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Background: Patient satisfaction has become an important indicator of primary care and healthcare system performance. Ethnic disparities in patient satisfaction and compliance with physician care have been studied in several countries. However, this issue has not received significant attention in Canada. The unique characteristics of the Canadian healthcare system and ethnic population make it worthwhile to examine this issue in this population. Therefore, we conducted a survey among Chinese and Whites in a Canadian city to determine 'their reported satisfaction, and perceptions of physicians.Methods: The survey was conducted in English, Mandarin and Cantonese in 2005 among Chinese and White Canadians, 18 years of age or older, who had visited at least one physician in Canada.Results: We analyzed 746 Chinese and 7I I Whites in the general practitioner (GP) visit group and 485 Chinese and 637 Whites in the specialist visit group. A lower proportion of Chinese compared to Whites reported that they were very satisfied or satisfied with GP (73.7% vs. 92.8%) and specialist care (75.5% vs. 85.6%) and the differences between the two groups remained after adjustment for demographic variables and chronic conditions (risk adjusted OR: 0.70, 95%Cl: 0.42-1.18 for the GP visit group and OR: 0.77, 95%Cl: 0.48-1.23 for the specialist visit group). A similar proportion of Chinese and Whites reported that they always followed a physician's advice (59.4% vs. 59.6% for the GP visit group and 67.2% vs. 62.8% for the specialist visit group). Non-English speaking Chinese and recent arrivals in Canada were less likely to be satisfied with GPs than Chinese born in Canada [risk adjusted OR: 0.5, 95%Cl: 0.3-0.9, 0.2 and 0.1-0.7, respectively].Conclusion: Chinese Canadians reported lower satisfaction with physicians and perceived physicians slightly more negatively than White Canadians. Particularly, Chinese with limited English and short length of stay in Canada were less satisfied than Canadian born Chinese. [ABSTRACT FROM AUTHOR]

Background: Symptoms tend to occur in what have been called symptom clusters. Early symptom cluster research was imprecise regarding the causal foundations of the coordinations between specific symptoms, and was silent on whether the relationships between symptoms remained stable over time. This study develops a causal model of the relationships between symptoms in cancer palliative care patients as they approach death, and investigates the changing associations among the symptoms and between those symptoms and well-being.Methods: Complete symptom assessment scores were obtained for 82 individuals from an existing palliative care database. The data included assessments of pain, anxiety, nausea, shortness of breath, drowsiness, loss of appetite, tiredness, depression and well-being, all collected using the Edmonton Symptom Assessment System (ESAS). Relationships between the symptoms and well-being were investigated using a structural equation model.Results: The model fit acceptably and explained between 26% and 83% of the variation in appetite, tiredness, depression, and well-being. Drowsiness displayed consistent effects on appetite, tiredness and well-being. In contrast, anxiety's effect on well-being shifted importantly, with a direct effect and an indirect effect through tiredness at one month, being replaced by an effect working exclusively through depression at one week.Conclusion: Some of the causal forces explaining the variations in, and relationships among, palliative care patients' symptoms changed over the final month of life. This illustrates how investigating the causal foundations of symptom correlation or clustering can provide more detailed understandings that may contribute to improved control of patient comfort, quality of life, and quality of death. [ABSTRACT FROM AUTHOR]

Background: We have previously described a method for dealing with missing data in a prospective cardiac registry initiative. The method involves merging registry data to corresponding ICD-9-CM administrative data to fill in missing data 'holes'. Here, we describe the process of translating our data merging solution to ICD-10, and then validating its performance.Methods: A multi-step translation process was undertaken to produce an ICD-10 algorithm, and merging was then implemented to produce complete datasets for 1995-2001 based on the ICD-9-CM coding algorithm, and for 2002-2005 based on the ICD-10 algorithm. We used cardiac registry data for patients undergoing cardiac catheterization in fiscal years 1995-2005. The corresponding administrative data records were coded in ICD-9-CM for 1995-2001 and in ICD-10 for 2002-2005. The resulting datasets were then evaluated for their ability to predict death at one year.Results: The prevalence of the individual clinical risk factors increased gradually across years. There was, however, no evidence of either an abrupt drop or rise in prevalence of any of the risk factors. The performance of the new data merging model was comparable to that of our previously reported methodology: c-statistic = 0.788 (95% CI 0.775, 0.802) for the ICD-10 model versus c-statistic = 0.784 (95% CI 0.780, 0.790) for the ICD-9-CM model. The two models also exhibited similar goodness-of-fit.Conclusion: The ICD-10 implementation of our data merging method performs as well as the previously-validated ICD-9-CM method. Such methodological research is an essential prerequisite for research with administrative data now that most health systems are transitioning to ICD-10. [ABSTRACT FROM AUTHOR]

Background: Under the current healthcare system in China, there is no government-sponsored health insurance program for children. Children from families who move from rural and interior regions to large urban centres without a valid residency permit might be at higher risk of being uninsured due to their low socioeconomic status. We conducted a survey in Shanghai to describe children's health insurance coverage according to their migration status.Method: Between 2005 and 2006, we conducted an in-person health survey of the adult care-givers of children aged 7 and under, residing in five districts of Shanghai. We compared uninsurance rates between temporary and permanent child residents, and investigated factors associated with child health uninsurance.Results: Even though cooperative insurance eligibility has been extended to temporary residents of Shanghai, the uninsurance rate was significantly higher among temporary (65.6%) than permanent child residents (21.1%, adjusted odds ratio (OR): 5.85, 95% confidence interval (95% CI): 4.62-7.41). For both groups, family income was associated with having child health insurance; children in lower income families were more likely to be uninsured (OR: 1.96, 95% CI: 1.40-2.96).Conclusion: Children must rely on their parents to make the insurance purchase decision, which is constrained by their income and the perceived benefits of the insurance program. Children from migrant families are at even higher risk for uninsurance due to their lower socioeconomic status. Government initiatives specifically targeting temporary residents and providing health insurance benefits for their children are urgently needed. [ABSTRACT FROM AUTHOR]

Background: The performance of the Charlson and Elixhauser comorbidity measures in predicting patient outcomes have been well validated with ICD-9 data but not with ICD-10 data, especially in disease specific patient cohorts. The objective of this study was to assess the performance of these two comorbidity measures in the prediction of in-hospital and 1 year mortality among patients with congestive heart failure (CHF), diabetes, chronic renal failure (CRF), stroke and patients undergoing coronary artery bypass grafting (CABG). Methods: A Canadian provincial hospital discharge administrative database was used to define 17 Charlson comorbidities and 30 Elixhauser comorbidities. C-statistic values were calculated to evaluate the performance of two measures. One year mortality information was obtained from the provincial Vital Statistics Department. Results: The absolute difference between ICD-9 and ICD-10 data in C-statistics ranged from 0 to 0.04 across five cohorts for the Charlson and Elixhauser comorbidity measures predicting inhospital or 1 year mortality. In the models predicting in-hospital mortality using ICD-10 data, the C-statistics ranged from 0.62 (for stroke) -- 0.82 (for diabetes) for Charlson measure and 0.62 (for stroke) to 0.83 (for CABG) for Elixhauser measure. Conclusion: The change in coding algorithms did not influence the performance of either the Charlson or Elixhauser comorbidity measures in the prediction of outcome. Both comorbidity measures were still valid prognostic indicators in the ICD-10 data and had a similar performance in predicting short and long term mortality in the ICD-9 and ICD-10 data. [ABSTRACT FROM AUTHOR]

Background: The Plant-specific AP2/ERF gene family encodes proteins involved in various biological and physiological processes. Although the genome of Coptis chinensis Franch, a plant producing benzylisoquinoline alkaloids (BIAs), has been sequenced at the chromosome level, studies on the AP2/ERF gene family in C. chinensis are lacking. Thus, a genome-wide identification of AP2/ERF gene family in C. chinensis was conducted to explore its role in BIAs biosynthesis., Results: A total of 96 CcAP2/ERF genes were identified and categorized into five subfamilies, including 43 ERFs, 32 DREBs, 17 AP2s, 3 RAVs, and 1 Soloist, based on their structural domains. These CcAP2/ERF genes were unevenly distributed across nine chromosomes. Analysis of gene duplication events identified 17 CcAP2/ERF gene pairs in the genome, with 7 involved in tandem duplication events and 10 involved in segmental duplicate events, indicating that both types of duplications contributed to the expansion of the AP2/ERF gene family. The Ka/Ks ratio analysis suggested that the CcAP2/ERF gene family underwent strong purifying selection. Two phytohormones, methyl jasmonate and abscisic acid, were identified as potential key inducers of BIAs biosynthesis due to the cis-acting element prediction. Analysis of the spatial transcriptomic data revealed that 28 differentially expressed AP2/ERF genes had the highest or relatively higher expression levels in the rhizome, 17 of which positively correlated with the tissue-specific accumulation of BIAs. Further real-time PCR verification and protein-protein interaction analysis indicated that DREB1B might be one of the central regulators in a highly complex BIAs biosynthesis network., Conclusion: These findings provide significant insight into the function of AP2/ERF genes in C. chinensis, particularly in the regulatory network of BIAs biosynthesis in C. chinensis. This study also identifies candidate genes for metabolic engineering to increase BIAs content in C. chinensis., (© 2024. The Author(s).)

Background: For youths, abnormalities in ambulatory blood pressure (ABP) patterns are known to be associated with increased cardiovascular disease risk and potential target organ damage. Body composition, including indicators such as lean mass index (LMI), fat mass index (FMI), and visceral fat level (VFL), plays a significant role in blood pressure (BP) regulation. However, little is known about the association between these body composition indicators and ABP. Therefore, the present study examined the association between these body composition indicators and BP among Chinese youths., Methods: A total of 477 college students aged 17 to 28 years old (mean ± Standard deviation = 18.96 ± 1.21) from a university in Changsha, Hunan Province, China, were included in this study. Body composition indicators were measured with a bioelectrical impedance body composition analyzer, and 24-hour ambulatory blood pressure monitoring (ABPM) was conducted. Multivariable logistic regression was performed to assess the relationship between body composition indicators and abnormal ABP., Results: The prevalence of abnormal BP, including 24-hour BP, daytime BP, nighttime BP, and clinic BP, were 4.8%, 4.2%, 8.6%, and 10.9%, respectively. After adjusting for potential covariates, LMI [abnormal 24-hour BP (OR = 1.85, 95%CI:1.31, 2.62), abnormal daytime BP (OR = 1.76, 95%CI:1.21, 2.58), abnormal nighttime BP (OR = 1.64, 95%CI:1.25, 2.14), abnormal clinic BP (OR = 1.84, 95%CI:1.38, 2.45)], FMI [abnormal 24-hour BP (OR = 1.20, 95%CI:1.02, 1.41), abnormal daytime BP (OR = 1.30, 95%CI:1.07, 1.57), abnormal nighttime BP (OR = 1.24, 95%CI:1.10, 1.39), abnormal clinic BP (OR = 1.42, 95%CI:1.22, 1.65)], and VFL [abnormal 24-hour BP (OR = 1.22, 95%CI:1.06, 1.39), abnormal daytime BP (OR = 1.29, 95%CI:1.10, 1.51), abnormal nighttime BP (OR = 1.24, 95%CI:1.12, 1.39), abnormal clinic BP (OR = 1.38, 95%CI:1.21, 1.57)] are positively linked to abnormal BP. Additionally, there were significant sex differences in the association between body composition and abnormal BP., Conclusions: Our findings suggested maintaining an individual's appropriate muscle mass and fat mass and focusing on the different relations of males' and females' body composition is crucial for the achievement of appropriate BP profiles., (© 2024. The Author(s).)

The skin epidermis is continually influenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels epidermal renovation and hair regeneration with powerful self-renewal ability, as well as keeping diverse signals that direct their activity under surveillance with quick response. The importance of epidermal stem cells in wound healing and immune-related skin conditions has been increasingly recognized, and their potential for clinical applications is attracting attention. In this review, we delve into recent advancements and the various physiological and psychological factors that govern distinct epidermal stem cell populations, including psychological stress, mechanical forces, chronic aging, and circadian rhythm, as well as providing an overview of current methodological approaches. Furthermore, we discuss the pathogenic role of epidermal stem cells in immune-related skin disorders and their potential clinical applications., (© 2024. The Author(s).)

Objective: Effective management of hypertension requires not only medical intervention but also significant patient self-management. The challenge, however, lies in the diversity of patients' personal barriers to managing their condition. The objective of this research is to identify and categorize personalized barriers to hypertension self-management using the TASKS framework (Task, Affect, Skills, Knowledge, Stress). This study aims to enhance patient-centered strategies by aligning support with each patient's specific needs, recognizing the diversity in their unique circumstances, beliefs, emotional states, knowledge levels, and access to resources. This research is based on observations from a single study focused on eight patients, which may have been a part of a larger project., Results: The analysis of transcripts from eight patients and the Global Hypertension Practice Guidelines revealed 69 personalized barriers. These barriers were distributed as follows: emotional barriers (49%), knowledge barriers (24%), logical barriers (17%), and resource barriers (10%). The findings highlight the significant impact of emotional and knowledge-related challenges on hypertension self-management, including difficulties in home blood pressure monitoring and the use of monitoring tools. This study emphasizes the need for tailored interventions to address these prevalent barriers and improve hypertension management outcomes., (© 2024. The Author(s).)

Background: This study, part of a multi-study program, aimed to identify a core set of cost-based quality and performance indicators using a modified Delphi research approach. Conceptually, this core set of cost-based indicators is intended for use within a broader health system performance framework for evaluating home care programming in Canada., Methods: This study used findings from a recently published scoping review identifying 34 cost-focused home care program PQIs. A purposive and snowball technique was employed to recruit a national panel of system-level operational and content experts in home care. We collected data through progressive surveys and engagement sessions. In the first round of surveying, the panel scored each indicator on Importance, Actionable, and Interpretable criteria. The panel set the second round of ranking the remaining indicators' consensus criteria. The panel ranked by importance their top five indicators from operational and system perspectives. Indicators selected by over 50% of the panel were accepted as consensus., Results: We identified 13 panellists. 12 completed the first round which identified that 30 met the predetermined inclusion criteria. Eight completed the ranking exercise, with one of the eight completing one of two components. The second round resulted in three PQIs meeting the consensus criteria: one operational and two systems-policy-focused. The PQIs: "Average cost per day per home care client," "Home care service cost (mean) per home care client 1y, 3y and 7y per health authority and provincially and nationally", and "Home care funding as a percent of overall health care expenditures.", Conclusions: The findings from this study offer a crucial foundation for assessing operational and health system outcomes. Notably, this research pioneers identifying key cost-based PQIs through a national expert panel and modified Delphi methodology. This study contributes to the literature on PQIs for home care and provides a basis for future research and practice. These selected PQIs should be applied to future research to test their applicability and validity within home care programming and outcomes. Researchers should apply these selected PQIs in future studies to evaluate their applicability and validity within home care programming and outcomes., (© 2024. The Author(s).)

Background: Myopericytoma is a rare spindle cell tumor of mesenchymal origin, typically benign, characterized by concentric proliferation of tumor cells around blood vessels within subcutaneous tissue. It primarily occurs in middle-aged adults and is often located in distal extremities, although cases have been reported in proximal extremities and head-neck regions. However, occurrences within the oral cavity are exceedingly rare. To date, literature reviews have identified only two cases in children under 10 years old and reported only five cases of myopericytoma occurring in the lip region. We provide a comprehensive review and analysis of all documented cases to better understand this condition., Case Presentation: A 7-year-old girl presented to oral and maxillofacial surgery with the discovery of a painless mass on the inner aspect of the upper lip. The diagnosis of myopericytoma was confirmed by histological examination (HE staining), alcian blue staining, and immunohistochemistry., Conclusions: Following surgical excision, there were no signs of recurrence at a 3-month follow-up. The pathological diagnosis of myopericytoma is quite challenging, and immunohistochemical testing is necessary., (© 2024. The Author(s).)

Background: To establish a nomogram to predict the probability of survival of patients with stage II/III gastric cancer (GC) who received incomplete peri-operative adjuvant chemotherapy (PAC)., Methods: The medical records of stage II/III GC patients who received curative resection and 1 to 5 cycles of PAC from two tertiary hospitals were retrospectively reviewed. Patients were randomly classified into either a training group or validation group at a ratio of 7:3. The nomogram was constructed based on various prognostic factors using Cox regression analysis in the training cohort, and was validated by the validation group. Concordance index and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Additionally, decision curve analysis (DCA) was used to compare the net clinical benefits of the nomogram and eighth version of TNM staging system., Results: A total of 1,070 consecutive patients were included and 749 patients were enrolled into the training group. Lower body mass index (< 18.5 kg/m 2 ), total gastrectomy, stage III disease and fewer cycles of PAC were identified to be independent predictors for poorer survival. The area under the curve (AUC) values of receiver operating characteristics (ROC) curve predicting 5-year survival probabilities and C-index were 0.768 and 0.742, 0.700 (95%CI: 0.674-0.726) and 0.689 (95%CI: 0.646-0.732) in the training and validation groups, respectively. The calibration curves in the validation cohort showed good agreement between the prediction and observation of 1-, 3- and 5-year survival probabilities. Furthermore, DCA showed that our model has a better net benefit than that of TNM staging system., Conclusions: The findings emphasize the value of completing PAC. The nomogram which was established to predict survival probability in patients with stage II/III GC receiving radical gastrectomy and incomplete PAC had good accuracy and was verified through both internal and external validation., (© 2024. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) describes a spectrum of chronic fattening of liver that can lead to fibrosis and cirrhosis. Diabetes has been identified as a major comorbidity that contributes to NAFLD progression. Health systems around the world make use of administrative data to conduct population-based prevalence studies. To that end, we sought to assess the accuracy of diabetes International Classification of Diseases (ICD) coding in administrative databases among a cohort of confirmed NAFLD patients in Calgary, Alberta, Canada., Methods: The Calgary NAFLD Pathway Database was linked to the following databases: Physician Claims, Discharge Abstract Database, National Ambulatory Care Reporting System, Pharmaceutical Information Network database, Laboratory, and Electronic Medical Records. Hemoglobin A1c and diabetes medication details were used to classify diabetes groups into absent, prediabetes, meeting glycemic targets, and not meeting glycemic targets. The performance of ICD codes among these groups was compared to this standard. Within each group, the total numbers of true positives, false positives, false negatives, and true negatives were calculated. Descriptive statistics and bivariate analysis were conducted on identified covariates, including demographics and types of interacted physicians., Results: A total of 12,012 NAFLD patients were registered through the Calgary NAFLD Pathway Database and 100% were successfully linked to the administrative databases. Overall, diabetes coding showed a sensitivity of 0.81 and a positive predictive value of 0.87. False negative rates in the absent and not meeting glycemic control groups were 4.5% and 6.4%, respectively, whereas the meeting glycemic control group had a 42.2% coding error. Visits to primary and outpatient services were associated with most encounters., Conclusion: Diabetes ICD coding in administrative databases can accurately detect true diabetic cases. However, patients with diabetes who meets glycemic control targets are less likely to be coded in administrative databases. A detailed understanding of the clinical context will require additional data linkage from primary care settings., (© 2024. The Author(s).)

Purpose: To compare the safety and efficacy of CPG in the rectus abdominis and intercostal regions., Materials and Methods: This retrospective study included 226 patients who underwent CPG at a single center, with the stoma placed in the rectus abdominis or intercostal region. Surgical outcomes and complications, such as pain and infection within 6 months postoperatively, were recorded., Results: The surgical success rate was 100%, and the all-cause mortality rate within 1 month was 0%. An intercostal stoma was placed in 56 patients; a rectus abdominis stoma was placed in 170 patients. The duration of surgery was longer for intercostal stoma placement (37.66 ± 14.63 min) than for rectus abdominis stoma placement (30.26 ± 12.40 min) (P = 0.000). At 1 month postsurgery, the rate of stoma infection was greater in the intercostal group (32.1%) than in the rectus abdominis group (20.6%), but the difference was not significant (P = 0.077). No significant difference was observed in the infection rate between the two groups at 3 or 6 months postsurgery (P > 0.05). Intercostal stoma patients reported higher pain scores during the perioperative period and at 1 month postsurgery (P = 0.000), but pain scores were similar between the two groups at 3 and 6 months postsurgery. The perioperative complication rates for intercostal and rectus abdominis surgery were 1.8% and 5.3%, respectively (P = 0.464), with no significant difference in the incidence of tube dislodgement (P = 0.514). Patient weight improved significantly at 3 and 6 months postoperatively compared to preoperatively (P < 0.05)., Conclusion: Rectus abdominis and intercostal stomas have similar safety and efficacy. However, intercostal stomas may result in greater short-term patient discomfort., (© 2024. The Author(s).)

Background: Population based surveillance of surgical site infections (SSIs) requires precise case-finding strategies. We sought to develop and validate machine learning models to automate the process of complex (deep incisional/organ space) SSIs case detection., Methods: This retrospective cohort study included adult patients (age ≥ 18 years) admitted to Calgary, Canada acute care hospitals who underwent primary total elective hip (THA) or knee (TKA) arthroplasty between Jan 1st, 2013 and Aug 31st, 2020. True SSI conditions were judged by the Alberta Health Services Infection Prevention and Control (IPC) program staff. Using the IPC cases as labels, we developed and validated nine XGBoost models to identify deep incisional SSIs, organ space SSIs and complex SSIs using administrative data, electronic medical records (EMR) free text data, and both. The performance of machine learning models was assessed by sensitivity, specificity, positive predictive value, negative predictive value, F1 score, the area under the receiver operating characteristic curve (ROC AUC) and the area under the precision-recall curve (PR AUC). In addition, a bootstrap 95% confidence interval (95% CI) was calculated., Results: There were 22,059 unique patients with 27,360 hospital admissions resulting in 88,351 days of hospital stay. This included 16,561 (60.5%) TKA and 10,799 (39.5%) THA procedures. There were 235 ascertained SSIs. Of them, 77 (32.8%) were superficial incisional SSIs, 57 (24.3%) were deep incisional SSIs, and 101 (42.9%) were organ space SSIs. The incidence rates were 0.37 for superficial incisional SSIs, 0.21 for deep incisional SSIs, 0.37 for organ space and 0.58 for complex SSIs per 100 surgical procedures, respectively. The optimal XGBoost models using administrative data and text data combined achieved a ROC AUC of 0.906 (95% CI 0.835-0.978), PR AUC of 0.637 (95% CI 0.528-0.746), and F1 score of 0.79 (0.67-0.90)., Conclusions: Our findings suggest machine learning models derived from administrative data and EMR text data achieved high performance and can be used to automate the detection of complex SSIs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Implementing Patient-reported Outcome Measures (PROMs) and Patient-reported Experience Measures (PREMs) is an effective way to deliver patient- and family-centered care (PFCC). Although Alberta Health Services (AHS) is Canada's largest and fully integrated health system, PROMs and PREMs are yet to be routinely integrated into the pediatric healthcare system. This study addresses this gap by investigating the current uptake, barriers, and enablers for integrating PROMs and PREMs in Alberta's pediatric healthcare system., Methods: Pediatric clinicians and academic researchers with experience using PROMs and PREMs were invited to complete a quantitative survey. Additionally, key stakeholders were qualitatively interviewed to understand current challenges in implementing pediatric PROMs and PREMs within AHS. Quantitative data gathered from 22 participants were descriptively analyzed, and qualitative data from 14 participants were thematically analyzed., Results: Participants identified 33 PROMs and 6 PREMs showing diversity in the types of pediatric PROMs and PREMs currently being used in Alberta and their mode of administration. The qualitatively identified challenges were associated with patients, family caregivers, and clinicians. The absence of system-level support, such as integration within electronic medical records, is considered a significant system-level challenge., Conclusions: The significant variation in the types of PROMs and PREMs used, the rationale for their use, and their mode of administration demonstrate the diverse and sporadic use of these measures in Alberta. These findings highlight the need for province-wide uniform implementation of pediatric PROMs and PREMs in Alberta. Our results could benefit healthcare organizations in developing evidence-based PROM and PREM implementation strategies in pediatrics., (© 2023. The Author(s).)

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are commonly used in the management of type 2 diabetes mellitus (T2DM) and have been found to worsen the reduction of skeletal muscle mass in individuals with T2DM. This study aims to examine the potential of exercise in mitigating the skeletal muscle atrophy induced by SGLT2i treatment., Methods: A rat model of T2DM (40 male Sprague-Dawley rats; T2DM induced by a combination of high-fat diet and streptozotocin) was used to examine the effects of six-week treatment with Dapagliflozin (DAPA, SGLT2i) in combination with either aerobic exercise (AE) or resistance training (RT) on skeletal muscle. T2DM-eligible rats were randomized into the T2DM control group (CON, n = 6), DAPA treatment group (DAPA, n = 6), DAPA combined with aerobic exercise intervention group (DAPA + AE, n = 6), and DAPA combined with resistance training intervention group (DAPA + RT, n = 6). To assess the morphological changes in skeletal muscle, myosin ATPase and HE staining were performed. mRNA expression levels of Atrogin-1, MuRF1, and Myostatin were determined using quantitative PCR. Furthermore, protein expression levels of AKT, p70S6K, mTOR, FoXO1/3A, NF-κB, and MuRF1 were examined through western blotting., Results: Both the administration of DAPA alone and the combined exercise intervention with DAPA resulted in significant reductions in blood glucose levels and body weight in rats. However, DAPA alone administration led to a decrease in skeletal muscle mass, whereas RT significantly increased skeletal muscle mass and muscle fiber cross-sectional area. The DAPA + RT group exhibited notable increases in both total protein levels and phosphorylation levels of AKT and p70S6K in skeletal muscle. Moreover, the DAPA, DAPA + AE, and DAPA + RT groups demonstrated downregulation of protein expression (FoXO1/3A) and mRNA levels (Atrogin-1, MuRF1, and Myostatin) associated with muscle atrophy., Conclusions: Our findings provide support for the notion that dapagliflozin may induce skeletal muscle atrophy through mechanisms unrelated to protein metabolism impairment in skeletal muscle, as it does not hinder protein metabolic pathways while reduces muscle atrophy-related genes. Additionally, our observations reveal that RT proves more effective than AE in enhancing skeletal muscle mass and muscle fiber cross-sectional area in rats with T2DM by stimulating protein anabolism within the skeletal muscle., (© 2023. The Author(s).)

Background: Prognostic information for patients with hypertension is largely based on population averages. The purpose of this study was to compare the performance of four machine learning approaches for personalized prediction of incident hospitalization for cardiovascular disease among newly diagnosed hypertensive patients., Methods: Using province-wide linked administrative health data in Alberta, we analyzed a cohort of 259,873 newly-diagnosed hypertensive patients from 2009 to 2015 who collectively had 11,863 incident hospitalizations for heart failure, myocardial infarction, and stroke. Linear multi-task logistic regression, neural multi-task logistic regression, random survival forest and Cox proportional hazard models were used to determine the number of event-free survivors at each time-point and to construct individual event-free survival probability curves. The predictive performance was evaluated by root mean squared error, mean absolute error, concordance index, and the Brier score., Results: The random survival forest model has the lowest root mean squared error value at 33.94 and lowest mean absolute error value at 28.37. Machine learning methods provide similar discrimination and calibration in the personalized survival prediction of hospitalizations for cardiovascular events in patients with hypertension. Neural multi-task logistic regression model has the highest concordance index at 0.8149 and lowest Brier score at 0.0242 for the personalized survival prediction., Conclusions: This is the first personalized survival prediction for cardiovascular diseases among hypertensive patients using administrative data. The four models tested in this analysis exhibited a similar discrimination and calibration ability in predicting personalized survival prediction of hypertension patients., (© 2022. The Author(s).)

Objective: A beta version (2018) of International Classification of Diseases, 11th Revision for MMS (ICD-11), needed testing. Field-testing involves real-world application of the new codes to examine usability. We describe creating a dataset and characterizing the usability of ICD-11 code set by coders. We compare ICD-11 against ICD-10-CA (Canadian modification) and a reference standard dataset of diagnoses. Real-world usability encompasses code selection and time to code a complete inpatient chart using ICD-11 compared with ICD-10-CA., Methods and Results: A random sample of inpatient records previously coded using ICD-10-CA was selected from hospitals in Calgary, Alberta (N = 2896). Nurses examined these charts for conditions and healthcare-related harms. Clinical coders re-coded the same charts using ICD-11 codes. Inter-rater reliability (IRR) and coding time improved with ICD-11 coding experience (23.6 to 9.9 min average per chart). Code structure comparisons and challenges encountered are described. Overall, 86.3% of main condition codes matched. Coder comments regarding duplicate codes, missing codes, code finding issues enabled improvements to the ICD-11 Browser, Coding Tool, and Reference Guide. Training is essential for solid IRR with 17,000 diagnostic categories in the new ICD-11. As countries transition to ICD-11, our coding experiences and methods can inform users for implementation or field testing., (© 2022. The Author(s).)

Background: As a valuable medicinal plant, Rhodiola has a very long history of folk medicine used as an important adaptogen, tonic, and hemostatic. However, our knowledge of the chloroplast genome level of Rhodiola is limited. This drawback has limited studies on the identification, evolution, genetic diversity and other relevant studies on Rhodiola., Results: Six Rhodiola complete chloroplast genomes were determined and compared to another Rhodiola cp genome at the genome scale. The results revealed a cp genome with a typical quadripartite and circular structure that ranged in size from 150,771 to 151,891 base pairs. High similarity of genome organization, gene number, gene order, and GC content were found among the chloroplast genomes of Rhodiola. 186 (R. wallichiana) to 200 (R. gelida) SSRs and 144 pairs of repeats were detected in the 6 Rhodiola cp genomes. Thirteen mutational hotspots for genome divergence were determined and could be used as candidate markers for phylogenetic analyses and Rhodiola species identification. The phylogenetic relationships inferred by members of Rhodiola cluster into two clades: dioecious and hermaphrodite. Our findings are helpful for understanding Rhodiola's taxonomic, phylogenetic, and evolutionary relationships., Conclusions: Comparative analysis of chloroplast genomes of Rhodiola facilitates medicinal resource conservation, phylogenetic reconstruction and biogeographical research of Rhodiola., (© 2022. The Author(s).)

Background: Osteosarcoma (OS) is a common malignant tumor, which occurs in the metaphysis of the long diaphysis from mesenchymal tissue. Previous studies have indicated that expression of microRNA-143 (miR-143) could affect cancer cell proliferation, migration and invasion. The present research was performed to figure out whethermiR-143 expression inhibits the growth and the invasion of OS., Methods: We conducted a literature search in the electronic databases of Medline, Embase, Web of Science, and the Cochrane Library, SinoMed, WanFang, China national knowledge infrastructure (CNKI) until January 2022. We used Review Manager 5.3 software to conduct our research., Results: Twelve eligible articles were included, 5 articles were reported outcomes about mice, 11 articles were reported outcomes about human. The results of mice demonstrated that the miR-143 group had significantly better results in tumor volume, tumor weight and survival rate. The results of human demonstrated that the high level of miR-143 group had significantly better results in the 3-year, 4-year, and 5-year survival rate, lung metastasis and tumor grade., Conclusions: MiR-143 has potentially important value in the treatment and prognosis of OS. However, more reliable animal and clinical trials are needed before miR-143 based therapies can be transferred from animal studies to human applications., (© 2022. The Author(s).)

Purpose: Osteosarcoma (OS) is a differentiation disease caused by the genetic and epigenetic differentiation of mesenchymal stem cells into osteoblasts. OS is a common, highly malignant tumor in children and adolescents. Fifteen to 20 % of the patients find distant metastases at their first visit. The purpose of our study was to identify biomarkers for tracking the prognosis and treatment of OS to improve the survival rate of patients., Materials and Methods: In this study, which was based on Therapeutically Applicable Research to Generate Effective Treatments (TARGET), we searched for m6A related lncRNAs in OS. We constructed a network between lncRNA and m6A, and built an OS prognostic risk model., Results: We identified 14,581 lncRNAs by using the dataset from TARGET. We obtained 111 m6A-related lncRNAs through a Pearson correlation analysis. A network was built between lncRNA and m6A genes. Eight m6A-related lncRNAs associated with survival were identified through a univariate Cox analysis. A selection operator (LASSO) Cox regression was used to construct a prognostic risk model with six genes (RP11-286E11.1, LINC01426, AC010127.3, DLGAP1-AS2, RP4-657D16.3, AC002398.11) obtained through least absolute shrinkage. We also discovered upregulated levels of DLGAP1-AS2 and m6A methylation in osteosarcoma tissues/cells compared with normal tissues/osteoblasts cells., Conclusion: We constructed a risk score prognosis model of m6A-related lncRNAs (RP11-286E11.1, LINC01426, AC010127.3, DLGAP1-AS2, RP4-657D16.3, AC002398.11) using the dataset downloaded from TRAGET. We verified the value of the model by dividing all samples into test groups and training groups. However, the role of m6A-related lncRNAs in osteosarcoma needs to be further researched by cell and in vivo studies., (© 2021. The Author(s).)

Background: Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI., Methods: Male Sprague-Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein., Results: PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes., Conclusion: Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM., (© 2021. The Author(s).)

Background: To develop a novel subjective-objective-combined (SOC) grading standard for auto-segmentation for each organ at risk (OAR) in the thorax., Methods: A radiation oncologist manually delineated 13 thoracic OARs from computed tomography (CT) images of 40 patients. OAR auto-segmentation accuracy was graded by five geometric objective indexes, including the Dice similarity coefficient (DSC), the difference of the Euclidean distance between centers of mass (ΔCMD), the difference of volume (ΔV), maximum Hausdorff distance (MHD), and average Hausdorff distance (AHD). The grading results were compared with those of the corresponding geometric indexes obtained by geometric objective methods in the other two centers. OAR auto-segmentation accuracy was also graded by our subjective evaluation standard. These grading results were compared with those of DSC. Based on the subjective evaluation standard and the five geometric indexes, the correspondence between the subjective evaluation level and the geometric index range was established for each OAR., Results: For ΔCMD, ΔV, and MHD, the grading results of the geometric objective evaluation methods at our center and the other two centers were inconsistent. For DSC and AHD, the grading results of three centers were consistent. Seven OARs' grading results in the subjective evaluation standard were inconsistent with those of DSC. Six OARs' grading results in the subjective evaluation standard were consistent with those of DSC. Finally, we proposed a new evaluation method that combined the subjective evaluation level of those OARs with the range of corresponding DSC to determine the grading standard. If the DSC ranges between the adjacent levels did not overlap, the DSC range was used as the grading standard. Otherwise, the mean value of DSC was used as the grading standard., Conclusions: A novel OAR-specific SOC grading standard in thorax was developed. The SOC grading standard provides a possible alternative for evaluation of the auto-segmentation accuracy for thoracic OARs.

Background: The International Classification of Diseases (ICD) is the reference standard for reporting diseases and health conditions globally. Variations in ICD use and data collection across countries can hinder meaningful comparisons of morbidity data. Thus, we aimed to characterize ICD and hospital morbidity data collection features worldwide., Methods: An online questionnaire was created to poll the World Health Organization (WHO) member countries that were using ICD. The survey included questions focused on ICD meta-features and hospital data collection systems, and was distributed via SurveyMonkey using purposive and snowball sampling. Accordingly, senior representatives from organizations specialized in the topic, such as WHO Collaborating Centers, and other experts in ICD coding were invited to fill out the survey and forward the questionnaire to their peers. Answers were collated by country, analyzed, and presented in a narrative form with descriptive analysis., Results: Responses from 47 participants were collected, representing 26 different countries using ICD. Results indicated worldwide disparities in the ICD meta-features regarding the maximum allowable coding fields for diagnosis, the definition of main condition, and the mandatory type of data fields in the hospital morbidity database. Accordingly, the most frequently reported answers were "reason for admission" as main condition definition (n = 14), having 31 or more diagnostic fields available (n = 12), and "Diagnoses" (n = 26) and "Patient demographics" (n = 25) for mandatory data fields. Discrepancies in data collection systems occurred between but also within countries, thereby revealing a lack of standardization both at the international and national level. Additionally, some countries reported specific data collection features, including the use or misuse of ICD coding, the national standards for coding or lack thereof, and the electronic abstracting systems utilized in hospitals., Conclusions: Harmonizing ICD coding standards/guidelines should be a common goal to enhance international comparisons of health data. The current international status of ICD data collection highlights the need for the promotion of ICD and the adoption of the newest version, ICD-11. Furthermore, it will encourage further research on how to improve and standardize ICD coding.

Background: It is very important to accurately delineate the CTV on the patient's three-dimensional CT image in the radiotherapy process. Limited to the scarcity of clinical samples and the difficulty of automatic delineation, the research of automatic delineation of cervical cancer CTV based on CT images for new patients is slow. This study aimed to assess the value of Dense-Fully Connected Convolution Network (Dense V-Net) in predicting Clinical Target Volume (CTV) pre-delineation in cervical cancer patients for radiotherapy., Methods: In this study, we used Dense V-Net, a dense and fully connected convolutional network with suitable feature learning in small samples to automatically pre-delineate the CTV of cervical cancer patients based on computed tomography (CT) images and then we assessed the outcome. The CT data of 133 patients with stage IB and IIA postoperative cervical cancer with a comparable delineation scope was enrolled in this study. One hundred and thirteen patients were randomly designated as the training set to adjust the model parameters. Twenty cases were used as the test set to assess the network performance. The 8 most representative parameters were also used to assess the pre-sketching accuracy from 3 aspects: sketching similarity, sketching offset, and sketching volume difference., Results: The results presented that the DSC, DC/mm, HD/cm, MAD/mm, ∆V, SI, IncI and JD of CTV were 0.82 ± 0.03, 4.28 ± 2.35, 1.86 ± 0.48, 2.52 ± 0.40, 0.09 ± 0.05, 0.84 ± 0.04, 0.80 ± 0.05, and 0.30 ± 0.04, respectively, and the results were greater than those with a single network., Conclusions: Dense V-Net can correctly predict CTV pre-delineation of cervical cancer patients and can be applied in clinical practice after completing simple modifications.

Background: Hypertension is a common chronic condition affecting nearly a quarter of Canadians. Hypertension surveillance in Canada typically relies on administrative data and/or national surveys. Routinely-captured data from primary care electronic medical records (EMRs) are a complementary source for chronic disease surveillance, with longitudinal patient-level details such as sociodemographics, blood pressure, weight, prescribed medications, and behavioural risk factors. As EMR data are generated from patient care and administrative tasks, assessing data quality is essential before using for secondary purposes. This study evaluated the quality of primary care EMR data from one province in Canada within the context of hypertension surveillance., Methods: We conducted a cross-sectional, descriptive study using primary care EMR data collected by two practice-based research networks in Alberta, Canada. There were 48,377 adults identified with hypertension from 53 clinics as of June 2018. Summary statistics were used to examine the quality of data elements considered relevant for hypertension surveillance., Results: Patient year of birth and sex were complete, but other sociodemographic information (ethnicity, occupation, education) was largely incomplete and highly variable. Height, weight, body mass index and blood pressure were complete for most patients (over 90%), but a small proportion of outlying values indicate data inaccuracies were present. Most patients had a relevant laboratory test present (e.g. blood glucose/glycated hemoglobin, lipid profile), though a very small proportion of values were outside a biologically plausible range. Details of prescribed antihypertensive medication, such as start date, strength, dose, frequency, were mostly complete. Nearly 80% of patients had a smoking status recorded, though only 66% had useful information (i.e. categorized as current, past, or never), and less than half had their alcohol use described; information related to amount, frequency or duration was not available., Conclusions: Blood pressure and prescribed medications in primary care EMR data demonstrated good completeness and plausibility, and contribute valuable information for hypertension epidemiology and surveillance. The use of other clinical, laboratory, and sociodemographic variables should be used carefully due to variable completeness and suspected data errors. Additional strategies to improve these data at the point of entry and after data extraction (e.g. statistical methods) are required.

Background: The Seattle Angina Questionnaire (SAQ) is a widely-used patient-reported outcomes measure in patients with heart disease. This study assesses the validity and reliability of the SAQ in a Canadian cohort of individuals with stable angina., Methods and Results: Data are from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry, a population-based registry of patients who received cardiac catheterization in Alberta, Canada. The cohort consists of 4052 patients undergoing cardiac catheterization for stable angina and completed the SAQ within 2 weeks. Exploratory factor analysis and confirmatory factor analysis (CFA) were used to assess the factorial structure of the SAQ. Internal and test-retest reliabilities of a new measure (i.e., SAQ-CAN) was measured using Cronbach α and intraclass correlation coefficient, respectively. CFA model fit was assessed using the root mean square error of approximation (RMSEA) and comparative fit index (CFI). Construct validity of the SAQ-CAN was assessed in relation to Hospital Anxiety and Depression Scales (HADS), Euro Quality of life 5 dimension (EQ5D), and original SAQ. Of the 4052 patients included in this analysis, 3281 (80.97%) were younger than 75 years old, while 3239 (79.94%) were male. Both exploratory and confirmatory factor analyses revealed a four-factorial structure consisting of 16 items that provided a better fit to the data (RMSEA = 0.049 [90% CI = (0.047, 0.052)]; CFI = 0.975). The 16-item SAQ demonstrated good to excellent internal reliability (Cronbach's α range from 0.77 to 0.90), moderate to strong correlation with the Original SAQ and EQ5D but negligible correlations with HADS., Conclusion: The SAQ-CAN has acceptable psychometric properties that are comparable to the original SAQ. We recommend its use for assessing coronary health outcomes in Canadian patients with Coronary Artery Disease.

Purpose: Margins are employed in radiotherapy treatment planning to mitigate the dosimetric effects of geometric uncertainties for the clinical target volume (CTV). Here, we proposed a margin concept that takes into consideration the beam direction, thereby generating a beam-specific planning target volume (BSPTV) on a beam entrance view. The total merged BSPTV was considered a target for optimization. We investigated the impact of this novel approach for lung intensity-modulated radiotherapy (IMRT) treatment, and compared the treatment plans generated using BSPTV with general PTV., Methods and Materials: We generated the BSPTV by expanding the CTV perpendicularly to the incident beam direction using the 2D version of van Herk's margin concept. The BSPTV and general PTV margin were analyzed using digital phantom simulation. Fifteen lung cancer patients were used in the planning study. First, all patient targets were performed with the CTV projection area analysis to select the suitable beam angles. Then, BSPTV was generated according to the selected beam angles. IMRT plans were optimized with the general PTV and BSPTV as the target volumes, respectively. The dosimetry metrics were calculated and evaluated between these two plans. The plan robustness of both plans for setup uncertainties was evaluated using worst-case analysis., Results: Both general PTV and BSPTV plans satisfied the CTV coverage. In addition, the BSPTV plans improved the sparing of high doses to target-surrounding lung tissues compared to the general PTV plans. Both D mean of Ring PTV and Ring BSPTV were significantly lower in BSPTV plans (38.89 Gy and 39.43 Gy) compared to the general PTV plans (40.27 Gy and 40.68 Gy). The V20, V5, and mean lung dose of the affected lung were significant lower in BSPTV plans (16.20%, 28.75% and 8.93 Gy) compared to general PTV plans (16.69%, 29.22% and 9.18 Gy). In uncertainty scenarios, about 80% of target coverage was achieved for both general PTV and BSPTV plans., Conclusions: The results suggested that plan robustness can be guaranteed in both the BSPTV and general PTV plans. However, the BSPTV plan spared normal tissues, such as the lungs, significantly better compared to the general PTV plans.

Background: Premature ovarian failure is characterized by amenorrhea, hypoestrogenism, and hypergonadotropinism, and occurs in women under 40 years of age. The prevalence of premature ovarian failure in women younger than 20 years of age is only 0.01%. Immune disorders are one of the causes of premature ovarian failure. Graves' disease and chronic urticaria are also associated with immune disorders., Case Presentation: We report a case of a 15-year-old Han Chinese girl with premature ovarian failure complicated by Graves' disease and chronic urticaria. She experienced menarche at 13 years of age and presented with amenorrhea after 7 months of irregular menstruation. Laboratory examinations indicated hypoestrogenism and hypergonadotropinism. Ultrasound imaging revealed that her uterus and ovaries were small in size. Gene and antibody tests related to premature ovarian failure returned negative results. Both thyroid peroxidase autoantibody and thyrotropin receptor antibody were positive. After reviewing the literature on the relationship between these three diseases and immune disorders, our patient was diagnosed as having atypical autoimmune polyglandular syndrome. After taking small doses of estrogen for 6 months, the size of her uterus increased, and her psychological anxiety was relieved., Conclusions: We report a case of an unusual association of premature ovarian failure, Graves' disease, and chronic urticaria. This case presents an atypical combination of adolescent autoimmune polyglandular syndrome, which is worthy of the attention of clinicians and presents an important lesson for them. Our case highlights that premature ovarian failure in adolescents requires long-term follow-up and medical treatment as well as psychological counselling.

Background: Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine (SP) has been largely reported among pregnant women. However, the profile of resistance markers to SP dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) in the general population are varied and not frequently monitored. Currently, SP is used as partner drug for artemisinin combination therapy (SP-artesunate) in some sub-Saharan African countries or as a prophylactic drug in intermittent preventive treatment of malaria during pregnancy and infants and in seasonal malaria chemoprevention (SMC). Profiling of P. falciparum-resistant genotypes to SP is dynamic and critical in providing data that would be useful for malaria control programmes. This study assessed the profile of dhfr and dhps genes genotypes among individuals with malaria in Lagos, Nigeria., Methods: Molecular markers of SP resistance were identified by nested PCR and sequenced among malaria positive dried blood spots (DBS) that were collected from individuals attending health facilities from January 2013 to February 2014 and during community surveys from October 2010 to September 2011 across different Local Government Areas of Lagos State, Nigeria., Results: A total of 242 and 167 samples were sequenced for dhfr and dhps, respectively. Sequence analysis of dhfr showed that 95.5% (231/242), 96.3% (233/242) and 96.7% (234/242) of the samples had N51I, C59R and S108N mutant alleles, respectively. The prevalence of dhps mutation at codons A437G, A613S, S436A, A581G, I431V and K540E were 95.8% (160/167), 41.9% (70/167), 41.3% (69/167), 31.1% (52/167), 25.1% (42/167), and 1.2% (2/167) respectively. The prevalence of triple mutations (CIRNI) in dhfr was 93.8% and 44.3% for the single dhps haplotype mutation (SGKAA). Partial SP-resistance due to quadruple dhfr-dhps haplotype mutations (CIRNI-SGKAA) and octuple haplotype mutations (CIRNI-VAGKGS) with rate of 42.6% and 22.0%, respectively has been reported., Conclusions: There was increased prevalence in dhfr triple haplotype mutations when compared with previous reports in the same environment but aligned with high prevalence in other locations in Nigeria and other countries in Africa. Also, high prevalence of dhfr and dhps mutant alleles occurred in the study areas in Lagos, Nigeria five to eight years after the introduction of artemisinin combination therapy underscores the need for continuous monitoring.

Background: Information on HPV-associated sinonasal squamous cell carcinoma (SNSCC) is very limited in China. The aim of this study was to determine the prevalence of HPV in a large cohort of SNSCC patients in China., Methods: Clinical records and formalin-fixed and paraffin-embedded tumor specimens from 30 SNSCC patients with associated inverted papilloma (IP-SNSCC) and 84 de novo SNSCC (DN-SNSCC) patients were retrieved between 2010 and 2017. HPV status was determined for each specimen using a combination of p16 immunohistochemistry and GP5+/6+ PCR., Results: Immunohistochemistry for p16 was positive in two IP-SNSCC patients (2/30, 6.7%) and in 16 DN-SNSCC patients (16/84, 19.0%). HPV DNA was detected in six IP-SNSCC patients (6/30, 20%) and in three DN-SNSCC patients (3/84, 3.8%). Expression of p16 was not correlated with the presence of HPV DNA ( p  = 0.150). Among 18 p16-positive SNSCC patients, only three were HPV DNA-positive. Furthermore, only three of nine HPV DNA-positive tumors exhibited high p16 expression. In IP-SNSCC patients, only one of six HPV DNA-positive tumors exhibited high p16 expression. In DN-SNSCC patients, two of three HPV DNA-positive tumors exhibited high p16 expression. The positive rates for both HPV DNA and p16 in IP-SNSCC patients and DN-SNSCC patients were 3.3 and 2.4%, respectively., Conclusions: Immunostaining for p16 is not a reliable surrogate marker of HPV status in SNSCC. The presence of HPV is rarely detected in DN-SNSCC patients in Eastern China. IP-SNSCC patients frequently lack of p16 overexpression despite the presence of high-risk HPV DNA., Competing Interests: Competing interestsThe authors declare that there are no conflicts of interest associated with the publication of this manuscript., (© The Author(s) 2020.)

Background: Data quality assessment presents a challenge for research using coded administrative health data. The objective of this study is to develop and validate a set of coding association rules for coded diagnostic data., Methods: We used the Canadian re-abstracted hospital discharge abstract data coded in International Classification of Disease, 10th revision (ICD-10) codes. Association rule mining was conducted on the re-abstracted data in four age groups (0-4, 20-44, 45-64; ≥ 65) to extract ICD-10 coding association rules at the three-digit (category of diagnosis) and four-digit levels (category of diagnosis with etiology, anatomy, or severity). The rules were reviewed by a panel of 5 physicians and 2 classification specialists using a modified Delphi rating process. We proposed and defined the variance and bias to assess data quality using the rules., Results: After the rule mining process and the panel review, 388 rules at the three-digit level and 275 rules at the four-digit level were developed. Half of the rules were from the age group of ≥65. Rules captured meaningful age-specific clinical associations, with rules at the age group of ≥65 being more complex and comprehensive than other age groups. The variance and bias can identify rules with high bias and variance in Alberta data and provides directions for quality improvement., Conclusions: A set of ICD-10 data quality rules were developed and validated by a clinical and classification expert panel. The rules can be used as a tool to assess ICD-coded data, enabling the monitoring and comparison of data quality across institutions, provinces, and countries.

Background: Primary care electronic medical record (EMR) data are emerging as a useful source for secondary uses, such as disease surveillance, health outcomes research, and practice improvement. These data capture clinical details about patients' health status, as well as behavioural risk factors, such as smoking. While the importance of documenting smoking status in a healthcare setting is recognized, the quality of smoking data captured in EMRs is variable. This study was designed to test methods aimed at improving the quality of patient smoking information in a primary care EMR database., Methods: EMR data from community primary care settings extracted by two regional practice-based research networks in Alberta, Canada were used. Patients with at least one encounter in the previous 2 years (2016-2018) and having hypertension according to a validated definition were included (n = 48,377). Multiple imputation was tested under two different assumptions for missing data (smoking status is missing at random and missing not-at-random). A third method tested a novel pattern matching algorithm developed to augment smoking information in the primary care EMR database. External validity was examined by comparing the proportions of smoking categories generated in each method with a general population survey., Results: Among those with hypertension, 40.8% (n = 19,743) had either no smoking information recorded or it was not interpretable and considered missing. Those with missing smoking data differed statistically by demographics, clinical features, and type of EMR system used in the clinic. Both multiple imputation methods produced fully complete smoking status information, with the proportion of current smokers estimated at 25.3% (data missing at random) and 12.5% (data missing not-at-random). The pattern-matching algorithm classified 18.2% of patients as current smokers, similar to the population-based survey (18.9%), but still resulted in missing smoking information for 23.6% of patients. The algorithm was estimated to be 93.8% accurate overall, but varied by smoking status category., Conclusion: Multiple imputation and algorithmic pattern-matching can be used to improve EMR data post-extraction but the recommended method depends on the purpose of secondary use (e.g. practice improvement or epidemiological analyses).

Background: The biological behavior of early recurrence is more invasive and the prognosis is worse in gastric cancer (GC). The risk of early recurrence (ER) for GC in stage II/III has not been reported of which the majority of GC patients are in China. Therefore, it is necessary to analyze the ER of gastric cancer in stage II/III., Methods: The medical records of 1511 consecutive stage II/III GC patients who received resections were retrospectively reviewed. They were randomly classified into either a development or validation group at a ratio of 7:3. The nomogram was constructed based on prognostic factors using logistic regression analysis and was validated by bootstrap resampling and validation dataset, respectively. Concordance index (C-index) values and calibration curves were used to evaluate the predictive accuracy and discriminatory capability., Results: Three hundred eleven patients experienced ER, accounting for 20.58% of the GC patients investigated. Multivariate logistic regression analysis identified tumors located at upper, middle third, or mixed, a positive lymph node ratio ≥ 0.335, pTNM stage III, lymphocyte count < 1.5 × 10 9 /L, postoperative infection complications and adjuvant chemotherapy < 6 cycles were all independent predictors for ER after curative resection of stage II/III GC. The C-index value obtained for the model was 0.780 (95% CI, 0.747-0.813), and the calibration curves of validation group yielded a C-index value of 0.739 (95% CI, 0.684-0.794), suggesting the practicability of the model., Conclusions: The nomogram which was developed for predicting ER of stage II/III GC after surgery had good accuracy and was verified through both internal and external validation. The nomogram established can assist clinicians in determining the optimal therapy strategies in counseling, adjuvant treatments, and subsequent follow-up planning.

Background: The Charlson comorbidity index (CCI) is commonly used to adjust for patient casemix. We reevaluated the CCI in an ischemic stroke (IS) cohort to determine whether the original seventeen comorbidities and their weights are relevant., Methods: We identified an IS cohort (N = 6988) from the Ontario Stroke Registry (OSR) who were discharged from acute hospitals (N = 100) between April 1, 2012 and March 31, 2013. We used hospital discharge ICD-10-CA data to identify Charlson comorbidities. We developed a multivariable Cox model to predict one-year mortality retaining statistically significant (P < 0.05) comorbidities with hazard ratios ≥1.2. Hazard ratios were used to generate revised weights (1-6) for the comorbid conditions. The performance of the IS adapted Charlson comorbidity index (ISCCI) mortality model was compared to the original CCI using the c-statistic and continuous Net Reclassification Index (cNRI)., Results: Ten of the 17 Charlson comorbid conditions were retained in the ISCCI model and 7 had reassigned weights when compared to the original CCI model . The ISCCI model showed a small but significant increase in the c-statistic compared to the CCI for 30-day mortality (c-statistic 0.746 vs. 0.732, p = 0.009), but no significant increase in c-statistic for in-hospital or one-year mortality. There was also no improvement in the cNRI when the ISCCI model was compared to the CCI., Conclusions: The ISCCI model had similar performance to the original CCI model. The key advantage of the ISCCI model is it includes seven fewer comorbidities and therefore easier to implement in situations where coded data is unavailable.

Background: Type A insulin resistance syndrome, one type of the hereditary insulin resistance syndromes, is a rare disorder. Patients with type A insulin resistance syndrome are nonobese and demonstrate severe hyperinsulinemia, hyperandrogenism, and acanthosis nigricans. The clinical features are more severe in affected females than in males, and they mostly become apparent at the age of puberty. In many cases, when severe insulin resistance is covered up by other signs or symptoms of type A insulin resistance syndrome, patients are often easily misdiagnosed with other diseases, such as polycystic ovary syndrome., Case Presentation: Our patient was a 27-year-old Han Chinese woman who sought treatment because of a menstrual disorder and hirsutism. Tests showed that her levels of insulin and testosterone were elevated, and gynecological color Doppler ultrasound suggested multiple cystic changes in the bilateral ovaries. After a diagnosis of polycystic ovary syndrome was made, pulsatile gonadotropin-releasing hormone therapy and metformin were administered, but the patient's symptoms did not improve in 1 year of follow-up. Considering that the previous diagnosis might have been incorrect, venous blood samples were collected from the patient and her relatives for genetic analysis. Subsequently, using Illumina sequencing, it was found that the proband, her father, and two brothers all had the c.3601C>T heterozygous missense mutation in exon 20 of the insulin receptor gene. The diagnosis was corrected to type A insulin resistance syndrome, and the patient's treatment was modified., Conclusion: We report a case of a young woman with type A insulin resistance syndrome that was misdiagnosed as polycystic ovary syndrome. We discuss the causes, clinical features, diagnosis, and treatment of type A insulin resistance syndrome to improve the recognition of the disease and reduce its misdiagnosis. Female patients with high androgen levels and severe hyperinsulinemia should be considered for the possibility of hereditary insulin resistance syndromes (such as type A insulin resistance syndrome). Gene sequencing helps in making an early diagnosis and developing a targeted treatment strategy.

Background: Tumor motion may compromise the accuracy of liver stereotactic radiotherapy. In order to carry out a precise planning, estimating liver tumor motion during radiotherapy has received a lot of attention. Previous approach may have difficult to deal with image data corrupted by noise. The iterative closest point (ICP) algorithm is widely used for estimating the rigid registration of three-dimensional point sets when these data were dense or corrupted. In the light of this, our study estimated the three-dimensional (3D) rigid motion of liver tumors during stereotactic liver radiotherapy using reconstructed 3D coordinates of fiducials based on the ICP algorithm., Methods: Four hundred ninety-five pairs of orthogonal kilovoltage (KV) images from the CyberKnife stereo imaging system for 12 patients were used in this study. For each pair of images, the 3D coordinates of fiducial markers inside the liver were calculated via geometric derivations. The 3D coordinates were used to calculate the real-time translational and rotational motion of liver tumors around three axes via an ICP algorithm. The residual error was also investigated both with and without rotational correction., Results: The translational shifts of liver tumors in left-right (LR), anterior-posterior (AP),and superior-inferior (SI) directions were 2.92 ± 1.98 mm, 5.54 ± 3.12 mm, and 16.22 ± 5.86 mm, respectively; the rotational angles in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were 3.95° ± 3.08°, 4.93° ± 2.90°, and 4.09° ± 1.99°, respectively. Rotational correction decreased 3D fiducial displacement from 1.19 ± 0.35 mm to 0.65 ± 0.24 mm (P<0.001)., Conclusions: The maximum translational movement occurred in the SI direction. Rotational correction decreased fiducial displacements and increased tumor tracking accuracy.

Background: Previous research revealed that luteolin could improve the activation of alkaline phosphatase (ALP) and osteocalcin in mouse osteoblasts. We aimed to determine the effect of luteolin on osteogenic differentiation of periodontal ligament cells (PDLCs)., Methods: Cultured human PDLCs (HPDLCs) were treated by luteolin at 0.01, 0.1, 1, 10, 100 μmol/L, Wnt/β-catenin pathway inhibitor (XAV939, 5 μmol/L) alone or in combination with 1 μmol/L luteolin. Immunohistochemical staining was performed to ensure cells source. Cell activity and the ability of osteogenic differentiation in HPDLCs were determined by MTT, ALP and Alizarin Red S staining. Real-time Quantitative PCR Detecting System (qPCR) and Western blot were performed to measure the expressions of osteogenic differentiation-related genes such as bone morphogenetic protein 2 (BMP2), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), Osterix (OSX) and Wnt/β-catenin pathway proteins members cyclin D1 and β-catenin., Results: Luteolin at concentrations of 0.01, 0.1, 1, 10, 100 μmol/L promoted cell viability, ALP activity and increased calcified nodules content in HPDLCs. The expressions of BMP2, OCN, OSX, RUNX2, β-catenin and cyclin D1 were increased by luteolin at concentrations of 0.01, 0.1, 1 μmol/L, noticeably, 1 μmol/L luteolin produced the strongest effects. In addition, XAV939 inhibited the expressions of calcification and osteogenic differentiation-related genes in HPDLCs, and 1 μmol/L luteolin availably decreased the inhibitory effect., Conclusion: 1 μmol/L luteolin accelerated osteogenic differentiation of HPDLCs via activating the Wnt/β-catenin pathway, which could be clinically applied to treat periodontal disease.

Background: The emergency department (ED) sensitive hospital standardized mortality ratio (ED-HSMR) measures risk-adjusted mortality for patients admitted to hospital with conditions for which ED care may improve health outcomes. This study aimed to describe in-hospital mortality across Canadian provinces using the ED-HSMR., Methods: Hospital discharge data were analyzed from April 2009 to March 2012. The ED-HSMR was calculated as the ratio of observed deaths among patients with emergency-sensitive conditions in a hospital during a year (2010-11 or 2011-12) to the expected deaths for the same patients during the reference year (2009-10), multiplied by 100. The expected deaths were estimated using predictive models fitted from the reference year. Aggregated provincial ED-HSMR values were calculated. A HSMR value above or below 100 respectively means that more or fewer deaths than expected occurred within a province., Results: During the study period, 1,335,379 patients were admitted to hospital in Canada with an emergency-sensitive condition as the most responsible diagnosis. More in-hospital deaths (95% confidence interval) than expected were respectively observed for the years 2010-11 and 2011-12 in Newfoundland [124.3 (116.3-132.6); & 117.6 (110.1-125.5)] and Nova Scotia [116.4 (110.7-122.5) & 108.7 (103.0-114.5)], while mortality was as expected in Prince Edward Island [99.9 (86.5-114.8) & 100.7 (87.5-115.3)] and Manitoba [99.2 (94.5-104.1) & 98.3 (93.5-103.3)], and less than expected in all other provinces and territories., Conclusions: Our study revealed important variation in risk-adjusted mortality for patients admitted to hospital with emergency-sensitive conditions among Canadian provinces. The ED-HSMR may be a useful outcome indicator to complement existing process indicators in measuring ED performance., Trial Registration: N/A - Retrospective cohort study.

Background: The oosome is the germline determinant in the wasp Nasonia vitripennis and is homologous to the polar granules of Drosophila. Despite a common evolutionary origin and developmental role, the oosome is morphologically quite distinct from polar granules. It is a solid sphere that migrates within the cytoplasm before budding out and forming pole cells., Results: To gain an understanding of both the molecular basis of oosome development and the conserved essential features of germ plasm, we quantified and compared transcript levels between embryo fragments that contained the oosome and those that did not. The identity of the differentially localized transcripts indicated that Nasonia uses a distinct set of molecules to carry out conserved germ plasm functions. In addition, functional testing of a sample of localized transcripts revealed potentially novel mechanisms of ribonucleoprotein assembly and pole cell cellularization in the wasp., Conclusions: Our results demonstrate that the composition of germ plasm varies significantly within Holometabola, as very few mRNAs share localization to the oosome and polar granules. Some of this variability appears to be related to the unique properties of the oosome relative to the polar granules in Drosophila, and some may be related to differences in pole formation between species. This work will serve as the basis for further investigation into the patterns of germline determinant evolution among insects, the molecular basis of the unique properties of the oosome, and the incorporation of novel components into developmental networks.

Background: There is a scarcity of data about the prognostic value of orbital invasion in esthesioneuroblastoma (ENB), as well as about its management strategies. Indications for the preservation of orbital contents remain controversial, and the evaluation of orbital invasion has been ill defined., Methods: This retrospective analysis contained 60 ENB patients with orbital invasion who underwent radiotherapy with or without surgery over the past 14 years. Orbital invasion was classified into three grades., Results: There were 52 patients at stage C and 8 at stage D, according to Foote classifications. Grade I, grade II and grade III orbital invasion was detected in 12, 23, and 25 patients, respectively. The median follow-up was 57 months (IQR 32-95 months). Fourteen patients received radical radiotherapy, with a 5-year overall survival (OS) of 63.5%; 46 received surgery plus radiation, with a 5-year OS of 70.7%; and the difference was not statistically significant (p = 0.847). Orbital preservation was feasible in 100% of cases, including 18 cases that extended to extraocular muscles or the eye globe. Five-year locoregional relapse-free survival was 100% in patients with prophylactic elective neck irradiation (PENI) and 58.1% in patients without PENI (p = 0.004). Univariate analysis showed that grade II/III orbital invasion was associated with poorer OS and progression-free survival. Neck metastasis (with a Foote stage of D) was independently associated with shorter OS and distant metastasis-free survival in multivariate analysis., Conclusions: Our data suggested that primary radiotherapy achieved comparable survival to surgery plus radiotherapy in advanced ENB. Invasion of either the extraocular muscles or the eye globe is not a contraindication for eye-sparing surgery. Orbital invasion in grade II/III was significantly associated with adverse survival outcomes. Prophylactic radiotherapy to the neck with N0 significantly reduces the risk of regional recurrence.

Background: Herpetospermum pedunculosum (Ser.) Baill is annual scandent herbs. They are used in the treatment of piles, inflammation of the stomach and the intestines. It can survive the extreme environment of the Tibetan Plateau (TP). However, the underlying mechanisms of this adaptation to H. pedunculosum from TP remain unclear. Here, we combined physiological and metabolomics methods to analyze H. pedunculosum response to altitude gradient differences., Results: At high altitude, increases in the activities of Ascorbate peroxidase (APX), Glutathione reductase (GR), Dehydroascorbate reductase (DHAR), Monodehydroascorbate reductase (MDHAR), Superoxide dismutase (SOD) have been observed in leaves. Total Glutathion content, total Ascorbate content and the ASA (ascorbic acid)/docosahexaenoic acid (DHA) ration were highly elevated from low altitude to high altitude. In addition, high altitude induces decrease of the Anthocyanidin content (ANTH) and increase of abscisic acid content (ABA). The GC-MS analyses identified of 50 metabolites from leaves of H. pedunculosum. In addition, a metabolic network was constructed based on metabolomic datasets using a weighted correlation network analysis (WGCNA) approach. The network analysis uncovered 4 distinguished metabolic modules highly associated with I, II, III and IV respectively. Furthermore, the analysis successfully classified 50 samples into seven groups: carbohydrates, amino acids, organic acids, lipid components, polyamine, secondary metabolism and others., Conclusions: In the present study, the content of parts of amino acid components increased in samples collected at higher altitudes, and most of metabolites, including carbohydrates and organic acids were assigned to the carbon metabolic pathway comprising reductive pentose phosphate pathway, glycolysis and TCA cycle, indicating the direct relationship between adaptability and the carbon metabolic pathway and amino acids in H. pedunculosum response to high altitude. The results of this study laid the foundation of the molecular mechanism on H. pedunculosum from high altitude.

Background: To investigate whether smoking adversely affects the short-term outcomes and the potential effects of cigarette dose and preoperative smoking cessation, in patients who underwent gastric cancer (GC) surgery., Methods: Two thousand, four hundred sixty-nine consecutive patients who underwent radical gastrectomy from November 2010 to July 2018 were included in the present study. Smokers (current or former smokers) were divided into 3 groups in accordance with the duration of smoking cessation preoperatively (≤ 2, 2 to 4, or ≥ 4 weeks) and the cigarette dose (≤ 20, 20 to 40, and ≥ 40 pack-years). The primary endpoint was postoperative complications (surgical site infection, pulmonary problems, bleeding, and others)., Results: A total of 1056 patients (42.8%) were smokers. Compared with non-smokers, smokers had significantly higher overall postoperative complications (11.3% vs 7.5%, P = 0.001), and in particular pulmonary problems. Smokers also had more major complications, needing intensive care unit care, and longer postoperative hospital stays. Multivariate analysis confirmed that smoking (odds ratio = 1.506, 95% confidence interval 1.131-2.004, P = 0.005) was an independent risk factor for postoperative complications. Further subgroup analysis identified that there was a positive relationship between the incidence of complications and cigarette dose, and > 20 pack-years was demonstrated to have increased significantly the risk of complications. Smokers who stopped smoking ≥ 4 weeks before surgery had lower pulmonary problems than those with a shorter period of smoking cessation., Conclusions: Preoperative smoking cessation should be encouraged to reduce postoperative complications in GC patients, especially for heavy smokers.

Background: Recurrence is not explicitly documented in cancer registry data that are widely used for research. Patterns of events after initial treatment such as oncology visits, re-operation, and receipt of subsequent chemotherapy or radiation may indicate recurrence. This study aimed to develop and validate algorithms for identifying breast cancer recurrence using routinely collected administrative data., Methods: The study cohort included all young (≤ 40 years) breast cancer patients (2007-2010), and all patients receiving neoadjuvant chemotherapy (2012-2014) in Alberta, Canada. Health events (including mastectomy, chemotherapy, radiation, biopsy and specialist visits) were obtained from provincial administrative data. The algorithms were developed using classification and regression tree (CART) models and validated against primary chart review., Results: Among 598 patients, 121 (20.2%) had recurrence after a median follow-up of 4 years. The high sensitivity algorithm achieved 94.2% (95% CI: 90.1-98.4%) sensitivity, 93.7% (91.5-95.9%) specificity, 79.2% (72.5-85.8%) positive predictive value (PPV), and 98.5% (97.3-99.6%) negative predictive value (NPV). The high PPV algorithm had 75.2% (67.5-82.9%) sensitivity, 98.3% (97.2-99.5%) specificity, 91.9% (86.6-97.3%) PPV, and 94% (91.9-96.1%) NPV. Combining high PPV and high sensitivity algorithms with additional (7.5%) chart review to resolve discordant cases resulted in 94.2% (90.1-98.4%) sensitivity, 98.3% (97.2-99.5%) specificity, 93.4% (89.1-97.8%) PPV, and 98.5% (97.4-99.6%) NPV., Conclusion: The proposed algorithms based on routinely collected administrative data achieved favorably high validity for identifying breast cancer recurrences in a universal healthcare system in Canada.

Background: Electronic health records (EHRs) are increasing in popularity across national and international healthcare systems. Despite their augmented availability and use, the quality of electronic health records is problematic. There are various reasons for poor documentation quality within the EHR, and efforts have been made to address these areas. Previous systematic reviews have assessed intervention effectiveness within the outpatient setting or within paper documentation. This systematic review aims to assess the effectiveness of different interventions seeking to improve EHR documentation within an inpatient setting., Methods: We will employ a comprehensive search strategy that encompasses four distinct themes: EHR, documentation, interventions, and study design. Four databases (MEDLINE, EMBASE, CENTRAL, and CINAHL) will be searched along with an in-depth examination of the grey literature and reference lists of relevant articles. A customized hybrid study quality assessment tool has been designed, integrating components of the Downs and Black and Newcastle-Ottawa Scales, into a REDCap data capture form to facilitate data extraction and analysis. Given the predicted high heterogeneity between studies, it may not be possible to standardize data for a quantitative comparison and meta-analysis. Thus, data will be synthesized in a narrative, semi-quantitative manner., Discussion: This review will summarize the current level of evidence on the effectiveness of interventions implemented to improve inpatient EHR documentation, which could ultimately enhance data quality in administrative health databases., Systematic Review Registration: PROSPERO CRD42017083494.

Background: Due to the heterogeneity of patient's individual respiratory motion pattern in lung stereotactic body radiotherapy (SBRT), treatment planning dose assessment using a traditional four-dimensional computed tomography (4DCT&#95;traditional) images based on a uniform breathing curve may not represent the true treatment dose delivered to the patient. The purpose of this study was to evaluate the accumulated dose discrepancy between based on the 4DCT&#95;traditional and true 4DCT (4DCT&#95;true) that incorporated with the patient's real entire breathing motion. The study also explored a novel 4D robust planning strategy to compensate for such heterogeneity respiratory motion uncertainties., Methods: Simulated and measured patient specific breathing curves were used to generate 4D targets motion CT images. Volumetric-modulated arc therapy (VMAT) was planned using two arcs. Accumulated dose was obtained by recalculating the plan dose on each individual phase image and then deformed the dose from each phase image to the reference image. The "4 D dose" (D 4D ) and "true dose" (D true ) were the accumulated dose based on the 4DCT&#95;traditional and 4DCT&#95;true respectively. The average worse case dose discrepancy ([Formula: see text]) between D 4D and D true in all treatment fraction was calculated to evaluate dosimetric /planning parameters and correlate them with the heterogeneity of respiratory-induced motion patterns. A novel 4D robust optimization strategy for VMAT (4D Ro-VMAT) based on the probability density function(pdf) of breathing curve was proposed to improve the target coverage in the presence of heterogeneity respiratory motion. The data were assessed with a paired t-tests., Results: With increasing breathing amplitude from 5 to 20 mm, target [Formula: see text], [Formula: see text] increased from 1.59,1.39 to 10.15%,8.66% respectively. When the standard deviation of breathing amplitude increased from 15 to 35% of the mean amplitude, [Formula: see text], [Formula: see text] increased from 4.06,3.48 to 10.25%,6.63% respectively. The 4D Ro-VMAT plan significantly improve the target dose compared to VMAT plan., Conclusion: When the breathing curve amplitude is more than 10 mm and standard deviation of amplitude is higher than 25% of mean amplitude, special care is needed to choose an appropriated dose accumulation approach to evaluate lung SBRT plan target coverage robustness. The proposed 4D Ro&#95;VMAT strategy based on the pdf of patient specific breathing curve could effectively compensate such uncertainties.