective analysis was conducted using linked population-based administrative data. The study included women diagnosed with breast cancer from 2017 to 2021, with follow-up data until 2022. Cases were matched with controls in a 1:5 ratio using birth year, local health integrative network, income quintile, and resource utilization band at baseline. Incremental costs were estimated using linear regression. The modified income quintile was the neighbourhood- or area-level income quintile., Results: Among the 37,133 cases matched with 185,665 controls, the average age at diagnosis was 62 years. For the entire study duration, cases incurred an additional cost of $27,485 per year, compared with controls. Costs rose with disease severity, ranging from $15,588 for stage I to $137,319 for stage IV. The highest incremental costs occurred during the first 12 months after diagnosis (initial: $43,408), followed by the last 12 months before death (terminal: $25,940), and then interim years (continuous: $9,533 per year). Additionally, the incremental cost of breast cancer was higher when diagnosis was before age 70 ($28,415), compared with diagnosis at age 70 and older ($25,254)., Interpretation: The findings align with previous studies on breast cancer costs for the health care system. Additionally, variations in costs based on disease severity, care phase, and age were emphasized, highlighting higher costs for metastatic breast cancer cases, women younger than 70 years, and the initial 12 months following diagnosis.

The automatic generation of accurate radiology reports is of great clinical importance and has drawn growing research interest. However, it is still a challenging task due to the imbalance between normal and abnormal descriptions and the multi-sentence and multi-topic nature of radiology reports. These features result in significant challenges to generating accurate descriptions for medical images, especially the important abnormal findings. Previous methods to tackle these problems rely heavily on extra manual annotations, which are expensive to acquire. We propose a multi-grained report generation framework incorporating sentence-level image-sentence contrastive learning, which does not require any extra labeling but effectively learns knowledge from the image-report pairs. We first introduce contrastive learning as an auxiliary task for image feature learning. Different from previous contrastive methods, we exploit the multi-topic nature of imaging reports and perform fine-grained contrastive learning by extracting sentence topics and contents and contrasting between sentence contents and refined image contents guided by sentence topics. This forces the model to learn distinct abnormal image features for each specific topic. During generation, we use two decoders to first generate coarse sentence topics and then the fine-grained text of each sentence. We directly supervise the intermediate topics using sentence topics learned by our contrastive objective. This strengthens the generation constraint and enables independent fine-tuning of the decoders using reinforcement learning, which further boosts model performance. Experiments on two large-scale datasets MIMIC-CXR and IU-Xray demonstrate that our approach outperforms existing state-of-the-art methods, evaluated by both language generation metrics and clinical accuracy.

Background Context: Symptomatic lumbar spinal stenosis is routinely treated with spinal decompression surgery, with an increasing trend towards minimally invasive techniques. Endoscopic decompression has emerged as a technique which minimizes approach-related morbidity while achieving similar clinical outcomes to conventional open or microscopic approaches., Purpose: To assess the safety and efficacy of endoscopic versus microscopic decompression for treatment of lumbar spinal stenosis., Study Design: Systematic review and meta-analysis., Methods: A systematic review on randomized and nonrandomized studies comparing endoscopic versus microscopic decompression was conducted, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Treatment effects were computed using pairwise random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk-of-bias and ROBINS-I tools for randomized and nonrandomized trials respectively. Quality of the overall body of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system., Results: A total of 19 primary references comprising 1,997 patients and 2,132 spinal levels were included. Endoscopic decompression was associated with significantly reduced intraoperative blood-loss (weighted mean differences [WMD]=-33.29 mL, 95% CI:-51.80 to -14.78, p=.0032), shorter duration of hospital stay (WMD=-1.79 days, 95% CI: -2.63 to 0.95, p=.001), rates of incidental durotomy (RR = 0.63, 95% CI: 0.43 to 0.91, p=.0184) and surgical site infections (RR=0.23, 95% CI: 0.10 to-0.51, p=.001), and a nonsignificant trend towards less back pain, leg pain, and better functional outcomes compared to its microscopic counterpart up to 2-year follow up., Conclusions: Endoscopic and microscopic decompression are safe and effective techniques for treatment of symptomatic lumbar spinal stenosis. Prospective studies of larger power considering medium to long-term outcomes and rates of iatrogenic instability are warranted to compare potential alignment changes and destabilization from either techniques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) accounts for 60-70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10-15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer's Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician's early diagnosis and treatment plan design., (© 2024. The Author(s).)

Background: Apathy is an important but unrecognised aspect of Parkinson's disease (PD). The optimal therapeutic options for apathy remain unclear. Early recognition and treatment of apathy can reduce the significant burden of disease for patients and their caregivers. Here we conducted a meta-analysis to evaluate the comparative efficacy of different treatment modalities of apathy in PD (CRD42021292099)., Methods: We screened Medline, Embase, and PsycINFO databases for articles on therapies for apathy in PD. The outcome of interest is the reduction in apathy scores post-intervention and is measured by standardised mean differences (SMD) with 95% credible intervals (CrI). We included only randomised controlled trials examining interventions targeted at reducing apathy., Results: Nineteen studies involving 2372 patients were included in the quantitative analysis. The network meta-analysis found pharmacotherapy to be the most efficacious treatment, significantly better than brain stimulation (SMD -0.43, 95% CrI -0.78 to -0.07), exercise-based interventions (SMD -0.66, 95% CrI -1.25 to -0.08), supplements (SMD -0.33, 95% CrI -0.67 to 0), and placebo (SMD -0.38, 95% CrI -0.56 to -0.23). Subgroup analysis of pharmacotherapy versus placebo found similar efficacy of dopamine agonists (SMD -0.36, 95% CI -0.59 to -0.12, P  = 0.003) and alternative medications (SMD -0.42, 95% CI -0.61 to -0.23, P  < 0.001). The remaining comparisons and subgroup analyses did not demonstrate any significant treatment effects., Conclusion: Our meta-analysis of randomised controlled trials showed that pharmacotherapy is the most efficacious treatment option, with dopamine agonists having similar efficacy as other medications. Further research is needed to determine the optimal management strategy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Patients with hematologic malignancies (HMs) are at risk of future cardiovascular (CV) events. We therefore conducted a systematic review and meta-analysis to quantify their risk of future CV events. We searched Medline and EMBASE databases from inception until January 31, 2023 for relevant articles using a combination of keywords and medical subject headings. Studies examining CV outcomes in patients with HM versus controls without HM were included. The outcomes of interest included acute myocardial infarction (AMI), heart failure (HF), and stroke. The outcomes were expressed as hazard ratios (HRs) and their 95% confidence intervals (CIs). This study is registered with PROSPERO at CRD42022307814. A total of 15 studies involving 1,960,144 cases (178,602 patients with HM and 1,781,212 controls) were included in the quantitative analysis. A total of 10 studies examined the risk of AMI, 5 examined HF, and 11 examined stroke. Compared with the control group, the HRs for HM for AMI, HF, and stroke were 1.65 (95% CI 1.29 to 2.09, p <0.001), 4.82 (95% CI 3.72 to 6.25, p <0.001), and 1.60 (95% CI 1.30 to 1.97, p <0.001), respectively. The sensitivity analysis of stroke risk based on lymphoma type showed an increased risk of stroke in patients with non-Hodgkin lymphoma compared with controls (HR 1.31, 95% CI 1.04 to 1.64, p = 0.03) but no significant difference for Hodgkin lymphoma (HR 1.67, 95% CI 0.86 to 3.23, p = 0.08). Patients with HM are at increased risk of future AMI, HF, and stroke, and these findings suggest that CV care of patients with HM should be considered as a growing priority., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Importance: Suicide risk may be increased in patients with Parkinson disease (PD), a common neurodegenerative condition. Mood disorders, especially depression, are prevalent in patients with PD who report suicidality., Objective: To address inconsistent results from studies of suicidal ideation and behavior in patients with PD., Data Sources: The study team searched MEDLINE and Embase from inception to June 14, 2023, and further screened the bibliographies of relevant studies to ensure a comprehensive search., Study Selection: Original studies, published in English, discussing either suicidal ideation, behavior, or both in adults with PD were included. Accepted study designs included cross-sectional, case-control, and cohort studies. Studies that only included patients with PD after deep brain stimulation were excluded., Data Extraction and Synthesis: This meta-analysis was conducted in line with the PRISMA guidelines. Two authors reviewed each study and extracted the data independently, with discrepancies referred to a third independent author., Main Outcomes and Measures: Outcomes included the prevalence of suicidal ideation and behavior, measured as proportions, and the risk of suicidal behavior in patients with PD relative to controls, measured in both odds ratio (OR) and hazards ratio (HR)., Results: A total of 28 studies comprising 505 950 PD patients were included in the final analysis. The prevalence of suicidal ideation was evaluated in 14 studies (22.2%; 95% CI, 14.6-32.3) and suicidal behavior in 21 studies (1.25%; 95% CI, 0.64-2.41). Excluding 4 outliers, prevalence of suicidal behavior was significantly higher in prospective studies (1.75%; 95% CI, 1.03-2.95) than retrospective studies (0.50%; 95% CI, 0.24-1.01). Excluding 1 outlier, OR of suicidal behavior was pooled across 10 studies and significant (OR, 2.15; 95% CI, 1.22-3.78; P = .01). HR of suicidal behavior was assessed in 9 studies (HR, 1.73; 95% CI, 1.40-2.14; P < .001)., Conclusions and Relevance: This meta-analysis involving more than 500 000 patients with PD found 22.2% and 1.25% of patients with PD to have suicidal ideation and behavior, respectively. Patients with PD had 2 times the risk of suicidal behavior than controls. Early recognition and management of suicidality in PD can help reduce mortality.

Deep learning has yielded promising results for medical image diagnosis but relies heavily on manual image annotations, which are expensive to acquire. We present Cross-DL, a cross-modality learning framework for intracranial abnormality detection and localization in head computed tomography (CT) scans by learning from free-text imaging reports. Cross-DL has a discretizer that automatically extracts discrete labels of abnormality types and locations from reports, which are utilized to train an image analyzer by a dynamic multi-instance learning approach. Benefiting from the low annotation cost and a consequent large-scale training set of 28,472 CT scans, Cross-DL achieves accurate performance, with an average area under the receiver operating characteristic curve (AUROC) of 0.956 (95% confidence interval: 0.952-0.959) in detecting 4 abnormality types in 17 regions while accurately localizing abnormalities at the voxel level. An intracranial hemorrhage classification experiment on the external dataset CQ500 achieves an AUROC of 0.928 (0.905-0.951). The model can also help review prioritization., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Screening for colorectal cancer (CRC) decreases cancer burden through removal of precancerous lesions and early detection of cancer. The COVID-19 pandemic has disrupted organised CRC screening programs worldwide, with some programs completely suspending screening and others experiencing significant decreases in participation and diagnostic follow-up. This study estimated the global impact of screening disruptions on CRC outcomes, and potential effects of catch-up screening., Methods: Organised screening programs were identified in 29 countries, and data on participation rates and COVID-related changes to screening in 2020 were extracted where available. Four independent microsimulation models (ASCCA, MISCAN-Colon, OncoSim, and Policy1-Bowel) were used to estimate the long-term impact on CRC cases and deaths, based on decreases to screening participation in 2020. For countries where 2020 participation data were not available, changes to screening were approximated based on excess mortality rates. Catch-up strategies involving additional screening in 2021 were also simulated., Findings: In countries for which direct data were available, organised CRC screening volumes at a country level decreased by an estimated 1.3-40.5% in 2020. Globally, it is estimated that COVID-related screening decreases led to a deficit of 7.4 million fewer faecal screens performed in 2020. In the absence of any organised catch-up screening, this would lead to an estimated 13,000 additional CRC cases and 7,900 deaths globally from 2020 to 2050; 79% of the additional cases and 85% of additional deaths could have been prevented with catch-up screening, respectively., Interpretation: COVID-19-related disruptions to screening will cause excess CRC cases and deaths, but appropriately implemented catch-up screening could have reduced the burden by over 80%. Careful management of any disruption is key to improving the resilience of colorectal cancer screening programs., Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment., Competing Interests: Karen Canfell is co-PI of an investigator-initiated trial of cervical screening, “Compass”, run by the Australian Centre for Prevention of Cervical Cancer (ACPCC), which is a government-funded not-for-profit charity. Compass receives infrastructure support from the Australian government and the ACPCC has received equipment and a funding contribution from Roche Molecular Diagnostics, USA. Karen Canfell is co-PI on a major implementation program Elimination of Cervical Cancer in the Western Pacific which has received support from the Minderoo Foundation and the Frazer Family Foundation and equipment donations from Cepheid Inc. Dr. Lew reports grants from National Health and Medical Research Council, during the conduct of the study. Dr. Feletto reports grants from National Health and Medical Research Council, outside the submitted work. Dr Coupé reports grants from Dutch Cancer Foundation, grants from Netherlands Organisation for Health Research and Development, and from Maag Lever Darm Stichting MLDS, outside the submitted work., (© 2023 The Authors.)

Background: Effective interventions during the coronavirus disease 2019 (COVID-19) pandemic require an understanding of patients' knowledge and perceptions that influence their behaviour. Our study assessed knowledge of COVID-19 among kidney transplant recipients and donors, hitherto unevaluated., Methods: We conducted a cross-sectional survey among 325 kidney transplant recipients and 172 donors between 1 May 2020 and 30 June 2020. The survey questionnaire assessed knowledge levels of COVID-19, sociodemographic data, health status, psychosocial impact of COVID-19 and precautionary behaviours during the pandemic., Results: The mean COVID-19 knowledge score of the study population was 7.5 (standard deviation: 2.2) out of 10. The mean score was significantly higher among kidney recipients compared to kidney donors (7.9 [1.9] vs. 6.7 [2.6]; P <0.001). Younger age (21-49 vs. ≥50 years) and higher education (diploma and higher vs. secondary and lower) were associated with significantly higher knowledge scores in donors, but not among recipients (P-interactions ≤0.01). In both kidney recipients and donors, financial concerns and/or social isolation were associated with lower knowledge levels., Conclusions: Concerted efforts are needed to improve COVID-19 knowledge in kidney transplant recipients and donors, particularly older donors, donors with lower education and patients with financial concerns or feelings of social isolation. Intensive patient education may mitigate the impact of education levels on COVID-19 knowledge levels., Competing Interests: None

Objectives: To evaluate the clinical care provided to cancer patients hospitalized for acute pulmonary embolism (PE), as well as the association between type of cancer, in-hospital care, and clinical outcomes., Methods: This study examined the in-hospital care (systemic thrombolysis, catheter-directed thrombolysis, and surgical thrombectomy/embolectomy) and clinical outcomes (mortality, major bleeding, and hemorrhagic stroke) among adults hospitalized due to acute PE between October 2015 to December 2018 using the National Inpatient Sample (NIS). Multivariable logistic regression analysis was used to determine adjusted odds ratios (aOR) with 95% confidence interval (95% CI)., Results: Of 1,090,130 hospital records included in the analysis, 216,825 (19.9%) had current cancer diagnoses, including lung (4.7%), hematological (2.5%), colorectal (1.6%), breast (1.3%), prostate (0.8%), and 'other' cancer (9.0%). Cancer patients had lower adjusted odds of receiving systemic thrombolysis, catheter-directed therapy, and surgical thrombectomy/embolectomy compared with their non-cancer counterparts (P < 0.001), except for systemic thrombolysis (aOR 0.96, 95% CI 0.85-1.09, P = 0.553) and catheter-directed therapy (aOR 0.82, 95% CI 0.67-1.00, P = 0.053) for prostate cancer. Cancer patients had greater odds of mortality (P < 0.05). Lung cancer patients had the highest odds of mortality (aOR 2.68, 95% CI 2.61-2.76, P < 0.001) and hemorrhagic stroke (aOR 1.75, 95% CI 1.61-1.90, P < 0.001), while colorectal cancer patients had the greatest odds of bleeding (aOR 2.04, 95% CI 1.94-2.15, P < 0.001)., Conclusion: Among those hospitalized for PE, cancer diagnoses were associated with lower odds of invasive management and poorer in-hospital outcomes, with metastatic status being an especially important determinant. Appropriateness of care could not be assessed in this study., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose Screening for lung cancer is recommended to reduce lung cancer mortality, but there is no consensus on patient selection for screening in Canada. Risk prediction models are more efficacious than the screening recommendations of the Canadian Task Force on Preventive Health Care (CTFPHC), but it remains to be determined which model and threshold are optimal. Methods We retrospectively applied the PLCO m2012 , PLCO all2014 and LLPv2 risk prediction models to 120 lung cancer patients from a Canadian province, at risk thresholds of ≥ 1.51% and ≥ 2.00%, to determine screening eligibility at time of diagnosis. OncoSim modelling was used to compare these risk thresholds. Results Sensitivities of the risk prediction models at a threshold of ≥ 1.51% were similar with 93 (77.5%), 96 (80.0%), and 97 (80.8%) patients selected for screening, respectively. The PLCO m2012 and PLCO all2014 models selected significantly more patients for screening at a ≥ 1.51% threshold. The OncoSim simulation model estimated that the ≥ 1.51% threshold would detect 4 more cancers per 100 000 people than the ≥ 2.00% threshold. All risk prediction models, at both thresholds, achieved greater sensitivity than CTFPHC recommendations, which selected 56 (46.7%) patients for screening. Conclusion Commonly considered lung cancer screening risk thresholds (≥1.51% and ≥2.00%) are more sensitive than the CTFPHC 30-pack-years criterion to detect lung cancer. A lower risk threshold would achieve a larger population impact of lung cancer screening but would require more resources. Patients with limited or no smoking history, young patients, and patients with no history of COPD may be missed regardless of the model chosen.

Background: The clinical, neuropsychological, and socioeconomic factors affecting Parkinson's disease (PD) during COVID-19 pandemic across different populations have not been systematically studied. To address this, we conducted a meta-analysis of factors that impact the well-being of PD patients during the pandemic., Methods: Medline and Embase were searched for articles published between 2020 and 2022. We conducted random-effects pooling of estimates and meta-regression., Results: Twenty-seven studies involving 13,878 patients from America, Europe, Asia, and Africa were included. There is a high prevalence of decreased physical activity and exercise, and worsening motor and neuropsychiatric symptoms (17-56%). Patients in lower-income countries more frequently reported worsening anxiety (adjusted OR [aOR] 8.94, 95% confidence interval [CI] 1.62-49.28, p = 0.012), sleep (aOR 5.16, 95% CI 1.15-23.17, p = 0.032), and PD symptoms (aOR 3.57, 95% CI 0.96-13.34, p = 0.058). Lockdown was associated with decreased exercise levels (aOR 0.13, 95% CI 0.02-0.78, p = 0.025) and worsening mood (aOR 0.48, 95% CI 0.24-0.95, p = 0.035). Younger age correlated with decreased physical activity (β -0.30, 95% CI -0.53 to -0.07, p = 0.012), exercise (β -0.11, 95% CI -0.15 to -0.07, p &lt; 0.001), worsening PD symptoms (β -0.08, 95% CI -0.15 to -0.01, p = 0.018), and sleep (β -0.14, 95% CI -0.27 to 0, p = 0.044). Female PD patients reported a greater decrease in physical activity (β 11.94, 95% CI 2.17-21.71, p = 0.017) and worse sleep (β 10.76, 95% CI 2.81-18.70, p = 0.008)., Conclusion: This large meta-analysis of PD patients in diverse populations identified a high prevalence of physical and mental worsening during the COVID-19 pandemic, with patients in lower-income countries being exceptionally vulnerable., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: There are limited treatment options for patients with neurodegenerative ataxia and spasticity. Non-invasive electrostimulation (NES) is receiving increasing interest because of its ease of implementation, cost-effectiveness and safety. A meta-analysis was conducted to evaluate the efficacy of NES., Methods: MEDLINE and Embase were screened for studies using NES in ataxias and spasticity. Key outcome measurements of effectiveness included changes in (1) Modified Ashworth Scale (MAS) scores, (2) cerebellar brain inhibition (CBI), (3) the nine-hole peg test (9HPT), (4) the 8-m walking time (8MWT), (5) International Cooperative Ataxia Rating Scale (ICARS) score and (6) the Scale for Assessment and Rating of Ataxia (SARA) scores., Results: Seven randomized controlled trials involving 203 patients were included. There were significant improvements in MAS (mean difference [MD] -0.42, 95% confidence interval [CI] -0.76 to -0.08, p = 0.015), CBI (MD -0.35%, 95% CI -0.42 to -0.28, p < 0.001), 8MWT (MD -1.88 s, 95% CI -3.26 to -0.49, p = 0.008), ICARS (MD -7.84, 95% CI -11.90 to -3.78, p < 0.001) and SARA (MD -3.01, 95% CI -4.74 to -1.28, p < 0.001). There was almost no heterogeneity across all outcomes except for CBI (I 2  = 79%). No significant changes in the 9HPT were observed comparing NES to a sham procedure (MD -3.52 s, 95% CI -9.15 to 2.10, p = 0.220). Most included studies were at low risk of bias, and no severe adverse effects were reported., Conclusion: It was demonstrated that NES is an effective treatment for improving coordination and balance and increased exercise capacity in patients with ataxia and spasticity. There was also a significant modulation of CBI in ataxic patients., (© 2022 European Academy of Neurology.)

Study Design: Retrospective longitudinal cohort study., Objective: To investigate the incidence and risk of axial spondyloarthritis (axSpA) in patients with scoliosis in Taiwan., Summary of Background Data: Scoliosis and axSpA causes back pain which reduces quality of life in many patients. Both scoliosis and axSpA had attracted numerous research attention, but the association between the two was hardly known., Methods: In this retrospective study, the data of 25,566 patients were obtained from Taiwan's National Health Insurance Research Database. We identified patients diagnosed with scoliosis and included them in the study cohort. We included age- and sex-matched patients without scoliosis in the control cohort. The total follow-up period was 7 years. Cox proportional hazards models were used to analyze the retrieved data. Hazard ratios (HRs) and adjusted HRs were calculated., Results: The study and control cohorts included 4261 and 21,305 patients, respectively. The incidences of axSpA were 141 and 46 per 100,000 person-years in the study and control cohorts, respectively. The crude HRs and adjusted HRs for patients with scoliosis were 2.98 (95% confidence interval, 1.87-4.73; P < 0.001) and 2.78 (95% confidence interval, 1.74-4.43; P < 0.001), respectively. The prevalence of comorbidities such as chronic obstructive pulmonary disease, osteoporosis, depression, autoimmune diseases (rheumatoid arthritis and systemic lupus erythematosus), and thyroid disease was significantly higher in the study cohort., Conclusion: Our findings indicate an association between scoliosis and axSpA. Additional studies should be performed to explain this phenomenon.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused significant psychological distress globally. Our study assessed the prevalence of psychological distress and associated factors during COVID-19 pandemic among kidney transplant recipients and kidney donors., Methods: A cross-sectional survey of 497 participants (325 recipients and 172 donors) was conducted from 1st May to 30th June 2020 in Singapore. The survey questionnaire assessed knowledge levels of COVID-19, socio-demographic data, health status, psychosocial impact of COVID-19, and precautionary behaviors during the pandemic. Psychological distress was defined as having anxiety, depression, or stress measured by the validated Depression, Anxiety and Stress Scale-21. Linear regression analyses were used to assess factors associated with higher psychological distress., Results: The prevalence of psychological distress was 14.3% (95% confidence interval: 11.5-17.6%) in the overall population; it was 12.8% (9.79-16.6%) in recipients and 13.4% (9.08-19.6%) in donors with no significant difference (P = 0.67). Younger age (21-49 vs. ≥50 years), unmarried status, non-Singapore citizen, worse health conditions, and worrying about physical and mental health were associated with higher psychological distress. Malays (versus Chinese), taking precautionary measures (hand sanitization), and receiving enough information about COVID-19 were associated with lower psychological distress. No interactions were observed between recipients and donors., Conclusions: At least one in ten recipients and donors suffer from psychological distress during COVID-19 pandemic. Focused health education to younger adults, unmarried individuals, non-Singapore citizens, and those with poor health status could potentially prevent psychological distress in recipients and donors., (© 2022. The Author(s).)

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes diverse human infections including chronic airway infection in patients with cystic fibrosis (CF). Comparing the genomes of CF and non-CF PA isolates has great potential to identify the genetic basis of pathogenicity. To gain a deeper understanding of PA adaptation in CF airways, we performed a genome-wide association study (GWAS) on 1,001 PA genomes. Genetic variations identified among CF isolates were categorized into (i) alterations in protein-coding regions, either large- or small-scale, and (ii) polymorphic variation in intergenic regions. We introduced each CF-associated genetic alteration into the genome of PAO1, a prototype PA strain, and validated the outcomes experimentally. Loci readily mutated among CF isolates included genes encoding a probable sulfatase, a probable TonB-dependent receptor (PA2332~PA2336), L-cystine transporter (YecS, PA0313), and a probable transcriptional regulator (PA5438). A promoter region of a heme/hemoglobin uptake outer membrane receptor (PhuR, PA4710) was also different between the CF and non-CF isolate groups. Our analysis highlights ways in which the PA genome evolves to survive and persist within the context of chronic CF infection., Competing Interests: The authors have declared that no competing interests exist.

Background: Population-based cancer screening can reduce cancer burden but was interrupted temporarily due to the COVID-19 pandemic. We estimated the long-term clinical impact of breast and colorectal cancer screening interruptions in Canada using a validated mathematical model., Methods: We used the OncoSim breast and colorectal cancers microsimulation models to explore scenarios of primary screening stops for 3, 6, and 12 months followed by 6-24-month transition periods of reduced screening volumes. For breast cancer, we estimated changes in cancer incidence over time, additional advanced-stage cases diagnosed, and excess cancer deaths in 2020-2029. For colorectal cancer, we estimated changes in cancer incidence over time, undiagnosed advanced adenomas and colorectal cancers in 2020, and lifetime excess cancer incidence and deaths., Results: Our simulations projected a surge of cancer cases when screening resumes. For breast cancer screening, a three-month interruption could increase cases diagnosed at advanced stages (310 more) and cancer deaths (110 more) in 2020-2029. A six-month interruption could lead to 670 extra advanced cancers and 250 additional cancer deaths. For colorectal cancers, a six-month suspension of primary screening could increase cancer incidence by 2200 cases with 960 more cancer deaths over the lifetime. Longer interruptions, and reduced volumes when screening resumes, would further increase excess cancer deaths., Conclusions: Interruptions in cancer screening will lead to additional cancer deaths, additional advanced cancers diagnosed, and a surge in demand for downstream resources when screening resumes. An effective strategy is needed to minimize potential harm to people who missed their screening.

Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. We screened a metagenome library consisting of 5760 bacterial artificial chromosome clones, with DNA inserts originating from mouse microbiomes, and identified two clones that efficiently hydrolyse TB into butyrate. Nucleotide sequence analysis indicated that inserts in these two clones are derived from unknown microbes. BLASTp analysis, however, revealed that each insert contains a gene homologous to acetylesterase or esterase genes, from Clostridium spp. and Bacteroides spp., respectively. Predicted structures of these two proteins both contain serine-histidine-aspartate catalytic triad, highly conserved in the family of esterases. Escherichia coli host expressing each of the two candidate genes invariably produced greater amounts of butyrate in the presence of TB. Importantly, administration of TB together with cloned E. coli cells alleviated inflammatory symptoms in a mouse model of acute colitis. Based on these results, we established an efficient on-site and real-time butyrate production system that releases butyrate in a controlled manner inside the intestine.

Background: The surgical management of hypertelorism is challenging for plastic surgeons, and limited long-term outcome data are available. The purpose of this long-term study was to report a single-surgeon experience with a staged reconstructive protocol for hypertelorism correction., Methods: This retrospective study reviewed the records of patients with hypertelorism who were surgically managed by a single surgeon between 1978 and 2000. Bone (orbital box osteotomy and orthognathic surgery) and soft tissue (rhinoplasty and epicanthoplasty) surgeries were performed based on a patient-specific surgical protocol. Included patients were divided into a childhood group and an adolescence or adulthood group according to their age at orbital repositioning (≤12 and >12 years, respectively). Patients were invited for clinical interviews in February 2020 to evaluate whether requests for revision surgery had been made. The photogrammetric analysis-based hypertelorism index was calculated at preoperative and long-term postoperative times. Satisfaction with the long-term outcome was judged by both surgical professionals and laypeople., Results: In total, 14 patients with hypertelorism of different etiologies were included, with no request for revision surgery during an average follow-up of 29 years. The preoperative hypertelorism index was higher than the long-term postoperative evaluation (all, P < 0.05) for both childhood and adolescence or adulthood groups. Intergroup comparison revealed no significant difference for the hypertelorism index and panel assessment-based satisfaction with long-term outcome analysis (all, P > 0.05)., Conclusions: Considering the complexity and wide spectrum of clinical presentation of soft tissue and bone deformities in hypertelorism and current outcomes, the surgical approach to these patients should be staged and individualized for achievement of a balanced result between functional (orbital, occlusion, and psychosocial) and aesthetic parameters., Competing Interests: Conflicts of interest and sources of funding: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Intracranial aneurysm (IA) is an enormous threat to human health, which often results in nontraumatic subarachnoid hemorrhage or dismal prognosis. Diagnosing IAs on commonly used computed tomographic angiography (CTA) examinations remains laborious and time consuming, leading to error-prone results in clinical practice, especially for small targets. In this study, we propose a fully automatic deep-learning model for IA segmentation that can be applied to CTA images. Our model, called Global Localization-based IA Network (GLIA-Net), can incorporate the global localization prior and generates the fine-grain three-dimensional segmentation. GLIA-Net is trained and evaluated on a big internal dataset (1,338 scans from six institutions) and two external datasets. Evaluations show that our model exhibits good tolerance to different settings and achieves superior performance to other models. A clinical experiment further demonstrates the clinical utility of our technique, which helps radiologists in the diagnosis of IAs., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

Multi-label brain segmentation from brain magnetic resonance imaging (MRI) provides valuable structural information for most neurological analyses. Due to the complexity of the brain segmentation algorithm, it could delay the delivery of neuroimaging findings. Therefore, we introduce Split-Attention U-Net (SAU-Net), a convolutional neural network with skip pathways and a split-attention module that segments brain MRI scans. The proposed architecture employs split-attention blocks, skip pathways with pyramid levels, and evolving normalization layers. For efficient training, we performed pre-training and fine-tuning with the original and manually modified FreeSurfer labels, respectively. This learning strategy enables involvement of heterogeneous neuroimaging data in the training without the need for many manual annotations. Using nine evaluation datasets, we demonstrated that SAU-Net achieved better segmentation accuracy with better reliability that surpasses those of state-of-the-art methods. We believe that SAU-Net has excellent potential due to its robustness to neuroanatomical variability that would enable almost instantaneous access to accurate neuroimaging biomarkers and its swift processing runtime compared to other methods investigated.

Oak wilt disease caused by Raffaelea quercus-mongolicae has emerged obviously in Korea. We selected antifungal isolates against R. quercus-mongolicae among 368 endophytic fungal isolates from different parts of oak and pine trees. The experiment was conducted in the primary and secondary screenings by dual culture test. The antifungal activity of the selected isolates was assessed in culture filtrate test based on the inhibition rates in mycelial growth, sporulation, and spore germination of oak wilt fungus. Five isolates, E089, E199, E282, E409 and E415, showed strong antifungal activity in culture filtrate test, and their antifungal activity decreased on the culture media supplemented with heated culture filtrate. Higher mycelial growth inhibitions on the unheated media were recorded in E409 ( Colletotrichum acutatum ), E089 ( Daldinia childiae ), E415 ( Alternaria alternata ) and E199 ( Daldinia childiae ) with the inhibition rates of 79.0%, 70.1%, 68.9% and 64.5%, respectively. These isolates also had the higher sporulation inhibitions on unheated media with the rates of 96.8%, 84.2%, 82.8% and 80.5%, respectively. The spore germination of the oak wilt fungus was completely inhibited by E282 ( Nectria balsamea ) on both unheated and heated media. These results showed that a higher number of potent antifungal isolates against oak wilt fungus was isolated from the petiole compared to the other parts. This study could contribute to the development of biological control approaches for the management of oak wilt disease caused by R. quercus-mongolicae ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

At present, aluminum-based optical payloads are widely used in the aviation and aerospace field, and the demand for aluminum mirrors has become increasingly urgent in the visible light region. The main processing of an aluminum alloy mirror involves single-point diamond turning followed by a combined polishing process. Among these processes, magnetorheological finishing (MRF) is an important method for improving a surface figure. During the MRF process, excessive impurity contaminants are introduced into the surface of the aluminum mirror, thereby reducing surface reflectivity. In this paper, theoretical analysis and time-of-flight secondary ion mass spectrometry depth profiling were used to obtain the cause of pollution, and the process scheme of femtosecond laser cleaning was proposed. After verifying the feasibility, a new, to the best of our knowledge, process route was implemented on a Φ 50 m m aluminum mirror. Finally, the surface figure of RMS 0.022 λ and the surface roughness of Ra 3.24 nm were obtained. In addition, reflectance in the visible light and near-infrared bands has increased by about 50%.

Introduction: Coronavirus Disease 2019 (COVID-19) has significantly affected the way healthcare is delivered in Singapore. Healthcare services such as renal transplantation had to rapidly adjust and meet the needs to (1) protect patients and staff, (2) ramp up, conserve or redeploy resources while (3) ensuring that critical services remained operational. This paper aims to describe the experience of the renal transplant programme at the Singapore General Hospital (SGH) in responding to the risks and constraints posed by the pandemic., Methods and Materials: This is a review and summary of the SGH renal transplant programme's policy and protocols that were either modified or developed in response to the COVID-19 Pandemic., Results: A multi-pronged approach was adopted to respond to the challenges of COVID-19. These included ensuring business continuity by splitting the transplant team into different locations, adopting video and tele-consults to minimise potential patient exposure to COVID-19, streamlining work processes using electronic forms, ensuring safe paths for patients who needed to come to hospital, ring-fencing and testing new inpatients at risk for COVID-19, enhancing precautionary measures for transplant surgery, ensuring a stable supply chain of immunosuppression, and sustaining patient and staff education programmes via video conferencing., Conclusions: Though the COVID-19 pandemic has reduced access to kidney transplantation, opportunities arose to adopt telemedicine into mainstream transplant practice as well as use electronic platforms to streamline work processes. Screening protocols were established to ensure that transplantation could be performed safely, while webinars reached out to empower patients to take precautions against COVID-19.

Background: Ovarian cancer is one of the most common gynecologic cancers and has high mortality rate due to the lack of early diagnosis method and efficient therapeutic agents. circCELSR1 is up-regulated in ovarian cancer, but its role and mechanisms in ovarian cancer are unclear., Methods: Gene expression of circCELSR1, miR-598 and BRD4 in ovarian cells was examined by qRT-PCR. Protein level was determined by Western blotting. Bioinformatic analysis and luciferase assay determined the molecular binding among circCELSR1, miR-598 and BRD4 3' UTR. Cell proliferation, migration, invasion and apoptosis were determined by colony formation, wound healing assay, transwell assay and flow cytometry analysis, respectively. An abdominal cavity metastasis nude mice model was used to determine the in vivo function of circCELSR1., Results: circCELSR1 and BRD4 were promoted, but miR-598 was suppressed in various ovarian cancer cells. circCELSR1 bound to miR-598 and promoted expression of its downstream target BRD4. Knockdown of circCELSR1 suppressed proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), but promoted apoptosis in ovarian cancer cells, and these effects were reversed by miR-598 inhibition or BRD4 overexpression. circCELSR1 inhibition decreased the expression of BRD4 and its downstream proliferation/migration related genes by targeting miR-598. Furthermore, knockdown of circCELSR1 suppressed ovarian cancer growth and metastasis in nude mice., Conclusion: Knockdown of circCELSR1 inhibited BRD4-mediated proliferation/migration related signaling via sponging miR-598, thereby repressing ovarian cancer progression. This study provides a new regulatory mechanism of ovarian cancer may facilitate the development of therapeutic agents for ovarian cancer.

Background: The pharyngeal phase is a particularly important clinical factor related to swallowing dysfunctions. Head and neck posture, as well as bolus volume, are important factors affecting the pharyngeal stages of normal swallowing., Objective: The aim of our study was to identify the effects of sitting posture and bolus volume on the activation of swallowing-related muscles., Materials and Methods: Twenty-four subjects participated in the study. The subjects were positioned in three sitting postures-slump sitting (SS), lumbo-pelvic upright sitting (LUS), and thoracic upright sitting (TUS). While sitting in the chair, the subject was instructed to swallow 10 and 20 mL of water. Surface electromyography (EMG) was used to measure the muscle activity of the supra-hyoid (SH) and infra-hyoid (IH) muscles. Also, sitting posture alignment (head, cervical and shoulder angle) was also performed. Data were analysed with a repeated measures analysis of variance (RMANOVA) using a generalised linear model., Results: There was no significant difference in terms of the head angle (P = .395). However, significant differences were found in relation to the cervical angle (P < .001) and shoulder angle (P < .001). The TUS produced the lowest SH EMG activity (P = .001), in comparison to SS and LUS. The bolus volume for 20 mL showed greater SH and IH EMG activity (P < .001) than did the bolus volume for 10 mL., Conclusions: Correcting sitting posture from SS to TUS may better assist swallowing-related muscles with less effort, irrespective of the bolus volume., (© 2020 John Wiley & Sons Ltd.)

Objective: Epithelial ovarian cancer (EOC) is a common gynecologic malignancy characterized by extensive peritoneal metastasis and high mortality rate. ABHD11 Antisense RNA1 (ABHD11-AS1) has recently been identified as a regulator of growth and metastasis in multiple tumors, including EOC. However, the biological function and potential mechanism of ABHD11-AS1 in EOC remains poorly understood., Methods: Immunohistochemistry, western blot, and qRT-PCR analysis were used to determine the expression pattern of ABHD11-AS1 and epidermal growth factor receptor (EGFR) in both EOC tissues and cell lines, respectively. Colony formation, transwell and wound healing assays were performed to evaluate the roles of EGFR and ABHD11-AS1 on the capacity of cell proliferation, migration, and invasion. Western blot analysis was performed to measure the regulation of EGFR pathway on STAT3. Moreover, chromatin immunoprecipitation was employed to demonstrate the interaction between ABHD11-AS1 and STAT3. RNA immunoprecipitation was subjected to prove the direct binding between ABHD11-AS1 and EZH2. Immunofluorescence staining was performed to measure the expression and localization of TIMP2. EOC mouse model was conducted for validating the role of ABHD11-AS1 in vivo., Results: EGFR and ABHD11-AS1 were highly expressed in EOC tissues and cell lines. Knockdown of EGFR or ABHD11-AS1 inhibited cell growth, migration, and invasion of EOC cells. Expression of ABHD11-AS1 was regulated by the activation of EGFR signaling pathway, mediated by STAT3. Besides, ABHD11-AS1 was shown to silence TIMP2 by binding to chromatin-modifying enzyme EZH2. Furthermore, inhibition of EGFR pathway or ABHD11-AS1 repressed the tumor growth of EOC., Conclusion: We defined the regulatory relationship between the EGFR signaling pathway, ABHD11-AS1, EZH2, and TIMP2 suggesting that ABHD11-AS1 may act as an oncogene and a potential target for antitumor therapies in ovarian cancer., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Recent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels., Results: Here, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice., Conclusions: Overall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection.

Owing to its material properties, aluminum-based optical loads are widely used in the aerospace field. At present, the main processing of an aluminum alloy mirror is single-point diamond turning followed by the combined polishing process. The surface will generate some white crystals during the chemical mechanical polishing process (CMP). These crystals can affect the improvement of surface quality and seriously reduce the processing efficiency of the whole process. In view of the above problems, four main factors of crystallization are obtained by interface theoretical analysis, Visual MINTEQ simulation of chemical morphological distribution, and experimental analysis. They are temperature, PH value of polishing fluid, solid-liquid contact angle, and impurity content of aluminum alloy. The crystallization phenomenon in the polishing process is successfully suppressed by improving the polishing process and selecting new materials. The experimental results showed that the surface roughness decreased from 7.21 to 2.98 nm without crystallization using the new method.

Intermittent fasting (ImF) is known to reduce oxidative stress and affects adult neurogenesis in the hippocampal dentate gyrus. However, it is unknown how ImF affects endogenous antioxidants expressions, cell proliferation, and neuroblast differentiation and their dendrite remodeling over 3 months in the dentate gyrus of adult gerbils. The present study subjected 6‑month old male gerbils to a normal diet or alternate‑day ImF for 1, 2 and 3 months. Changes in body weight were not significantly different between gerbils fed a normal diet and on ImF. The present study also investigated the effects of ImF on antioxidant enzymes [superoxide dismutase (SOD)‑1, SOD2 and catalase] using immunohistochemistry, and endogenous cell proliferation, neuroblast differentiation and neuroblast dendrite complexity by using Ki67 (a cell proliferation marker) and doublecortin (neuroblast differentiation marker) immunohistochemistry in the dentate gyrus. SOD1, SOD2 and CAT immunoreactivities were shown in cells in the granule cell and polymorphic layers. SOD1, SOD2 and catalase immunoreactivity in the cells peaked at 2, 1 and 1 month, respectively, following ImF. Cell proliferation was ~250, 129 and 186% of the control, at 1, 2 and 3 months of ImF, respectively. Neuroblast differentiation was ~41, 32 and 12% of the control, at 1, 2 and 3 months of ImF, respectively, indicating that dendrites of neuroblasts were more arborized and developed at 3 months of ImF. Taken together, these results indicate that ImF for 3 months improves endogenous SOD1, SOD2 and catalase expressions and enhances cell proliferation, and neuroblast dendrites complexity and maturation in the adult gerbil dentate gyrus.

Background : Ovarian cancer (OC) is the gynecologic malignant tumor with high mortality. Accumulating evidence indicates that M2-like tumor-associated macrophages (TAMs) can secret EGF to participate in ovarian cancer growth, migration, and metastasis. An EGF-downregulated lncRNA, LIMT (lncRNA inhibiting metastasis), was identified as a critical regulator of mammary cell migration and invasion. Nevertheless, whether EGF secreted from M2-like TAMs regulates LIMT expression in ovarian cancer progression remains largely unknown. Methods : The human OC cell lines OV90 and OVCA429 were recruited in this study. The differentiation of the human monocyte cell line THP-1 into M2-like TAMs was confirmed using flow cytometry within the application of phorbol 12-myristate 13-acetate (PMA). ELISA was performed to detect EGF concentration in co-culture system of M2-like TAMs and OC cell lines. Moreover, CCK-8, flow cytometry and immunofluorescence staining of Ki67 were performed to assess the capacity of cell proliferation. Besides, cell migration and invasion were determined by wound healing and transwell assays. Furthermore, the expression levels of epithelial-mesenchymal transition (EMT) markers and EGFR/ERK signals were analyzed by qRT-PCR and western blot. Female athymic nude mice (8-12 weeks of age; n = 8 for each group) were recruited for in vivo study. Results : In the present study, THP-1 cells exhibited the phenotype markers of M2-like TAMs with low proportion of CD14 + marker and high proportion of CD68 + , CD204 + , CD206 + markers within the application of PMA. After co-culturing with M2-like TAMs, EGF concentration in the supernatants was significantly increased in a time-dependent manner. Besides, OC cells presented better cell viability, higher cell proliferation, and stronger migration and invasion. The expression of EMT-related markers N-cadherin, Vimentin and EGFR/ERK signals were markedly up-regulated, while E-cadherin was significantly decreased. However, these effects induced by co-culture system were reversed by the application of AG1478 (an EGFR inhibitor) or LIMT overexpression. Furthermore, the endogenous expression of LIMT was decreased in OC cell lines compared with the control group. Also, the in vivo experiments verified that the inhibition of EGFR signaling by AG1478 or overexpression of LIMT effectively repressed the tumor growth. Conclusion : Taken together, we demonstrated that EGF secreted by M2-like TAMs might suppress LIMT expression via activating EGFR-ERK signaling pathway to promote the progression of OC.

Intermittent fasting has been shown to have neuroprotective effects against transient focal cerebral ischemic insults. However, the effects of intermittent fasting on transient global ischemic insult has not been studied much yet. The present study examined effects of intermittent fasting on endogenous antioxidant enzyme expression levels in the hippocampus and investigated whether the fasting protects neurons 5 days after 5 min of transient global cerebral ischemia. Gerbils were randomly subjected to either ad libitum or alternate‑day intermittent fasting for two months and assigned to sham surgery or transient ischemia. Changes of antioxidant enzymes were examined using immunohistochemistry for cytoplasmic superoxide dismutase 1 (SOD1), mitochondrial (SOD2), catalase (CAT), and glutathione peroxidase (GPX). The effects of intermittent fasting on ischemia‑induced antioxidant changes, neuronal damage/degeneration and glial activation were examined. The weight of fasting gerbils was not different from that of control gerbils. In controls, SOD1 and GPX immunoreactivities were strong in pyramidal neurons of filed cornu ammonis 1 (CA1). Transient ischemia in controls significantly decreased expressions of SOD1 and GPX in CA1 pyramidal neurons. Intermittent fasting resulted in increased expressions of SOD2 and CAT, not of SOD1 and GPX, in CA1 pyramidal neurons. Nevertheless, CA1 pyramidal neurons were not protected in gerbils subjected to fasting after transient ischemia, and inhibition of glial‑cell activation was not observed in the gerbils. In summary, intermittent fasting for two months increased SOD2 and CAT immunoreactivities in hippocampal CA1 pyramidal neurons. However, fasting did not protect the CA1 pyramidal neurons from transient cerebral ischemia. The results of the present study indicate that intermittent fasting may increase certain antioxidants, but not protect neurons from transient global ischemic insult.

We propose a novel 360° scene representation for converting real scenes into stereoscopic 3D virtual reality content with head-motion parallax. Our image-based scene representation enables efficient synthesis of novel views with six degrees-of-freedom (6-DoF) by fusing motion fields at two scales: (1) disparity motion fields carry implicit depth information and are robustly estimated from multiple laterally displaced auxiliary viewpoints, and (2) pairwise motion fields enable real-time flow-based blending, which improves the visual fidelity of results by minimizing ghosting and view transition artifacts. Based on our scene representation, we present an end-to-end system that captures real scenes with a robotic camera arm, processes the recorded data, and finally renders the scene in a head-mounted display in real time (more than 40 Hz). Our approach is the first to support head-motion parallax when viewing real 360° scenes. We demonstrate compelling results that illustrate the enhanced visual experience - and hence sense of immersion-achieved with our approach compared to widely-used stereoscopic panoramas.

This paper proposes a real-time method for 3D eye performance reconstruction using a single RGBD sensor. Combined with facial surface tracking, our method generates more pleasing facial performance with vivid eye motions. In our method, a novel scheme is proposed to estimate eyeball motions by minimizing the differences between a rendered eyeball and the recorded image. Our method considers and handles different appearances of human irises, lighting variations and highlights on images via the proposed eyeball model and the -based optimization. Robustness and real-time optimization are achieved through the novel 3D Taylor expansion-based linearization. Furthermore, we propose an online bidirectional regression method to handle occlusions and other tracking failures on either of the two eyes from the information of the opposite eye. Experiments demonstrate that our technique achieves robust and accurate eye performance reconstruction for different iris appearances, with various head/face/eye motions, and under different lighting conditions.

Background: The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms., Methods: We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity., Results: Compared to no screening, biennial gFOBT screening between age 50-74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50-74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45-80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300., Interpretation: Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand.

Aims: The economic burden of cancer care is substantial, including steep increases in costs for breast cancer management. There is mounting evidence that women age ≥ 60 years with grade I/II T1N0 luminal A (ER/PR+, HER2- and Ki67 ≤ 13%) breast cancer have such low local recurrence rates that adjuvant breast radiotherapy might offer limited value. We aimed to determine the total savings to a publicly funded health care system should omission of radiotherapy become standard of care for these patients., Materials and Methods: The number of women aged ≥ 60 years who received adjuvant radiotherapy for T1N0 ER+ HER2- breast cancer in Ontario was obtained from the provincial cancer agency. The cost of adjuvant breast radiotherapy was estimated through activity-based costing from a public payer perspective. The total saving was calculated by multiplying the estimated number of luminal A cases that received radiotherapy by the cost of radiotherapy minus Ki-67 testing., Results: In 2010, 748 women age ≥ 60 years underwent surgery for pT1N0 ER+ HER2- breast cancer; 539 (72%) underwent adjuvant radiotherapy, of whom 329 were estimated to be grade I/II luminal A subtype. The cost of adjuvant breast radiotherapy per case was estimated at $6135.85; the cost of Ki-67 at $114.71. This translated into an annual saving of about $2.0million if radiotherapy was omitted for all low-risk luminal A breast cancer patients in Ontario and $5.1million across Canada., Conclusion: There will be significant savings to the health care system should omission of radiotherapy become standard practice for women with low-risk luminal A breast cancer., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Prolonged ambulatory ECG monitoring after cryptogenic stroke improves detection of covert atrial fibrillation, but its long-term cost-effectiveness is uncertain., Methods: We estimated the cost-effectiveness of noninvasive ECG monitoring in patients aged ≥55 years after a recent cryptogenic stroke and negative 24-hour ECG. A Markov model used observed rates of atrial fibrillation detection and anticoagulation from a randomized controlled trial (EMBRACE) and the published literature to predict lifetime costs and effectiveness (ischemic strokes, hemorrhages, life-years, and quality-adjusted life-years [QALYs]) for 30-day ECG (primary analysis) and 7-day or 14-day ECG (secondary analysis), when compared with a repeat 24-hour ECG., Results: Prolonged ECG monitoring (7, 14, or 30 days) was predicted to prevent more ischemic strokes, decrease mortality, and improve QALYs. If anticoagulation reduced stroke risk by 50%, 30-day ECG (at a cost of USD $447) would be highly cost-effective ($2000 per QALY gained) for patients with a 4.5% annual ischemic stroke recurrence risk. Cost-effectiveness was sensitive to stroke recurrence risk and anticoagulant effectiveness, which remain uncertain, especially at higher costs of monitoring. Shorter duration (7 or 14 days) monitoring was cost saving and more effective than an additional 24-hour ECG; its cost-effectiveness was less sensitive to changes in ischemic stroke risk and treatment effect., Conclusions: After a cryptogenic stroke, 30-day ECG monitoring is likely cost-effective for preventing recurrent strokes; 14-day monitoring is an attractive value alternative, especially for lower risk patients. These results strengthen emerging recommendations for prolonged ECG monitoring in secondary stroke prevention. Cost-effectiveness in practice will depend on careful patient selection., (© 2016 American Heart Association, Inc.)

Background: Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario., Methods: An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt., Results: From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated., Conclusions: Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption.

Unlabelled: The cost-effectiveness of a less intensive fracture liaison service is unknown. We evaluated a fracture liaison service that had been educating and referring patients for secondary prevention of osteoporotic fractures for 6 years. Our results suggest that a less intensive fracture liaison service, with moderate effectiveness, can still be worthwhile., Introduction: Fragility fractures are common among older patients; the risk of re-fracture is high but could be reduced with treatments; different versions of fracture liaison service have emerged to reduce recurrent osteoporotic fractures. But the cost-effectiveness of a less intensive model is unknown. The objective of this study was to assess the cost-effectiveness of the Ontario Fracture Clinic Screening program, a fracture liaison service that had been educating and referring fragility fracture patients across Ontario, Canada to receive bone mineral density testing and osteoporosis treatments since 2007., Methods: We developed a Markov model to assess the cost-effectiveness of the program over the patients' remaining lifetime, using rates of bone mineral density testing and osteoporosis treatment and cost of intervention from the program, and supplemented it with the published literature. The analysis took the perspective of a third-party health-care payer. Costs and benefits were discounted at 5 % per year. Sensitivity analyses assessed the effects of different assumptions on the results., Results: The program improved quality-adjusted life-years (QALYs) by 4.3 years and led to increased costs of CAD $83,000 for every 1000 patients screened, at a cost of $19,132 per QALY gained. The enhanced model, the Bone Mineral Density (BMD) Fast Track program that includes ordering bone mineral density testing, was even more cost-effective ($5720 per QALY gained)., Conclusions: The Ontario Fracture Clinic Screening program appears to be a cost-effective way to reduce recurrent osteoporotic fractures.

In the province-wide colorectal cancer (CRC) screening program in Ontario, Canada, individuals with a family history of CRC are offered colonoscopy screening and those without are offered guaiac fecal occult blood testing (gFOBT, Hemoccult II). We used microsimulation modeling to estimate the cumulative number of CRC deaths prevented and colonoscopies performed between 2008 and 2038 with this family history-based screening program, compared to a regular gFOBT program. In both programs, we assumed screening uptake increased from 30% (participation level in 2008 before the program was launched) to 60%. We assumed that 11% of the population had a family history, defined as having at least one first-degree relative diagnosed with CRC. The programs offered screening between age 50 and 74 years, every two years for gFOBT, and every ten years for colonoscopy. Compared to opportunistic screening (2008 participation level kept constant at 30%), the gFOBT program cumulatively prevented 6,700 more CRC deaths and required 570,000 additional colonoscopies by 2038. The family history-based screening program increased these numbers to 9,300 and 1,100,000, a 40% and 93% increase, respectively. If biennial gFOBT was replaced with biennial fecal immunochemical test (FIT), annual Hemoccult Sensa or five-yearly sigmoidoscopy screening, both the added benefits and colonoscopies required would decrease. A biennial gFOBT screening program that identifies individuals with a family history of CRC and recommends them to undergo colonoscopy screening would prevent 40% (range in sensitivity analyses: 20-51%) additional deaths while requiring 93% (range: 43-116%) additional colonoscopies, compared to a regular gFOBT screening program., (© 2015 UICC.)

In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial "whole-mount" dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system.

The participation of Na(+)/H(+) exchanger (NHE) in neuronal damage/death in the hippocampal CA1 region (CA1) induced by transient forebrain ischemia has not been well established, although acidosis may be involved in neuronal damage/death. In the present study, we examined the effect of ischemic preconditioning (IPC) on NHE1 immunoreactivity following a 5min of transient forebrain ischemia in gerbils. The animals used in the study were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group and IPC+ischemia-operated-group). IPC was induced by subjecting animals to 2min of ischemia followed by 1day of recovery. A significant neuronal loss was found in the stratum pyramidale (SP) of the CA1, not the CA2/3, of the ischemia-operated-group at 5days post-ischemia. However, in the IPC+ischemia-operated-group, neurons in the SP of the CA1 were well protected. NHE1 immunoreactivity was not detected in any regions of the CA1-3 of the sham- and IPC+sham-operated-groups. However, the immunoreactivity was apparently expressed in the SP of the CA1-3 after ischemia, and the NHE1immunoreactivity was very weak 5days after ischemia; however, at this point in time, strong NHE1immunoreactivity was found in astrocytes in the CA1. In the CA2/3, NHE1immunoreactivity was slightly changed, although NHE1immunoreactivity was expressed in the SP. In the IPC+ischemia-operated-groups, NHE1 immunoreactivity was also expressed in the SP of the CA1-3; however, the immunoreactivity was more slightly changed than that in the ischemia-operated-groups. In brief, our findings show that IPC dramatically protected CA1 pyramidal neurons and strongly inhibited NHE1 expression in the SP of the CA1 after ischemia-reperfusion. These findings suggest that the inhibition of NHE1 expression may be necessary for neuronal survival from transient ischemic damage., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Graph cut has proven to be an effective scheme to solve a wide variety of segmentation problems in vision and graphics community. The main limitation of conventional graph-cut implementations is that they can hardly handle large images or videos because of high computational complexity. Even though there are some parallelization solutions, they commonly suffer from the problems of low parallelism (on CPU) or low convergence speed (on GPU). In this paper, we present a novel graph-cut algorithm that leverages a parallelized jump flooding technique and an heuristic push-relabel scheme to enhance the graph-cut process, namely, back-and-forth relabel, convergence detection, and block-wise push-relabel. The entire process is parallelizable on GPU, and outperforms the existing GPU-based implementations in terms of global convergence, information propagation, and performance. We design an intuitive user interface for specifying interested regions in cases of occlusions when handling video sequences. Experiments on a variety of data sets, including images (up to 15 K × 10 K), videos (up to 2.5 K × 1.5 K × 50), and volumetric data, achieve high-quality results and a maximum 40-fold (139-fold) speedup over conventional GPU (CPU-)-based approaches.

We present a novel artistic-verisimilitude driven system for watercolor rendering of images and photos. Our system achieves realistic simulation of a set of important characteristics of watercolor paintings that have not been well implemented before. Specifically, we designed several image filters to achieve: 1) watercolor-specified color transferring; 2) saliency-based level-of-detail drawing; 3) hand tremor effect due to human neural noise; and 4) an artistically controlled wet-in-wet effect in the border regions of different wet pigments. A user study indicates that our method can produce watercolor results of artistic verisimilitude better than previous filter-based or physical-based methods. Furthermore, our algorithm is efficient and can easily be parallelized, making it suitable for interactive image watercolorization.

We analyzed the whole genome sequence and resistome of the outbreak Klebsiella pneumoniae strain MP14 and compared it with those of K. pneumoniae carbapenemase- (KPC-) producing isolates that showed high similarity in the NCBI genome database. A KPC-2-producing multidrug-resistant (MDR) K. pneumoniae clinical isolate was obtained from a patient admitted to a Korean hospital in 2011. The strain MP14 was resistant to all tested β-lactams including monobactam, amikacin, levofloxacin, and cotrimoxazole, but susceptible to tigecycline and colistin. Resistome analysis showed the presence of β-lactamase genes including bla KPC-2, bla SHV-11, bla TEM-169, and bla OXA-9. MP14 also possessed aac(6'-)Ib, aadA2, and aph(3'-)Ia as aminoglycoside resistance-encoding genes, mph(A) for macrolides, oqxA and oqxB for quinolone, catA1 for phenicol, sul1 for sulfonamide, and dfrA12 for trimethoprim. Both SNP tree and cgMLST analysis showed the close relatedness with the KPC producers (KPNIH strains) isolated from an outbreak in the USA and colistin-resistant strains isolated in Italy. The plasmid-scaffold genes in plasmids pKpQil, pKpQil-IT, pKPN3, or pKPN-IT were identified in MP14, KPNIH, and Italian strains. The KPC-2-producing MDR K. pneumoniae ST258 stain isolated in Korea was highly clonally related with MDR K. pneumoniae strains from the USA and Italy. Global spread of KPC-producing K. pneumoniae is a worrying phenomenon.